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Mommy Wellness: Tipped Uterus

LilSugar — Tue, 24 Feb 2009 08:00:00 -0800

Early pregnancy can bring on surprises and one of those is a tipped uterus. The pear shaped organ that normally sits upright maybe tilted toward the back of the pelvis for various reasons. According to American Pregnancy Association:

As a woman matures the uterus may not move into a forward position.

Childbirth can tip the uterus forward or backward. If the ligaments holding the uterus in place stretch, or lose their tension during pregnancy, the uterus can become tipped. In most cases, the uterus returns to a forward position after childbirth

Scarring from adhesions as a result of endometriosis or fibroids can also cause the uterus to shift to a tilted or retroflexed state. Sometimes a uterine suspension is used in conjunction with treatments for endometriosis to prevent the formation of adhesions after surgery.

By the 10th to 12th week of pregnancy, the uterus normally moves into the proper position.
Source

Menstrual disorders

FitSugar — Wed, 08 Oct 2008 17:34:59 -0700

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

“No-Period” Pill Approved

In May 2007, the FDA approved Lybrel, the first birth control pill that completely eliminates monthly menstrual periods. Lybrel contains low doses of the estrogen estradiol and the progesterone levonorgestrol. The active pills are taken 365 days a year -- with no inactive pill breaks. In clinical trials, 59% of women who took Lybrel completely stopped menstrual periods by the end of the first year. Some women, however, continued to have occasional unscheduled bleeding or spotting during the first 3 - 6 months.

Other Options for Eliminating Menstrual Periods

In addition to Lybrel, women with menstrual problems have several other options for stopping periods:

Levonorgestrol-Releasing Intrauterine System (LNG-IUS). The LNG-IUS is an intrauterine device (IUD) that is placed in the uterus. The LNG-IUS releases levonorgestrol for up to 5 years. Over the course of the first year, it reduces menstrual bleeding. Many women find that their periods completely stop. Doctors often recommend this contraceptive device as a treatment for menorrhagia (heavy bleeding) and an alternative to hysterectomy. In the U.S., the LNG-IUS is marketed as Mirena.
Depo-Provera. Depo-Provera is an injectable progestin contraceptive. Most women who use Depo-Provera stop menstruating after a year. However, Depo-Provera is associated with serious side effects, including loss of bone density. Because of this risk, the FDA recommends that Depo-Provera should not be used for more than 2 years. Weight gain is also a common side effect.
Hysterectomy. Hysterectomy, the surgical removal of the uterus, is a permanent cure for menorrhagia, but it is an invasive procedure that also ends fertility.

Menstruation in Girls and Adolescents

According to a 2006 report from the American Academy of Pediatrics and the American College of Obstetricians and Gynecologists:

Most girls begin to menstruate when they are between 12 - 13 years old.
Menstruation usually starts 2 - 3 years after initial breast development.
Girls who have not begun menstruation by the age of 15 should see a doctor for an evaluation.

Introduction

The Primary Organs and Structures in the Reproductive System.

The uterus is a pear-shaped organ located between the bladder and lower intestine. It consists of two parts, the body and the cervix.
When a woman is not pregnant the body of the uterus is about the size of a fist, with its walls collapsed and flattened against each other. During pregnancy, the walls of the uterus are pushed apart as the fetus grows.
The cervix is the lower portion of the uterus. It has a canal opening into the vagina with an opening called the os, which allows menstrual blood to flow out of the uterus into the vagina.
Leading off each side of the body of the uterus are two tubes known as the fallopian tubes. Near the end of each tube is an ovary.
Ovaries are egg-producing organs that hold 200,000 - 400,000 follicles (from folliculus, meaning "sack" in Latin). These cellular sacks contain the materials needed to produce ripened eggs, or ova.
The inner lining of the uterus is called the endometrium, and during pregnancy it thickens and becomes enriched with blood vessels to house and support the growing fetus. If pregnancy does not occur, the endometrium is shed and a woman starts her menstrual flow (or "period"). Menstrual flow also consists of blood and mucus from the cervix and vagina.

The uterus is a hollow muscular organ located in the female pelvis between the bladder and rectum. The ovaries produce the eggs that travel through the fallopian tubes. Once the egg has left the ovary it can be fertilized and implant itself in the lining of the uterus. The main function of the uterus is to nourish the developing fetus prior to birth.

Reproductive Hormones. The hypothalamus (an area in the brain) and the pituitary gland control the reproductive hormones. In women, six hormones help regulate the reproductive system:

Click the icon to see an image of the hypothalamus and pituitary gland.

Gonadotropin-releasing hormone (GnRH) is released by the hypothalamus.
GnRH stimulates the pituitary gland to produce follicle-stimulating hormone (FSH) and luteinizing hormone (LH).
Estrogen, progesterone, and the male hormone testosterone are secreted by the ovaries at the command of FSH and LH.

Click the icon to see an image of the pituitary gland.

Ovulation. The process leading to fertility is very intricate. It depends on the healthy interaction of two sets of organs and hormone systems in both the male and female. In addition, reproduction is limited by the phases of female fertility. Nevertheless, this astonishing process results in conception within a year for about 80% of couples. Only 15% conceive within a month of their first attempts, however, and about 60% succeed after 6 months.

A woman's ability to produce children occurs after she enters puberty and begins to menstruate. The process to conception is complex:

With the start of each menstrual cycle, FSH stimulates several follicles to mature over a two-week period until their eggs nearly triple in size. Only one follicle becomes dominant, however, during a cycle.
FSH signals this dominant follicle to produce estrogen, which enters the bloodstream and reaches the uterus. There, estrogen stimulates the cells in the uterine lining to reproduce, therefore thickening the walls.
Estrogen levels reach their peak around the 14th day of the cycle (counting days beginning with the first day of a period). At that time, they trigger a surge of LH.

LH serves two important roles:

First, the LH surge around the 14th cycle day stimulates ovulation. It does this by causing the dominant follicle to burst and release its egg into one of the two fallopian tubes. Once in the fallopian tube, the egg is in place for fertilization.
Next, LH causes the ruptured follicle to develop into the corpus luteum. The corpus luteum provides a source of estrogen and progesterone during pregnancy.

Fertilization. The so-called "fertile window" is 6 days long and starts 5 days before ovulation and ends the day of ovulation. Fertilization occurs as follows:

The sperm can survive for up to 3 days once it enters the fallopian tube. The egg survives 12 - 24 hours unless it is fertilized by a sperm.
If the egg is fertilized, it moves about 2 - 4 days later from the fallopian tube into the uterus where it is implanted in the uterine lining and begins its nine-month incubation.
The placenta forms at the site of the implantation. The placenta is a thick blanket of blood vessels that nourishes the fertilized egg as it develops.
The corpus luteum (the yellow tissue formed from the ruptured follicle) continues to produce estrogen and progesterone during pregnancy.

Click the icon to see an image of the placenta.

Click the icon to see an image of the corpus luteum.

If the egg is not fertilized, the corpus luteum degenerates into a form called the corpus albicans, and estrogen and progesterone levels drop. Finally, the endometrial lining sloughs off and is shed during menstruation.


Menstrual Phases	Typical No. of Days	Hormonal Actions
Follicular (Proliferative) Phase	Cycle Days 1 through 6: Beginning of menstruation to end of blood flow.	Estrogen and progesterone start out at their lowest levels. FSH levels rise to stimulate maturity of follicles. Ovaries start producing estrogen and levels rise, while progesterone remains low.
	Cycle Days 7 - 13: The endometrium thickens to prepare for the egg implantation.
Ovulation	Cycle Day 14:	Surge in LH. Largest follicle bursts and releases egg into fallopian tube.
Luteal (Secretory) Phase, also known as the Premenstrual Phase	Cycle Days 15 - 28:	Ruptured follicle develops into corpus luteum, which produces progesterone. Progesterone and estrogen stimulate blanket of blood vessels to prepare for egg implantation.
	If fertilization occurs:	Fertilized egg attaches to blanket of blood vessels that supplies nutrients for the developing placenta. Corpus luteum continues to produce estrogen and progesterone.
	If fertilization does not occur:	Corpus luteum deteriorates. Estrogen and progesterone levels drop. The blood vessel lining sloughs off and menstruation begins.

Click the icon to see an animation about the menstrual cycle.

What is Menstruation? Menstruation, also called a "period," is the cyclical flow of blood from the uterus in women between the ages of puberty and menopause.

Onset of Menstruation (Menarche). The onset of menstruation, called the menarche, typically begins between the ages of 12 - 13 years. Menarche generally occurs 2 - 3 years after initial breast development (breast budding). African-American and Hispanic girls tend to mature slightly earlier than Caucasian girls. A higher body mass index (BMI) during childhood is associated with an earlier onset of puberty. Environmental factors and nutrition may also affect menarche timing.

Length of Monthly Cycle. The menstrual cycle can be very irregular during the first 1 - 2 years, ranging from 21 - 45 days. The length then generally stabilizes to an average of 28 days, although the cycle length may range from 21 - 34 days and still be considered normal. A variation of 10 days or more -- either more or fewer days -- may have an impact on fertility, however. The cycle lengthens when a woman is in her 40s, reaching an average of 31 days by age 49. A number of factors can affect cycle length at any age.


Shorter Cycles	Longer Cycles
Regular alcohol use.	Being under 21 and over 44.
Stressful jobs.	Being very thin (also at risk for short bleeding periods).
	Competitive athletics (also at risk for short bleeding periods).

Length of Periods. Periods average 6.6 days in adolescent girls. By the age of 21, menstrual bleeding averages 6 days until women approach menopause. However, about 5% of healthy women menstruate fewer than 4 days and 5% menstruate more than 8 days.

Normal Absence of Menstruation. Normal absence of periods can occur in any woman under the following circumstances:

Menstruation stops during the duration of pregnancy. Some women continue to have irregular bleeding during the first trimester. This bleeding may indicate a threatened miscarriage and requires immediate attention by the doctor.
When women breastfeed they are unlikely to ovulate. After that time, menstruation usually resumes and they are fertile again.
Perimenopause starts when the intervals between periods begin to lengthen, and it ends with menopause itself (the complete cessation of menstruation). Menopause usually occurs at about age 51, although smokers often go through menopause earlier.

Menstrual Disorders

There are a number of different menstrual disorders. Problems can range from heavy, painful periods to no period at all.

Dysmenorrhea is severe, frequent cramping during menstruation. Pain occurs in the lower abdomen but can spread to the lower back and thighs. Dysmenorrhea is usually referred to as primary or secondary.

Primary dysmenorrhea. Cramps occur from contractions in the uterus. These contractions are a normal part of the menstrual process. With primary dysmenorrhea, cramping pain is directly related to and caused by menstruation. About half of menstruating women experience primary dysmenorrhea. It usually begins 2 - 3 years after a women begins to menstruate. The pain typically develops when the bleeding starts and continues for 32 - 48 hours. Cramps are generally most severe during heavy bleeding.

Secondary dysmenorrhea. Secondary dysmenorrhea is menstrually related pain that accompanies another medical or physical condition, such as endometriosis or uterine fibroids.

During a normal menstrual cycle, the average woman loses about 1 ounce (30 mL) of blood. Most women change their tampons or pads around 3 - 6 times per day. Menorrhagia is the medical term for significantly heavier bleeding. Menorrhagia occurs in 9 - 14% of all women and can be caused by a number of factors. Women often overestimate the amount of blood lost during their periods. Clot formation is fairly common during heavy bleeding and is not a cause for concern. However, women should consult their doctor if any of the following occurs:

Soaking through at least one pad or tampon every 1 - 2 hours for several hours
Heavy periods that regularly last 10 or more days
Bleeding between periods or during pregnancy. Spotting or light bleeding between periods is common in girls just starting menstruation and sometimes during ovulation in young adult women, but it is still a good idea to speak with a doctor.

Amenorrhea is the absence of menstruation. There are two categories: primary amenorrhea and secondary amenorrhea. These terms refer to the time when menstruation stops:

Primary amenorrhea occurs when a girl does not begin to menstruate. Girls who show no signs of sexual development (breast development and pubic hair) by age 13 should be evaluated by a doctor. Any girl who does not have her period by age 15 should be evaluated for primary amenorrhea.
Secondary amenorrhea occurs when periods that were previously regular become absent for at least three cycles.

Oligomenorrhea is a condition in which menstrual cycles are infrequent. It is very common in early puberty and does not usually indicate a medical problem. When girls first menstruate they often do not have regular cycles for a couple of years. Even healthy cycles in adult women can vary by a few days from month to month. In some women, periods may occur every 3 weeks and in others, every 5 weeks. Flow also varies and can be heavy or light. Skipping a period and then having a heavy flow may occur; this is most likely due to missed ovulation rather than a miscarriage. Women should be concerned when periods come less than 21 days or more than 3 months apart, or if they last more than 10 days. Such events may indicate ovulation problems.

Premenstrual syndrome (PMS) is a set of physical, emotional, and behavioral symptoms that occur during the last week of the luteal phase (a week before menstruation) in most cycles. The symptoms typically do not start until at least day 13 in the cycle, and resolve within 4 days after bleeding begins. Women may begin to experience premenstrual syndrome symptoms at any time during their reproductive years. Once established, the symptoms tend to remain fairly constant until menopause, although they can vary from cycle to cycle. About 100 symptoms have been identified with the premenstrual phase. [See In-Depth Report #79: Premenstrual syndrome.]

Causes

Menstrual disorders can be triggered by a number of different factors, such as hormone imbalances, genetic factors, clotting disorders, and pelvic diseases.

Contraction-Causing Chemicals. Powerful chemicals known as prostaglandins and arachidonic acid can induce uterine muscle contractions. Prostaglandins also play a large role in the heavy bleeding that causes dysmenorrhea.
Abnormal Nervous System Response. Some women with primary dysmenorrhea may have autonomic nervous systems that are overly sensitive to menstrual cycle changes. The autonomic nervous system regulates heart rate and blood pressure, and it contains the pain receptors in nerve fibers in the uterus and pelvic area. As a result, women with autonomic nervous system abnormalities may have a more intense response to pain.
Abnormalities in the Arteries in the Uterus.Impaired blood flow through the arteries in the uterus may cause severe dysmenorrhea for some women.
Genetic Factors. Genetic factors may play an important role in over half of primary dysmenorrhea cases.
Endometriosis. Endometriosis is a chronic and often progressive disease that develops when the tissue that lines the uterus (endometrium) grows onto other areas, such as the ovaries, bowels, or bladder. [See In-Depth Report #74: Endometriosis.]

Endometriosis is the condition in which the tissue that normally lines the uterus (endometrium) grows on other areas of the body causing pain and irregular bleeding.

Uterine Fibroids. Fibroids are noncancerous growths that grow on the walls of the uterus. They can cause heavy bleeding during menstruation and cramping pain. [See In-Depth Report #73: Uterine fibroids.]
Other Causes. Pelvic inflammatory disease, ovarian cysts, and ectopic pregnancy. The intrauterine device (IUD) contraceptive can also cause dysmenorrhea.

Hormonal imbalances and uterine fibroids are the most common causes of menorrhagia. Other causes of menorrhagia include:

Dysfunctional Uterine Bleeding (DUB). DUB is a general term for abnormal bleeding. It is usually caused by hormonal problems and is one of the primary causes of menorrhagia. DUB usually occurs either when girls begin to menstruate or when women approach menopause, but it can occur at any time in during a woman's reproductive life. About 90% of DUB events occur when ovulation is not occurring (anovulatory DUB). In such cases, women do not properly develop and release a mature egg. When this happens, the corpus luteum does not form. As a result, estrogen is produced continuously, causing an overgrowth of the uterus lining. The period is delayed in such cases, and when it occurs menstruation can be very heavy and prolonged. The other 10% of DUB cases occur in women who are ovulating (ovulatory DUB), but progesterone secretion is prolonged because estrogen levels are low. This causes irregular shedding of the uterine lining and break-through bleeding.
Von Willebrand Disease and Other Bleeding Disorders. Bleeding disorders that stop blood from clotting can cause heavy menstrual bleeding. Most of these disorders have a genetic basis. Von Willebrand disease is the most common of these bleeding disorders and may be underdiagnosed in many women with unexplained menorrhagia.
Abnormal Blood Vessel Growth. Every month, blood vessels regrow in the uterus to replace the blood-rich uterine lining lost during menstruation. Abnormalities in this growth process (called arteriogenesis or angiogenesis) may occur in some women with menorrhagia.
Abnormalities in the Uterus. Structural problems or other abnormalities in the uterus may cause bleeding. They include uterine polyps (small benign growths in the uterus), uterine fibroids, endometriosis, adenomyosis, and miscarriage. Infections or inflammation in the vagina or pelvic area can also cause heavy bleeding.
Medications. Certain drugs, including anticoagulants and anti-inflammatory medications, can cause heavy bleeding.
Cancer. Uterine, ovarian, and cervical cancer can cause excessive bleeding but these are rare causes.
Other Medical Conditions. Systemic lupus erythematosus, diabetes, pelvic inflammatory disorder, and thyroid disorders can cause heavy bleeding. Women who have migraine headaches may be more likely to experience menorrhagia and endometriosis.

Fibroid tumors may not need to be removed if they are not causing pain, bleeding excessively, or growing rapidly.

Normal causes of skipped or irregular periods include pregnancy, breastfeeding, hormonal contraception, and perimenopause. Skipped periods are also common during adolescence, when it may take a while before ovulation occurs regularly. Consistently absent periods may be due to the following factors:

Delayed Puberty. The most common cause of primary amenorrhea is delayed puberty due to some genetic factor that delays physical development.
Weight Loss and Eating Disorders. Extreme weight loss and reduced fat stores lead to hormonal changes that include low thyroid levels (hypothyroidism) and elevated stress hormone levels (hypercortisolism). These changes produce a reduction in reproductive hormones. A syndrome known as the female athlete triad is associated with hormonal changes that occur with eating disorders in young women who excessively exercise. It comprises anorexia (severe weight loss), amenorrhea, and osteoporosis (decrease in bone density).
Polycystic Ovarian Syndrome (PCOS). PCOS is a condition in which the ovaries produce high amounts of androgens (male hormones), particularly testosterone. PCOS occurs in about 6% of women, and amenorrhea or oligomenorrhea (infrequent menses) is quite common. According to some studies, nearly 30% of obese women with PCOS have amenorrhea.
Elevated Prolactin Levels (Hyperprolactinemia). Prolactin is a hormone produced in the pituitary gland that stimulates breast development and milk production in association with pregnancy. High levels of prolactin (hyperprolactinemia) in women who are not pregnant or nursing can reduce gonadotropin hormones and inhibit ovulation, thus causing amenorrhea. It is the cause of between 10 - 40% of cases of secondary amenorrhea.
Premature Ovarian Failure (POF). POF is the early depletion of follicles before age 40. In most cases it leads to premature menopause. POF is a significant cause of infertility.
Structural Problems. In some cases, structure problems or scarring in the uterus may prevent menstrual flow. Inborn genital tract abnormalities may also cause primary amenorrhea. A specific malformation called Mullerian agenesis, in which no vagina or uterus develops, is rare but still causes about 16% of primary amenorrhea cases.
Stress. Physical and emotional stress may block the release of luteinizing hormone, causing temporary amenorrhea
Other Medical Conditions. Epilepsy, thyroid problems, celiac sprue, metabolic syndrome, and Cushing's disease are associated with amenorrhea.

If the ovaries produce too much androgen (hormones such as testosterone) a woman may develop male characteristics. This ovarian imbalance can be caused by tumors in the ovaries or adrenal glands, or polycystic ovarian disease. Virilization may include growth of excess body and facial hair, amenorrhea (loss of menstrual period) and changes in body contour.

Risk Factors

Age plays a key role in menstrual disorders. Girls who start menstruating at age 11 or younger are at higher risk for severe pain, longer periods, and longer menstrual cycles. Between 20 - 90% of teenage girls report menstrual pain and about 15% report that it is severe. Adolescents may experience amenorrhea before their ovulating cycles become regular.

Women who are approaching menopause (perimenopause) may also skip periods. Occasional episodes of heavy bleeding are also common as women approach menopause.

Other risk factors include:

Weight. Being either excessively overweight or underweight can increase the risk for dysmenorrhea and amenorrhea.
Smoking and Alcohol Use. Smokers have a 50% higher risk than nonsmokers for menstrual pain. Alcohol does not cause menstrual pain, but in women with existing dysmenorrhea, alcohol consumption may prolong the pain.
Stress. Physical and emotional stress may block the release of luteinizing hormone, causing temporary amenorrhea. Emotional problems, including history of sexual abuse, may predispose to dysmenorrhea.
Menstrual Cycles and Flow. Longer and heavier menstrual cycles can cause dysmenorrhea.
Pregnancy History. Women who have had a higher number of pregnancies are at increased risk for menorrhagia. Women who have never given birth are at increased risk of dysmenorrhea, while women who first gave birth at a young age are at lower risk.
Chronic Pelvic Pain. Many women experience chronic pain in the pelvic area. This pain can be due to gynecologic reasons (fibroids, endometriosis, pelvic inflammatory disease) or non-gynecologic causes (irritable bowel syndrome, interstitial cystitis, diverticulitis).

Exercise and oral contraceptive use may help protect against dysmenorrhea.

Complications

An estimated 10 - 15% of all women in their reproductive years have chronic gynecologic problems. Nearly 30% of women reporting such problems spend one or more days in bed per year because of them. In fact, menstrual pain is the primary cause of short-term absences in school age girls. In adult women, who have not received treatment, it is an important cause of reduced work productivity.

Menorrhagia is the most common cause of anemia in premenopausal women. A blood loss of more than 80mL per menstrual cycle can trigger anemia. According to one report, 10% of women in their reproductive years have iron deficiencies, and between 2 - 5% have iron levels low enough to cause anemia. Although poor diets play a role in many cases, the problem is compounded in women who have heavy periods.

Most cases of anemia are mild. Nevertheless, even mild anemia can reduce oxygen transport in the blood, causing fatigue and a diminished physical capacity. (Some studies indicate that even iron deficiency without anemia can produce a subtle but still lower capacity for exercise.) Moderate-to-severe iron-deficiency anemia is known to reduce endurance.

Moderate-to-severe anemia can also cause shortness of breath, rapid heart rate, lightheadedness, headaches, ringing in the ears (tinnitus), irritability, pale skin, restless legs syndrome, and mental confusion. Heart problems can occur in prolonged and severe anemia that is not treated. Pregnant women who are anemic, particularly in the first trimester, have an increased risk for a poor pregnancy outcome. [See In-Depth Report #57: Anemia.]

Amenorrhea caused by reduced estrogen levels increases the risk for osteoporosis (loss of bone density). Conditions that are associated with low estrogen levels include eating disorders, the female-athlete triad (excessive exercise and weight loss), pituitary tumors, and premature ovarian failure. Because bone growth is at its peak in adolescence and young adulthood, losing bone density at that time is very dangerous, and early diagnosis and treatment is essential for long-term health. [See In-Depth Report #18: Osteoporosis.]

Osteoporosis is a condition characterized by progressive loss of bone density, thinning of bone tissue, and increased vulnerability to fractures. Osteoporosis may result from disease, dietary or hormonal deficiency, or advanced age. Regular exercise and vitamin and mineral supplements can reduce and even reverse loss of bone density.

Some conditions associated with heavy bleeding, such as ovulation abnormalities, fibroids, or endometriosis, are important contributors to infertility. Many conditions that cause amenorrhea, such as ovulation abnormalities and polycystic ovary syndrome, can also cause infertility. Irregular periods from any cause may make it more difficult to conceive. In some cases treating the underlying condition can restore fertility. In other cases, specific fertility treatments that use assisted reproductive technologies may be beneficial. [See In-Depth Report #22: Infertility in women.]

Diagnosis

A doctor needs to have a complete history of any medical or personal conditions that might be causing menstrual disorders. This information can help determine whether a menstrual problem is caused by another medical condition. For example, non-menstrual conditions that may cause abdominal pain include appendicitis, urinary tract infections, ectopic pregnancy, and irritable bowel syndrome. Endometriosis and fibroids may cause heavy bleeding and pain. Doctors may ask questions concerning:

Menstrual cycle patterns -- length of time between periods, number of days that periods last, number of days of heavy or light bleeding
The presence or history of any medical conditions that might be causing menstrual problems
Any family history of menstrual problems
History of pelvic pain
Regular use of any medications (including vitamins and over-the-counter drugs)
Diet history, including caffeine and alcohol intake
Past or present contraceptive use
Any recent stressful events
Sexual history (it is very important that patients trust their doctor enough to describe any sexual activity that might be risky)

Menstrual Diary. A menstrual diary is a helpful way to keep track of changes in menstrual cycles. Patients can record when their period starts, how long it lasts, and the amount of bleeding and pain that occurs during the course of menstruation.

Pelvic Examination. A pelvic exam is a standard part of diagnosis. A Pap test may be done during this exam.

Blood tests can help rule out other conditions that cause menstrual disorders. For example, a doctor may test thyroid function to make sure that low thyroid (hypothyroidism) is not present. Blood tests can also check follicle-stimulating hormone, estrogen, and prolactin levels. Patients who have menorrhagia may get tests for bleeding disorders. If patients are losing a lot of blood, they should also get tested for anemia.

Patients who have amenorrhea may need to receive special hormonal tests. The progestational challenge test uses oral or injected progesterone to test for a functional uterine lining (endometrium):

Bleeding that occurs up to 3 weeks after the progesterone dose suggests that the woman has normal estrogen levels but is not ovulating, particularly if thyroid and prolactin levels are normal. In such cases, the doctor will check for stress, recent weight loss, and any medications. Such results could also suggest polycystic ovaries or stress.
A failure to bleed could indicate an abnormal uterus that prevents outflow or insufficient estrogen. In such cases, the next step may be to administer estrogen followed by progestin. If bleeding occurs after that, then the cause of amenorrhea is related to low estrogen levels. The doctor will then check for ovarian failure, anorexia, or other causes of low estrogen. If bleeding does not occur, then the doctor would check for obstructions that are preventing outflow of menstruation.

Imaging techniques are often used to detect certain conditions that may be causing menstrual disorders. Imaging can help diagnose fibroids, endometriosis, or structural abnormalities of the reproductive organs.

Ultrasound and Sonohysterography. Ultrasound is the standard imaging technique for evaluating the uterus and ovaries, detecting fibroids, ovarian cysts and tumors, and finding obstructions in the urinary tract. It uses sound waves to produce an image of the organs. Ultrasound carries no risk and causes very little discomfort.

Transvaginal sonohysterography uses ultrasound along with saline injected into the uterus to enhance the visualization of the uterus.

Hysteroscopy. Hysteroscopy is a procedure that may be used to detect the presence of fibroids, polyps, or other causes of bleeding. It may miss cases of uterine cancer, however, and is not a substitute for more invasive procedures, such as D&C or endometrial biopsy, if cancer is suspected.

It is done in the office setting and requires no incisions. The procedure uses a long flexible or rigid tube called a hysteroscope, which is inserted into the vagina and through the cervix to reach the uterus. A fiber optic light source and a tiny camera in the tube allow the doctor to view the cavity. The uterus is filled with saline or carbon dioxide to inflate the cavity and provide better viewing. This can cause cramping.

Hysteroscopy is non-invasive, but 30% of women report severe pain with the procedure. The use of an anesthetic spray such as lidocaine may be highly effective in preventing pain from this procedure. Other complications include excessive fluid absorption, infection, and uterine perforation. Hysteroscopy is also performed as part of surgical procedures.

Laparoscopy. Diagnostic laparoscopy, an invasive surgical procedure, is currently the only definitive method for diagnosing endometriosis. Laparoscopy normally requires a general anesthetic, although the patient can go home the same day. The procedure is as follows:

Click the icon to see an image of laparoscopy.

The surgeon makes tiny abdominal incisions through which a fiber optic tube, equipped with small camera lenses, is inserted. The doctor uses these devices to view the uterus, ovaries, tubes, and peritoneum (lining of the pelvis) on a video monitor.
Carbon dioxide gas is injected into the abdomen, distending it and pushing the bowel away so that the doctor has a wider view.
A blue dye may be flushed through the fallopian tubes to determine blockage; if there is an obstruction, the dye will not flow through the tube.
If the surgeon needs to remove small endometrial cysts or other lesions during the procedure (operative laparoscopy), tiny surgical instruments are passed through a tube.

The procedure is used for detecting and staging endometriosis to determine its severity. In some cases, the procedure itself will restore fertility in women with endometriosis.

Transvaginal Hydrolaparoscopy. Transvaginal hydrolaparoscopy is a new and less invasive approach than laparoscopy, since the instruments are inserted through the vagina, not through incisions in the abdomen. It requires only sedation, does not use CO2 to distend the abdomen, and has a much shorter and easier recovery than with standard laparoscopy. When used by a skilled professional, it is as accurate as laparoscopy, but is not yet widely available.

Endometrial Biopsy With or Without Dilation and Curettage (D&C). When heavy or abnormal bleeding occurs, an endometrial (uterine) biopsy can be performed in the office along with an ultrasound. It is usually used with a procedure called dilation and curettage (D&C), which is particularly important to rule out uterine (endometrial) cancer. A D&C is a somewhat invasive procedure:

A D&C is usually done in an outpatient setting so that the patient can return home the same day, but it sometimes requires a general anesthetic. It may need to be performed in the operating room to rule out serious conditions or treat some minor ones that may be causing the bleeding.
The cervix (the neck of the uterus) is dilated (opened).
The surgeon scrapes the inside lining of the uterus and cervix.

The procedure is used to take samples of the tissue and to relieve heavy bleeding in some instances. D&C can also be effective in scraping off small endometrial polyps, but it is not very useful for most fibroids, which tend to be larger and more firmly attached.

Click the icon to see an image of a D&C.

Treatment

Making dietary adjustments starting about 14 days before a period may help some women with certain mild menstrual disorders, such as cramping. The general guidelines for a healthy diet apply to everyone; they include eating plenty of whole grains, fresh fruits and vegetables, and avoiding saturated fats and commercial junk foods.

Dietary Fats. A 2000 study reported that women who followed a low-fat vegetarian diet for two menstrual cycles experienced less pain and bloating and a shorter duration of premenstrual symptoms than those who ate meat. Women who are losing too much blood, however, may need meat to help maintain iron levels. Choosing more fish and eggs may be a helpful alternative.

More than one study has reported less menstrual pain with a higher intake of omega 3 fatty acids (fat compounds found in oily fish, such as salmon and tuna). In one study, supplements of fish oil also appeared to reduce heavy bleeding in adolescent girls.

Salt Restriction. Limiting salt may help bloating.

Reducing Caffeine, Sugar, and Alcohol. Reducing caffeine, sugar, and alcohol intake may be beneficial. The effects of alcohol are mixed. One study found that women who drank less wine had less menstrual pain than those who drank more wine. Another reported that regular consumption of alcohol lowered the risk for developing cramps, but it actually increased the length of cramping time in certain women. In any case, alcohol is certainly not recommended for relieving menstrual disorders.

Forms of Iron. Women who have heavy menstrual bleeding can sometimes become anemic. Eating iron-rich foods can help prevent anemia. Iron found in foods is either in the form of heme or non-heme iron. Heme iron is better absorbed than non-heme iron.

Foods containing heme iron are the best for increasing or maintaining healthy iron levels. Such foods include (in order of iron-richness) clams, oysters, organ meats, beef, pork, poultry, and fish.
Non-heme iron is less well absorbed. About 60% of iron in meat in non-heme (although meat itself helps absorb non-heme iron). Eggs, dairy products, and iron-containing vegetables only have the non-heme form. Such vegetable products include dried beans and peas, iron-fortified cereals, bread, and pasta products, dark green leafy vegetables (chard, spinach, mustard greens, kale), dried fruits, nuts, and seeds.

The absorption of non-heme iron often depends on the food balances in meals. The following are foods that enhance absorption of non-heme iron:

Meat and fish not only contain heme iron, the best form for maintaining stores, but they also help absorb non-heme iron.
Increasing intake of vitamin C rich foods can enhance absorption of non-heme iron during a single meal. In any case, vitamin C rich foods are healthful and include broccoli, cabbage, citrus fruits, melon, tomatoes, and strawberries. One orange or six ounces of orange juice can double the amount of iron the body absorbs from plant foods. (Taking vitamin C supplements does not appear to have any significant effect on iron stores.)

Exercise may help reduce menstrual pain. It is not clear, however, how intense the exercise should be to reduce dysmenorrhea. For example young female athletes in a 2001 study were only half as likely to suffer from dysmenorrhea as their non-active peers. However, they were also three times more likely to experience an absence of periods. Exercise may be very helpful for women with menstrual pain due to endometriosis. It relieves stress and tension and may reduce hormonal levels that could contribute to endometrial growth.

Sexual Activity. There have been reports that orgasm reduces the severity of menstrual cramps.

Applying Heat. One study found that continuously applying a heated abdominal pad for 12 hours 2 days in a row was as effective in reducing menstrual cramps as ibuprofen (Advil). A warm bath may also be helpful.

Menstrual Hygiene. Tampons should be changed every 4 - 6 hours. Scented pads and tampons should be avoided; feminine deodorants can irritate the genital area. Women should not douche during or between periods. Women who douche on a weekly basis are more likely to contract cervical cancer than those who do not. Douching may destroy the natural bacteria normally present in the vagina. Bathing regularly is sufficient.

Acupuncture and Acupressure. Some studies, including a small well-conducted trial, have reported relief from pelvic pain after acupuncture or acupressure, a technique that applies small pins or pressure to specific points on the body. Some women report relief with reflexology, an acupuncture technique that uses manual pressure on acupuncture points on the ears, hands, and feet.

Yoga and Meditative Techniques. Yoga and meditative techniques that promote relaxation may help relieve menstrual cramps.

Chiropractic. Some women with primary dysmenorrhea have sought help from chiropractors trained in spinal manipulation. One study compared a high-force spinal manipulation technique with a low-force maneuver used as a placebo technique. Both showed lower scores on tests that measure pain, perhaps indicating that a simple back rub by a sympathetic partner or friend may be helpful.

Herbs and Supplements. Studies have not generally found herbal or natural remedies to be any more effective than placebos for reducing menstrual disorders. Natural remedies for menstrual symptoms include:

Evening primrose oil. Evening primrose oil contains a polyunsaturated fatty acid known as gamma linolenic acid. This compound seems to block the release of cytokines and prostaglandins, immune system factors that are manufactured by the endometrium. These factors are involved in uterine muscle contraction and cramping. Foods that contain gamma linolenic acid include black currant oil and cold-water fish.
Omega-3 fatty acids. There is some evidence that the fatty acids found in fish oil have anti-inflammatory properties that may help relieve menstrual cramps. Omega-3 fatty acids are available in supplement pill form, but diets that include cold-water fish (tuna, salmon, mackerel) provide the best source for these nutrients.
Ginger. Ginger tea or capsules may help to relieve nausea and bloating.
Aromatherapy. Aromatherapy with topically-applied lavender, sage, and rose oils may help ease menstrual cramps, according to a small 2006 study.
Pycnogenol. Pycnogenol, an extract from the bark of the French maritime pine tree, may help reduce menstrual pain and discomfort, according to some small studies.

Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like with drugs, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been a number of reported cases of serious and even lethal side effects from herbal products. Patients should check with their doctor before using any herbal remedies or dietary supplements.

The following are special concerns for people taking natural remedies for menstrual disorders:

Valerian has been used by some women for menstrual cramps. This herb is listed on the FDA's list of generally safe products. However, its calming effects can be dangerously increased if it is used with sedative drugs. Other interactions and long-term side effects are unknown.
Black cohosh (also known as Cimicifuga racemosa or squawroot) contains a plant estrogen and is the most studied herbal remedy for treating menopausal symptoms, although a 2006 study indicated it is ineffective. Some women also use it for dysmenorrhea. Black cohosh has been used for decades in Germany and appears to be safe, but because its actions resemble estrogen more clinical studies are needed to confirm both long-term safety and effectiveness. Headaches and gastrointestinal problems are common side effects. At this time, experts do not recommend taking it for more than 6 months.

Medications

There are a number of different medicines prescribed for menstrual disorders.

Nonsteroidal Anti-inflammatory Drugs (NSAIDs). Nonsteroidal anti-inflammatory drugs (NSAIDs) block prostaglandins, the substances that increase uterine contractions. They are effective painkillers that also help control the inflammatory factors that may be responsible for heavy menstrual bleeding. Aspirin is the most common NSAID, but there are dozens of others available over the counter or by prescription.

Among the most effective NSAIDs for menstrual disorders are ibuprofen (Advil, Motrin, Midol PMS), naproxen (Aleve, Naprosyn, Naprelan, Anaprox), and mefenamic acid (Ponstel). In a comparison study of ibuprofen and naproxen, both were effective, but the effects of naproxen lasted longer. Naproxen, however, may carry a higher risk for gastrointestinal (GI) effects than ibuprofen. Long-term use of any NSAID can increase the risk for GI bleeding and ulcers. Long-term NSAID use can also increase the risk for heart attack and stroke.

An ulcer is a crater-like lesion on the skin or mucous membrane caused by an inflammatory, infectious, or malignant condition. To avoid irritating an ulcer a person can try eliminating certain substances from their diet such as caffeine, alcohol, aspirin, and avoid smoking. Patients can take certain medicines to suppress the acid in the stomach causing the erosion of the stomach lining. Endoscopic therapy can be used to stop bleeding from the ulcer.

Acetaminophen. Some evidence suggests that acetaminophen (Tylenol) reduces levels of female hormones (gonadotropins and estradiol, an estrogen), which may have some beneficial effect on menstrual disorders. A combination of acetaminophen and pamabrom (Women's Tylenol Menstrual Relief) is specifically aimed at treating menstrual pain and bloating. (Pamabrom is a diuretic, a drug used to reduce fluid build-up and bloating.) One study indicated that acetaminophen is less effective than NSAIDs for dysmenorrhea, but does not have the same potentially harmful effects on the gastrointestinal tract.

Oral contraceptives (OCs), commonly called "the Pill" collectively, contain combinations of an estrogen and a progestin (either a natural progesterone or the synthetic form called progestogen). The estrogen compound used in most combination OCs is estradiol. There are many different progestins, but commonly used types include levonorgestrol, drospirenone, norgestrol, norethindrone, and desogestrel. (Combination contraceptives are also available in other forms, including patches and vaginal rings, but they may increase the risk for menstrual cramping and bleeding.)

Click the icon to see an image of hormone-based contraceptives.

OCs are often used to regulate periods in women with menstrual disorders, including menorrhagia (heavy bleeding), dysmenorrhea (severe pain), and amenorrhea (absence of periods). Oral contraceptives are as effective for treating pain from endometriosis as the more potent gonadotropin releasing hormone agonists. They also protect against ovarian and endometrial cancers.

High-dose OCs have been specifically helpful for adolescents with severe dysmenorrhea. Studies with low-dose OCs have also shown they can reduce menstrual pain for adolescents and adults.

OCs may be taken in cycles that include pills of the same or different strengths. These are categorized as monophasic (one-phase), biphasic (two-phase), or triphasic (three-phase). Monophasic pills contain the same amount of hormones in each dose. Biphasic and triphasic pills contain different dosages of hormones with the pill packs. The monophasic regimen is the most studied regimen and is usually recommended for dysmenorrhea as well as premenstrual symptoms.

Continuous-Dosing OCs. Standard OCs usually come in a 28-pill pack with 21 days of “active” (hormone) pills and 7 days of “inactive” (placebo) pills. Newer “continuous-dosing” (also called “continuous-use”) oral contraceptives aim to reduce -- or even eliminate -- monthly menstrual periods. These OCs contain a combination of estradiol and the progesterone levonorgestrel, but use extending dosing of active pills.

Seasonale, the first continuous-dosing contraceptive, was approved in 2003. It contains 81 days of active pills followed by 7 days of inactive pills. Women who take Seasonale have on average a period every 3 months. Seasonique, a follow-up to Seasonale, was approved in 2006. As with Seasonale, it produces about 4 periods a year. With Seasonique, a woman takes 84 days of levonorgestrol-estradiol pills followed by 7 days of pills that contain only low-dose estradiol.

In 2007, the FDA approved Lybrel, which supplies a daily low dose of levonorgestrol and estradiol with no inactive pills. Because Lybrel contains only active pills, which are taken 365 days a year, it completely eliminates monthly menstrual periods. In clinical trials, 59% of women who took Lybrel completely stopped menstrual periods by the end of the first year. Some women, however, experienced occasional unscheduled bleeding or spotting during the first 3 - 6 months.

Side effects. Common side effects of combination OCs include headache, nausea, bloating, breast tenderness, and bleeding between periods. The estrogen component in combination OCs is usually responsible for these side effects. In general, today’s OCs are much safer than OCs of the past because they contain much lower dosages of estrogen.

However, all OCs can increase the risk for migraine, stroke, heart attack, and blood clots. The risk is highest for women who smoke or who have a history of heart disease risk factors (such as high blood pressure or diabetes) or past cardiac events. Women who have certain metabolic disorders, such as polycystic ovary syndrome (PCOS), are also at higher risk for the heart-related complications associated with these pills.

Progestins (either natural progesterone or synthetic progestogen) are used by women with irregular or skipped periods to restore regular cycles. Because of this, they may also help menstrual pain. They also reduce heavy bleeding and may protect against uterine and ovarian cancers. Progestin-only contraceptives may be a good option for women who are not candidates for estrogen-containing OCs, such as women smokers over the age of 35.

Progestins can be delivered in various forms:

Levonorgestrel-Releasing Intrauterine System (LNG-IUS). An intrauterine device (IUD) that releases progestin can be very beneficial for menstrual disorders, regardless of its contraceptive effects. In the United States, a levonorgestrel-releasing intrauterine system, also called an LNG-IUS, is sold under the brand name Mirena. The LNG-IUS has been proven to reduce heavy bleeding and pain in many women who suffer from menorrhagia and dysmenorrhea. In a 3-year study, the proportion of women with dysmenorrhea using the LNG-IUS dropped from 60% to about 30%. Some studies suggest that the LNG-IUS is more effective than oral contraceptives for controlling heavy menstrual bleeding.

Many experts now recommend the LNG-IUS as a first-line treatment for menorrhagia, particularly for women who may face hysterectomy (removal of uterus), conservative surgery such as endometrial resection (removal of endometrial lining), or endometrial ablation (destruction of endometrial lining). Studies report that about 60% of women with menorrhagia who use the LNG-IUS are able to avoid hysterectomy. Some clinical trials suggest that endometrial resection or ablation may be better at reducing menstrual bleeding than the LNG-IUS. Other studies report that the device is as effective as conservative surgery. Research also indicates that women who choose the LNG-IUS are as satisfied with their quality of life as those who choose surgery.

The LNG-IUS remains in place in the uterus and releases the progestin levonorgestrel for up to 5 years. Progestin released by an IUD mainly affects the uterus and cervix, and so it causes fewer widespread side effects than progestin pills do. (However, the other major IUD -- the Copper T -- may increase bleeding.)

After the LNG-IUS is inserted, heaver periods may occur during the first 3 - 6 months as the lining of the uterus is shed. This shedding may also cause irregular periods and light bleeding (“spotting”) between menstrual cycles. Eventually, the LNG-IUS results in a shorter period, with little or no blood flow. For many women, the LNG-IUS completely stops menstrual periods.

Common side effects include cramping, acne, back pain, breast tenderness, headache, mood changes, and nausea. The LNG-IUS may increase the risk for ovarian cysts, but such cysts usually cause no symptoms and resolve on their own. Women who have a history of pelvic inflammatory disease or who have had a serious pelvic infection should not use the LNG-IUS.

Injections (Depo-Provera). Depo-Provera uses a progestin called medroxyprogesterone. Most women who use Depo-Provera stop menstruating altogether after a year. Depo-Provera may be beneficial for women with heavy bleeding, severe cramps, or both. Women who eventually want to have children should be aware that Depo-Provera can cause persistent infertility for up to 22 months after the last injection, although the average is 10 months.

Weight gain can be a problem, particularly in women who are already overweight. Women should not use Depo-Provera if they have a history of liver disease, blood clots, stroke, or cancer of the reproductive organs.

Long-term (more than 2 years) use of Depo-Provera can cause loss of bone density. In 2004, the FDA added a “black box” warning to the Depo-Provera label advising of this risk. The warning notes that the decline in bone density increases with duration of use and may not be completely reversible even after the drug is discontinued. Based on this information, the FDA recommends that Depo-Provera should not be used for longer than 2 years unless other birth control methods are inadequate. [See In-Depth Report #91: Birth control options for women.]

Gonadotropin releasing hormone (GnRH) agonists are sometimes used to treat menorrhagia. GnRH agonists block the release of the reproductive hormones LH (luteinizing hormone) and FSH (follicular-stimulating hormone). As a result, the ovaries stop ovulating and no longer produce estrogen. GnRH agonists include goserelin (Zoladex), buserelin, a monthly injection of leuprolide (depot Lupron), and a nasal spray, Nafarelin (Synarel). Such drugs may be used alone or in preparation for procedures used to destroy the uterine lining. They are not generally suitable for long-term use.

Commonly reported side effects, which can be severe in some women, include menopausal-like symptoms. These symptoms include hot flashes, night sweats, changes in the vagina, weight change, and depression. The side effects vary in intensity depending on the GnRH agonist. They may be more intense with leuprolide and persist after the drug has been stopped.

The most important concern is possible osteoporosis from estrogen loss. Women ordinarily should not take these drugs for more than 6 months. Certain approaches may preserve enough estrogen to protect bones and still effectively relieve endometriosis symptoms:

Add-back therapy, which provides doses of estrogen and progestin that are high enough to maintain bone density, but are too low to offset the beneficial effects of the GnRH agonist.
Intermittent leuprolide, which uses repeated 6-month courses of GnRH agonists followed by an average of 9 months of symptom control only.
Taking GnRH agonists in very low doses is an alternate approach, but is still largely untested.
Adding a bone-protective drug called a bisphosphonate (alendronate or etidronate) may be helpful.
Other drugs are being tested in combination with a GnRH agonist to preserve bone. They include parathyroid hormone or selective estrogen-receptor modulators (SERMs).

GnRH treatments used alone do not prevent pregnancy. Furthermore, if a woman becomes pregnant during their use, there is some risk for birth defects. Women who are taking GnRH agonists should use non-hormonal birth control methods, such as the diaphragm, cervical cap, or condoms while on the treatments.

Danazol (Danocrine) is a synthetic substance that resembles a male hormone. It suppresses estrogen, and therefore menstruation, and is used (sometimes in combination with an oral contraceptive), to help prevent heavy bleeding. It may also improve surgical success rates in women with menorrhagia when used before ablation or resection to destroy the uterine lining. It is not suitable for long-term use.

Adverse side effects include facial hair, deepening of the voice, weight gain, acne, and dandruff. It may also increase the risk for unhealthy cholesterol levels. Pregnant women or those trying to become pregnant should not take this drug because it may cause birth defects. [See In-Depth Report #74: Endometriosis or In-Depth Report #63: Uterine fibroids.]

Surgery

Women with heavy menstrual bleeding, dysmenorrhea, or both have medical and surgical options available to them. Most procedures eliminate the possibility for childbearing, however. Hysterectomy removes the entire uterus while ablation and resection destroy most or all of uterine lining.

For some women, an intrauterine device (IUD) that releases hormones is proving to be a good medical alternative to surgery. The levonorgestrel-releasing intrauterine system, or LNG-IUS (Mirena), is increasingly being used to treat menorrhagia. Many experts recommend it as a first-line treatment for heavy bleeding. Studies have found the LNG-IUS to work just as well as ablation and resection. Women should be sure to ask their doctors about all medical options before undergoing surgical procedures.

In either standard endometrial resection or ablation, the entire lining of the uterus (the endometrium) is removed or destroyed. The standard endometrial ablation and resection techniques are equally effective in reducing bleeding. In general, either one reduces bleeding by about half. About 15% of women require a hysterectomy later on. Some recent studies report that microwave endometrial ablation may work better than resection, and considerably reduce the need for future hysterectomy. Women should discuss with their surgeon which procedure may be best for them.

Hormonal Pretreatment. Hormonal drugs, such as GnRH analogs or danazol, are sometimes used before the procedures to help prepare the uterus by thinning the endometrial lining. However, a 2005 study suggested that drug preparation may not be required before microwave endometrial ablation.

Postoperative Effects of Endometrial Ablation or Resection Procedures. Postoperative effects of either procedure include the following:

Anesthesia may cause nausea and even vomiting for a few hours following the operation.
Cramping and pain occurs but can usually be relieved using over-the-counter painkillers.
Patients may experience frequent urination for the first day after the procedure and blood-tinged, watery vaginal discharge for more than a month.

Complications of Endometrial Ablation or Resection Procedures. Complications from either procedure may include perforation of the uterus, injury to the intestine, hemorrhage, or infection.

In standard resection and ablation, the uterine cavity is expanded by filling it with fluid. In rare instances, excess glycine from the fluid instilled in the uterus builds up in the bloodstream and causes an abnormal drop in sodium levels. This can be a serious event resulting in mental confusion, convulsions, and, very rarely, death. General anesthesia may pose a lower risk for this complication than local. Some of the newer ablation procedures do not require fluid instillation.

In a 2002 study, 10% of patients who were given standard ablation using the roller ball technique experienced blockage or blood build-up in the fallopian tubes that require a follow-up procedure or a hysterectomy later on.

Resection procedures benefit those women who have very heavy menstrual bleeding but do not have any other underlying uterine problems, such as polyps, hyperplasia of the endometrium, or cancer. Resection also seems to have a higher success rate in reducing bleeding and relieving pain in older women than younger women.

Resection procedures typically involve the following:

The patients are given a local or general anesthesia.
The surgeon dilates (widens) the cervix and fills the uterine cavity with fluid to improve visualization.
The surgeon then removes the uterine lining.

Endometrial ablation involves the destruction of the uterine lining using a number of approaches that include heat, electricity, laser energy, and other methods. The standard ablation approach uses hysteroscopy to allow the doctor to view the uterus.

A typical procedure uses the following approach:

The doctor uses hysteroscopy to view the uterine cavity. This is a fiber optic light source inside a long flexible or rigid tube, which is inserted into the uterus in order to view the cavity. The image of the uterine cavity is transmitted by camera lenses to a video screen.
The uterine cavity is filled with fluid for better visualization. A special substance such as glycine, sorbitol, or mannitol may be added to the fluid so that it does not conduct electricity. This process prevents accidental burns.
With ablation, uterine tissue is usually vaporized using a thin powerful laser beam or high electric voltage. One ablation technique, known as electrocautery with roller ball diathermy, uses a device that looks like a tiny steamroller. This device applies heat and destroys endometrial tissue as it rolls across the uterine lining.
The procedure typically takes 15 - 45 minutes. Although a general anesthetic is usually required, the patient can go home the same day.

It takes about 3 months to determine whether the procedure has been effective. There should be a follow-up appointment about 2 weeks after the procedure. One study revealed 80% of the women were satisfied with ablation. However, this was lower than the 89% satisfaction rate reported by women who had hysterectomy. About 30% of women who have this procedure still require additional surgeries, including hysterectomies, within 5 years. The risk is higher in younger women. The risk for complications increases with repeat ablations.

Newer endometrial ablation techniques (described below) do not use the hysteroscopy. These “second-generation” procedures are technically easier to perform than standard ablation and may be less dependent on the skill of the surgeon. A 2005 review found that second-generation procedures reduce surgery time. Women who had the newer procedures were less likely to experience fluid buildup, perforation of the uterus, cervical cuts and tears, or accumulation of blood in the uterus. However, women did experience more nausea, vomiting, and cramping.

Balloon Endometrial Ablation. Balloon ablation (ThermaChoice in the U.S., Cavaterm in Europe) is proving to be very effective:

A balloon at the tip of a catheter tube is filled with fluid and inflated until it conforms to the walls of the uterus.
A probe in the balloon heats the fluid to destroy the endometrial lining.
After 8 minutes the fluid is drained out and the balloon is removed.

Studies show that bleeding is controlled in 70 - 90% of patients for at least 5 years. It is fast, simple to perform, and comparison studies suggest that it is as effective as resection and standard ablation.

Treatment is less likely to succeed in younger women, those with a tipped uterus, when the uterine lining is 4 mm or thicker, and when menstrual bleeding is prolonged. Pregnancy is possible if some of the lining is maintained, but generally women should not depend on it to preserve fertility.

Electric Wand Ablation. This approach involves inserting a slender wand up through the cervix (the NovaSure System). A triangular mesh-like device is then passed through the wand and expands to fit the uterus. Electrical energy is passed through it for about 90 seconds and the mesh and wand are then withdrawn. As with many other second-generation ablation techniques, it is quick, effective, and does not require pretreatment to expand the uterus. In a 2003 study, it achieved significantly lower bleeding rates than balloon ablation.

Freezing (Cryoablation). With cryoablation (Her Option Uterine Cryoablation Therapy System), the uterine tissue is frozen, which destroys the lining. The procedure takes about 10 minutes to destroy the lining, and it requires no fluid to expand the uterus and little anesthetic. Ultrasound is used to guide the procedure so that the surgeon can view the depth of the ablation. In a 2003 study, cryoablation was slightly less successful than a standard ablation procedure. However, bleeding still declined by 92% with the freezing technique, and quality of life significantly improved.

Hot Saline. Another recently approved technique [Hydro-Therm-Ablator (HTA) system] uses hot saline (salt water) to destroy the lining. It takes about 10 minutes to do this. This is not a "blind" procedure but uses hysteroscopy so that the surgeon can view the uterus.

Laser Ablation. Endometrial laser intrauterine thermotherapy (ELITT) is an ablation technique that does not require either fluid or devices for expanding the uterus or direct contact with the endometrium. This appears to be a very effective approach.

Microwave Endometrial Ablation. Microwave endometrial ablation applies very low-power microwaves to the uterus, which limits tissue destruction only to the lining without causing any unnecessary harm to other tissues. It takes about 3 minutes. Studies report success rates equal to standard ablation and resection procedures.

Until recently, hysterectomy was the only surgical option for uterine fibroids. Other procedures, however, are now available:

Myomectomy. Myomectomy is the surgical removal of only one or more fibroids. Myomectomy usually involves a laparotomy (a procedure that uses a wide abdominal incision) or less invasive surgical techniques, such as laparoscopy and hysteroscopy. In such cases, unlike with hysterectomy, this technique may preserve fertility.
Uterine Artery Embolization (UAE). UAE, also called uterine fibroid embolization (UFE), is a non-surgical radiology procedure. An interventional radiologist injects small plastic particles through a catheter placed in the uterine artery. The particles block the blood supply to the fibroids and cause them to shrink.
Other Procedures. Endometrial ablation (destruction of the lining of the uterus) may be useful in women with small fibroids and heavy bleeding. Myolysis is another procedure best suited for women with specific types of small fibroids. Magnetic resonance-guided focused ultrasound (MRgFUS) is the newest type of fibroid procedure. Myolysis and MRgFUS use heat to cut off the blood supply to fibroids.

Women should discuss each option with their doctor. Deciding on the surgical procedure depends on the location, size, and number of fibroids. Certain procedures affect a women’s fertility and are recommended only for women who are past childbearing age or who do not want to become pregnant. The risk for bleeding increases with the surgeon's inexperience, so patients are urged to investigate the surgeon's track record. [See In-Depth Report #73: Uterine fibroids.]

Hysterectomy is the surgical removal of the uterus and is the second most frequently performed surgery in premenopausal women (Cesarean sections are first). About 600,000 hysterectomies are performed each year in the U.S., which is among the highest rate of all countries. By age 60, about a third of American women have had this procedure. The highest hysterectomy rates are in women age 40 - 44. Women in the southern and midwestern areas of the United States are more likely to have the operation than those in the northeast and west.

Click the icon to see an illustrated series detailing a hysterectomy.

A 2007 study suggested that a combination of factors predicts whether a woman will decide to have a hysterectomy. A woman who meets all three of these factors has a 95% chance of having a hysterectomy:

Presence of symptoms (pelvic pain, bleeding, symptomatic fibroids)
Lack of symptom improvement or resolution despite treatment
Previous use of GnRH agonist drugs

Heavy bleeding, often from fibroids, is the reason for about two-thirds of all hysterectomies. However, in about half of these hysterectomies, no abnormalities are detected to explain the bleeding. In one European study, women with menorrhagia were more likely to choose hysterectomy over conservative treatment if they also had pelvic pain and were inconvenienced by the heavy bleeding. The number of procedures has continued to increase, but the rise has slowed substantially in recent years.

In its support, hysterectomy, unlike medical treatments and less invasive procedures, cures menorrhagia completely, and most women are satisfied with the procedure. Less invasive hysterectomy procedures are also improving recovery rates and increasing satisfaction afterward.

Still, in one study in 70% of cases when doctors recommended hysterectomies, they did not give their patients alternative choices or adequate diagnostic evaluations. Some studies suggest that the levonorgestrel-releasing intrauterine system (Mirena) might help avoid hysterectomy in 80% of cases. Any woman, even one who has reached menopause, uncertain about a recommendation for a hysterectomy for fibroids or heavy bleeding should certainly seek a second opinion.

[See In-Depth Report #73: Uterine fibroids or In-Depth Report #74: Endometriosis.]

Some evidence suggests that surgically cutting the pain-conducting nerve fibers leading from the uterus diminishes the pain from dysmenorrhea. Two procedures, uterine nerve ablation and laparoscopic presacral neurectomy, can block such nerves. Small studies have shown benefits from these procedures, but stronger evidence is needed before they can be recommended for women with severe primary dysmenorrhea.

Laparoscopic Uterosacral Nerve Ablation (LUNA). LUNA is a recent approach that uses either laser or cauterization to destroy nerves in a small segment of the ligaments that connect the cervix with the lower back. The ligaments do not appear to provide any structural support. There are few side effects from the procedure. The patient does not lose any sensations associated with sexual activity.

Laparoscopic Presacral Neurectomy (LPSN). LPSN uses laser techniques to sever a web of nerves between the lower spine and tail bone that transmit pain from the uterus. The procedure does not affect fertility. Studies suggest that it may work better than LUNA in the long term, but it also poses a higher risk of complications. These complications include constipation, diarrhea, and urinary problems. However, many women find that these symptoms eventually improve.

Resources

www.acog.org -- American College of Obstetricians and Gynecologists
www.resolve.org -- National Infertility Association
www.asrm.com -- American Society for Reproductive Medicine
www.endometriosisassn.org -- Endometriosis Association
www.pelvicpain.org -- International Pelvic Pain Society

References

American Academy of Pediatrics Committee on Adolescence; American College of Obstetricians and Gynecologists Committee on Adolescent Health Care; Diaz A, Laufer MR, Breech LL. Menstruation in girls and adolescents: using the menstrual cycle as a vital sign. Pediatrics. 2006 Nov;118(5):2245-50.

Archer DF, Jensen JT, Johnson JV, Borisute H, Grubb GS, Constantine GD. Evaluation of a continuous regimen of levonorgestrel/ethinyl estradiol: phase 3 study results. Contraception. 2006 Dec;74(6):439-45. Epub 2006 Sep 18.

Han SH, Hur MH, Buckle J, Choi J, Lee MS. Effect of aromatherapy on symptoms of dysmenorrhea in college students: A randomized placebo-controlled clinical trial. J Altern Complement Med. 2006 Jul-Aug;12(6):535-41.

Learman LA, Kuppermann M, Gates E, Gregorich SE, Lewis J, Washington AE. Predictors of hysterectomy in women with common pelvic problems: a uterine survival analysis. J Am Coll Surg. 2007 Apr;204(4):633-41. Epub 2007 Feb 23.

Review Date:
6/16/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M., Inc. is accredited by URAC, also known as the American Accreditation HealthCare Commission (www.urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows rigorous standards of quality and accountability. A.D.A.M. is among the first to achieve this important distinction for online health information and services. Learn more about A.D.A.M.'s editorial policy, editorial process and privacy policy. A.D.A.M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health on the Net Foundation (www.hon.ch).

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adam.com

Endometriosis

FitSugar — Wed, 08 Oct 2008 17:34:57 -0700

In This Report

Highlights
Introduction
Causes
Symptoms
Risk Factors
Complications
Diagnosis
Treatment
Lifestyle Changes
Medications
Conservative Surgery
Hysterectomy
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approval

Women with menstrual pain due to endometriosis have a new treatment option. In May 2007, the FDA approved Lybrel, a continuous-dose oral contraceptive that completely eliminates menstrual periods. Lybrel, which contains low doses of the estrogen estradiol and the progesterone levonorgestrol, is taken 365 days a year with active pills. Some women may, however, experience unscheduled bleeding or spotting.

Endometriosis and Adenomyosis

Women who continue to experience menstrual and pelvic pain after surgery for endometriosis may actually have adenomyosis, suggests a 2006 study in Fertility and Sterility. Adenomyosis occurs when knots of endometrial tissue develop within the muscles of the uterus. With endometriosis, endometrial tissue grows outside of the uterus.

Predictors of Hysterectomy

Three factors combined can predict whether a woman will decide to have a hysterectomy, according to a 2007 study published in the Journal of the American College of Surgeons. Women who met all three criteria had a 95% chance of having a hysterectomy:

Presence of symptoms (pelvic pain, bleeding, symptomatic fibroids)
Lack of symptom improvement despite treatment
Previous use of GnRH agonist drugs

Hysterectomy and Sexual Function

Women who have both their uterus and cervix removed (total hysterectomy) are no more likely to experience sexual problems than women who have only their uterus removed (subtotal hysterectomy), suggests a 2006 review in the Cochrane Database. The review also found no differences between total and subtotal hysterectomy for urinary and bowel problems. However, women who had subtotal hysterectomy were more likely to experience cyclical bleeding during the year after surgery than women who had a total hysterectomy.

Hormone Replacement Therapy (HRT) and Breast Cancer Risk

Estrogen-only HRT after hysterectomy does not increase breast cancer risk in the short term (up to 20 years), according to several 2006 studies. Combination estrogen-progestin HRT does increase breast cancer risk.

Introduction

Endometriosis is a condition in which the cells that line the uterus grow outside of the uterus. The condition can interfere with a woman's fertility and ability to become pregnant. Endometriosis can also cause severe pelvic pain, especially during menstruation.

Endometriosis is a common gynecological condition. It was described in medical literature more than 300 years ago and has since been recognized as a chronic, painful, and often progressive disease in women. However, the causes of endometriosis are unknown, it is widely variable in symptoms and severity, and it is difficult to diagnose. In fact, some experts believe that endometriosis is actually several disorders, not just one.

Endometriosis. Endometriosis occurs when cells from the mucus membrane lining the uterus (endometrium) form implants that attach, grow, and function outside the uterus, generally in the pelvic region. Endometrial implants consist of both following cell types:

Gland cells. These cells secrete hormones and other fluids and are normally located in the uterine lining.
Stroma cells. These are the framework cells that build supportive tissue.

Endometrial cells contain receptors that bind to estrogen and progesterone, which promote uterine growth and thickening. During endometriosis these cells become implanted in organs and structures outside the uterus, where these hormonal activities continue to occur, causing bleeding and scarring.

Endometriosis is the condition in which the tissue that normally lines the uterus (endometrium) grows on other areas of the body, causing pain and irregular bleeding.

Endometrial implants vary widely in size, shape, and color. Over the years, they may diminish in size or disappear, or they may grow.

Early implants are usually very small and look like clear pimples.
If they continue to grow they may form flat injured areas (lesions), small nodules, or cysts called endometriomas, which can range from sizes smaller than a pea to larger than a grapefruit.
Implants also vary in color; they may be colorless, red, or very dark brown. These so-called chocolate cysts are endometriomas filled with thick, old, dark brown blood that usually appear on the ovaries.

Implants can form in many areas, most commonly in the following:

The peritoneum. This is the smooth surface lining that covers the entire wall of the abdomen and folds over inner organs in the pelvic area.
On or next to the ovaries.

Less commonly they occur in other areas:

Cul-de-sac, an area between the uterus and rectum
Connective tissue that supports the uterus (called the uterosacral ligaments)
Vagina
Fallopian tube
Urinary tract (in about 20% of cases, usually without causing symptoms).
Gastrointestinal tract (in 12 - 37% of patients)

Click the icon to see an image of the female reproductive anatomy.

Very rarely, they appear in areas far from the pelvis, including the lungs and even the arms and thighs.

The process of endometriosis mimics menstruation at certain stages:

Each month, the exiled endometrial implants respond to the monthly cycle just as they would in the uterus. They fill with blood, thicken, break down and bleed.
Products of the endometrial process cannot be shed through the vagina as menstrual blood and debris are. Instead, the implants develop into collections of blood that form cysts, spots, or patches.
Lesions may grow or reseed as the cycle continues.

The lesions are not cancerous, but they can develop to the point that they cause obstruction or adhesions (web-like scar tissue) that attach to nearby organs, causing pain, inflammation, and sometimes infertility.

The primary structures in the reproductive system are as follows:

The uterus is a pear-shaped organ located between the bladder and lower intestine. It consists of two parts, the body and the cervix.
When a woman is not pregnant the body of the uterus is about the size of a fist, with its walls collapsed and flattened against each other. During pregnancy the walls of the uterus are pushed apart as the fetus grows.
The cervix is the lower portion of the uterus. It has a canal opening into the vagina with an opening called the os, which allows menstrual blood to flow out of the uterus into the vagina.
Leading off each side of the body of the uterus are two tubes known as the fallopian tubes. Near the end of each tube is an ovary.
Ovaries are egg-producing organs that hold 200,000 - 400,000 follicles (from folliculus, meaning "sack" in Latin). These cellular sacks contain the materials needed to produce ripened eggs, or ova.

The inner lining of the uterus is called the endometrium, and during pregnancy it thickens and becomes enriched with blood vessels to house and support the growing fetus. If pregnancy does not occur, the endometrium is shed as part of the menstrual flow. Menstrual flow also consists of blood and mucus from the cervix and vagina.

Reproductive Hormones. The hypothalamus (an area in the brain) and the pituitary gland regulate the reproductive hormones. The pituitary gland is often referred to as the master gland because of its important role in many vital functions, many of which require hormones. In women, six key hormones serve as chemical messengers that regulate the reproductive system:

The hypothalamus first releases the gonadotropin-releasing hormone (GnRH).
This chemical, in turn, stimulates the pituitary gland to produce follicle-stimulating hormone (FSH) and luteinizing hormone (LH).
Estrogen, progesterone, and the male hormone testosterone are secreted by the ovaries at the command of FSH and LH and complete the hormonal group necessary for reproductive health.

Causes

Endometriosis occurs among women all over the world, but researchers have been unable to determine its cause. A combination of genetic, biologic, and environmental factors appear to work together to trigger the initial process, to produce implantation, and to trigger subsequent reseeding and spreading of the implants.

Retrograde Menstruation. One explanation for the development of endometriosis implants involves retrograde menstruation. This occurs during a woman's period, when menstrual tissue flows backward through the fallopian tubes rather than out through the vagina. Early theorists suggested that, in some cases, the redistributed uterine tissue attached and grew in areas outside the uterus, forming endometriosis implants. This theory does not fully explain endometriosis, however. Many women experience some retrograde menstruation, but not all of them develop endometrial cysts. Consequently, other factors must explain why uterine tissue becomes implanted and grows in areas outside the uterus.

Lymphatic Transport. This theory suggests that endometriosis first develops when uterine tissue is separated and then is transported to other organs by way of the lymphatic system or the bloodstream.

The lymphatic system filters fluid from around cells. It is an important part of the immune system. When people refer to swollen glands in the neck, they are usually referring to swollen lymph nodes. Common areas where lymph nodes can be easily felt, especially if they are enlarged, are: the groin, armpits (axilla), above the clavicle (supraclavicular), in the neck (cervical), and the back of the head just above hairline (occipital).

Environmental Toxins. Other suspects for causing initial development of endometriosis are chemicals called organochlorines, which include dioxins (such as PCBs and furans). These chemicals have estrogen-like effects and are widely found in pesticides and other common products. The organochlorines have a particularly powerful impact on the ovary. Organochlorines have been associated with infertility, certain reproductive cancers, and autoimmune disorders, conditions that also occur with higher frequency in women with endometriosis.

Candida. There is absolutely no evidence that endometriosis is caused by candida (commonly called yeast infection), as claimed in some consumer publications.

There are two basic mysteries surrounding the persistence and growth of endometriosis:

Why do endometrial implants survive the attack by the immune system, which is typically launched against any foreign presence in the body?
How do these endometrial travelers develop new blood vessels and implant themselves in other locations?

Impaired Immune System.Some research is focused on possible immune disorders in women with endometriosis. One theory proposes that women with endometriosis have fewer natural killer (NK) cells, which are factors in the immune system important for surveillance. In their absence, the immune system is weakened and may allow endometrial tissue to invade and take root. A recent study suggests that other types of immune system cells are also underactive in women with endometriosis, allowing the woman's body to tolerate the implanted tissue.

Some evidence suggests that endometriosis represents an autoimmune condition, in which the immune system launches an attack on its own cells and tissue. Much of the evidence rests on the relatively high incidence of other inflammatory autoimmune disorders (multiple sclerosis, rheumatoid arthritis, lupus) that occur in women with endometriosis. It is unclear, however, how this response relates to endometriosis itself and whether endometriosis should be treated as an autoimmune condition.

Growth Factors and Angiogenesis. Macrophages also produce growth factors, which are of particular interest because they play important roles in angiogenesis, a natural process by which new blood vessels form.

Vascular endothelial growth factor (VEGF) is secreted by endometrial cells, and so is of special interest. Under normal conditions, VEGF is secreted within the uterus. When oxygen levels drop following menstruation and blood loss, VEGF levels rise and promote the growth of new blood vessels. This process is important for repairing the uterus following menstruation.

When endometrial cells land outside the uterus, however, investigators theorize that this same process occurs with unfortunate results. The cells secrete VEGF when they are deprived of blood and oxygen, which in turn stimulates blood vessel growth. In this case, however, blood vessel growth serves to promote implantation outside the womb.

Other growth factors involved in angiogenesis that may play a role in endometriosis include transforming growth factors (such as TGF-beta), platelet-derived endothelial growth factor (PD-ECGF), and tumor necrosis growth factors.

Inflammatory Response. The damage, infertility, and pain produced by endometriosis may be due to an overactive response by the immune system to the early presence of endometrial implants. The body, perceiving the implants as hostile, launches an attack. Levels of large white blood cells called macrophages are elevated in endometriosis. Macrophages produce very potent factors, which include cytokines (particularly those known as interleukins) and prostaglandins. Such factors are known to produce inflammation and damage in tissues and cells.

A major study is underway to uncover the genetic factors that predispose certain women to endometriosis. The incidence of endometriosis in women who have a mother or sister with the disorder may be up to 10 times higher than average.

Symptoms

Pain at the time of menstruation (dysmenorrhea ) is the primary symptom and occurs in nearly all girls and women with endometriosis. Studies suggest that endometriosis is the cause of about 15% of cases of pain in the pelvic region in women.

Timing of Pain. In addition to menstruation, endometrial pain can occur at other times of the month. A survey published by the Endometriosis Association reported the following findings on the timing of endometrial pain:

71% of women reported pain within 2 days after their periods started.
47% reported pain in the middle of a cycle. (A sharp pain during ovulation may be due to an endometrial cyst located in the fallopian tube that ruptures as the egg passes through.)
40% reported pain at other times of the month.
20% reported continual pain.
7% said there was no pattern.
Many women with endometriosis experience pain during intercourse.
Adolescents are more likely to experience pain that occurs both during their periods and at other times in the cycle, while in older women endometrial pain is more likely to occur during menstruation.

Location of Pain. Nearly all women with endometrial pain experience it in the pelvic area (the lower part of the trunk of the body). The pain is often a severe cramping that occurs on both sides of the pelvis, radiating to the lower back and rectal area and even down the legs.

Occasionally, however, pain may also occur in other regions if endometriosis affects other part of the pelvic area, such as the bladder or intestine.

Severity of Pain. The severity of the pain also varies widely and does not appear to be related to the extent of the endometriosis itself. In other words, a woman can have very small or few implants and have severe pain, while those with extensive endometriosis may have very few signs of the disorder except for infertility. Large cysts can rupture and cause very severe pain at any time.

Patients may experience additional symptoms, which include the following:

Joint and muscle aches
Fatigue
Bloating
Nausea
Dizziness
Heavy menstrual bleeding
Headaches
Depression and malaise (feeling generally low)
Sleep problems

Risk Factors

Endometriosis affects at least 5.5 million women in North America and millions more worldwide. An estimated 2 - 4% of all premenopausal adult women have detectable endometriosis, and over a third of these women experience noticeable pain. Because many women with endometriosis have no symptoms, the actual percentage of premenopausal women with the disorder may be as high as 15%. Some experts believe endometriosis may be responsible for between 45 - 70% of chronic menstrual pain in adolescence.

Age. Endometriosis can occur in women of all ages. It has been reported in girls as young as age 8 (and has been documented before the onset of menstruation), and in women over age 75, with the average age being between 25 - 29. About 40 - 60% of women with endometriosis report symptoms before age 25.

Ethnic Groups. Endometriosis is most common among Asian women, with Caucasians next. It is reported least frequently in African-American women.

Women at higher risk for endometriosis tend to have more problems with menstruation. Those at higher risk have a shorter than normal cycle, heavier periods, and longer periods. Heavier, more frequent periods, or longer exposure may simply make the risk for retrograde menstruation more likely. (This is the condition in which menstrual flows backward and is believed to be at least partially responsible for the initial development of endometriosis.) Menopause usually brings an end to mild-to-moderate endometriosis, although if women with a history of endometriosis take hormone replacement therapy (HRT), the condition may be reactivated.

Not having children has been associated with a greater risk for endometriosis. Some evidence suggests that early pregnancy may be protective against endometriosis because the cervix becomes dilated during labor, which reduces the risk for retrograde menstruation (menstrual backflow). On the other hand, endometriosis itself can increase the risk for infertility, so it may be a cause rather than a result of not having children. Some studies have found no protection against endometriosis with pregnancy, although women with the condition find relief from symptoms during pregnancy.

Some experts report that almost 7% of first-degree female relatives of endometriosis patients also develop it. A family history of endometriosis not only puts women at high risk for the condition but possibly a more severe manifestation of it as well.

Women may also be at higher risk for endometriosis if they were born with uterine abnormalities that obstruct the normal outflow of blood and cause retrograde menstruation.

There have been reports of endometriosis developing after cesarean sections, including implants developing in surgical scars and in the urinary tract. Some experts believe endometriosis should be suspected in women with urinary tract symptoms and a history of cesarean section.

Various disorders occur in greater rates in women who have endometriosis. In some cases, these disorders and endometriosis may be caused by common factors, but it is not clear what they are.

They include:

Certain cancers, particularly for early-onset breast and ovarian cancers, non-Hodgkin's lymphomas, and melanoma.
Autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis. In all of these diseases, the immune system launches a destructive inflammatory response against the body's own cells (which differ in location depending on the disease). These are uncommon disorders, but in a major 2002 survey of women with endometriosis, they occurred in 12% of these women. This provides some support to the theory that endometriosis, too, is an autoimmune condition.
Hypothyroidism. In the same 2002 survey mentioned above, 42% of women had low thyroid or some other hormonal disorder.
Fibromyalgia and chronic fatigue syndrome. In the same survey, 31% reported one of these conditions.
Diabetes.
Allergies and asthma. Endometriosis is more prevalent in women with a family history of asthma and allergies, including food and skin allergies and hay fever.
Migraine. A small 2006 study suggested that women who have migraine headaches are at increased risk of endometriosis.

Some studies have reported a higher incidence of certain factors in women with endometriosis:

Women with endometriosis tend to be taller and thinner than average.
Women with red hair have an increased risk for endometriosis. Experts guess that the gene determining red hair might be located near other genes that make such women susceptible to endometriosis.

Alcohol and caffeine use have been associated with a higher risk.

Complications

Endometriosis is a chronic disease that is difficult to diagnose and treat. Without treatment, endometriosis gets progressively worse in 65 - 80% of patients. Even with treatment, endometriosis continues to advance in 20% of patients. Cysts and implants may grow and spread to other parts of the pelvis, and in very severe cases, to the urinary or intestinal tracts. Eventually adhesions may form. These are dense, web-like structures of scar tissue that can attach to nearby organs and cause pain, infertility, and intestinal obstruction.

Pain is the most common complaint for women with endometriosis, and it can significantly impair the quality of life. The pain experienced around menstruation can be so debilitating that up to 25% of women with the condition are incapacitated for 2 - 6 days of each month. In severe cases, regular activities may be curtailed for up to 2 weeks per month. Sleeping problems have been reported in 75% of patients, mostly due to pain.

Endometriosis may account for as many as 30% of infertility cases. Some evidence suggests that between 30 - 50% of women with endometriosis are infertile. Often, however, it is difficult to determine if endometriosis is the primary cause of infertility, particularly in women who have mild endometriosis. In an attempt to determine the chances for infertility with endometriosis, researchers have come up with a staging system based on findings during diagnostic surgery.

Endometriosis rarely causes an absolute inability to conceive, but it can contribute to infertility both directly and indirectly.

Direct Effect of Endometrial Cysts. Endometrial cysts may directly prevent infertility in a number of ways:

If implants occur in the fallopian tubes, they may block the egg's passage.
Implants that occur in the ovaries prevent the release of the egg.
Severe endometriosis can eventually form rigid webs of scar tissue (adhesions) between the uterus, ovaries, and fallopian tubes, thereby preventing the transfer of the egg to the tube.

Immune Factors and the Inflammatory Response. Researchers are focusing on defects in the immune system that not only may be responsible for endometriosis in the first place but also may cause the infertility associated with endometriosis. Even in early stage endometriosis, investigators have observed increased immune system activity. It is possible that in such cases, the body perceives these foreign endometrial implants as hostile, and launches an attack.

In this process, the body overproduces specific immune factors that contribute to infertility:

Cytokines. Cytokines are very potent immune factors that, when overproduced, cause damage and inflammation in the very regions that are directed to protect. Such damage could produce scarring and obstructions that interfere with implantation and development of a fertilized egg. In severe endometriosis, there is inflammation in the fluid surrounding the uterus, which could create a hostile environment for the sperm.
Prostaglandins. Elevated levels of these hormone-like factors not only produce inflammation but also increase uterine contractions. (Women with endometriosis have a higher than average risk for miscarriage.)
Other Immune Factors. Growth factors, which stimulate growth of new blood vessels, and toxins produced by implants may impair fertility.

Other Conditions Linking Endometriosis and Infertility. Researchers have noted unusually low levels of specific substances that enable a fertilized egg to adhere to the uterine lining. Such abnormalities are more often a factor in infertility in women with mild-to-moderate endometriosis than in those with severe cases.

One study found that the eggs in women with endometriosis appeared to have more genetic abnormalities than those in women without the disorder.

Implants can also occur in the bladder (although rare) and cause pain and even bleeding during urination. Implants also sometimes form in the intestine and cause painful bowel movements, constipation, or diarrhea. Hormonal treatments, the standard therapies for endometriosis, are not helpful in such cases, and surgery may be needed.

Endometriosis has characteristics that are similar to cancerous tumors, including cellular invasion of other tissues, unrestrained growth, development of new blood vessels, and impaired ability of cells to naturally self-destruct. It is not a malignant disease, however, but experts have been debating for years whether it represents any significant danger.

The possible risks for ovarian and endometrial cancers are of specific concern. Some researchers have identified certain genetic mutations that may transform endometrial cells into ovarian or endometrial cancers in rare cases. Some evidence suggests that ovarian cancer associated with endometriosis may differ from most ovarian cancer cases, and, in fact, have a better outlook.

Of additional concern are studies suggesting that women with endometriosis have a higher risk for other cancers, particularly for early-onset breast cancer and non-Hodgkin's lymphoma (NHL).

The emotional effect of severe endometriosis can be almost as devastating as the pain. It can affect marriage and work. In one survey conducted by the Endometriosis Association, patients reported the following emotional effects from this disease:

84% of patients reported feeling depressed during periods of pain
75% felt irritable
More than 50% reported feelings of anxiety and anger
About 20% said they felt hopeless

In one study, during the days around menstruation 30% of women with endometriosis increased their alcohol intake compared to 14% of women with other gynecological problems and only 9.5% of women with no gynecological disorders.

Diagnosis

Although endometriosis is the most commonly diagnosed uterine disorder, it is often misdiagnosed or missed altogether. In a study of women with proven endometriosis, more than half of them had been told by a doctor that nothing was wrong. In another study, half of women with endometriosis reported that they visited a doctor five or more times before they were diagnosed.

Endometriosis frequently begins to develop in adolescence, but it is not typically diagnosed until a woman is in her mid-20s or early 30s. There are a number of reasons for this:

The symptoms vary widely, and sometimes do not occur at all. Some women do not know they have endometriosis until they fail to become pregnant and seek help for infertility.
Pain in the pelvic or abdominal area can be caused by so many conditions that it is often difficult to pin down the precise cause.

Endometriosis should be highly suspected in women with severe menstrual cramps who are also infertile. Laparoscopy, an invasive diagnostic procedure, is the only definitive method for diagnosing endometriosis. However, a trial using one of several hormonal therapies is usually sufficient to confirm or rule out endometriosis. Such drugs include danazol, GnRH agonists, and progestins.

Many conditions cause pelvic pain. In many cases, the cause is unknown and it often resolves on its own. In one study, pelvic pain improved or resolved without treatment in 77% of women over a 15-month period. However, some causes of pelvic pain can be serious and should be ruled out during a work-up for endometriosis.

Primary Dysmenorrhea. Primary dysmenorrhea is recurrent pelvic pain associated with menstruation. Dysmenorrhea is common in many women. [See In-Depth Report #100: Menstrual disorders.]

Adenomyosis. A condition called adenomyosis occurs when nodules (knots) of endometrial tissue develop within the deep muscle layers of the uterus. This disorder is often classified with endometriosis, but adenomyosis is a different disease. (Endometriosis occurs when endometrial tissue grows and functions outside the uterus.) Adenomyosis is a significant cause of severe pelvic pain and menstrual irregularities. Until recently adenomyosis was diagnosed only after a hysterectomy, but advanced imaging techniques using ultrasound and magnetic resonance imaging scans may be able to detect it. A 2006 study indicated that women who have had surgery for endometriosis, yet continue to suffer from menstrual and pelvic pain, may actually have adenomyosis.

Adenomyosis typically occurs in women who have uterine fibroids, women age 40 - 50, and women who have had children. [See In-Depth Report #73: Uterine fibroids.]

Fibroid tumors may not need to be removed if they are not causing pain, bleeding excessively, or growing rapidly.

Other Causes of Pelvic Pain. Many conditions cause pelvic pain that may or may not be related to menstruation. Some causes of pelvic pain can be serious and should be ruled out:

Uterine fibroids
Pelvic inflammatory disease (which is a result of infections in the pelvic area)
Miscarriage
Ectopic pregnancy

Click the icon to see an image of an ectopic pregnancy.

Pelvic cancer (rare)
Uterine polyps
The use of an intrauterine device (IUD) for contraception

Conditions that may mimic symptoms of endometriosis but which are unrelated to problems in the reproductive organs include:

Severe kidney or urinary tract infections
Celiac disease
Appendicitis
Interstitial cystitis
Inflammatory bowel disease
Diverticulitis
Irritable bowel syndrome

The doctor may be able to feel tender masses or nodules during a pelvic examination, but these signs can indicate many conditions and do not necessarily mean endometriosis is present.

Click the icon to see an image of laparoscopy.

The procedure is as follows:

The surgeon makes tiny abdominal incisions through which a fiber optic tube, equipped with small camera lenses, is inserted. The doctor uses these devices to view the uterus, ovaries, tubes, and peritoneum (lining of the pelvis) on a video monitor.
Carbon dioxide gas is injected into the abdomen, distending it and pushing the bowel away so that the doctor has a wider view.
A blue dye may be flushed through the fallopian tubes to determine blockage; if there is an obstruction, the dye will not flow through the tube.
If the surgeon needs to remove small endometrial cysts or other lesions during the procedure (operative laparoscopy), tiny surgical instruments are passed through a tube.

The procedure is used for detecting and staging endometriosis to determine its severity. In some cases, the procedure itself will restore fertility in women with endometriosis.

Hysteroscopy. Hysteroscopy is a procedure that may be used to detect the presence of fibroids, polyps, or other causes of bleeding. (It may miss cases of uterine cancer, however, and is not substitute for more invasive procedures, such as D&C or endometrial biopsy, if cancer is suspected.)

An ultrasound is performed in cases where other conditions are suspected, such as uterine fibroids, ovarian cysts, or ectopic pregnancy. This non-invasive imaging technique can detect endometriomas, or cysts that are usually located on the ovaries and filled with thick dark blood. Ultrasound can also pick up cysts larger than 1 cm (about 1/3 inch), but will miss smaller cysts, or small and shallow endometrial implants on the surface of ovaries, or on the peritoneum (lining of the pelvis).

Once a diagnosis is made, more sophisticated imaging techniques, such as computed tomography (CT) scanning or magnetic resonance imaging (MRI), may be used to obtain a more accurate image of severe endometriosis.

Investigators are studying certain chemicals detected in blood tests that may prove to help diagnose endometriosis and so avoid invasive diagnostic procedures in many women. Among the most studied to date are CA-125 and CA19-9. Both are elevated in women with severe endometriosis. Higher levels of both chemicals occur in many other diseases, however, including ovarian cancer, so results using this test alone do not provide enough information for a definitive diagnosis of endometriosis.

During laparoscopy, the surgeon determines the number, size, and location of endometrial implants and adhesions. This information helps rank endometriosis by the extent of the disease and give the likelihood of infertility:

Minimal (stage I)
Mild (stage II)
Moderate (stage III)
Severe (stage IV)

A number of experts do not believe these categories are useful, because they often do not relate to the intensity of the pain, or to treatment success rates.

Some experts believe it is more accurate to further categorize endometriosis by the depth of penetration:

Superficial Endometriosis. Endometriosis that lies more on the surface is more highly associated with infertility than deep implants.
Infiltrative Endometriosis. Implants deeper than 5 - 6 mm; deep implants are believed to be the best indicator of progression and severe symptoms.

Treatment

There is no perfect way of managing endometriosis. The three basic treatment approaches are:

Watchful waiting (to relieve symptoms)
Hormonal therapy (to reduce endometrial implants)
Surgery (to reduce endometrial implants, restore fertility, or possibly cure the condition)

The choice depends on a number of factors, including the woman's symptoms, her age, whether fertility is a factor, and the severity of the disease.

In general, watchful waiting is a good initial choice for:

Women with mild pain who, if fertile, do not wish to become pregnant. If women with mild endometriosis wish to become pregnant, the doctor may recommend unprotected sex for 6 months to year. If pregnancy does not occur, then treatment may be started.
Women approaching menopause.

Some experts believe that early diagnosis and treatment in young women without symptoms might prevent some cases of infertility later on. Unfortunately, however, some treatments for endometriosis may actually trigger symptoms in those who do not yet experience them.

Hormone therapies are used to mimic states in which ovulation does not occur (such as pregnancy or menopause) or to directly block ovulation. Hormonal drugs include oral contraceptives, progestins, GnRH agonists, and danazol. They can be very effective in relieving endometriosis symptoms. Some of these drugs may also be used after surgery to help prevent recurrence of endometriosis. There is also some evidence that GnRH agonists and danazol may improve immune factors associated with endometriosis. But there are downsides:

None of these drugs can cure the problem. Symptoms recur in about half of patients within 5 years of treatment.
They do not improve fertility rates and may delay conception in women who use them.
Side effects of these drugs can be distressing. There is a high dropout rate with the use of nearly all these hormonal treatments.
Women who take GnRH agonists, danazol, or similar drugs should use non-hormonal birth control methods (such as the diaphragm, cervical cap, or condoms) because these drugs can increase the risk for birth defects.

Surgery is an option for the following women:

Women with severe pain that does not respond to watchful waiting and medical treatment.
Women who want to become pregnant and endometriosis is most likely the major contributor to infertility.

There are two basic surgical approaches for endometriosis:

Conservative Surgery (Laparoscopy or Laparotomy). Conservative surgery uses laparotomy or laparoscopy to remove the endometriosis implants without removing any other reproductive organs. It is a good option for women who wish to become pregnant or who cannot tolerate hormone therapy. Some experts believe that laparoscopy surgery should be the treatment of choice for women with endometriosis. Endometriosis often recurs after conservative surgery, however. Recurrence rates at 2 years range from 2 - 47%. The risk for recurrence or residual pain after any procedure increases with the severity of the condition, particularly if endometriosis has affected areas outside the uterus.
Radical Surgical Therapy (Hysterectomy). Hysterectomy with removal of ovaries (oophorectomy) along with all endometrial implants is the only potential cure for endometriosis. If endometriosis has developed outside the uterus than even this procedure is not curative. Removing only the uterus with hysterectomy, in any case, has the same risk for recurrence as conservative surgery.

Click the icon to see an illustrated series detailing hysterectomy.

In choosing between hysterectomy (with or without oophorectomy) and conservative surgeries, age and the desire for children are important factors. One study reported a greater sense of loss, more residual symptoms, and more pain in younger women (under age 30) who have undergone hysterectomy than in older women. In one study, 37% of such younger women regretted their decision to have a hysterectomy.

Once careful instruction is given for all the risks and benefits of the different surgical options, the doctor must respect any decision a patient makes to retain as much of her reproductive system as she wants, even if she is past menopause. Both the patient and the doctor should also be clear about the possibility of changing procedures once the operation has begun, depending on what the surgeon may observe. For example, the surgeon may find abnormalities that require more extensive surgery.

Much of the success of any procedure relies on the experience of the surgeon. A woman should always ask for a doctor's track record, or the number of times the doctor has performed the procedure in question. The more, the better. Asking for complication rates may be helpful, but a patient should realize that an experienced surgeon may have a higher number of high-risk patients, and therefore, a higher complication rate than a less experienced surgeon with fewer serious cases.

For women with severe endometriosis who want to become pregnant, conservative surgery (typically laparoscopy) is the appropriate approach for restoring fertility. Hormonal therapies that treat endometriosis itself, such as GnRH agonist or progestins, are generally considered not to help fertility. However, a 2002 study suggested that the use of the GnRH agonists after surgery helped improve conception rates in women who subsequently undergo assisted reproductive techniques (ART), such as in vitro fertilization (IVF). A 2006 study indicated that GnRH agonists given along with infertility treatments may help improve a woman's chance of becoming pregnant. This research is still preliminary.

In any case, ART and hyperstimulation of the ovary using fertility drugs to produce eggs are the standard fertility treatments available to women if surgery fails. ART includes techniques such as in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). Hyperstimulation is the less expensive approach. In a 2003 study, however, ART achieved much greater conception rates in women with endometriosis, particularly those with late-stage disease.

It is not clear whether women with early -stage endometriosis do any better with fertility treatment than simply trying to become pregnant through non-aggressive means. Women with endometriosis who are trying to conceive should discuss all treatment options with a specialist. [See In-Depth Report #22: Infertility in women.]

Lifestyle Changes

Some women report relief by avoiding dairy products and having a diet rich in fiber and low in saturated (animal) fats. Fiber-rich foods (such as fruits and vegetables) along with plenty of fluids (water or juice, not caffeine) are not only healthy but help prevent constipation, which can intensify symptoms. If women choose a diet that limits dairy products, they should be sure to have sufficient calcium from other sources.

A 2005 study involving over 500 women reported that red meat and ham consumption increased the risk for endometriosis. Diets high in green vegetables and fresh fruit appeared to protect against it.

Fat compounds called omega-3 fatty acids may have specific anti-inflammatory effects. They are found in certain oily fish (sardines, mackerel) and can be obtained in supplements. Supplements may be labeled either omega-3 fatty acids or EPA-DHA (which are the important compounds). Evening primrose oil and black currant oil, found in health food stores, contain similar fatty acids that may be helpful. However, food sources are the healthier choice.

Omega-3 fatty acids, found plentifully in oily fish and flaxseed and canola oils, are beneficial to people who have IBD (inflammatory bowel disease).

Drinking alcohol and and smoking cigarettes may increase endometriosis risk. It is unclear whether caffeine is a significant risk factor.

A sitz bath is simply sitting in a basin of water. Some people report relief by alternating between sitting 3 minutes in a hot water basin and then 1 minute in a cold water basin. This is repeated three times. The procedure is performed twice a day 3 - 4 days a week, except during menstruation.

A warm bath or application of heated abdominal pad may help relieve painful menstrual cramps.

Kegel exercises are designed to strengthen the muscles of the pelvic floor that both support the bladder and close the sphincters. Some people find they help endometriosis. The exercises consist of tightening and releasing the pelvic muscle. Since the muscle is internal and sometimes difficult to isolate, doctors often recommend practicing while urinating on the toilet. The patient tries to contract the muscle until the flow of urine is slowed or stopped and then releases it. (However, once learned, Kegel exercises should not be regularly performed while urinating as this practice may eventually weaken the muscles.)

Exercise may be very helpful for women with endometriosis. It relieves stress and tension and may reduce hormonal levels that can contribute to endometrial growth.

Acupuncture and Acupressure. Some studies have reported relief from pelvic pain after acupuncture or acupressure, a technique that applies small pins or pressure to specific points on the body. Some women report relief with reflexology, a technique that uses manual pressure on acupuncture points on the ears, hands, and feet.

Click the icon to see an image of acupuncture.

Transcutaneous Electrical Nerve Stimulation. Transcutaneous electric nerve stimulation (TENS) applies electrodes to certain parts of the body and administers low-level electrical pulses to those locations. Research suggests that it works by altering the body's ability to receive pain signals. The standard approach is to give 80 - 100 pulses per second, for 45 minutes, three times a day. TENS is painless and patients are barely aware of the sensation. A 2002 analysis suggested that this approach may help some women with dysmenorrhea.

Yoga and Meditative Techniques. Yoga and meditative techniques that promote relaxation may also be helpful for menstrual cramps.

Herbal and Other So-Called Natural Remedies for Cramp Relief. Researchers have not conducted many rigorous studies on herbal remedies for menstrual and pelvic pain. Small studies have suggested that pycnogenol, a plant extract derived from the bark of the French maritime pine tree, may help reduce endometriosis symptoms. Some patients have reported relief from menstrual cramps with aromatherapy using lavender, sage, and rose oils.

Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been a number of reported cases of serious and even lethal side effects from herbal products. Always check with your doctor before using any herbal remedies or dietary supplements.

Medications

The basic approach in hormonal treatments for endometriosis is to block production of female hormones (estrogen and progesterone) or to prevent ovulation. Hormonal drugs are used for pain relief only. None have been proven to improve fertility rates and in some cases may delay conception. Specific hormonal drugs may have different effects for women with endometriosis.

Inducing Pseudopregnancy. Oral contraceptives that contain estrogen and progestins mimic a pregnant state and block ovulation. (Progestins are natural or synthetic forms of progesterone). Progestins may also be used alone, since they have specific effects that can cause the endometrial tissue itself to atrophy.
Inducing Pseudomenopause. Gonadotropin-releasing hormone (GnRH) agonists or gestrinone, an anti-progesterone that mimic menopause. They reduce estrogen and progesterone to their lowest level.
Inducing On-going Blockage of Ovulation. Danazol, a derivative of male hormones, is a powerful ovulation blocker.

Studies report that around 80% of women achieve pain relief after taking these drugs. To date, comparison studies have found few differences in effectiveness among the major hormonal treatments. Differences occur mostly in their side effects. Women should discuss the effects of particular medications with their doctors to determine the best choice.

Oral contraceptives (OCs), commonly called "the Pill," contain combinations of an estrogen and a progestin (either a natural progesterone or the synthetic form called progestin). For some patients, OCs may provide better endometriosis pain relief than gonadotropin releasing hormone agonist drugs. OCs may reduce the risk of ovarian cancer by 30 - 50% and of endometrial cancer by 50%, a potentially important benefit in women with endometriosis. Patch contraceptives are available, but they may increase the risk for menstrual cramping.

Click the icon to see an illustrated series detailing the birth control pill.

When used throughout a menstrual cycle, OCs suppress the actions of other reproductive hormones (luteinizing hormone, or LH, and follicle stimulating hormone, or FSH) and prevent ovulation. There are many brands available. The estrogen compound used in most oral contraceptives is estradiol. Many different progestins are used, and there are many brands. None to date have proven to be superior over others. Women should discuss the best options for their individual situations with their doctor.

Standard OCs come in a 28-pill pack that contains 21 active pills and 7 inactive pills. Newer “continuous-dosing” (also called “continuous-use”) oral contraceptives aim to reduce -- or even eliminate -- monthly periods and thereby prevent the pain and discomfort that often accompanies menstruation. These OCs contain a combination of estradiol and the progesterone levonorgestrel, but use extending dosing of active pills.

In 2007, the FDA approved Lybrel, which supplies a daily low dose of levonorgestrel and estradiol with no inactive pills. Because Lybrel contains only active pills, which are taken 365 days a year, it completely eliminates monthly menstrual periods. In clinical trials, 59% of women who took Lybrel completely stopped menstrual periods by the end of the first year. Some women, however, experienced occasional unscheduled bleeding or spotting during the first 3 - 6 months.

Estrogen and progestin each cause different side effects. The most serious side effects are due to the estrogen in the combined pill. Uncommon but more dangerous complications of OCs include high blood pressure and deep-vein blood clots (thrombosis), which may contribute to heart attack or stroke. Studies have been conflicting about whether estrogen in oral contraception increases the chances for breast cancer and, if it does, which women are at risk.

Progestins alone may be helpful and are the oldest drugs used for endometriosis. Progestins can prevent ovulation and reduce the risk for endometriosis in the following ways:

They block luteinizing hormone (LH), one of the reproductive hormones important in ovulation.
They change the lining of the uterus and eventually cause it to atrophy.
They may provide pain relief equivalent to the more powerful hormone drugs. Some experts recommend them as the first choice for women with endometriosis who do not want to become pregnant.

Specific Progestins. Progestins are available in pill or injectable form, or as a progestin-releasing intrauterine device (IUD). Medroxyprogesterone (Depo-Provera), which is administered by injection every 3 months, is one of the standard progestins used. A new low-dose formulation, Depo-subQ Provera 104, was approved in 2005. Oral progestins include norethindrone (Micronor, Aygestin, Norlutate). Norethindrone is also known as norethisterone.

A 2006 study compared low-dose depot medroxyprogesterone with the gonadotropin releasing hormone (GnRH) agonist leuprolide (Lupron). The two drugs worked equally well in controlling endometriosis pain. However, leuprolide caused more loss of bone mineral density, a condition associated with osteoporosis. Patients who received medroxyprogesterone injections had fewer hot flashes than those who received leuprolide, but they had more episodes of bleeding and spotting.

Progestin-releasing IUDs can be very helpful for many women with endometriosis, particularly an advanced version called the levonorgestrel-releasing intrauterine system, or LNG-IUS (Mirena). Studies suggest that the LNG-IUS reduces endometrial cell proliferation and increases cell self-destruction. Progestin released by the IUD mainly affects the uterus and cervix and causes fewer widespread side effects than other forms of progestins.

The LNG-IUS has proved effective for heavy bleeding (menorrhagia), and studies indicate that it helps control the symptoms of minimal-to-moderate endometriosis. Studies indicate that the LNG-IUS works as well as GnRH agonists in managing endometriosis pain, and causes less loss of estrogen. Some experts think that the LNG-IUS could become the treatment of choice for women with endometriosis pelvic pain who do not wish to become pregnant.

Click the icon to see an image of an IUD.

Side Effects of Progestins. Side effects of progestin occur in both the combination oral contraceptives and any contraceptive that uses only progestin, although they may be less or more severe depending on the form and dosage of the contraceptive. Side effects may include:

Changes in uterine bleeding, such as higher amounts during periods, spotting and bleeding between periods (called break-through bleeding), or absence of periods
Unexpected flow of breast milk
Abdominal pain or cramps
Diarrhea
Fatigue, unusual tiredness, weakness
Hot flashes
Decreased sex drive
Nausea
Trouble sleeping
Acne or skin rash (although low-dose OCs actually improve acne)
Depression, irritability, or other mood changes
Swelling in the face, ankles, or feet
Weight gain

Newer formulations of combination pills that use low-dose estrogen and newer progestins may reduce and even avoid many of these side effects. Progestins used in non-oral contraceptives, such as the LNG-IUS IUD, also may not pose as high a risk for these side effects. If side effects persist or are severe, a woman should always talk to her doctor. Many women do not experience these side effects, or if they do, their bodies eventually adjust.

Gonadotropin releasing hormone (GnRH) agonists are effective hormone treatments for endometriosis. They are able to block the release of the reproductive hormones LH (luteinizing hormone) and FSH (follicular-stimulating hormone). As a result, the ovaries stop ovulating and no longer produce estrogen. Ovulation and menstruation resume around 4 - 10 weeks after stopping the drug. The specific length of time depends on the type of GnRH agonist used.

Women with endometriosis often have a difficult time getting pregnant. A 2006 review suggested that GnRH agonists may help women with endometriosis become pregnant when the drug is given along with in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). (IVF and ICSI are standard infertility treatments.) The review found that 3 - 6 months of GnRH therapy in combination with infertility treatment quadrupled the pregnancy rate. However, the study did not supply data on how many women actually gave birth. In addition, there is not enough information on whether these drugs may adversely affect a woman or her fetus.

Specific GnRH Agonists. GnRH agonists include goserelin (Zoladex), buserelin, a monthly injection of leuprolide (depot Lupron), and a nasal spray, Nafarelin (Synarel). Studies have reported that nafarelin shrank all implants and significantly relieved symptoms in 85% of patients, delayed recurrence of endometriosis after surgery, and in comparison with leuprolide, was less expensive, had fewer side effects, and a provided better quality of life.

Side Effects and Complications. Commonly reported side effects (which can be severe in some women) include menopause-like symptoms that include hot flashes, night sweat, and changes in the vagina, weight change, and depression. The side effects vary in intensity depending on the GnRH agonist. They may be more intense with leuprolide and persist after the drug has been stopped.

The most important concern is possible osteoporosis from estrogen loss. Women ordinarily should not take GnRH agonists for more than 6 months. Certain approaches may preserve enough estrogen to protect bones and still effectively relieve endometriosis symptoms:

Add-back therapy provides doses of estrogen and progestin that are high enough to maintain bone density, but are too low to offset the beneficial effects of the GnRH agonist. Studies suggest this is safe and effective for protecting bone.
Intermittent leuprolide uses repeated 6-month courses of GnRH agonists followed by an average of 9 months of symptom control only.
Taking GnRH agonists in very low doses is an alternate approach, but is still largely untested.
Adding bone-protective drugs may be helpful. The standard ones are bisphosphonates and include alendronate (Fosamax), risedronate (Actonel), and etidronate (Didronel). Other drugs are being tested in combination with a GnRH agonist to preserve bone. They include the parathyroid hormone teriparatide (Forteo) and selective estrogen-receptor modulators (SERMs), such as raloxifene (Evista).

Danazol (Danocrine) is a synthetic drug that resembles a male hormone (androgen). It suppresses the pathway leading to ovulation. Studies have shown symptomatic improvement in 90% of women, although in one study, only about 58% of women expressed satisfaction with this therapy. A high drop-out rate occurs, most often because of adverse side effects, particularly male characteristics, such as growth of facial hair, acne, weight gain, dandruff and deepening of the voice.

Danazol may increase the risk for unhealthy cholesterol levels. A few cases of blood clots and strokes have also been reported, as well as rare cases of liver damage. One study reported that taking a low dose may relieve endometrial symptoms and reduce the risk for these side effects. Exercise may also help reduce side effects. As with GnRH drugs, pregnant women or those trying to become pregnant should not take this drug because it may cause birth defects.

Antiprogestins are promising drugs for endometriosis because they reduce both estrogen and progesterone receptors.

Gestrinone. Gestrinone is the most studied antiprogestin and appears comparable to GnRH agonists in reducing pain and while causing fewer menopausal symptoms. In one study, bone density even increased slightly. Adverse effects of gestrinone include male hormone symptoms, such as acne, and possibly the development of unhealthy cholesterol levels.

Mifepristone. Mifepristone (Mifeprex) is another antiprogestin that may be helpful for treating endometriosis. In one 6-month study, mifepristone improved symptoms and reduced endometrial implants without causing menopausal side effects. Long-term use, however, may cause changes in the uterine tissue and cell proliferation.

Nonsteroidal Anti-inflammatory Drugs (NSAIDs). Over-the-counter NSAIDs may be sufficient for about 75% of women with endometrial pain. NSAIDs block prostaglandins (the substances that increase uterine contractions). They are effective painkillers and also have other properties that act against inflammatory factors. Aspirin is the most common NSAID, but there are dozens of others available over the counter or by prescription. Among the most effective NSAIDs for menstrual disorders are ibuprofen (Advil, Motrin, Midol PMS), naproxen (Aleve, Naprosyn, Naprelan, Anaprox), and mefenamic acid (Ponstel). For maximum benefit, they should be taken 7 - 10 days before a period is expected. However, long-term use of NSAIDs can increase the risk for gastrointestinal bleeding and ulcers. One study of women with iron deficiency anemia reported that overuse of NSAIDs for menstrual disorders contributes to anemia.

Acetaminophen. Acetaminophen (Tylenol) reduces levels of female hormones (gonadotropins and estradiol, an estrogen), which may have some beneficial effect on menstrual disorders. A combination of acetaminophen and pamabrom (Women's Tylenol Menstrual Relief) is specifically aimed at treating menstrual pain and bloating. (Pamabrom is a diuretic, a drug used to reduce fluid build-up and bloating.)

Opioids. Drugs containing codeine should not generally be used for endometriosis pain management. They can cause pelvic congestion and constipation, which can worsen symptoms in patients with gastrointestinal distress.

GnRH Antagonists. GnRH antagonists include ganirelix (Antagon) and cetrorelix (Cetrotide). These newer drugs differ from GnRH agonists in that they have a direct effect on the pituitary gland. The result is quicker action. They also pose a lower risk for complications and side effects.

Aromatase Inhibitors.Drugs that inhibit aromatase, an enzyme that is a major source of estrogen, are being studied for effects against endometriosis. Such drugs include anastrozole, letrozole, exemestane, and vorozole. Aromatase levels may be abnormal in women with endometriosis. A 2004 pilot study of letrozole combined with a progestin showed reduction of endometriosis as well as decrease in pelvic pain, suggesting that this treatment holds promise.

Selective Estrogen-Receptor Modulators (SERMs). Drugs known as selective estrogen-receptor modulators (SERMs) are thought to act like estrogen in some tissues but behave like estrogen blockers (antiestrogens) in others. They have not been widely studied for endometriosis since tamoxifen (Nolvadex), the most commonly used SERM, may worsen endometriosis. However, the actions of other SERMs, such as raloxifene (Evista) or tibolone (only available in Europe), may be beneficial and warrant more research.

Selective Progesterone Receptor Modulators (SPRMs). SPRMs, also called mesoprogestins, have both agonist and antagonist properties. This new class of drugs may be effective for suppressing endometrial growth.

Other investigational drugs for treatment of endometriosis include tumor necrosis factor alpha (TNF-alpha) inhibitors, angiogenesis inhibitors, and various immune modulators.

Conservative Surgery

The goal of conservative surgery is to aggressively remove as many endometrial implants and cysts as possible without causing surgical scarring and subsequent adhesions that could cause fertility problems. The two conservative procedures used are either laparoscopy or laparotomy.

Improving Fertility. Surgery has been shown to improve infertility rates in women with severe endometriosis (stages III and IV). Whether it offers any advantage in pregnancy rates in women with mild-to-moderate endometriosis (stage I or II) is unclear. Nevertheless, some doctors recommend conservative surgery even in early-stage endometriosis, because of the progressive nature of the disorder some evidence suggests it improves fertility. Fertility can often be restored even if the surgery does not remove all the endometrial implants. However, the best fertility rates in such cases occur in the early postoperative period. They decline over time if implants have not been completely eliminated. Subsequent surgeries become less effective in restoring fertility.

Reducing Pain and its Recurrence. Studies report pain reduction after surgery in more than 60% of women. Conservative surgery, however, can miss microscopic implants that may continue to cause pain and other symptoms after the procedure.

Even with very successful surgery, endometriosis usually recurs within a period of between 2 months and several years. In one study, the risk for recurrence after conservative surgery was highest in women who have had previous surgery or who have stage IV disease (large endometriotic cysts). Other factors including age, pregnancy, or the number of cysts, did not seem to influence the degree of risk. An earlier study indicated that women who became pregnant after surgery for endometriosis had a lower risk for recurrence, but pregnancy itself does not cure endometriosis. The use of GnRH agonists after surgery may delay recurrence without affecting fertility.

Both laparoscopy and laparotomy are effective, but there are differences. Some experts believe that laparoscopy surgery should be the treatment of choice for women with endometriosis.

Laparoscopy is currently the gold standard treatment for endometriosis. It is usually done under general anesthetic and involves the following:

Carbon dioxide gas is injected into the abdomen, distending it and pushing the bowel away so that the doctor has a wider view.
The procedure requires making small incisions at the navel and above the pubic bone.
The laparoscope (a hollow tube equipped with camera lenses and a fiber optic light source) is inserted through the incision at the navel (the umbilical incision).
A probe is then inserted through the second incision, allowing the doctor to directly view the outside surface of the uterus, fallopian tubes, and ovaries.
One or two additional small incisions can be made on either side of the lower abdomen through these incisions. Surgical instruments or other devices are passed through these accessory incisions to destroy or remove abnormal tissue. Implants can be removed by excision (surgical removal) using a laser or scissors or by destroying the area with lasers or with electricity (or electrocautery).

In one study, laparoscopy achieved pain relief in over 62% of women. A more recent study conducted 3 - 12 months post-surgery in women with severe (stage III/IV) endometriosis suggested 88% of patients were satisfied with the procedure.

In addition, pregnancy rates can range from 20% to over 50% after laparoscopy. (The procedure does not reduce the chances for pregnancy in women who must still undergo assisted reproductive techniques to conceive.) Still, recurrence rates for laparoscopy are no better than those with laparotomy -- the more invasive procedure.

Laparotomy uses a wide abdominal incision and conventional surgical instruments. It is more invasive and requires a longer recovery time. In some severe cases, the doctor may need a wider view of the pelvic area and will perform this procedure. Laparotomy is typically used for infiltrating endometriosis, although the less invasive laparoscopy is showing increasing effectiveness, even for deep implants.

Complications after Surgery. Many patients experience temporary but severe discomfort in the shoulders after laparoscopy due to residual carbon dioxide gas that puts pressure on the diaphragm. The incisions, even with laparoscopy, may cause pain afterward, which can usually be treated effectively with mild pain relievers. There are small risks for bleeding, infection, and reaction to anesthesia. Surgery in the pelvic area may also cause scarring, which may cause pain and interfere with fertility.

Preoperative Drug Treatment. Hormonal drugs administered before laparoscopy and laparotomy are being investigated to reduce the size of endometrial cysts and so perhaps to improve outlook. A 2000 study, for example, reported that the GnRH agonist goserelin injected monthly 12 weeks before laparoscopy resulted in much smaller implants and better treatment of the disease than treatment with surgery alone.

Postoperative Drug Treatment. A number of studies have also been conducted to determine if taking hormonal drugs after surgery can provide further pain relief. Results have been mixed, and the benefits, if any, are probably slight.

Hysterectomy

Hysterectomy, the surgical removal of the uterus, is the second most frequently performed surgery in premenopausal women (Cesarean sections are first). About 600,000 hysterectomies are performed each year in the U.S., which is among the highest rate of all countries. By age 60, about a third of American women have had this procedure. The highest hysterectomy rates are in women age 40 - 44. Women in the southern and midwestern areas of the United States are more likely to have the operation than those in the northeast and west.

Presence of symptoms (pelvic pain, bleeding, symptomatic fibroids)
Lack of symptom improvement or resolution despite treatment
Previous use of GnRH agonist drugs

The number of procedures has continued to increase, but only slightly in recent years. Endometriosis accounts for 18% of these procedures, but the rates vary widely by ethnic group, with the great majority of endometriosis-related hysterectomies performed in Caucasian women.

Hysterectomy does not necessarily cure endometriosis. One study reported that endometriosis reappeared in 13% of women within 3 years of a hysterectomy and in 40% after 5 years.

Most women are satisfied with the procedure. A major analysis of evidence on hysterectomies reported that symptoms related to menstrual problems decline significantly in most women, although none completely disappear for all women. The majority of women also experience improved quality of life and emotional functioning. Women who have a hysterectomy are less likely to experience hot flashes than women who have a natural menopause.

Still, one study suggested that 70% of recommendations for hysterectomies did not meet the standard of care as determined by expert groups. In such cases, patients were not given alternative choices or adequate diagnostic evaluations. Any woman, even one who has reached menopause, who is uncertain about a recommendation for a hysterectomy should certainly seek a second opinion.

Once a decision for a hysterectomy has been made, the patient should discuss with her doctor what will be removed. The common choices are:

Total Hysterectomy (Removal of uterus and cervix). Removing only the uterus with hysterectomy has the same risk for recurrence as conservative surgery.
Supracervical Hysterectomy (Removal of uterus and preservation of the cervix). Procedure is performed in about 20 - 25% of cases.
Bilateral Salpingo-Oophorectomy (Removal of the fallopian tubes and ovaries). It can be used with either total or supracervical hysterectomy. This is the only potential cure for endometriosis. If endometriosis has developed outside the uterus then even this procedure is not curative.

Hysterectomy is surgical removal of the uterus, resulting in inability to become pregnant. This surgery may be done for a variety of reasons including, but not restricted to, chronic pelvic inflammatory disease, uterine fibroids and cancer. A hysterectomy may be done through an abdominal or a vaginal incision.

Total Hysterectomy. In a total hysterectomy the uterus and cervix are removed; this eliminates the risk of uterine and cervical cancer. (Given technical advances and growing surgical experience, a total hysterectomy may eventually be unnecessary except in special circumstances, such as when cancer is present.)

Supracervical Hysterectomy. In a supracervical hysterectomy (also called subtotal hysterectomy), only the uterus is removed. Retaining the cervix helps support the pelvic floor and may help maintain full sexual sensation, but the risk for cervical cancer remains. Women may experience cyclical bleeding for up to a year after surgery.

Bilateral Oophorectomy. Bilateral oophorectomy is the removal of both ovaries. (When only one ovary is removed, the procedure is called oophorectomy.) Bilatera salpingo-oophorectomy is the removal of both fallopian tubes plus both ovaries. These procedures may be performed with either total or supracervical hysterectomy. When a woman decides to have her ovaries removed, she should be aware of both the positive and negative consequences.

Oophorectomy significantly reduces the rates of re-operation and endometrial pain recurrence compared to hysterectomy alone. By removing the ovaries, oophorectomy causes estrogen loss and helps to reduce the risk for ovarian cancer and breast cancer. Premenopausal women should realize, however, that oophorectomy causes immediate menopause, which poses a risk for a number of health problems. These problems include osteoporosis, heart disease, skin wrinkling, and reduction in muscle tone. Estrogen replacement can help offset them. Women who have a bilateral oophorectomy and do not receive hormone replacement therapy may experience more severe hot flashes than women who enter menopause naturally.

There is still a further choice, which is whether the hysterectomy should be performed through an incision in the abdomen or through the vagina. A variant of vaginal hysterectomy, called laparoscopic-assisted vaginal hysterectomy (LAVH), is yet another option.

Abdominal Hysterectomy. Abdominal hysterectomy is the most common procedure and is used in over 80% of hysterectomies in African-American women and about 60% in Caucasian and other ethnic groups. With the abdominal procedure, a wide incision is required to open the abdominal area, from which the surgeon removes the uterus. If possible, the incision should cut horizontally across the top of the pubic hairline (called a bikini incision). This incision heals faster and is less noticeable than a vertical incision, which is used in more complicated cases. The patient may need to remain in the hospital for 3 - 4 days, and recuperation at home takes about 4 - 6 weeks.

Vaginal Hysterectomy. Vaginal hysterectomy requires only a vaginal incision through which the uterus is removed. It is used in less than 20% of cases in African-American women and slightly under 40% among Caucasian and other groups.

A variation of the vaginal approach is called laparoscopic-assisted vaginal hysterectomy (LAVH). It uses several small abdominal incisions through which the surgeon severs the attachments to the uterus and ovaries. They can then be removed through the vaginal incision, as in the standard approach. Hospitalization stays may be longer and costs are greater than with standard vaginal hysterectomy. The use of LAVH has risen significantly and is now employed in over a quarter of vaginal procedures. LAVH is very costly, however, and some experts question whether it adds any significant benefits compared to the standard vaginal procedure.

If possible, a patient should ask a family member or friend to help out for the first few days at home. The following are some of the precautions and tips for postoperative care:

For a day or two after surgery, the patient is given medications to prevent nausea and painkillers to relieve pain at the incision site.
As soon as the doctor recommends it, usually within a day of the operation, the patient should get up and walk in order to help prevent pneumonia, reduce the risk of blood-clot formation, and to hasten recovery.
Walking and slow, deep breathing exercises may help to relieve gas pains, which can cause major distress for the first few days.
Coughing can cause pain, which may be reduced by holding a pillow over a surgical abdominal wound or by crossing the legs after vaginal surgery.
Patients are advised not to lift heavy objects, not to douche or take baths, and not to climb stairs or drive for several weeks.
For the first few days after surgery, many women weep frequently and unexpectedly. These mood swings may be due to depression from the loss of reproductive capabilities and form abrupt changes in hormones, particularly if the ovaries have been removed.

The patient should discuss with the doctor when they can start exercise programs that more intense than walking. The abdominal muscles are important for supporting the upper body, and recovering strength may take a long time. Even after the wound has healed, the patient may experience an on-going feeling of overall weakness, which can be demoralizing, particularly in women used to physical health. Some women do not feel completely well for as long as a year; others may recover in only a few weeks.

Minor complications after hysterectomy are very common. About half of women develop minor and treatable urinary tract infections. There is usually mild pain and light vaginal bleeding post operation. The infrequent occurrence of severe bleeding or hemorrhaging after vaginal hysterectomy, or laparoscopic-assisted vaginal hysterectomy, may be promptly treated by laparoscopy.

More serious complications, such as those described below, are uncommon, but patients should be aware of their symptoms and call the doctor immediately if they occur.

Among the three procedures, a 2001 study reported that complication rates were 44% for abdominal hysterectomy, 24% for vaginal hysterectomy, and only 2% for LAVH. (LAVH is used in less than 4% of hysterectomies, however.)

Infection. Infection occurs in 10 - 15% of patients, the risk being higher with abdominal than with vaginal surgery. Risk factors for infection appear to be obesity, a longer than normal operative time, and low socioeconomic status. Patients should be aware of any symptoms and call the doctor immediately if they occur:

Continuing or increasingly severe pain
Fever
Heavy discharge
Bleeding (antibiotics given at the time of surgery help to reduce this risk)

Blood Clots. There is a slight risk for small blood clots, usually in veins of the legs (thrombophlebitis). A sudden swelling or discoloration in the leg can indicate this condition and require immediate medical attention.

Click the icon to see an image of thrombophlebitis.

Other Serious Complications. Other serious and even life-threatening complications are rare but can include:

Pulmonary embolism (blood clots that travel to the lung)

Click the icon to see an image of a pulmonary embolism.

Surgical injury of the urinary or intestinal tracts.
Abscesses.
Perforation of the bowel.
Fistulas (a passage that bores from an organ to the skin or to another organ).
Dehiscence (opening of the surgical wound).

Long-Term Complications. Women who have had a total hysterectomy are at higher risk for the following long-term complications:

Muscle weakness in the pelvic area.
Prolapse (descent) of the bladder, vagina, and rectum if the muscle’s walls are overly weakened; may require further surgery.
Bowel problems may develop if adhesions (extensive scarring) have formed and obstruct the intestines, sometimes requiring additional surgery.
Shortening of the vagina is a possible complication specific to vaginal hysterectomy. It can cause pain during intercourse.

Such complications are uncommon.

After hysterectomy, women may experience hot flashes, a symptom of menopause, even if they retain their ovaries. However, women who have a hysterectomy are less likely to experience hot flashes than women who have a natural menopause. Surgery may have temporarily blocked blood flow to the ovaries, therefore suppressing estrogen release. If both ovaries have been removed in premenopausal women, the procedure causes premature menopause. Other menopausal symptoms include vaginal dryness and irritation, insomnia, and weight gain.

The most important complications occur in women who have had their ovaries removed. This causes estrogen loss, which places women at risk for osteoporosis (loss of bone density) and a possible increase in risks for heart disease and stroke. A number of drugs are available that can help protect both bones and heart.

Women have typically taken hormone replacement therapy (HRT) after surgery if their ovaries have been removed. HRT can help prevent hot flashes. There have been concerns about HRT-related health risks, including the risk for breast cancer. However, several 2006 studies of postmenopausal women who had hysterectomy indicated that estrogen-only HRT does not increase the risk for breast cancer, except if it is taken for many decades. (Two studies showed no increased risk for breast cancer after 7 years and 15 years, respectively. Women who took estrogen-only HRT for more than 20 years after hysterectomy had only a moderately increased risk.) Combination estrogen-progestin HRT does increase breast cancer risk.

In premenopausal women, such preventive measures are not needed if the ovaries are left intact. The ovaries will usually continue to function and secrete hormones even after the uterus is removed, but the lifespan of the ovaries is reduced by an average of 3 - 5 years. In rare cases, complete ovarian failure occurs right after hysterectomy, presumably because the surgery has permanently cut off the blood supply to the ovaries.

Sexual intercourse may resume 4 - 6 weeks following surgery. The effect of hysterectomy on sexuality is unclear. Studies have reported that up to 25% of women experience increased sexual drive. Nevertheless, some women report no change, and other women develop problems related to sexual function. For example, around 10% of women experience vaginal dryness, about 2% of women develop pain during sex, and another 2% also appear to lose capacity for orgasm.

Two procedures associated with hysterectomy may affect sexuality directly.

Although the clitoris can trigger orgasm even if the cervix is removed, some experts believe that uterine contractions stimulated by sexual intercourse also cause a so-called “deep orgasm.” Retaining the cervix may help to retain this sensation. However, a 2006 review found that women who undergo a total hysterectomy (removal of both uterus and cervix) are no more likely to have sexual difficulties or problems with urinary and bowel function than women who have only their uterus removed.
Patients who have both ovaries removed may be at higher risk for loss of sexuality. Ovaries produce small amounts of testosterone (the male hormone responsible for sexual drive) even after menopause.

Testosterone Replacement. Testosterone replacement therapy may restore sexuality in women who experience a decline in sexual drive. Occasionally, oral or injection treatments can produce male characteristics such as facial hair and voice change. A slow-release pellet inserted every 6 months under the skin in the hip appears to reduce these side effects. Taking hormones long-term almost always carries some risk, and it is not yet known what danger testosterone replacement may pose in women.

Annual Pap smears are recommended for all women with an intact cervix who are 18 years or older or who have become sexually active. After a total hysterectomy, in which the cervix has been removed, a woman does not need annual Pap smears of the cervix. However, she still should get regular pelvic and breast exams. Also, women with a history of abnormal Pap smears usually require annual screening.

Resources

www.asrm.com -- American Society for Reproductive Medicine
www.acog.com -- American College of Obstetricians and Gynecologists
www.endometriosisassn.org -- The Endometriosis Association
www.nichd.nih.gov -- National Institute of Child Health and Human Development
www.endozone.org -- Endometriosis Zone
www.pelvicpain.org -- International Pelvic Pain Society
www.endocenter.org -- Endometriosis Research Center
www.resolve.org -- National Infertility Association

References

Chen WY, Manson JE, Hankinson SE, Rosner B, Holmes MD, Willett WC, et al. Unopposed estrogen therapy and the risk of invasive breast cancer. Arch Intern Med. 2006 May 8;166(9):1027-32.

Lethaby A, Ivanova V, Johnson NP. Total versus subtotal hysterectomy for benign gynaecological conditions. Cochrane Database Syst Rev. 2006 Apr 19;(2):CD004993.

Parker JD, Leondires M, Sinaii N, Premkumar A, Nieman LK, Stratton P. Persistence of dysmenorrhea and nonmenstrual pain after optimal endometriosis surgery may indicate adenomyosis. Fertil Steril. 2006 Sep;86(3):711-5. Epub 2006 Jun 16.

Stefanick ML, Anderson GL, Margolis KL, Hendrix SL, Rodabough RJ, Paskett ED, et al. Effects of conjugated equine estrogens on breast cancer and mammography screening in postmenopausal women with hysterectomy. JAMA. 2006 Apr 12;295(14):1647-57.

Review Date:
6/16/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Uterine fibroids and hysterectomy

FitSugar — Wed, 08 Oct 2008 17:35:01 -0700

In This Report

Highlights
Introduction
Causes
Symptoms
Risk Factors
Complications
Diagnosis
Lifestyle Changes
Medications
Surgery
Other Procedures
Hysterectomy
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Uterine Artery Embolization Versus Standard Surgery

Many women with fibroids are considering a procedure called uterine artery embolization (UAE) as an alternative to standard surgery such as hysterectomy or myomectomy. A study published in 2007 in the New England Journal of Medicine compared these treatment approaches. The study suggested that UAE results in shorter hospital stay and faster recovery time, but a small percentage of women may later need repeat embolization or a hysterectomy. There were similar improvements in quality of life regardless of whether a woman had UAE or standard surgery.

Magnetic-Resonance Guided Focused Ultrasound (MRgFUS)

MRgFUS is a new non-surgical approach for treating fibroids. A 2006 study in Obstetrics and Gynecology indicated that taking gonadotropin-releasing hormone (GnRH) agonist drugs before this procedure may help reduce fibroid volume and improve outcomes.

Predictors of Hysterectomy

Combined factors can predict whether a woman will decide to have a hysterectomy, according to a 2007 study published in the Journal of the American College of Surgeons. Women who met all three criteria had a 95% chance of having a hysterectomy:

Presence of symptoms (pelvic pain, bleeding, symptomatic fibroids)
Lack of symptom improvement despite treatment
Previous use of GnRH agonist drugs

Hysterectomy and Sexual Function

Hormone Replacement Therapy (HRT) and Breast Cancer Risk

Estrogen-only HRT after hysterectomy does not appear to increase breast cancer risk when used in the short term (up to 20 years), according to several 2006 studies. Combination estrogen-progestin HRT does increase breast cancer risk.

Introduction

A uterine fibroid (known medically as a leiomyoma or myoma ) is a noncancerous (benign) growth composed of smooth muscle and connective tissue. The size of a fibroid varies from that of a pinhead to larger than a melon. Fibroids have been reported weighing more than 20 pounds.

Fibroids originate from the thick wall of the uterus and are categorized by the direction in which they grow:

Intramural fibroids grow within the middle and thickest layer of the uterus (called the myometrium). They are the most common fibroids.
Subserosal fibroids grow out from the thin outer fibrous layer of the uterus (called the serosa). Subserosal can be either stalk-like (pedunculated) or broad-based (sessile). These are the second most common fibroids.
Submucous fibroids grow from the uterine wall toward and into the inner lining of the uterus (the endometrium). Submucous fibroids can also be stalk-like or broad-based. Only about 5% of fibroids are submucous.

Fibroid tumors may not need to be removed if they are not causing pain, bleeding excessively, or growing rapidly.

The Primary Organs and Structures in the Reproductive System. The primary structures in the reproductive system are as follows:

The uterus is a pear-shaped organ located between the bladder and lower intestine. It consists of two parts, the body and the cervix.
When a woman is not pregnant the body of the uterus is about the size of a fist, with its walls collapsed and flattened against each other. During pregnancy the walls of the uterus are pushed apart as the fetus grows.
The cervix is the lower portion of the uterus. It has a canal opening into the vagina with an opening called the os, which allows menstrual blood to flow out of the uterus into the vagina.
Leading off each side of the body of the uterus are two tubes known as the fallopian tubes. Near the end of each tube is an ovary.
Ovaries are egg-producing organs that hold 200,000 - 400,000 follicles (from folliculus, meaning "sack" in Latin). These cellular sacks contain the materials needed to produce ripened eggs, or ova.

The inner lining of the uterus is called the endometrium. During pregnancy this inner lining thickens and becomes enriched with blood vessels to house and support the growing fetus. If pregnancy does not occur, the endometrium is shed as part of the menstrual flow. Menstrual flow also consists of blood and mucus from the cervix and vagina.

In women, six key hormones serve as chemical messengers that regulate the reproductive system:

The hypothalamus first releases the gonadotropin-releasing hormone (GnRH).
This chemical, in turn, stimulates the pituitary gland to produce follicle-stimulating hormone (FSH) and luteinizing hormone (LH).
Estrogen, progesterone, and the male hormone testosterone are secreted by the ovaries at the command of FSH and LH and complete the hormonal group necessary for reproductive health.

Click the icon to see an image of the uterus.

Click the icon to see an image of the pituitary gland.

Click the icon to see an image of the hypothalamus.

Causes

Inherited genetic factors may be important in many cases of fibroids. Researchers are investigating unique genetic factors that regulate hormones. Proteins called growth factors may be responsible for some of the abnormalities leading to uterine muscle overgrowth and fibroids. Scientists have identified chromosomes carrying a total of 145 genes that may affect fibroid growth. Some experts report that uterine fibroids are inherited from paternal (the father's) genes.

Uterine fibroids often grow during pregnancy, and they degenerate after menopause. From these observations and certain studies researchers are fairly certain that the female hormones, both estrogen and progesterone, play a role in their growth. Their role, however, is not clear. Some theories about the relationship to fibroids and estrogen include the following:

Estrogen patterns in fibroids are similar to those in pregnancy. That is, like smooth muscle cells in the uterus during pregnancy, fibroid cells exposed to female hormones do not respond normally to signals that would make them self-destruct and return to a nonpregnant state. (This natural self-destruction is a process called apoptosis). Instead, they continue to grow.
Some evidence suggests that estrogen may inhibit a tumor-suppressor gene called p53 in fibroid tissue, therefore triggering cell proliferation leading to fibroid growth. (P53 plays a role in some cancer-cell growth, although in this case the process is not cancerous.)

The formation of fibroids may be attributable to abnormalities in substances called growth factors. These are special proteins, secreted by different cell types, that are responsible for cell-to-cell interaction. Many of these substances regulate a process called angiogenesis, which causes new blood vessels to sprout from pre-existing ones. The production of new blood vessels then feeds any existing growth, such as fibroids.

The growth factors that appear to play an important role in many female reproductive disorders are Basic Fibroblast Growth Factor (BFGF) and Vascular Endothelial Growth Factor (VEGF). BFGFs are involved in the proliferation of cells that form connective tissue, which supports the body's organs and structure. VEGFs are involved with cell growth in smooth muscles that line blood vessels. Some evidence suggests they play a role in uterine fibroids.

Other growth factors being studied specifically for fibroids include Insulin-like Growth Factor (IGF)-I, Epidermal Growth Factor (EGF), Platelet Derived Growth Factor (PDGF), and Transforming Growth Factor (TGF).

Symptoms

Fewer than 25% of patients with fibroids experience symptoms. When they do, they include:

The most common symptom is prolonged and heavy bleeding during menstruation. This is caused by fibroid growth bordering the uterine cavity. In severe cases, heavy bleeding may last as many as 2 weeks. Fibroids rarely bleed between periods, except in a few cases of very large fibroids.
Large fibroids can also cause pressure and pain in the abdomen or lower back that sometimes feels like menstrual cramps.
As the fibroids grow larger, some women feel them as hard lumps in the lower abdomen.
Very large fibroids may give the abdomen the appearance of pregnancy and cause a feeling of heaviness and pressure. In fact, large fibroids are defined by comparing the size of the uterus to the size it would be at specific months during gestation.
Unusually large fibroids may press against the bladder and urinary tract and cause frequent urination or the urge to urinate, particularly during the night when a woman is lying down.
Abnormal pain during intercourse (called dyspareunia).
If the fibroids press on the ureters (the tubes going from the kidneys to the bladder), obstruction or blockage of urine may result.
Fibroid pressure against the rectum can cause constipation.

Risk Factors

Uterine fibroids are the most common tumor found in female reproductive organs. It is estimated that over 50% of women age 30 - 50 have fibroids, although they cause symptoms in only about 25%. A survey of 1,364 women suggested an even higher prevalence of over 80% in African-American women and almost 70% in white women. A number of possible risk factors have been identified, but very little research exists to confirm them.

Uterine fibroids are particularly common in African-American women, with an estimated prevalence of 50 - 75%. These women are also more likely to have severe pain, anemia, and larger and more numerous fibroids than women in other population groups. Although genetics may play a role, women of African descent who live in other countries do not appear to have as high an incidence of fibroids. This suggests that diet or other environmental factors are at work in the development of fibroids in African-American women.

Fibroids can start to grow soon after puberty, although usually they are detected when a woman reaches young adulthood. Women with fibroids are at risk for accelerated fibroid growth when estrogen levels are high or when lifestyle behaviors keep estrogen levels high.

Some examples of risk factors for fibroids that are also associated with high estrogen exposure include:

Early onset of menstrual period (before age 12)
Being overweight and sedentary
Never being pregnant. The risk for fibroids decreases with more children. (This risk factor, however, may be due to a greater risk for infertility caused by fibroids in the first place.)

Combined Oral Contraceptives. Combined oral contraceptives contain estrogen and progesterone and the evidence on their effects on fibroids have been conflicting. Early reports suggested they might be a risk factor. Most studies conducted more recently, however, have found no association and some even suggest that the newer low-dose OC combinations may be protective.

Hormone Replacement Therapy. Hormone replacement therapies (HRT) contain estrogen alone or estrogen plus progesterone. After menopause, fibroids usually shrink. Researchers are investigating whether the hormones used in HRT could cause existing fibroids to persist or even grow. Some studies, but not all, have found greater fibroid growth with the use of patch-administered hormone drugs. (In one of the studies, taking oral estrogen, however, had no effect.) A 2001 systematic review of studies reported some fibroid growth in women taking HRT, but usually without any significant symptoms.

If HRT has an effect on fibroid growth, it is unlikely to be severe. Any increase in fibroid growth during menopause must be evaluated surgically by a gynecologist since such growth, even if a woman is on hormone replacement therapy, may mean cancer.

High blood pressure (hypertension) may be associated with increased fibroid risk according to a 2005 epidemiologic study. The prospective study tracked women in the Nurses’ Health Study for 10 years and found that for every 10 mm/Hg increase in diastolic blood pressure, the risk for developing fibroids increased by 8 - 10%. (Interestingly, women who used antihypertensive medications had the highest risk.). Researchers reported that women with hypertension were 24% more likely to develop fibroids and that the longer a woman had hypertension, the greater her risk.

Complications

Effect on Fertility. The effect of fibroids on fertility is controversial. A 2002 analysis suggested that they may account for infertility in only 1 - 2.4% of women who have trouble conceiving. Large fibroids may cause infertility by:

Impairing the uterine lining
Blocking the fallopian tubes
Distorting the shape of the uterine cavity
Altering the position of the cervix and preventing sperm from reaching the uterus

Some evidence suggests that even small fibroids may reduce the chances of pregnancy in women who are undergoing assisted reproductive techniques. Treatments to reduce fibroids may be helpful in such women, although there has been little research on this subject.

Effect on Pregnancy.Fibroids can increase pregnancy complications and delivery risks. These include:

Cesarean section delivery
Breech presentation (baby enters the birth canal upside down with feet or buttocks emerging first)
Preterm birth
Placenta previa (placenta covers the cervix)
Excessive bleeding after giving birth (postpartum hemorrhage)

A 2006 study found that pregnant women with at least one fibroid had the following increased risks: cesarean delivery (57%), breech birth (64%), preterm delivery (45%), placenta previa (86%), and postpartum hemorrhage (157%).

Anemia due to iron deficiency can develop if fibroids cause excessive bleeding. Oddly enough, smaller fibroids, usually submucous, are more likely to cause abnormally heavy bleeding than larger ones.

Most cases of anemia are mild. Mild anemia can cause weakness and fatigue. Moderate-to-severe anemia can cause shortness of breath, rapid heart rate, lightheadedness, headaches, ringing in the ears (tinnitus), irritability, pale skin, restless legs syndrome, and mental confusion. Heart problems can occur if prolonged and severe anemia is not treated. Pregnant women who are anemic, particularly in the first trimester, have an increased risk for a poor pregnancy outcome.

Large fibroids that press against the bladder occasionally result in urinary tract infections. Pressure on the ureters may cause urinary obstruction and kidney damage.

The female and male urinary tracts are relatively the same except for the length of the urethra.

Fibroids can cause cramping during a period, which can be quite intense at times.

Pain can also develop if the blood supply is cut off from the fibroid tissue. In such cases, the cells blacken and die (a process called necrosis) from lack of oxygen. This event may occur under the following circumstances:

A very large fibroid outgrows its own blood supply.
A pedunculated fibroid (one that grows on a stem from the uterine wall) becomes twisted, thus cutting off its blood supply.
Pregnancy occurs, in which the risk for fibroid cell degeneration and necrosis increases.

Rarely, a fibroid breaks away from the uterus and develops in other locations. They are typically one of the following:

Benign Metastasizing Leiomyoma or BML (which usually spreads to the lung)
Disseminated Peritoneal Leiomyomatosis (which spreads to the abdominal wall)

Neither is cancerous, although there is some evidence that BML, which often occurs after menopause, may represent a slow-growing variant of leiomyosarcoma.

Fibroids are nearly always noncancerous, even if they have abnormal cell shapes. Cancer of the uterus nearly always develops in the lining of the uterus (endometrial cancer). Only in rare cases (less than 0.1%) does cancer develop from a malignant change in a fibroid (called leiomyosarcoma). Nevertheless, rapidly enlarging fibroids in a premenopausal woman or even slowly enlarging fibroids in a postmenopausal woman require surgical evaluation to rule out cancer.

Click the icon to see an image of uterine cancer.

Diagnosis

A doctor will perform a pelvic examination to check for pregnancy-related conditions and signs of fibroids or other abnormalities, such as ovarian cysts.

The doctor needs to have a complete history of any medical or personal conditions that might be causing heavy bleeding:

Any family history of menstrual problems or bleeding disorders.
The presence or history of any medical conditions that might be causing heavy bleeding. Women who visit their gynecologist with menstrual complaints, particularly heavy bleeding, pelvic pain, or both may actually have an underlying medical disorder, which must be ruled out.
The pattern of the menstrual bleeding. (If it occurs during regular menstruation, nonhormonal treatments are tried first. If bleeding is irregular, occurs between periods, with premenstrual pain, after sex, or is associated with pelvic pain, the doctor should look for specific conditions that may cause these problems.)
Regular use of any medications (including vitamins and over-the-counter drugs).
Diet history, including caffeine and alcohol intake.
Past or present contraceptive use.
Any recent stressful events.
Sexual history. (It is very important that the patient trust the doctor enough to describe any sexual activity that might be risky.)

Almost all women, at some time in their reproductive life, experience heavy bleeding during menstrual periods ( menorrhagia ). Being taller, older, and having a higher number of pregnancies increase the chances for heavier-than-average bleeding. In some cases the cause of heavy bleeding is unknown, but a number of conditions can cause menorrhagia or contribute to the risk:

Miscarriage. An isolated instance of heavy bleeding usually after the period due date may be due to a miscarriage. If the bleeding occurs at the usual time of menstruation, however, miscarriage is less likely to be a cause.
Having late periods or approaching menopause. These events may cause occasional menorrhagia.
Uterine polyps. (These are small benign growths in the uterus.)
Certain contraceptives. (Oral contraceptives or an intrauterine device, an IUD.)

The intrauterine device (IUD) shown uses copper as the active contraceptive; others use progesterone in a plastic device. IUDs are very effective at preventing pregnancy (less than 2% chance per year for the progesterone IUD, less than 1% chance per year for the copper IUD). IUDs come with an increased risk of ectopic pregnancy and perforation of the uterus, and do not protect against sexually transmitted disease. IUDs are prescribed and placed in the uterus by a health care provider.

Bleeding disorders. Bleeding disorders that impair blood clotting can cause heavy menstrual bleeding and, according to different studies, have been associated with between 10 - 17% of menorrhagia cases. Von Willebrand disease, a genetic condition, is the most common of these bleeding disorders. Most, but not all, studies report this problem to be more common in African-American than Caucasian women. Most bleeding disorders have a genetic basis and should be suspected in adolescent girls who experience heavy bleeding.
Uterine cancer.
Pelvic infections.
Endometriosis. (These are small implants of uterine tissue. They are more likely to cause pain than bleeding.)

Click the icon to see an image of endometriosis.

Adenomyosis. This condition occurs when glands from the uterine lining become embedded in the uterine muscle. Its symptoms are nearly identical to fibroids (heavy bleeding and pain), and in one study fibroids were also present in 62% of cases. It is most likely to develop in middle-aged women who have had many children.
A number of medical conditions, including thyroid problems, systemic lupus erythematosus, diabetes, certain cancers and chemotherapies, and some uncommon blood disorder.
Certain drugs, including anticoagulants and anti-inflammatory medications.
In many cases, the cause of heavy bleeding is unknown.

Hysteroscopy is a procedure that may be used to detect the presence of fibroids, polyps, or other causes of bleeding. Although less invasive procedures can also detect causes of abnormal uterine bleeding, hysteroscopy has the added advantage of serving as a surgical procedure for the removal of submucous fibroids. It is also quite useful in ruling out cancer. If cancer is suspected, more invasive procedures, such as dilation and curettage (D&C) or endometrial biopsy, are warranted.

Hysteroscopy is non-invasive; however, 30% of women report severe pain with the procedure. The use of an anesthetic spray, such as lidocaine, may be highly effective in preventing pain during this procedure. Other complications include excessive fluid absorption, infection, and uterine perforation.

Ultrasound and Sonohysterography. Ultrasound is the standard imaging technique for evaluating the uterus and ovaries, detecting fibroids, ovarian cysts and tumors, and also obstructions in the urinary tract. It uses sound waves to produce an image of the organs and entails no risk and very little discomfort.

Transvaginal sonohysterography uses ultrasound along with saline infused into the uterus, which enhances the visualization of the uterus. This technique is proving to be more accurate than standard ultrasound in identifying potential problems. Some experts believe it should be the first-line tool for diagnosing heavy bleeding.

Magnetic Resonance Imaging. Magnetic resonance imaging (MRI) provides a better image of any fibroids that might be causing bleeding. An MRI can help the doctor decide if a woman is a candidate for minimally invasive uterine artery embolization (UAE). Fibroids with low blood flow (“nonviable tumors”) may not be suitable for UAE. An MRI may also be better than an ultrasound for evaluating uterine size and fibroid location.

When heavy or abnormal bleeding occurs, an endometrial (uterine) biopsy can be performed in the office along with an ultrasound. It is usually used with a procedure called dilation and curettage (D&C), which is particularly important to rule out uterine (endometrial) cancer. A D&C is a somewhat invasive procedure:

A D&C is usually done in an outpatient setting so that the patient can return home the same day, but it sometimes requires a general anesthetic. It may need to be performed in the operating room to rule out serious conditions or treat some minor ones that may be causing the bleeding.
The cervix (the neck of the uterus) is dilated (opened).
The surgeon scrapes the inside lining of the uterus and cervix.

Click the icon to see an image of a D&C.

Lifestyle Changes

Because fibroids are almost never life-threatening, watchful waiting is a reasonable option for many women (even those with large fibroids), particularly if they are approaching menopause.

Any woman who chooses watchful waiting should be sure other causes of heavy bleeding have been ruled out. She should also have regular pelvic examinations and ultrasounds performed to monitor the growth of the fibroid.

Foods for Maintaining Healthy Iron Stores. The following are some suggestions for increasing iron levels in the diet:

The best foods for increasing or maintaining healthy iron levels contain absorbable iron, called heme iron. Such foods include (in order of iron-richness) clams, oysters, organ meats, beef, pork, poultry, and fish.
About 60% of iron in meat is poorly absorbed; this is a form called non-heme iron. Eggs, dairy products, and vegetables that contain iron only have the non-heme form. Such plants include dried beans and peas, iron-fortified cereals, bread, and pasta products, dark green leafy vegetables (chard, spinach, mustard greens, kale), dried fruits, nuts, and seeds.
Increasing intake of vitamin-C rich foods can enhance absorption of non-heme iron during a single meal, although regular intake of vitamin C does not appear to have any significant effect on iron stores. In any case, vitamin-C rich foods are healthy and include broccoli, cabbage, citrus fruits, melon, tomatoes, and strawberries. One orange or 6 ounces of orange juice can double the amount of iron your body absorbs from plant foods.

Like most vitamins, vitamin C may be obtained in the recommended amount with a well-balanced diet, including some enriched or fortified foods.

Foods containing riboflavin (vitamin B2) may help enhance the response of hemoglobin to iron. Sources include liver, dried fortified cereals, and yogurt.
Cooking in cast iron pans and skillets is known to increase iron content of food. According to one study, however, boiling, steaming, or stir-frying many vegetables in utensils composed of any material significantly increases the release of iron stored in plants so it is available to the body.
Certain nutrients, such as tannin (found in tea) or phytic acid (found in foods such as seeds and bran) interfere with the body's absorption of dietary iron. (It is commonly believed that fiber impedes iron absorption, but researchers report that it most likely has no effect.)

Sources of Vitamins B12 and Folate. Vitamins B12 and folate are important for prevention of anemia related to nutritional deficiencies. Although this anemia is not necessarily related to fibroids, these vitamins are very important for good health in general and for reproductive health in women.

The only natural dietary sources of B12 are animal products such as meats, dairy products, eggs, and fish (clams and oily fish are very high in B12). Like other B vitamins, B12 is added to commercial dried cereals. The recommended daily allowance (RDA) is 2.4 mcg a day. Deficiencies are rare in young people, although the elderly may have trouble absorbing natural vitamin B12 and require synthetic forms from supplements and fortified foods.

Click the icon to see an image of vitamin B12 sources.

Folate is best found in avocado, bananas, orange juice, cold cereal, asparagus, fruits, green, leafy vegetables, dried beans and peas, and yeast. The synthetic form, folic acid, is added to commercial grain products. Vitamins are usually made from folic acid, which is about twice as strong as folate. Many experts recommend that adults have 400 mcg of folic acid daily, which is considerably higher than standard recommendations of 400 mcg of folate. Low levels of folate during pregnancy are common without supplements; deficiencies at that time increase the risk of neural tube defects in newborns. Women who are planning to get pregnant should take 400 mcg of folic acid before conception as well as when they are pregnant or breast feeding.

Click the icon to see an image of folate sources.

Iron Supplements. Iron supplements are best for restoring iron levels, but they should be used only when dietary measures have failed. Women should always discuss such supplements with their doctor.

See In-Depth Report #57: Anemia.]

Many women with menstrual disorders may resort to alternative treatments. There has been little research on whether any such therapies benefit fibroids.

Acupuncture. Some women report relief from pelvic pain and heaviness after acupuncture

Click the icon to see an image of acupuncture.

Yoga. Yoga exercises help some women relieve sensations of heaviness and pressure.

Herbal Remedies. Herbal remedies used for fibroids include ginseng or herbal combinations of rhubarb, cinnamon, and sargassum seaweed. There is no scientific evidence that these herbs are effective. Pycnogenol is a plant extract from the bark of the French maritime tree. Studies suggest it may provide some relief for menstrual pain (dysmenorrhea).

Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been a number of reported cases of serious and even lethal side effects from herbal products. Patients should check with their doctor before using any herbal remedies or dietary supplements.

Medications

Because fibroid growth tends to stop and regress after menopause, the important reproductive hormones -- estrogen, progesterone, or both -- most likely play a critical role in their survival. Some drugs that block either of these hormones are used to treat severe fibroids with some success.

Oral contraceptives (OCs) are sometimes used to control the heavy menstrual bleeding (menorrhagia) associated with fibroids, but they do not help prevent fibroid growth. Newer types of continuous-dosing OCs, such as Seasonique, reduce the number of periods a woman has per year. In May 2007, the FDA approved Lybrel, a continuous-dosing OC that completely eliminates periods.

Intrauterine devices (IUDs) that release progestin can be very beneficial for menorrhagia. Specifically, the levonorgestrel-releasing intrauterine system, or LNG-IUS (Mirena, FibroPlant), has shown excellent results. Many experts now recommend the LNG-IUS as a first-line treatment for menorrhagia, particularly for women who may face hysterectomy (removal of uterus), conservative surgery such as endometrial resection (removal of endometrial lining), or endometrial ablation (destruction of endometrial lining). [See In-Depth Report #100: Menstrual disorders.]

Gonadotropin releasing hormone (GnRH) blocks the release of the reproductive hormones LH (luteinizing hormone) and FSH (follicular-stimulating hormone). As a result, the ovaries stop ovulating and no longer produce estrogen. GnRH agonists include goserelin (Zoladex), buserelin, a monthly injection of leuprolide (depot Lupron), and nafarelin (Synarel), a nasal spray. Such drugs may be used alone or in preparation for procedures used to destroy the uterine lining.

These drugs may be used in the following situations:

As preoperative treatment 3 - 4 months before uterine surgery. In a major analysis, the use of GnRH agonists reduced fibroid size and uterus volume, helped correct any existing anemia due to blood loss, reduced blood loss during surgery, and reduced the duration of hospital stay. (Some experts question, however, whether the benefits outweigh the costs.)
For women with fibroids nearing menopause. (Such women only need them for a short period.)
Possibly helpful in improving subsequent fertility. (However, women should not try to become pregnant while taking these drugs, as they pose a risk for birth defects.)

While GnRH agonists can reduce fibroids by between 30 - 90% of original size, they have certain limitations:

They are not permanent cures, and fibroids regrow after the drugs are discontinued.
They are injected drugs and cannot be taken orally.
They are expensive.
Long-term use of GnRh agonists causes bone density loss, which can lead to osteoporosis.

Before using these drugs, the doctor should be certain that no other complicating conditions are present, particularly leiomyosarcoma (cancer). The use of these drugs can delay treatment of the malignancy and cause severe complications.

Commonly reported side effects, which can be severe in some women, include menopausal-like symptoms. These symptoms include hot flashes, night sweats, changes in the vagina, weight change, and depression. The side effects vary in intensity, depending on the GnRH agonist. They may be more intense with leuprolide and persist after the drug has been stopped.

The most important concern is possible osteoporosis from estrogen loss. Women should not take these drugs for more than 6 months. Certain approaches may preserve enough estrogen to protect bones and still effectively relieve endometriosis symptoms:

Add-back therapy, which provides doses of estrogen and progestin that are high enough to maintain bone density but too low to offset the beneficial effects of the GnRH agonist.
Intermittent leuprolide, which uses repeated 6-month courses of GnRH agonists followed by an average of 9 months of symptom control only.
Taking GnRH agonists in very low doses is an alternate approach, but is still largely untested.
Adding a bone-protective drug may be helpful. The standard ones are bisphosphonates, which include alendronate (Fosamax), risedronate (Actonel), and etidronate (Didronel). Other drugs are being tested in combination with a GnRH agonist to preserve bone. They include the parathyroid hormone teriparatide (Forteo) and selective estrogen-receptor modulators (SERMs), such as raloxifene (Evista).

Danazol (Danocrine) resembles a male hormone. It suppresses estrogen and is effective for heavy menstrual bleeding caused by fibroids. In some women it produces male characteristics, such as facial hair and voice change. Other side effects include weight gain, acne, and dandruff. It may increase the risk for unhealthy cholesterol levels. A few cases of blood clots and strokes have been reported. There is no available long-term experience using danazol for fibroids.

Gestrinone. Antiprogestins are promising drugs for fibroids. Gestrinone has been shown to reduce uterine volume and stop bleeding. In addition, benefits appear to persist. In one study, 89% of the women maintained smaller uterine volume for at least 18 months after stopping the treatment. In another study, bone density even increased slightly. Adverse effects of gestrinone include male hormone symptoms, such as acne, and possibly the development of unhealthy cholesterol levels.

Mifepristone. Mifepristone (Mifeprex) is an anti-progestin that has reduced fibroid size in some studies. In one study, it reduced fibroids as significantly as GnRH agonists, and the fibroids were less likely to recur. However, this medicine can have severe side effects.

Asoprisnil. A promising new antiprogestin called Asoprisnil has been shown to reduce fibroids. The drug is in late-stage clinical trials.

Although they have not been studied for fibroids, nonsteroidal anti-inflammatory drugs (NSAIDs) taken on a regular schedule reduce heavy menstrual bleeding and pain from unknown causes. These drugs reduce inflammation, in part by their action against prostaglandins, the chemicals that stimulate uterine contractions and cause pain. Aspirin is the most common NSAID, but there are dozens of others, including ibuprofen (Advil, Motrin) and naproxen (Aleve, Anaprox, Naprosyn). Both ibuprofen and naproxen are recommended for menstrual pain. However, long-term use of any NSAID can increase the risk for gastrointestinal bleeding and ulcers. In addition, long-term use of high-dose NSAIDs (with the exception of aspirin) can increase the risk for heart attacks and strokes. To reduce these risks, it is best to take the lowest dose of NSAIDs for the shortest time possible.

A number of other drugs are under investigation for treating fibroids:

Selective estrogen-receptor modulators (SERMs) are drugs that have some of the effects of estrogen but do not produce some of its complications, such as a higher risk for uterine cancer. Raloxifene (Evista) is proving to help prevent bone loss in patients taking GnRH agonists for uterine fibroids, and may also be helpful as a single drug for preventing fibroid growth.
Drugs that block growth factors believed to play a role in fibroids are also under investigation. Pirfenidone is one such drug, which blocks fibroid cell reproduction. Another is interferon alpha, substance that inhibits angiogenesis (the growth of new blood vessels).
Drugs derived from retinoids (vitamin A compounds) may inhibit cell proliferation in fibroid tissue.
Fulvestrant (Faslodex) blocks estrogen and has been studied for uterine fibroids and endometriosis, although progress in these areas has stalled in favor of research for its use in breast cancer.

Surgery

If nonsurgical strategies do not relieve symptoms, surgery may be the best option for treatment. Surgery may be indicated depending on a number of factors:

Intractable Side Effects. Surgery may be warranted if fibroids are causing distressing and intractable symptoms that have not been relieved by nonsurgical or minimally invasive therapies. Assuming, however, that symptoms do not pose serious health or life-threatening conditions, a woman should make her decision based on the factors she deems important (the desire for children, for example).

Ureteral Obstruction. Large fibroids sometimes press down on the ureters (the tubes going from each kidney to the bladder), thereby blocking urine from emptying into the bladder. Because ureteral obstructions can permanently damage kidneys, surgery may be indicated.

Inability to Evaluate Ovaries. The risk for missing a diagnosis of ovarian cancer is higher when fibroids are too large to permit evaluation of the ovaries by pelvic examination or ultrasound. Ovarian cancer is particularly deadly because it is so difficult to catch early enough for curative treatment. The risk for this cancer, however, is very low in women without a family history, especially before menopause. Women with a family history of ovarian cancer and large fibroids may need to consider surgery.

Enlarging Fibroids. Rapidly growing fibroids may signify cancer (leiomyosarcoma), which must be ruled out. In postmenopausal women, even slow growth raises suspicions for cancer. However, many hysterectomies have been inappropriately performed because of large noncancerous fibroids that were only suspected to be cancerous. Women should be sure that diagnostic procedures have been as thorough as possible if they want to avoid an unnecessary hysterectomy.

Severe Anemia from Heavy Bleeding. When iron supplementation, resection (surgical removal) of submucous fibroids by hysteroscopy, or GnRH agonist therapy fails to resolve anemia and bleeding, major surgery (myomectomy or hysterectomy) may be recommended.

Hysterectomy. Until recently, hysterectomy was the only surgical option for uterine fibroids. This procedure involves the surgical removal of the uterus and is often accompanied by oophorectomy (the removal of the ovaries). With this procedure, fertility is not preserved. Other options may be available for many women, even those who have large fibroids. Discuss all possibilities with your physician.
Myomectomy. Myomectomy is the surgical removal of only one or more fibroids. Myomectomy usually involves a laparotomy (a procedure that uses a wide abdominal incision) or less invasive surgical techniques, such as laparoscopy and hysteroscopy. In such cases, unlike with hysterectomy, this technique may preserve fertility.
Uterine Artery Embolization (UAE). UAE, also called uterine fibroid embolization (UFE), is a non-surgical radiology procedure. An interventional radiologist injects small plastic particles through a catheter placed in the uterine artery. The particles block the blood supply to the fibroids and cause them to shrink
Other Procedures. Endometrial ablation (destruction of the lining of the uterus) may be useful in women with small fibroids and heavy bleeding. Myolysis is another procedure best suited for women with specific types of small fibroids. Magnetic resonance-guided focused ultrasound (MRgFUS) is the newest type of fibroid procedure. Myolysis and MRgFUS use heat to cut off the blood supply to fibroids.

A study published in 2007 in the New England Journal of Medicine compared outcomes for uterine artery embolization (UAE) versus standard surgery (hysterectomy or myomectomy). Researchers found that after 1 year, women experienced similar improvements in quality of life regardless of the procedure. Women who had UAE had shorter hospitalizations and faster recovery than those who had standard surgery. However, around 10% of women who had UAE required a repeat procedure (embolization or hysterectomy) during the first year, and another 10% required additional treatment after the first year.

Other Procedures

In order to operate on the uterus, the surgeon may choose to reach the area through a wide abdominal incision (laparotomy) or use less invasive measures with the use of endoscopy. The decision is usually based on the severity of the case. Women should discuss all options very carefully and be sure that their surgeons have had experience with any procedure they choose.

Laparotomy. Laparotomy is the standard abdominal surgical procedure. It is invasive and usually requires a wide abdominal horizontal incision right above the pubic bone, the so-called bikini incision.

Endoscopy. Endoscopic techniques used for uterine disorders are hysteroscopy and laparoscopy. Endoscopic techniques are used increasingly to replace conventional surgical techniques for many disorders. A common factor in all endoscopic procedures is the use of a fiberoptic scope and tubes, tiny camera lenses, and minuscule surgical instruments. Any incisions made are very small, Band-Aid size.

Operative Hysteroscopy. In this procedure, the cervix is dilated, which requires either a local or general anesthetic. A device called a hysteroscopy is inserted up through the vagina and cervix into the uterine cavity. It contains tiny surgical instruments as well as a mini-camera and light source to view images of the uterus, which are transmitted to a video monitor. This approach is becoming increasingly common. Complication rates include excessive fluid absorption, infection, and uterine perforation.
Laparoscopy. This procedure uses two or more small incisions, one at the navel, and one or more in the lower abdomen. Carbon dioxide gas is injected into the abdomen, distending it and pushing the bowel away. A laparoscope is inserted through the navel incision and a probe is inserted through a second incision above the pubic hairline. The probe allows the doctor to directly view the abdominal cavity, including the outer walls of the uterus, fallopian tubes, and ovaries. The doctor manipulates surgical instruments that are passed through additional small abdominal incisions, using the image of the uterus on the video monitor as the guide.

GnRH agonists, usually depo-Lupron or Synarel, are often used for 2 - 3 months before many uterine surgical procedures.

These drugs may help by:

Reducing the volume of fibroids by 40 - 60%, in some cases to the extent that a less invasive procedure may be performed
Reducing the risk of bleeding
Shortening surgical time
Reducing postoperative symptoms

Treatments may not be useful, however, for small fibroids, which may shrink to the point that they are no longer visible at the time of surgery. Since fibroids regrow after treatment, the problem would recur.

There has also been some question whether these drugs provide any additional advantages for myomectomies that use conventional surgical techniques. Ultrasound may be useful in helping to detect fibroids most likely to benefit from GnRH agonists before such a procedure.

A myomectomy surgically removes only the fibroids and leaves the uterus intact, often preserving fertility. Myomectomy may also help regulate abnormal uterine bleeding caused by fibroids. Not all women are candidates for myomectomy. If the fibroids are numerous or large, myomectomy can become complicated, resulting in increased blood loss. If cancer is found, conversion to a full hysterectomy may be necessary.

To perform a myomectomy, the surgeon may use standard surgical approaches (laparotomy) or less invasive ones (hysteroscopy or laparoscopy).

Laparotomy. Laparotomy uses a wide abdominal incision and conventional surgery. It is used for subserosal or intramural fibroids that are very large (usually more than 4 inches), that are numerous, or when cancer is suspected. Using this approach, the doctor may be able to feel the fibroids, particularly intramural types, which can be missed during laparoscopy or hysteroscopy. (The doctor can only view the uterine cavity or outside surface with these latter procedures.) After the fibroids are removed, careful reconstruction of the uterine wall is critical in both laparotomy and laparoscopy, so that bleeding and infection do not occur. While complete recovery takes less than a week with laparoscopy and hysteroscopy, recovery from a standard abdominal myomectomy takes as many as 6 - 8 weeks. It also poses a higher risk for scarring and blood loss than with the less invasive procedures, which is a concern for women who want to retain fertility.
Hysteroscopy. A hysteroscopic myomectomy may be used for submucous fibroids found in the uterine cavity. With this procedure, fibroids are removed using an instrument called a hysteroscopic resectoscope, which is passed up into the uterine cavity through the vagina and cervical canal. A wire loop carrying electrical current is then used to shave off the fibroid. In one study, nearly 60% of patients conceived after this procedure. However, it is not appropriate for many women.
Laparoscopy. Women whose uterus is no larger than it would be at a 6-week pregnancy and who have a small number of subserous fibroids may be eligible for treatment with laparoscopy. Laparoscopy requires incisions, but they are much smaller than with laparotomy. As with hysteroscopy, a thin scope is employed that contains surgical and viewing instruments. In centers with extensive experience, laparoscopy has fewer complications, and also shorter recovery time and lower costs than laparotomy. On the other hand, compared to the invasive surgery, laparoscopy has a greater chance for fibroid recurrence (over 16% at 5 years in one study), and a greater danger for a weakened uterine wall, which could threaten pregnancies.

Complications and Postoperative Factors. Any procedure for myomectomy is very complex. To reduce the risk for complication, patients should seek a surgeon experienced in myomectomies. Complications that occur during a myomectomy from any procedure include:

Excessive blood loss (occurs more often with laparotomy)
Uterine weakening and rupture during pregnancy (more of a concern with laparoscopy)
Development of scar tissue called adhesions (more common with laparotomy)
Infection
Damage to the bowel or bladder (more common with laparotomy)

Pregnancies After Myomectomy. Studies suggest that pregnancy can be restored in more than half of women after the procedure. In appropriate candidates, there appears to be no differences in fertility rates and pregnancy complications between laparotomy or laparoscopy. The best candidates for retaining fertility include women with pedunculated and superficial serosal fibroids (stalk-like fibroids that grow out from the uterine surface). Women with deep intramural fibroids are at higher risk for infertility after myomectomy.

Although studies indicate that between 40 - 58% of women become pregnant after myomectomy, only about a quarter of the women carry their babies to term. Women who become pregnant face a higher risk for cesarean section or miscarriage. It is unclear whether laparoscopic myomectomy weakens the uterine walls and poses a higher risk for rupture during pregnancy than laparotomy.

Recurrence of Fibroids and Recurrent Surgeries. The recurrence rate for fibroid growth after myomectomy is high. Between 11 - 26% of patients will have recurring fibroids that are severe enough to need additional treatment. One study suggested that women who had uteruses that were less than the equivalent size of a 12-week pregnancy and women who were overweight had a higher risk for needing repeat surgery.

Uterine Artery Embolization (UAE), also called uterine fibroid embolization (UFE), is a relatively new way of treating fibroids. UAE deprives fibroids of their blood supply, causing them to shrink. UAE is a minimally invasive radiology treatment and is technically a nonsurgical therapy. It is much less invasive than hysterectomy and myomectomy, and involves a shorter recovery time than the other procedures. The patient remains conscious, although sedated, during the procedure, which takes around 60 - 90 minutes.

The procedure is typically performed in the following manner:

The patient receives a sedative to cause drowsiness, and a local anesthetic is applied to the skin around the groin.
An interventional radiologist makes a small quarter-inch incision in the skin and inserts a catheter (a thin tube) into the femoral artery. The femoral artery is a large artery that begins in the lower abdomen and extends down to the thigh. The radiologist then threads the catheter into the uterine artery.
Small plastic particles are injected into the artery. These particles block the blood supply to the tiny arteries that feed fibroid cells, and the tissue eventually dies.
Patients usually stay in the hospital overnight after UAE and are given pain medication. Pelvic cramps are common for the first 24 hours after the procedure.
It takes 1 - 2 weeks for the patient to recover from the procedure and return to work. It may take 2 - 3 months for the fibroids to shrink enough so that symptoms improve.

Effect on Fertility. In general, UAE is considered an option for only those who have completed childbearing. Although UAE may protect fertility in many women, the procedure does pose some risk for ovarian failure and infertility. In 2004, the American College of Obstetricians and Gynecologists issued an opinion statement advising women who wish to have children that it is not yet known how this procedure affects their potential for becoming pregnant. A 2005 British study of 671 women who underwent UAE found that the procedure did not interfere with fertility. The study did find a slight increase in caesarean section delivery.

Complications and Postoperative Effects. UAE has a lower rate of complication than hysterectomy and myomectomy and a shorter hospital stay. Compared to other procedures, women who undergo UAE miss fewer days of work. Serious complications occur in less than 0.5% of cases, and no deaths have been associated with the procedure.

Pain. Abdominal cramps and pelvic pain after the procedure are nearly universal and may be intense. Pain usually begins soon after the procedure and typically plateaus by 6 hours. On-demand painkillers may be required. The pain usually improves each day over the next several days. A low-grade fever is also common in the first week after the procedure.
Fibroid slough. Around 2 – 3% of patients pass small fragments of fibroid tissue during the first few days after UAE. This can cause intense labor-like pain and also increase the risk for infection. Some women may require dilation and curettage (D&C) to make sure that infection does not develop.
Early menopause. Most women who have UAE will continue to have normal menstrual periods. Around 1 – 5% of women, however, experience menopause after the procedure. Menopause is more likely to occur in women over age 45 who undergo UAE.

Success Rates. Studies on uterine artery embolization show high patient satisfaction (over 90%) and low complication rates. A 2003 study reported 83% improvement in heavy bleeding, 77% reduction in menstrual cramps, and 85% improvement in urinary symptoms. Results from the first long-term UAE study, presented at the 2005 annual scientific meeting of the Society of Interventional Radiology, reported that 73% of women experienced symptom relief that lasted for 5 years. The success rate for UAE was comparable to that of myomectomy. A 2006 study reported a success rate of 89% for UAE compared to 100% for hysterectomy.

For around 10 - 20% of women, symptom control fails or fibroids reoccur. Some studies suggest that women with large fibroids are not good candidates for UAE.

In either endometrial ablation or endometrial resection, the entire lining of the uterus (the endometrium) is removed or destroyed. These procedures are useful for women with severe heavy menstrual bleeding, including some with fibroids. They are generally not useful for large fibroids. Standard resection uses an electrosurgical wire loop to surgically remove the lining. With ablation, uterine tissue is usually vaporized using a thin powerful laser beam or high electric voltage. Newer ablation procedures include balloon ablation (ThermaChoice) and techniques that use electric wands, freezing, hot saline, lasers, microwaves, and radiofrequency.

Myolysis, or laparoscopic leiomyoma coagulation, uses either lasers or electrosurgery to heat and coagulate and destroy the fibroid tissue. This approach may prove to be beneficial for women with fibroids that measure a diameter of 10 cm (about 4 inches) or less and that respond to hormone treatments with GnRH agonists.

Myolysis uses a needle or a Nd:YAG laser that rapidly punctures a number of holes in the fibroid, heating and destroying the tissue in various locations. This widespread destruction cuts off the blood supply and shrinks the fibroid over ensuing months. The uterus is left intact, but tissue destruction makes childbearing unlikely.

In one study, myolysis performed either alone or with endometrial resection was successful in avoiding the need for major surgery in 97% of women. Advanced techniques that are performed by surgeons who are highly skilled in the procedure may make it possible to destroy even large intramural fibroids, but further study is required.

In most cases, patients return home the same day and can return to normal activities within a week. There are few side effects. However, as the fibroids degenerate over time, many women report considerable pain.

MRgFUS is a non-invasive procedure that uses high-intensity ultrasound waves to heat and destroy (ablate) uterine fibroids. This “thermal ablation” procedure is performed with a device that combines magnetic resonance imaging (MRI) with ultrasound. The FDA approved this device, the ExAblate 2000 System, in 2004.

During the 3-hour procedure, the patient lies inside an MRI machine. The patient receives a mild sedative to help relax but remains conscious throughout the procedure. The radiologist uses the MRI to target the fibroid tissue and direct the ultrasound beam. The MRI also helps the radiologist monitor the temperature generated by the ultrasound.

MRgFUS is appropriate only for women who have completed childbearing or who do not intend to become pregnant. The procedure cannot treat all types of fibroids. Fibroids that are located near the bowel and bladder, or outside of the imaging area, cannot be treated.

Research presented at the 2005 Radiological Society of North America annual meeting reported that MRgFUS helps improve fibroid symptoms and reduce fibroid size. A 2006 study indicated that the procedure provides symptom relief for up to 1 year. Another 2006 study indicated that pre-treatment with GnRH-agonist drugs before the MRgFUS procedure may help improve outcomes. However, because this procedure is new and long-term results are not yet available, some insurance companies do not pay for this treatment.

Hysterectomy

Presence of symptoms (pelvic pain, bleeding, symptomatic fibroids)
Lack of symptom improvement or resolution despite treatment
Previous use of GnRH agonist drugs

The number of procedures has continued to increase, but the rise has slowed substantially in recent years. The percentage of hysterectomies performed because of fibroids, however, has risen significantly. Fibroids now account for 38% of these operations, but the rates vary widely by ethnic group. In a major 2002 government report, 68% of fibroid-related hysterectomies were performed in African-American women, 33% in Caucasians, and 45% among women of other ethnic groups.

Most women are satisfied with the procedure. A major analysis on hysterectomies reported that symptoms related to menstrual problems decline significantly in most women (although none completely disappear for all women). Most women also experience improved quality of life and mood. Women who have a hysterectomy are less likely to experience hot flashes than women who have a natural menopause.

Still, in one study in 70% of cases when doctors recommended hysterectomies, they did not give their patients alternative choices or adequate diagnostic evaluations. Any woman, even one who has reached menopause, uncertain about a recommendation for a hysterectomy for fibroids should certainly seek a second opinion.

Once a decision for a hysterectomy has been made, the patient should discuss with her doctor what will be removed. The common choices are:

Total Hysterectomy (removal of uterus and cervix).
Supracervical Hysterectomy (removal of uterus and preservation of the cervix); performed in about 20 - 25% of cases.
Bilateral Salpingo-Oophorectomy (removal of the fallopian tubes and ovaries); used with either total or supracervical hysterectomy.

Total Hysterectomy. In a total hysterectomy the uterus and cervix are removed, which eliminates the risk of uterine and cervical cancer. (Given technical advances and growing surgical experience, a total hysterectomy may eventually be unnecessary except in special circumstances, such as when cancer is present.)

Supracervical Hysterectomy. In a supracervical hysterectomy (also called subtotal hysterectomy) the uterine body is removed, and the cervix is retained. Retaining the cervix helps support the pelvic floor and may help maintain full sexual sensation, but the risk for cervical cancer remains. Women may experience cyclical bleeding for up to a year after surgery.

Bilateral Oophorectomy. Bilateral oophorectomy is the removal of both ovaries. (When only one ovary is removed, the procedure is called oophorectomy.) Bilateral salpingo-oophorectomy is the removal of both fallopian tubes and ovaries. These procedures may be performed with either total or supracervical hysterectomy. When deciding to remove the ovaries, a woman must be aware of various consequences, both positive and negative.

Oophorectomy helps to reduce the risk for ovarian cancer, by elimination of ovaries, and breast cancer, by causing estrogen loss. Ovarian cancer is very rare, in any case, except in women with a family history of the disease. Even in these women, removal is not 100% preventive. Cancer can still develop from cancer cells that may be present in the lining of the pelvis (the peritoneum).
Removal of the ovaries ceases estrogen and testosterone production, which can increase the risk for menopause-related conditions. These include osteoporosis, heart disease, skin wrinkling, and reduced muscle tone. Estrogen replacement, however, can help offset these problems. Women who have a bilateral oophorectomy and do not receive hormone replacement therapy may experience more severe hot flashes than women who enter menopause naturally.

Abdominal Hysterectomy. Abdominal hysterectomy is the most common procedure and is used in over 80% of hysterectomies in African American women and about 60% in Caucasian and other ethnic groups. It is best suited for women with large fibroids, when the ovaries need to be removed, or when cancer or pelvic disease is present. With the abdominal procedure, a wide incision is required to open the abdominal area from which the surgeon removes the uterus. If possible, the incision should cut horizontally across the top of the pubic hairline (the bikini incision). This incision heals faster and is less noticeable than a vertical incision, which is used in more complicated cases. The patient may need to remain in the hospital for 3 - 4 days, and recuperation at home takes about 4 - 6 weeks.

Vaginal Hysterectomy. Vaginal hysterectomy requires only a vaginal incision through which the uterus is removed. This approach is most often performed for small fibroids (although advances in imaging and other techniques may allow it to be used on larger fibroids). At this time, it is used in fewer than 20% of African-American women and slightly under 40% of Caucasians and other groups.

A variation of the vaginal approach is called laparoscopic-assisted vaginal hysterectomy (LAVH). It uses several small abdominal incisions through which the surgeon severs the attachments to the uterus and ovaries. They can then be removed through the vaginal incision, as in the standard approach. Hospital stays may be longer and costs are greater than with standard vaginal hysterectomy. The use of LAVH has risen significantly and is used in over a quarter of vaginal procedures. LAVH is very costly and time consuming, however, and some experts question whether it adds any significant benefits compared to the standard vaginal procedure.

The patient should ask a family member or friend to help out for the first few days at home. The following are some of the precautions and tips for postoperative care:

For a day or two after surgery, the patient is given medications to prevent nausea and painkillers to relieve pain at the incision site.
As soon as the doctor recommends it, usually within a day of the operation, the patient should get up and walk in order to help prevent pneumonia, reduce the risk of blood-clot formation, and speed recovery.
Walking and slow, deep breathing exercises may help to relieve gas pains, which can cause major distress for the first few days.
Coughing can cause pain, which may be reduced by holding a pillow over a surgical abdominal wound or by crossing the legs after vaginal surgery.
Patients are advised not to lift heavy objects, not to douche or take baths, and not to climb stairs or drive for several weeks.
For the first few days after surgery, many women weep frequently and unexpectedly. These mood swings may be due to depression from the loss of reproductive capabilities and from abrupt changes in hormones, particularly if the ovaries have been removed.

The patient should discuss with the doctor when exercise programs more intense than walking can be started. The abdominal muscles are important for supporting the upper body, and recovering strength may take a long time. Even after the wound has healed, the patient may experience an on-going feeling of overall weakness, which can be demoralizing, particularly in women used to physical health. Some women do not feel completely well for as long as a year while others may recover in only a few weeks.

More serious complications, such as those described below, are uncommon, but patients should be aware of their symptoms and call the doctor immediately if they occur.

Infection. Infection occurs in 10 - 15% of patients, the risk being higher with abdominal than with vaginal surgery. Risk factors for infection include obesity, a longer than normal operative time, and low socioeconomic status. Patients should be aware of any symptoms and call the doctor immediately if they occur. Symptoms of infection include:

Continuing or increasingly severe pain
Fever
Heavy discharge
Bleeding (antibiotics given at the time of surgery help to reduce this risk)

Other Serious Complications. Other serious and even life-threatening complications are rare but can include:

Pulmonary embolism (blood clots that travel to the lung).
Surgical injury of the urinary or intestinal tracts.
Abscesses.
Perforation of the bowel.
Fistulas (a passage that bores from an organ to the skin or to another organ).
Dehiscence (opening of the surgical wound).

Long-Term Complications. Women who have had a total hysterectomy are at higher risk for the following long-term complications:

Muscle weakness in the pelvic area.
Prolapse (descent) of the bladder, vagina, and rectum if the muscle's walls are overly weakened; may require further surgery.
Bowel problems if adhesions (extensive scarring) have formed and obstruct the intestines; may require additional surgery.
Shortening of the vagina is a possible complication specific to vaginal hysterectomy. It can cause pain during intercourse.

Such complications are uncommon.

Two procedures associated with hysterectomy may affect sexuality directly:

Although the clitoris can trigger orgasm even if the cervix is removed, many experts believe that uterine contractions stimulated by sexual intercourse also cause a so-called “deep orgasm.” Retaining the cervix may help to retain this sensation. However, a 2006 review found that women who undergo a total hysterectomy (removal of both uterus and cervix) are no more likely to have sexual difficulties or problems with urinary and bowel function than women who have only their uterus removed.
Patients who have both ovaries removed may be at higher risk for loss of sexuality. Ovaries produce small amounts of testosterone (the male hormone responsible for sexual drive) even after menopause.

Testosterone Replacement. Testosterone replacement therapy may restore sexuality in women who experience a decline in sexual drive. Occasionally, oral or injection treatments can produce male characteristics such as facial hair and voice change. A slow-release pellet inserted every 6 months under the skin in the hip appears to reduce these side effects. Taking hormones long term almost always carries some risk, and it is not yet known what danger testosterone replacement may pose in women.

Resources

www.asrm.com -- American Society for Reproductive Medicine
www.acog.com -- American College of Obstetricians and Gynecologists
www.sirweb.org -- Society of Interventional Radiology
www.nuff.org -- National Uterine Fibroids Foundation
www.rsna.org -- Radiological Society of North America
www.radiologyinfo.org -- Radiology info from the American College of Radiology and the Radiological Society of North America
www.radiologyinfo.org/content/interventional/ufibroid-embol.htm -- Information on uterine fibroid embolization
www.fibroids.net -- Brigham and Women's Hospital, Center for Uterine Fibroids
www.nichd.nih.gov -- National Institute of Child Health and Human Development

References

Chen WY, Manson JE, Hankinson SE, Rosner B, Holmes MD, Willett WC, et al. Unopposed estrogen therapy and the risk of invasive breast cancer. Arch Intern Med. 2006 May 8;166(9):1027-32.

Edwards RD, Moss JG, Lumsden MA, Wu O, Murray LS, Twaddle S, et al. Uterine-artery embolization versus surgery for symptomatic uterine fibroids. N Engl J Med. 2007 Jan 25;356(4):360-70.

Lethaby A, Ivanova V, Johnson NP. Total versus subtotal hysterectomy for benign gynaecological conditions. Cochrane Database Syst Rev. 2006 Apr 19;(2):CD004993.

Smart OC, Hindley JT, Regan L, Gedroyc WG. Gonadotrophin-releasing hormone and magnetic-resonance-guided ultrasound surgery for uterine leiomyomata. Obstet Gynecol. 2006 Jul;108(1):49-54.

Review Date:
2/28/2008
Reviewed By:
A.D.A.M. Editorial Team: David Zieve, MD, MHA, Greg Juhn, MTPW, David R. Eltz, Kelli A. Stacy, ELS. Previously reviewed by Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital (6/16/2007).

A.D.A.M. Copyright

adam.com

Infertility in women

FitSugar — Wed, 08 Oct 2008 17:35:02 -0700

In This Report

Highlights
Introduction
The Reproductive System
Risk Factors
Causes
Diagnosis
Treatment
Lifestyle Changes
Medications
Assisted Reproductive Techn...
Complications of Assisted R...
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

New At-Home Fertility Test for Couples

Fertell is a new at-home fertility test kit for couples. It screens for sperm motility concentrations and follicle-stimulating hormone (FSH) levels. Fertell may be helpful as an initial test for infertility, but for a definitive diagnosis it is important to consult a doctor. Infertility can be due to many different factors.

Intracytoplasmic Sperm Injection Overused for Female Infertility

The assisted reproductive technology intracytoplasmic sperm injection (ICSI) is being increasingly used in combination with in vitro fertilization (IVF), even for couples who do not have problems with male infertility, suggests a 2007 study in the New England Journal of Medicine. Researchers found that use of ICSI has increased 5-fold in the past decade. Some doctors are now recommending ICSI for women who have failed prior IVF cycles or who have few or poor-quality eggs. Doctors caution that ICSI should be used only to improve pregnancy chances for couples with male-factor infertility.

Clomiphene Best for PCOS-Associated Infertility

The infertility drug clomiphene (Clomid) works better than the diabetes drug metformin (Glucophage) for treating infertility resulting from polycystic ovarian syndrome (PCOS), indicates a 2007 study in the New England Journal of Medicine.

Fertility Drugs and Breast Cancer

Fertility drugs such as clomiphene and gonadotropins do not increase the risk for breast cancer, indicate several studies. In fact, according to a 2006 study in the Archives of Internal Medicine, clomiphene may decrease breast cancer risk.

Iron Deficiency and Female Infertility

Iron deficiency may increase the risk for ovulatory infertility, suggests a 2006 study in Obstetrics and Gynecology. Researchers found that women who took daily iron supplements were 40% less likely to be infertile than women who did not take supplements. Some experts recommend screening for iron deficiency as part of the clinical evaluation for infertility.

Introduction

Infertility is the failure of a couple to become pregnant after one year of regular, unprotected intercourse. In both men and women the fertility process is complex.

About 10% of couples who wish to have a baby are still unable to after a year of unprotected sex. About half of these couples can achieve pregnancy within 2 years after appropriate treatment of the woman, the man, or both. Even under ideal circumstances, the probability that a woman will get pregnant during a single menstrual cycle is only about 30%. And, when conception does occur, only 50 - 60% of pregnancies advance beyond the 20th week. (The inability of a woman to produce a live birth because of abnormalities that cause miscarriages is called infecundity and is not discussed in detail in this report.)

Males and females each account for 40% of infertility. In the remaining 20%, either both partners are responsible or the cause is unclear. Although this report specifically addresses infertility in women, it is equally important for the male partner to be tested at the same time. [See In-Depth Report #67: Infertility in men.]

The Reproductive System

The Primary Organs and Structures in the Reproductive System. The primary structures in the reproductive system are:

The uterus is a pear-shaped organ located between the bladder and lower intestine. It consists of two parts, the body and the cervix.
When a woman is not pregnant the body of the uterus is about the size of a fist, with its walls collapsed and flattened against each other. During pregnancy the walls of the uterus are pushed apart as the fetus grows.
The cervix is the lower portion of the uterus. It has a canal opening into the vagina with an opening called the os, which allows menstrual blood to flow out of the uterus into the vagina.
Leading off each side of the body of the uterus are two tubes known as the fallopian tubes. Near the end of each tube is an ovary.
Ovaries are egg-producing organs that hold 200,000 - 400,000 follicles (from folliculus, meaning "sack" in Latin). These cellular sacks contain the materials needed to produce ripened eggs, or ova.
The inner lining of the uterus is called the endometrium. During pregnancy, it thickens and becomes enriched with blood vessels to house and support the growing fetus. If pregnancy does not occur, the endometrium is shed as part of the menstrual flow. Menstrual flow also consists of blood and mucus from the cervix and vagina.

Reproductive Hormones. The hypothalamus (an area in the brain) and the pituitary gland regulate the reproductive hormones.

Click the icon to see an image of the hypothalamus and pituitary gland.

The pituitary gland is often referred to as the master gland because of its important role in many vital functions, many of which require hormones. In women, six key hormones serve as chemical messengers that regulate the reproductive system:

The hypothalamus first releases the gonadotropin-releasing hormone (GnRH).
This chemical, in turn, stimulates the pituitary gland to produce follicle-stimulating hormone (FSH) and luteinizing hormone (LH).

Click the icon to see an image of the pituitary gland.

Estrogen, progesterone, and the male hormone testosterone are secreted by the ovaries at the command of FSH and LH and complete the hormonal group necessary for reproductive health.

A woman's ability to produce children occurs after she enters puberty and begins to menstruate. The process of conception is complex:

With the start of each menstrual cycle, follicle-stimulating hormone (FSH) stimulates several follicles to mature over a 2-week period until their eggs nearly triple in size. Only one follicle becomes dominant, however, during a cycle.
FSH signals this dominant follicle to produce estrogen, which enters the bloodstream and reaches the uterus. There, estrogen stimulates the cells in the uterine lining to reproduce, therefore thickening the walls.
Estrogen levels reach their peak around the 14th day of the cycle (counting days beginning with the first day of a period). At that time, they trigger a surge of luteinizing hormone (LH).

LH serves two important roles:

First, the LH surge around the 14th cycle day stimulates ovulation. It does this by causing the dominant follicle to burst and release its egg into one of the two fallopian tubes. Once in the fallopian tube, the egg is in place for fertilization.
Next, LH causes the ruptured follicle to develop into the corpus luteum. The corpus luteum provides a source of estrogen and progesterone during pregnancy.

Click the icon to see an image of the corpus luteum.

Fertilization. The so-called "fertile window" is 6 days long and starts 5 days before ovulation and ends the day of ovulation. Fertilization occurs as follows:

The sperm can survive for up to 3 days once it enters the fallopian tube. The egg survives 12 - 24 hours unless it is fertilized by a sperm.
If the egg is fertilized, about 2 - 4 days later it moves from the fallopian tube into the uterus where it is implanted in the uterine lining and begins its 9-month incubation.
The placenta forms at the site of the implantation. The placenta is a thick blanket of blood vessels that nourishes the fertilized egg as it develops.

Click the icon to see an image of the placenta.

The corpus luteum (the yellow tissue formed from the ruptured follicle) continues to produce estrogen and progesterone during pregnancy.


Menstrual Phases	Typical No. of Days	Hormonal Actions
Follicular (Proliferative) Phase	Cycle Days 1 - 6: Beginning of menstruation to end of blood flow.	Estrogen and progesterone start out at their lowest levels. FSH levels rise to stimulate maturity of follicles. Ovaries start producing estrogen and levels rise, while progesterone remains low.
	Cycle Days 7 - 13: The endometrium (the inner lining of the uterus) thickens to prepare for the egg implantation.
Ovulation	Cycle Day 14:	Surge in LH. Largest follicle bursts and releases egg into fallopian tube.
Luteal (Secretory) Phase, also known as the Premenstrual Phase	Cycle Days 15 - 28:	Ruptured follicle develops into corpus luteum, which produces progesterone. Progesterone and estrogen stimulate blanket of blood vessels to prepare for egg implantation.
	If fertilization occurs:	Fertilized egg attaches to blanket of blood vessels that supplies nutrients for the developing placenta. Corpus luteum continues to produce estrogen and progesterone.
	If fertilization does not occur:	Corpus luteum deteriorates. Estrogen and progesterone levels drop. The blood vessel lining sloughs off and menstruation begins.

Onset of Menstruation (Menarche). Previous evidence had set the onset of menstruation, called the menarche, at an average age of 12 or 13. Recent studies, however, set the time of onset earlier by about 1 year in Caucasian girls and 2 years in African-American girls. Currently, the youngest possible age for normal puberty is 7 years old for Caucasians and 6 years old for African-Americans, down from a previous low of 8 years for both.

Evidence is pointing to the increasing incidence of childhood obesity as a major cause of the trend in earlier menarche onset. (Obesity is also highly associated with hormonal disorders in girls entering puberty at young ages.) Environmental estrogens found in chemicals and pesticides are also suspects.

Length of Monthly Cycle. The menstrual cycle can be very irregular for the first 1 - 2 years, usually being longer than the average of 28 days. The length then generally stabilizes to an average of 28 days, although the cycle length may range from 20 - 45 days and still be considered normal. A variation of 10 days or more -- either more or fewer days -- may have an impact on fertility, however. When a woman reaches her 40s the cycle lengthens, reaching an average of 31 days by age 49. Several factors can affect cycle length at any age.


Risk Factors for Shorter Cycles	Risk Factors for Longer Cycles
Regular alcohol use	Being under 21 and over 44
Stressful jobs	Being very thin (also at risk for short bleeding periods)
	Competitive athletics (also at risk for short bleeding periods)

Length of Periods. Periods average 6.6 days in young girls. By the age of 21, menstrual bleeding averages 6 days until women approach menopause. However, about 5% of healthy women menstruate less than 4 days, and 5% menstruate more than 8 days.

Normal Absence of Menstruation. Normal absence of periods can occur in any woman under the following circumstances:

Menstruation stops during the duration of pregnancy. Some women continue to have irregular bleeding during the first trimester. This bleeding may indicate a threatened miscarriage and requires immediate attention by the doctor.
When women breastfeed they are unlikely to ovulate. After that time, menstruation usually resumes, and they are fertile again.
Perimenopause starts when the intervals between periods begin to lengthen, and it ends with menopause itself (the complete cessation of menstruation). Menopause usually occurs at about age 51, although smokers often go through menopause earlier.

Risk Factors

In the U.S., an estimated 10.2% of women ages 15 - 44, or about 6.1 million women, have impaired fertility, and the incidence is increasing. About 25% of women experience some period of infertility during their reproductive years.

As a woman ages, her chances for fertility decline. Infertility in older women appears to be mostly due to a higher risk for chromosomal abnormalities that occur in her eggs as they age. Older women are also more likely to have health problems that may interfere with fertility. If fertilization occurs, older, healthy women can usually successfully bear a fetus to term, although they have a higher risk for miscarriage. Using population studies, experts have come up with estimated odds for pregnancy at different ages, given no fertility intervention. One analysis of pregnancy rates based on conception on the day of ovulation suggested that women ages 19 - 26 have twice the pregnancy rates as those ages 35 - 39.


Age	Fertility %
Up until age 34	90%
By age 40	Declining to 67%
By age 45	Declining to 15%

Although most of a woman's estrogen is manufactured in her ovaries, 30% is produced in fat cells by a process that transforms circulating adrenal male hormones into estrogen. Because a normal hormonal balance is essential for the process of conception, it is not surprising that extreme weight levels, either high or low, can contribute to infertility.

Being Overweight. Being overweight or obese (fat levels that are 10 - 15% above normal) can contribute to infertility in various ways. Obesity is highly associated with polycystic ovarian syndrome (PCOS), which is the cause of infertility in some cases. In one study, overweight women without PCOS were classified in one of five grades, depending on the severity of the obesity. The risk for irregular or absent periods increased two-fold by each increase in grade. In this group, amenorrhea (absent periods) was also highly associated with type 2 diabetes and blood sugar abnormalities.

Being Underweight. Body fat levels 10 - 15% below normal can completely shut down the reproductive process. Women at risk include:

Women with eating disorders, such as anorexia or bulimia.
Women on very low-calorie or restrictive diets are at risk, especially if their periods are irregular.
Strict vegetarians might have difficulties if they lack important nutrients, such as vitamin B12, zinc, iron, and folic acid.
Marathon runners, dancers, and others who exercise very intensely. (Lower body fat contributes to menstrual irregularities in competitive athletes, but other mechanisms are also involved.)

Exposure to environmental hazards (herbicides, pesticides, industrial solvents) may affect fertility. Estrogen-like hormone-disrupting chemicals are of particular concern for infertility in men and for effects on offspring of women.

Phthalates, chemicals used to soften plastics, are under particular scrutiny for their ability to disrupt hormones. Specific phthalates of special concern include dibutyl phthalate (DBP) and others found in many products, including cosmetics and clay products sold to children (Fimo, Sculpey). Animals exposed to phthalates have significantly impaired sperm count and abnormalities in reproductive structures, such as the testes. In addition, there is some concern that exposure in pregnant women may affect the offspring.

Neurotransmitters (chemical messengers) act in the hypothalamus gland, which controls both reproductive and stress hormones. Severely elevated levels of stress hormone can, in fact, shut down menstruation. Whether stress has any significant effect on fertility or fertility treatments is unclear. One 2005 study found that psychological stress does not affect the success or failure of in vitro fertilization.

Click the icon to see an image of the hypothalamus.

Causes

Causes of infertility can be found in about 90% of infertility cases but, despite extensive tests, about 10% of couples will never know why they cannot conceive. Between 10 - 30% of cases of infertility have more than one cause. Male or female infertility each account for about 30 - 40% of cases. In men, sperm defects (their quality and quantity) are usually responsible. Female infertility is more complex.

Pelvic inflammatory disease (PID) is the major cause of female infertility worldwide. PID comprises a variety of infections caused by different bacteria that affect the reproductive organs, appendix, and parts of the intestine that lie in the pelvic area. The sites of infection most often implicated in infertility are in the fallopian tubes, a specific condition referred to as salpingitis.

Causes of PID. PID may result from many different conditions that cause infections. Among them are:

Sexually transmitted diseases (cause of most PIDs). Chlamydia trachomatis is an infectious organism that causes 75% of infertility in the fallopian tubes. Gonorrhea is responsible for most of the remaining cases.
Pelvic tuberculosis (a growing global problem as tuberculosis cases increase)
Nonsterile abortions
Ruptured appendix
Herpes virus (suggested for some cases, but not confirmed as a cause).

Symptoms of PID. The infection may be subclinical (occurring without any symptoms), or there may be fever, chills, or pelvic pain indicating inflammation of the entire pelvic area.

Effects of PID. Severe or frequent attacks of PID can eventually cause scarring, abscess formation, and tubal damage that result in infertility. About 20% of women who develop symptomatic PID become infertile. PID also significantly increases the risk of ectopic pregnancy (fertilization in the fallopian tubes). The severity of the infection, not the number of the infections, appears to pose the greater risk for infertility.

Endometriosis may account for as many as 30% of infertility cases. Some evidence suggests that between 30 - 50% of women with endometriosis are infertile. Often, however, it is difficult to determine if endometriosis is the primary cause of infertility, particularly in women who have mild endometriosis. Endometriosis rarely causes an absolute inability to conceive, but, nevertheless, it can contribute to it both directly and indirectly.

Endometriosis is the condition in which the tissue that normally lines the uterus (endometrium) grows on other areas of the body causing pain and irregular bleeding.

Direct Effect of Endometrial Cysts. Endometrial cysts may directly cause infertility in several ways:

If implants occur in the fallopian tubes, they may block the egg's passage.
Implants that occur in the ovaries prevent the release of the egg.
Severe endometriosis can eventually form rigid webs of scar tissue (adhesions) between the uterus, ovaries, and fallopian tubes, thereby preventing the transfer of the egg to the tube.

Immune Factors and the Inflammatory Response. Researchers are focusing on defects in the immune system that not only may be responsible for endometriosis in the first place but may also cause the infertility associated with endometriosis. Even in early stage endometriosis, investigators have observed increased immune system activity.

Other Conditions Linking Endometriosis and Infertility. Researchers have sometimes noted unusually low levels of specific substances that enable a fertilized egg to adhere to the uterine lining. (Such abnormalities are more often a factor in infertility in women with mild-to-moderate endometriosis than in those with severe cases.)

One study found that the eggs in women with endometriosis appeared to have more genetic abnormalities than those in women without the disorder.

Polycystic ovarian syndrome (PCOS) is a condition in which the ovaries produce high amounts of androgens (male hormones), particularly testosterone. PCOS occurs in about 6% of women, and amenorrhea or oligomenorrhea (infrequent menses) is quite common. According to one study, nearly 30% of obese women with PCOS had amenorrhea. (The rate was lower -- 4.7% -- in women with normal weight.)

Click the icon to see an image of polycystic ovarian syndrome.

In PCOS, increased androgen production produces high luteinizing hormone (LH) levels and low follicle-stimulating hormone (FSH) levels, so that follicles are prevented from producing a mature egg. Without egg production, the follicles swell with fluid and form into cysts. Every time an egg is trapped within the follicle, another cyst forms, so the ovary swells, sometimes reaching the size of a grapefruit. Without ovulation, progesterone is no longer produced, whereas estrogen levels remain normal.

The elevated levels of androgens (hyperandrogenism) can cause obesity, facial hair, and acne, although not all women with PCOS have such symptoms. Other male characteristics, such as deepening voice and clitoral enlargement, are rare.

PCOS also poses a high risk for insulin resistance, particularly in women who are also obese. Insulin resistance is associated with diabetes type 2, in which insulin levels are normal or high but the body cannot use this hormone efficiently. About half of PCOS patients, in fact, also have diabetes.

Premature ovarian failure is the early depletion of follicles before age 40, which, in most cases, leads to premature menopause. It affects about 1% of women and is typically preceded by irregular periods, which might continue for years. In this condition, follicle-stimulating hormone (FSH) levels are elevated, as they are during perimenopause. Premature ovarian failure is a significant cause of infertility, and women who have this condition have only a 5 - 10% chance to conceive without fertility treatments.

Causes of Premature Ovarian Failure. There are numerous causes of premature ovarian failure. Often the cause of this disorder or other causes of premature ovarian failure is unknown. In some cases, premature ovarian failure may represent an acceleration of the aging process.

The following conditions may produce premature ovarian failure:

Adrenal, pituitary, or thyroid gland deficiencies.
Genetic factors related to the X chromosome. A woman needs two functioning X chromosomes for normal reproduction. When one is abnormal, ovarian function fails. The most severe example is Turner syndrome, a genetic condition, in which one of the two X-chromosomes is missing or malfunctioning. Milder cases of ovarian failure can occur in fragile X syndrome and other rare inherited conditions that cause partial X-chromosome abnormalities.
Cancer treatments (radiation, chemotherapy, or both). Women who are undergoing cancer treatments and who want to become pregnant should see a reproductive specialist to discuss their options. According to the American Society of Clinical Oncology's 2006 guidelines, the fertility preservation method with the best chance of success is embryo cryopreservation. This procedure involves harvesting a woman's eggs (oocytes), followed by in vitro fertilization and freezing of embryos for later use. Other treatments under investigation include egg preservation, collecting and freezing unfertilized eggs, removing and freezing a part of the ovary for later reimplantation, and using hormone therapy to protect the ovaries during chemotherapy. Women may be able to access these investigational approaches through enrolling in clinical trials.
Autoimmunity. Autoimmune diseases -- including type 1 diabetes, systemic lupus erythematosus, autoimmune hypothyroidism, and autoimmune Addison's disease -- are associated with a higher risk for early menopause. Autoimmunity, however, may also play a role in some cases of premature ovarian failure without the presence of specific autoimmune diseases. In such cases, antibodies specifically attack the cells that secrete reproductive hormones thus causing ovarian failure.
Other causes of premature ovarian failure include sarcoidosis, mumps, some sexually transmitted diseases, and tuberculosis. Women with epilepsy are at higher risk for premature ovarian failure.

Idiopathic hypogonadotropic hypogonadism is a rare condition in which follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are underproduced, preventing the development of functional ovaries. There are no other abnormalities in the hypothalamus-pituitary axis (such as tumors or abnormal stress hormones or prolactin). In most cases, the causes of hypergonadotropic hypogonadism are unknown. Genetic factors, including Kallman syndrome, have been identified in about 20% of these cases.

Functional hypothalamic amenorrhea (FHA) is the absence of menstruation due to disturbances in the thyroid gland and hypothalamus-pituitary-adrenal (HPA) system, which regulates reproduction and other important functions. The eating disorders anorexia and bulimia are most often associated with FHA. FHA may be due to other different factors, most unknown.

Luteal phase defect is a general term referring to problems in the corpus luteum that result in inadequate production of progesterone. Because progesterone is necessary for thickening and preparing the uterine lining, the ovum fails to successfully implant in the endometrium. Between 25 - 60% of women who have recurrent miscarriages may have a luteal phase defect. A luteal phase defect, however, can also occur in fertile women, so other factors may be responsible for implantation failure.

Benign fibroid tumors in the uterus are extremely common in women in their 30s. The effect of fibroids on fertility is controversial. One analysis suggested that they may account for infertility in only 1 - 2.4% of women who are having trouble conceiving.

Large fibroids may cause infertility impairing the uterine lining, by blocking the fallopian tube, or by distorting the shape of the uterine cavity or altering the position of the cervix.

Click the icon to see an image of uterine fibroids.

Prolactin is a hormone produced in the pituitary gland that stimulates breast development and milk production in association with pregnancy. High levels of prolactin (hyperprolactinemia) reduce gonadotropin hormones and inhibit ovulation. Hyperprolactinemia in women who are not pregnant or nursing can be caused by hypothyroidism or pituitary adenomas. (These are benign tumors that secrete prolactin. They can cause headache and visual problems as well as breast secretions.) Some drugs, including oral contraceptives and some antipsychotic drugs, can also elevate levels of prolactin.

Secretions from the breast not related to pregnancy or nursing (called galactorrhea) are a telltale symptom of high prolactin levels and should be investigated.

Inborn Abnormalities. Inborn genital tract abnormalities may cause infertility. Mullerian agenesis is a specific malformation in which no vagina or uterus develops. Even in these cases, some women can become mothers by undergoing in vitro fertilization and having the fertilized egg implanted in another woman who is willing and able to carry the pregnancy (a surrogate mother).

Uterine or Abdominal Scarring. Bands of scar tissue that bind together after abdominal or pelvic surgery or infection (called adhesions) can restrict the movement of ovaries and fallopian tubes and may cause infertility. Asherman syndrome, for example, is scarring in the uterus that can cause obstructions and secondary amenorrhea. It may be caused by surgery, repeated injury, or unknown factors. Laparoscopic surgery is less likely to cause adhesions than standard open surgery.

In some of these cases, surgery may be helpful. One technique, called pressure lavage under ultrasound guidance (PLUG), may prove to be useful for treating some cases of mild scarring in the uterus (intrauterine adhesions). This technique is based on transvaginal sonohysterography, which uses ultrasound along with saline infused into the uterus to enhance visualization. Continuous accumulation of saline in the procedure is used to break up the scars.

Ectopic Pregnancies. Ectopic pregnancies increase the risk for infertility, although subsequent pregnancy rates are quite variable. Ectopic pregnancies that terminate without treatment appear to pose a lower risk for future infertility. Even a ruptured tube does not appear to reduce the chance for a future pregnancy in most women. Such an event however can be dangerous and even life threatening for the woman. Laparoscopic surgery to remove a fallopian tube affected by an ectopic pregnancy may preserve fertility better than traditional abdominal surgery.

Click the icon to see an image of an ectopic pregnancy.

Medications. Among the medications that can cause temporary infertility are those used to treat chronic disorders, as well as antidepressants, hormones, painkillers, and antipsychotic drugs.

Inflammatory Bowel Disease. Inflammatory bowel disease (particularly Crohn's disease or surgery for ulcerative colitis) can affect fertility.

Click the icon to see an image of Crohn's disease.

Celiac Sprue. Celiac sprue is a disease in which the patient cannot tolerate gluten, a common food chemical. The disorder is also highly associated with infertility in men and women, possibly through multiple effects on nutrition, immune factors, and hormones. The mechanisms are not altogether clear, but infertility is usually reversible with strict dietary control.

Click the icon to see an image of celiac sprue.

Iron Intake. Nutritional iron deficiency may contribute to female infertility. According to a 2006 study, women who take iron supplements are 40% less likely to experience ovulatory infertility than women who do not take iron supplements. Some researchers suggest that screening for iron deficiency should be part of the standard work-up of infertility tests.

Epilepsy. In one study of women with epilepsy, fertility rates were 33% lower than among women in the general population, perhaps due to certain antiepileptic drugs that increase the risk for birth defects. The social effects of epilepsy may also lead to marriage at an older age, which can be associated with delayed attempts to get pregnant and thereby affect fertility.

Thyroid Problems. Thyroid problems, either too much thyroid hormone (hyperthyroidism) or too little (hypothyroidism), can interrupt cycles.

Click the icon to see an image of hyperthyroidism.

Click the icon to see an image of hypothyroidism.

Metabolic Syndrome (also Called Syndrome X). Doctors diagnose this condition when at least three of the following abnormalities are present:

Abdominal obesity
Low HDL (good) cholesterol levels
High triglyceride levels
High blood pressure
Insulin resistance

Metabolic syndrome is a pre-diabetic condition that is significantly associated with heart disease. One study reported that, as with polycystic ovarian syndrome, women with metabolic syndrome have higher levels of male hormones and are therefore at risk for infertility. Another study estimated that 24% of the population now has this condition.

Other Medical Conditions. Medical conditions associated with delayed puberty and amenorrhea (absence of periods) include Cushing's disease, sickle cell disease, HIV, kidney disease, and diabetes. Genetic mutations that affect luteinizing hormone may also be responsible for some cases of light or absent menstruation. Other rare genetic disorders, such as Kallman syndrome, cause abnormalities in the hypothalamus of the brain.

Diagnosis

In any fertility work-up, both male and female partners are tested if pregnancy fails to occur after a year of regular unprotected sexual intercourse. Fertility testing should be done earlier if a woman is over 35 years old or if either partner has known risk factors for infertility. An analysis of the man's semen should be performed before the female partner undergoes any invasive testing.

The first step in any infertility work up is a complete medical history and physical examination. Sexual technique and timing, menstrual history, lifestyle issues (such as smoking and drug, alcohol, and caffeine consumption), any medications being taken, and a profile of the patient's general medical and emotional health can help the doctor decide on appropriate tests.

Before embarking on an expensive fertility work-up, the following steps are free or low-cost and can be helpful:

Monitor basal body temperature. This is accurate in determining if ovulation is actually taking place.
Test the consistency of your cervical mucus. Collect some mucus between your two fingers and stretch it apart. If you are near the time of ovulation, the mucus will stretch more than 1 inch before it breaks. As an alternative, at-home kits can test saliva as substitute for checking cervical mucus.
Take an over-the-counter urine test for detecting luteinizing hormone (LH) surges. This helps determine the day of ovulation.
Fertell is the first at-home test kit for couples that is approved by the Food and Drug Administration. Women can test their urine for levels of follicle-stimulating hormone (FSH), while men can test their semen for sperm motility (ability of sperm to move). Fertell became available online and in some pharmacies in June 2007.

Several laboratory tests may be used to detect the cause of infertility and monitor treatments:

Hormonal Levels. Blood and urine tests are taken to evaluate hormone levels. Hormonal tests for ovarian reserve (the number of follicles and quality of the eggs) are especially important for older women.

Examples of possible results include:

High follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels and low estrogen levels suggest premature ovarian failure or hypogonadotropic hypogonadism.
High LH and low FSH may suggest polycystic ovary syndrome or luteal phase defect.
High FSH and high estrogen levels on the third day of the cycle predicts poor success rates in older women trying fertility treatments.
LH surges indicate ovulation.
Blood tests for prolactin levels and thyroid function are also measured. These are hormones that may indirectly affect fertility.

Clomiphene Challenge Test. Clomiphene citrate (Clomid, Serophene), a standard fertility drug, may be used to test for ovarian reserve. With this test, the doctor measures FSH on day 3 of the cycle. The woman takes clomiphene orally on days 5 and 9 of the cycle. The doctor measures FSH on the tenth day. High levels of FSH either on day 3 or day 10 indicate a poor chance for a successful outcome.

Tissue Samples. To rule out luteal phase defect, premature ovarian failure, and absence of ovulation, the doctor may take tissue samples of the uterus 1 - 2 days before a period to determine if the corpus luteum is adequately producing progesterone. Tissue samples taken from the cervix may be cultured to rule out infection.

Tests for Autoimmune Disease. Tests for autoimmune disease, such as hypothyroidism and diabetes, should be considered in women with recent ovarian failure that is not caused by genetic abnormalities.

If an initial fertility work-up does not reveal abnormalities, as happens in about 40% of cases, more extensive tests will reveal abnormal tubal or uterine findings. The three major approaches for examining the uterus are ultrasound (particularly a variation called saline-infusion sonohysterography), hysterosalpingography, and hysteroscopy. Although combinations of these diagnostic approaches are often used to confirm diagnoses, one study indicated that with the introduction of saline-infusion sonohysterography, all are equally accurate and combinations do not increase accuracy. Furthermore, the ultrasound procedure is significantly less painful than the other two, suggesting that this should be the procedure of choice, if available.

Transvaginal sonohysterography uses ultrasound along with saline infused into the uterus, which enhances the visualization of the uterus. This technique is proving to be more accurate than standard ultrasound in identifying potential problems. It is currently the gold standard for diagnosing polycystic ovaries.

Magnetic Resonance Imaging. Magnetic resonance imaging (MRI) gives a better image of any fibroids that might be causing bleeding, but it is expensive and not usually necessary.

Hysteroscopy. Hysteroscopy is a procedure that may be used to detect the presence of endometriosis, fibroids, polyps, pelvic scar tissue, and blockage at the ends of the fallopian tubes. Some of these conditions can be corrected during the procedure by cutting away any scar tissue that may be binding organs together or by destroying endometrial implants. (It may miss cases of uterine cancer, however, and is not a substitute for more invasive procedures, such as dilation and curettage ( D&C) or endometrial biopsy, if cancer is suspected.)

It is done in the office setting and requires no incisions. The procedure uses a long flexible or rigid tube called a hysteroscope, which is inserted into the vagina and through the cervix to reach the uterus. A fiber optic light source and a tiny camera in the tube allow the doctor to view the cavity. The uterus is filled with saline or carbon dioxide to inflate the cavity and provide better viewing. This frequently causes cramping.

There are small risks of bleeding, infection, and reactions to anesthesia. Many patients experience temporary discomfort in the shoulders after the operation due to residual carbon dioxide that puts pressure on the diaphragm. The wound itself is minimally painful.

Hysterosalpingography. Hysterosalpingography is performed to discover possible blockage in the fallopian tubes and abnormalities in the uterus:

The doctor inserts a tube into the cervix through which a special dye is injected. (The patient may experience some cramping and discomfort.)
The dye passes into the uterus and up through the fallopian tubes.
An x-ray is taken of the dye-filled uterus and tubes.
If the dye is seen emerging from the end of the tube, no blockage is present. (In some cases, hysterosalpingography may even restore fertility by clearing away tiny tubal blockages.)
If results show blockage or abnormalities, the test may need to be repeated. In case of blockage, hysterosalpingography may reveal a number of conditions, including endometrial polyps, fibroid tumors, or structural abnormalities of the uterus and tubes.

The test has significant rates of false diagnoses, both positive and negative. There is a small risk of pelvic infection, and antibiotics may be prescribed prior to the procedure. One study suggested that flushing the tubes with an oil-based fluid (lipiodol) during this procedure may improve fertility rates in women with infertility of unknown causes.

As women age, the number of follicles (and therefore their egg supply) declines. Researchers are developing tests that may help determine how many are left. Such tests include the following:

Calculating the volume of the ovaries. In general, the smaller the ovaries, the fewer the remaining eggs.
Counting antral follicles. Antral follicles are those that develop but do not become dominant follicles. Instead, they form a fluid-filled space called an antrum. Women who have fewer than three to five antral follicles appear to have a poor chance of fertility.
Measuring inhibin B. Inhibin B is a growth factor produced in the ovaries. Low levels suggest fewer eggs.

Eventually these markers may be useful for determining which women need more aggressive treatments.

Genetic testing may be warranted in cases of male infertility or when genetic factors may be causing pregnancy failure in the woman. If genetic abnormalities are suspected in either partner, counseling is recommended.

A technique called preimplantation genetic diagnosis (PGD) is now available in some centers that can examine all the chromosomes in a human embryo. It helps identify abnormalities that increase the risk for infertility, treatment failures, or genetic defects in the offspring.

Treatment

Some doctors recommend that if a couple fails to conceive after 1 - 2 years of frequent unprotected sex, they should consult a fertility expert. Women who are 35 or older, however, may want to begin exploring their options if they do not become pregnant within 6 months to a year.

Several approaches can treat infertility, depending on the cause:

Lifestyle measures (healthy lifestyle, planning sexual activity with ovulation cycle, managing stress and emotions)
Treatments for endometriosis, fibroids, or menstrual disorders
Use of anti-estrogen drugs, such as clomiphene, to induce ovulation in women with ovarian dysfunction
Surgery (standard or laparoscopic) to unblock fallopian tubes
Use of hormone treatments (clomiphene or progestins) for luteal phase defect
Assisted reproductive technologies (ART) such as in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI)

Choosing a good fertility clinic is important. Those offering assisted reproductive techniques are not always regulated by the government, and abuses have been reported, including lack of informed consent, unauthorized use of embryos, and failure to routinely screen donors for disease.

The clinic should always provide the following information:

The live-birth rate (not just pregnancy success rate) for other couples with similar infertility problems. (Multiple births, such as twins or triplets, are counted as one live birth.)
Such statistics should include high-risk women, such as those who are older or fail to produce eggs. (Some disreputable clinics give success percentages that exclude high-risk women from their total, thereby making the percentage of success much higher.)

Advanced fertility procedures and medications are extremely expensive and often not covered by insurance. Couples should be cautious about offers of rebates in the event of failure; the clinics offering them are often significantly more expensive than those that don't offer such gimmicks.


Causes of Infertility	Treatments
Endometriosis	Conservative surgery (typically laparoscopy) is the appropriate approach for restoring fertility. GnRH agonists or progestins, used to treat endometriosis itself, have no effect on fertility. Possible exceptions are GnRH agonists used after surgery. In one study, this treatment helped improve conception rates in women who subsequently underwent assisted reproductive techniques. Assisted reproductive technologies (ART). (Fertility drugs alone have no effect.) It is not clear, in any case, whether either laparoscopy for removing endometrial implants or ART has additional advantages in many of these women compared to simply trying to become pregnant through non-aggressive means.
Hyperprolactinemia	Dopamine agonists, including bromocriptine (Parlodel) or cabergoline (Dostinex). Surgery in some cases.
Luteal phase defect	Clomiphene or superovulation drugs (FSH drugs or hMG).
Hyperprolactinemia (elevated prolactin)	Bromocriptine, cabergoline to shrink tumors that result in over secretion of prolactin. Cabergoline is more effective, but bromocriptine has been used longer. Once ovulation starts, women who want to become pregnant should stop cabergoline one month before attempting conception. Surgery may be needed for women who do not respond to medications or who have large tumors.
Hypogonadotropic Hypogonadism	Fertility drugs (hMG preferable to FSH alone) with or without assisted reproductive technologies.
Pelvic Inflammatory Disease	Screening high-risk women for the presence of Chlamydia trachomatis and treating the organism before it causes symptoms could reduce the risk of PID by almost 60%. If any sexually transmitted infection is detected, both partners should receive antibiotics, even if there are no symptoms. If PID symptoms develop, particularly lower abdominal pain, fertility can be preserved if women receive antibiotics within 2 days. A delay significantly increases the risk for scarring.
Polycystic Ovarian Syndrome	Lifestyle changes (weight loss and exercise in women who are overweight.) Clomiphene is the standard first-line treatment for polycystic ovarian syndrome (PCOS)-related infertility. Although some research has indicated that the diabetes drug metformin (Glucophage) might help treat infertility in women with PCOS, a 2007 study in the New England Journal of Medicine indicated that clomiphene is much more effective.
Premature Ovarian Failure	Assisted reproductive technologies with donor eggs.
Preserving fertility after cancer treatments	Removal and freezing (called cryopreservation) of ovarian tissue containing embryos or freezing immature and unfertilized eggs to use for later reimplantation. (Freezing before cancer treatment appears to offer the best chance.) Under investigation: Ovarian transplantation procedures and gonadotropin-releasing hormone analogues, which put women in a temporary pre-pubescent state during chemotherapy and may preserve fertility.
Fallopian tubal blockage	Surgical procedures (laparoscopy or salpingostomy) to clear the tubes. (Average pregnancy rate after salpingostomy is about 30%, but they can vary widely.) Flushing the tubes with an oil-based fluid (lipiodol) during hysterosalpingography (investigative). In a 2002 study, this procedure improved pregnancy rates in women with infertility of unknown causes. Assisted reproductive technologies.
Unexplained infertility	Lifestyle measures. Fertility drugs. Assisted reproductive technologies.

Lifestyle Changes

Although there are no dietary or nutritional cures for infertility, a healthy lifestyle is important. Ovulatory problems are reversible by changing behavioral patterns. Such conditions include:

Maintain a healthy weight. Women who are either over- or underweight are at risk for fertility failure, including a lower chance for achieving success with fertility procedures. Everyone should have a diet rich in fresh fruits and vegetables and whole grains and low in saturated fats.
Stop smoking. Smoking increases the risk for infertility in both men and women, and poses a future health risk for the mother and infant. Everyone should quit.
Avoid caffeine and alcohol.
Avoid excessive exercise if it causes menstrual irregularity. However, moderate and regular exercise is essential for good health. Few women exercise to the extent that their periods are affected. For those who do, one study found that simply adding calories can restore menstruation in many cases.
Don't use electric blankets. In one study, a 74% higher incidence of spontaneous abortion was associated with using an electric blanket during the month of conception. There was no association with heated waterbeds or electromagnetic waves.
Avoid any unnecessary medications.

There is no evidence of harm to a developing fetus from low exposure to microwaves or electromagnetic waves. Women who remain anxious may derive comfort by avoiding some of these devices (such as cellular phones or electric blankets) and remaining a foot or so away from others (such as computers or microwave ovens).

Both male and female hormone levels fluctuate according to the time of day, and they vary from day to day and month to month. Some timing tips might be helpful.

Male Hormone Levels and Sexual Activity. Male hormone levels are highest in the morning. (Sexual interest also tends to be higher in the morning.) In one study of men, their sexual activity was highest in October, when conception rates were also high.

Fertility and Seasonal Changes. Different studies have reported higher sperm counts in the winter than in the summer. For women, fertility rates as measured by treatment success are highest in months when days are longest.

Monitoring Basal Body Temperature. To determine the most likely time of ovulation and therefore the time of fertility, a woman is instructed to take her body temperature, called her basal body temperature. This is the body's temperature as it rises and falls in accord with hormonal fluctuations.

Each morning before rising, the woman takes her temperature with a specialized basal body thermometer and marks the result on a graph-paper chart.
The woman also notes the days of menstruation and sexual activity.
The so-called "fertile window" is 6 days long, starts 5 days before ovulation, and ends the day of ovulation.
The chances for fertility are considered to be highest between days 10 and 17 in the menstrual cycle (with day 1 being the first day of the period, and ovulation occurring about 2 weeks later). However, cycles vary from woman to woman. Researchers suggest that women track the length of their cycles, which can run anywhere from between 19 and 60 days. A long cycle, for example, suggests a delayed ovulation date.
Immediately after ovulation the body temperature increases sharply in about 80% of cases. (Some women can be ovulating normally yet not show this temperature pattern.)

By studying the temperature patterns after a few months, couples can begin to anticipate ovulation and plan their sexual activity accordingly. Couples must try to avoid becoming fixated on the chart, however, in scheduling their sexual activity. Spontaneity can be lost, and the stress on the relationship can be quite severe.

Hormone Monitoring Systems. A device called a saliva fertility monitor (Fertility Tracker) uses a microscope to view slides containing saliva and monitors estrogen levels. Home test kits that monitor reproductive hormone levels in the urine (ClearBlue) are also available. They are less costly than the saliva test but are messier. Monitoring hormones levels helps to determine when a woman is ovulating.

Frequency of Intercourse. The question of how often a couple should have intercourse is in debate. Some doctors say that having sex more than 2 days a week adds no benefits. Moreover, frequent sexual activity lowers sperm count per ejaculation. Other studies have indicated, however, that having intercourse every day, or even several times a day, before and during ovulation, improves pregnancy rates. Although sperm count per ejaculation is low, a constantly replenished semen supply is more likely to result in a fertilized egg.

The fertility process is a roller coaster of emotions that are present throughout and in both failure and success. There are almost no sure ways to predict which couples will eventually conceive. Some couples with multiple problems will overcome great odds, while other, seemingly fertile, couples fail to conceive. Many of the new treatments are remarkable, but a live birth is never guaranteed. The emotional burden on the couple is considerable, and some planning is helpful.

Planning for Emotional Turmoil.

Decide in advance how many and what kind of procedures will be emotionally and financially acceptable and attempt to determine a final limit. Fertility treatments are expensive. A successful pregnancy often depends on repeated attempts.
Determine alternatives (adoption, donor sperm or egg, or having no children) as early as possible in the fertility process. This can reduce anxiety during treatments and feelings of hopelessness in case conception does not occur.

Managing Emotional Stress During the Process. Managing negative emotions can be viewed as important as medical treatment. The following are some ways women reduce stress while trying to conceive:

Talking to one's spouse, family, and friends is very beneficial. The best support comes from the spouse. Studies suggest that a positive attitude on the husband's part is essential for enabling his wife to deal effectively with either the success or failure of fertility treatments. Men and women may cope differently with the stress, and each should understand the other's special needs. Women tend to want greater personal space and also to want to share the burden with their husbands. Men tend to cope by seeking to improve themselves (for example being strong, or being the "best").
Almost half of women seeking fertility treatments practice good-luck rituals, including praying and wearing charms or special jewelry. No evidence exists that these practices increase fertility, but they may help reduce anxiety and enhance a sense of control.
Cognitive-behavioral therapy, which uses methods that include relaxation training and stress-management, have been associated with higher pregnancy rates. (In one study, 42% became pregnant without medical intervention.)
Attending support groups or counseling services before and after treatment helps many women endure the process and ease the grief should treatment fail. One study indicated that pregnancy rates were twice as high in women who coped with their depression by reaching out to others rather than repressing guilt or rage. (These results held only in cases in which women, not their mates, were infertile.)
Acupuncture may help some women. Some evidence suggests that this alternative treatment has beneficial effects on chemicals in the brain involved with stress and reproduction. Acupuncture is safe, but studies have been mixed on whether it can help improve pregnancy rates. One study indicated that women who received acupuncture achieved significantly higher success rates during fertility treatments (42.5%) than those who did not receive it (26.3%). Several 2006 studies suggested that acupuncture may improve pregnancy success for women who undergo in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) procedures. One of these studies found that acupuncture had a positive effect if it was given during the luteal phase (post-ovulatory period of menstrual cycle.) Another study suggested that acupuncture should be given on the day of embryo transfer.

Managing the Emotional Effects of the Outcome. After enduring the process, the couple must face the outcome, and even a positive outcome has emotional repercussions.

Effects of Failure. The emotional stress of failure can be devastating even on the most loving and affectionate relationships and even in those who have prepared for the possibility of failure. Neither the male nor female partner should hesitate to seek professional help if the emotional burdens are too heavy.
Effects of Genetic Testing. As advanced technologies allow testing and greater genetic information at the earliest stage, potential parents will have to learn to deal with the uncertainties of possible chromosomal abnormalities, which may or may not be significant.
Effects of Successful Treatments. Some studies have indicated that even if successful, some women experience higher stress and fear of failure during pregnancy. According to one study, however, women who achieved pregnancy using fertility treatments felt increasingly better and had higher self esteem and less anxiety as the pregnancy progressed than women whose pregnancies were not due to medical intervention.
Effects of Multiple Births. A successful pregnancy that results in a multiple birth introduces new complexities and emotional problems. One study reported a very high rate of depression in women with triplets, particularly if they had little help from others, and especially if their husbands weren't involved.
Effects on Parenting. Once the fertility treatment-assisted child arrives, parents (both men and women) are more likely to be anxious and to have less confidence than those who conceive naturally.

Medications

Fertility drugs are often used alone as initial treatment to induce ovulation. If they fail as sole therapy, they may be used with assisted reproductive procedures or artificial insemination to produce multiple eggs, a process called superovulation.

Clomiphene citrate (Clomid, Serophene) is usually the first fertility drug of choice for women with infrequent periods and long cycles. Unlike more potent drugs used in superovulation, clomiphene is gentler and works by blocking estrogen, which tricks the pituitary into producing

follicle-stimulating hormone (FSH) and luteinizing hormone (LH). This boosts follicle growth and the release of the egg. Clomiphene can be taken orally, is relatively inexpensive, and the risk for multiple births (about 5%, mostly twins) is lower than with other drugs.

Women with the best chances for success with this drug are those who have the following conditions:

Polycystic ovarian syndrome (PCOS)
Ability to menstruate but irregular menstrual cycle

Women with poorer chances of success with this drug have the following conditions:

Infertility but with normal ovulation
Low estrogen levels
Premature ovarian failure (early menopause)

One or two tablets are taken each day for 5 days, usually starting 2 - 5 days after the period starts. If successful, ovulation occurs about a week after the last pill has been taken. If ovulation does not occur, then a higher dose may be given for the next cycle. If this resgimen is not successful, treatment may be prolonged or additional drugs may be added. Doctors usually do not recommend more than 6 cycles.

Clomiphene often reduces the amount and quality of cervical mucus and may cause thinning of the uterine lining. In such cases, other hormonal drugs may be given to restore thickness. Other side effects of clomiphene include ovarian cysts, hot flashes, nausea, headaches, weight gain, and fatigue. There is a 5% chance of having twins with this drug, and a slightly increased risk for miscarriage.

If clomiphene does not work or is not an appropriate choice, gonadotropin drugs are a second option. Gonadotropins include several different types of drugs that contain either a combination of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), or only FSH. Clomiphene works indirectly by stimulating the pituitary gland to secrete FSH, which prompts follicle production. In contrast, the gonadtropin hormones directly stimulate the ovaries to produce multiple follicles.

Gonadotropins are given in a shot. (Your doctor may show you how to self-administer the injection.) Gonadotropins include:

Human Menopausal Gonadtropins (hMG), also called menotropins
Human Chorionic Gonadotropins (hCG)
Urofollitropin and Follitropin, natural and synthetic forms of FSH
Gonadotropin-releasing hormone (GnRH) analogs, which include GnRH agonists and GnRH antagonists

Gonadotropin drugs are either natural compounds extracted from urine or synthetic compounds that are genetically engineered in a laboratory using recombinant DNA.

Human Menopausal Gonadotropin (hMG). HMG drugs, also called menotropins, contain a mixture of both FSH and LH. These drugs (Pergonal, Repronex, Metrodin, Humegon) are all derived from the urine of postmenopausal women. HMG is administered as a series of injections 2 - 3 days after the period starts. Injections are usually given for 7 - 12 days, but the time may be extended if ovulation does not occur. In such cases, a shot of human chorionic gonadotropin (hCG) may trigger ovulation.

Human Chorionic Gonadotropin (hCG). Human chorionic gonadotropin (hCG) is similar to LH. It mimics the LH surge, which stimulates the follicle to release the egg. Natural hCG drugs, derived from the urine of pregnant women, include Pregnyl, Profasi, Novarel, APL, Chorex, and Follutein. Ovidrel is the only available genetically modified hCG drug. Ovidrel has fewer side effects at the injection site, and its quality can be better controlled than the natural drugs. It is generally used after hMG or FSH to stimulate the final maturation stages of the follicles. Ovulation, if it occurs, does so about 36 - 72 hours after administration.

Urofollitropin and Follitropin. Urofollitropin (Bravelle, Fertinex) is a purified form of FSH, derived from the urine of postmenopausal women. Follitropin drugs (Gonal-F, Follistim) are synthetic versions of FSH. These FSH drugs are sometimes given in combination with an hCG drug.

GnRH Analogs (Agonists or Antagonists). Gonadotropin-releasing hormone (GnRH) is a hormone produced in the hypothalamus part of the brain. GnRH stimulates the pituitary gland to produce LH and FSH. GnRH analogs are synthetic drugs that are classified as either agonists or antagonists. They are similar to natural GnRH but have very different actions. While natural GnRH stimulates LH and FSH, these drugs actually prevent the LH and FSH surge that occurs right before ovulation. This action helps prevent the premature release of the eggs before they can be harvested for assisted reproductive technologies.

GnRH agonists include leuprolide (Lupron), nafarelin (Synarel), and goserelin (Zoladex).
GnRH antagonists include ganirelix (Antagon) and cetrorelix (Cetrotide). GnRH antagonists suppress FSH and LH more than GnRH agonists, and they may require fewer injections.

Women with endometriosis often have an especially hard time getting pregnant. A 2006 review suggested that GnRH agonists may help women with endometriosis quadruple their chances of becoming pregnant when the drug is used 3 - 6 months prior to in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). [See In-Depth Report #74: Endometriosis.]

Multiple Births. Overproduction of follicles can lead to ovarian enlargement. This event increases the risk for multiple births. There is a 25% chance of multiple births (about 17% for twins and 8% for triplets and or more).

Ovarian Hyperstimulation Syndrome. The most serious complication with superovulation is ovarian hyperstimulation syndrome (OHS), which is associated with the enlarged ovary (although the precise cause is unknown). This can result in dangerous fluid and electrolyte imbalances and endanger the liver and kidney. OHS is also associated with a higher risk for blood clots. In rare cases, it can be fatal. Symptoms include abdominal bloating, nausea, vomiting, and shortness of breath.

Bleeding and Rupture of Ovarian Cysts. Overproduction of follicles, if unchecked, may result in bleeding and rupture of ovarian cysts.

Cancer Concerns. There has been concern that clomiphene and gonadotropins may increase the risks for ovarian and breast cancer. Most evidence to date does not indicate that ovulation-stimulating drugs increase the risks for these types of cancers. However, more research needs to be done. Some studies suggest that clomiphene, which is chemically related to the breast cancer drug tamoxifen, may actually decrease the risk for breast cancer.

Progesterone. Progesterone is a hormone that is produced by the body during the menstrual cycle. Progesterone drugs are sometimes given to women who have experienced frequent miscarriages (a possible sign of progesterone deficiency). A progesterone drug may also be given after egg retrieval during an in vitro fertilization (IVF) cycle to help thicken the uterine lining (endometrium) so it can better hold the egg following implantation.

Aromatase Inhibitors. Aromatase inhibitors block aromatase, an enzyme that is a major source of estrogen in many major body tissues. These drugs include anastrozole (Arimidex) and letrozole (Femara). These drugs are used for treating breast cancer and are being investigated for stimulating ovulation in infertile women. Although letrozole is not approved for treatment of infertility, it has become widely used for this purpose in recent years. Some doctors were concerned that letrozole could increase the risk of birth defects. However, a major 2006 study indicated that letrozole does not increase risk to the fetus. The study compared the rate of birth defects among babies whose mothers conceived with letrozole and those who used clomiphene (the standard first-line fertility drug). Researchers found no differences in birth outcomes between the two groups.

Tamoxifen. Tamoxifen (Nolvadex) is a drug known as a selective estrogen-receptor modulator (SERM). It is used to prevent breast cancer in high-risk women. Studies suggest that it may equal clomiphene in its ability to induce ovulation. It may be especially useful when used along with IVF for preserving fertility in breast cancer patients. This drug is less expensive than clomiphene, but it poses some health hazards, including a risk for blood clots and uterine cancer.

Glucocorticoids. Glucocorticoids are steroid hormones that are sometimes used in combination with IVF and intracytoplasmic sperm injection (ICSI). It is thought that anti-inflammatory effect of these drugs can help make the lining of the uterus more responsive to egg implantation. However, a 2007 review indicated that glucocorticoids do not help improve pregnancy success rates and should not be used routinely with assisted reproductive technologies.

Regimens to induce ovulation vary widely according to individual need. A typical procedure, involving superovulation and in vitro fertilization (IVF) may be as follows:

Doctors make sure that the patient is not pregnant or in the luteal phase of her menstrual cycle (the premenstrual period).
Injections of either human menopausal gonadtropins, which contains luteinizing hormone (LH) and follicle-stimulating hormone (FSH) or pure FSH are administered daily 2 - 4 days after day 1 of the next cycle. Either drug may be used.
After 4 - 8 days of treatment, estrogen levels are monitored. Increasing levels on the fourth day of treatment may be strong indicators of success. If estrogen levels indicate that ovaries are responding, ultrasound is then performed to detect possible overproduction of follicles. Such evaluation should then be conducted every 1 - 2 days and dosages adjusted accordingly.
Gonadotropin-releasing hormone analogs are used to prevent a premature release of LH hormone (and therefore ovulation). GnRH agonists are typically administered either early on or a few days after ovulation in the cycle previous to the one planned for IVF. This approach is referred to as the long protocol, and it serves to suppress the pituitary gland and allows time for the eggs to mature before harvesting. Other protocols using GnRH antagonists are under investigation, but to date the long protocol has the best pregnancy rates.
When at least three follicles have reached a diameter of 18 mm, human chorionic gonadotropins (hCG) is typically administered to release the egg. It is not given if there are signs of overproduction of follicles, which suggests a risk for ovarian hyperstimulation syndrome (OHS), a dangerous complication. (One study reported that giving high doses of progesterone to high-risk women the day of hCG administration may prevent OHS.)
Egg retrieval may be performed about 36 hours following hCG administration, with the transfer of the embryo (the fertilized egg) back into the woman 2 - 3 days after retrieval.
Embryos are transferred to the uterus through a small tube. This process does not require an anesthetic, although the procedure can cause cramping.

Natural (Unstimulated) In Vitro Fertilization Cycles. An alternative to superovulation for some couples is natural in vitro fertilization (IVF) cycles. It allows multiple, consecutive cycles of treatment. Natural IVF is far less expensive than standard hyperstimulation methods and avoids their risks, including multiple births and ovarian hyperstimulation syndrome (OHS).

The process involves ultrasound and hormonal monitoring starting 5 days before the estimated ovulation day.
No superovulation drugs are used, such as follicle-stimulating hormone (FSH) and human menopausal gonadtropins (hMG). The doctor, however, may administer an injection of human chorionic gonadotropins (hCG) to stimulate the luteinizing hormone (LH) surge.
The egg retrieval timing is based on detecting LH surge.
A single egg is retrieved. The procedure that follows is similar to other IVF cycles.

The basic disadvantage to this approach is that the eggs may be released before there is a chance for them to be harvested. Women report far lower stress levels with this approach, however, even though it requires more treatment cycles. In one study, the live-birth rate was 32%. Not all women are appropriate candidates, however. Women should have regular menstrual cycles and infertility of unknown cause or associated with problems in the fallopian tubes. Pregnancy rates are still very low in older women.

Clomiphene. Another gentler alternative to superovulation is the use of clomiphene before IVF, which works slightly better than unstimulated IVF.

Assisted Reproductive Technologies

Assisted reproductive technologies (ART) are medical techniques that help couples conceive. These procedures involve either:

A couple’s own eggs or sperm
Donor eggs, sperm, or embryos

Fertilization may occur either in the laboratory or in the uterus. In the U.S., the number of live birth deliveries from ART increased by 128% between 1996 and 2002. More than 45,000 babies are now born in the U.S. each year using assisted reproductive technologies.

ART includes fertility drug treatments, artificial insemination (AI), in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), and other procedures.

Artificial insemination (AI) is the least complex of the assisted reproductive technologies and is often tried first in uncomplicated cases of infertility. AI either involves placing the sperm directly in the cervix (called intracervical insemination) or into the uterus (called intrauterine insemination, or IUI). IUI is the standard AI procedure.

It is useful under the following circumstances:

When the woman's cervical mucus is unreceptive
When donor sperm are required
If the man's sperm count is very low
When unexplained infertility exists in both partners

Those in whom AI fails, couples with specific fertility defects, or older women may be candidates for more advanced reproductive technologies.

Pregnancy Rates. A review of 45 studies reported that in unexplained infertility cases, the per-cycle pregnancy rates were 4% for intrauterine insemination (IUI) alone and 8 - 17% per cycle for IUI combined with superovulation, a procedure that uses fertility drugs to bolster egg recovery.

Researchers in one study suggested IUI as a reasonable first option for many women under age 43. It is less expensive and poses less risk for multiple births than the more advanced assisted reproductive technologies (ART), such as in vitro fertilization. Although IVF procedures are more effective per cycle, couples tend to be able to afford more IUI cycles, so the pregnancy rates over time are very similar.

The Artificial Insemination Procedure. The AI procedure is as follows:

A woman usually (but not always) takes fertility drugs in advance.
The man must produce sperm at the time the woman is ovulating.
The sperm are subjected to certain so-called "washing" procedures. They are then inserted into the uterine cavity through a long, thin catheter.

The administration of fertility drugs and sperm retrieval is timed so that the process can coincide with ovulation.

About 71% of assisted reproductive technologies (ART) procedures now use in vitro fertilization (IVF) with the woman's own eggs. An in vitro procedure is one that is performed in the laboratory. Advances in these procedures have dramatically increased the rate of live births.

The best candidates for IVF are women with damaged fallopian tubes, and some experts believe it is a better option than attempting surgical repair. IVF is also used when infertility is unexplained or when the male partner has the infertility problem. A typical IVF procedure is as follows:

The doctor first induces superovulation using fertility drugs so that several eggs can be harvested from the ovary before they have been released from the follicles. Higher doses of fertility drugs for subsequent cycles do not appear to add any advantage in women who have a poor response the first time.
To harvest eggs, the doctor generally inserts a probe into the vagina and is guided by ultrasound. A needle is then used to drain the liquid from the follicles, and several eggs are retrieved.
The eggs and sperm are combined in a Petri dish. Between 48 - 72 hours later the eggs are usually fertilized.
The resulting embryos (the first stage toward the development of the fetus) are reimplanted into the woman's uterus.
It takes about 2 weeks to determine if the process is successful.

IVF success rates for the first three cycles of treatment are about equal. They then decline modestly for the fourth cycle and drop significantly after the fifth cycle.

Gamete/Zygote Intrafallopian Transfer. Gamete intrafallopian transfer (GIFT) and zygote intrafallopian transfer (ZIFT) are adaptations of IVF. GIFT and ZIFT are used in unexplained female infertility and in mild male infertility. The success rates are similar to those of IVF, but a woman must have at least one functioning fallopian tube.

GIFT: The procedure is as follows:

The eggs are harvested as in IVF.
They are mixed with the sperm but not actively fertilized.
They are immediately injected back into the woman. Laparoscopy, a technique that employs a miniature viewing device, is used with this procedure to guide the placement of the embryos or egg through a long, thin catheter into the fallopian tubes.
The sperm and egg are placed exactly where they would be in natural fertilization.

ZIFT: The procedure is as follows.

The eggs are harvested as in IVF.
They are then mixed with the sperm and, in this case, are fertilized in the laboratory.
They are then implanted in the fallopian tubes as in GIFT. (The advantage of this procedure over GIFT is that the doctor and couple are assured that fertilization has taken place, and the eggs can be examined for defects before implantation.)

In 2002, more than 45,000 American babies were born using in vitro fertilization (IVF). Success rates have increased in all age groups (although they are still considerably lower in older than in younger women). Chances for assisted reproductive technologies (ART) success are also greater among women who do not have uterine abnormalities and have had previous successful pregnancies.

Success rates are also higher or lower depending on whether the woman uses her own eggs or whether they are donated and also whether the eggs are fresh or frozen. The highest live birth rates are with donated fresh eggs (an average of 50% per transfer). The lowest rates are when a woman uses her own frozen eggs (an average of 29% per transfer). However, using frozen eggs is less expensive than fresh eggs, so a couple may be able to afford more cycles with frozen eggs.

Use of Donor Eggs. Older women are more likely to use donor eggs. In a 2002 study, success rates were the same for women who used donors with an age range of 20 - 40. There were also no differences in delivery rates for recipients up to age 45. Women over 45, however, increasingly had problems with implantation, pregnancy, and delivery.

Use of Frozen Eggs. Frozen eggs tend to have lower success rates because of toxins released by cells damaged in the freezing and thawing tissues.

Intracytoplasmic sperm injection (ICSI) is an assisted reproductive technology used for couples when male infertility is the main problem. It involves injecting a single sperm into an egg obtained from in vitro fertilization (IVF). The procedure is very simple:

A tiny glass tube (called a holding pipet) stabilizes the egg.
A second glass tube (called the injection pipet) is used to penetrate the egg's membrane and deposit a single sperm into the egg.
The egg is released into a drop of cultured medium.
If fertilized, the egg is allowed to develop for 1 - 2 days, then it is either frozen or implanted.

The greatest concern with this procedure has been whether it increases the risk for birth defects. However, several studies have reported no higher risks of birth defects in children born using ICSI procedures. While some studies have shown a higher number of birth defects in children conceived with ICSI, experts think that this may have more to do with the genetic background of the parents than ICSI itself. Recent research suggests that ICSI children develop normally. A 2006 study of 8-year-old children conceived with ICSI found no important differences between these children and children who were conceived naturally.

A 2007 study in the New England Journal of Medicine indicated that ICSI use has increased 5-fold over the past decade, even though the proportion of men receiving treatment for male infertility has remained the same. In 1995, 11% of IVF cycles used ICSI. By 2004, 57.5% of IVF cycles used ICSI. Doctors caution that while ICSI is an important assisted reproductive technology for male infertility, it may be overused. Some doctors recommend ICSI for women who have failed prior IVF attempts or who have few or poor-quality eggs, even if their male partners have normal semen measurements. There is little evidence that ICSI helps improve pregnancy success for couples who do not have a problem with male factor infertility, according to the Society for Assisted Reproductive Technology.

In Vitro Maturation. A technique called in vitro maturation allows fertilization without the use of fertility drugs. In this process, follicles are harvested a few days before ovulation. In such cases, up to 50 have already begun to mature. At this time, about 15 of these maturing follicles can be removed, out of which 2 or 3 can produce healthy embryos.

Blastocyst Transfer. Blastocyst transfer is very promising. Instead of implanting the standard 2- or 3-day-old embryos in the uterus, the procedure implants blastocysts, which are more complex, 5-day-old embryos. Fewer blastocysts than embryos need to be implanted, reducing the risk for multiple births. (There is, however, a higher risk for identical twins compared to other procedures.) Offspring may be more likely to be males than females. Pregnancy rates are about 36% with a first attempt but then drop significantly. The procedure is more likely to be successful in younger than older women.

Ooplasmic Transfer. Ooplasmic transfer is a controversial experimental procedure that uses the woman's own egg and a female donor's egg and the male sperm for fertilization. Genetic material from the donor's egg plus the sperm are added to the woman's own egg. This has been successful in a few cases, but studies are very early and long-term effects are unknown. Research on this and similar procedures is currently conducted outside the U.S.

Complications of Assisted Reproductive Technologies

Since assisted reproductive technology (ART) procedures have become more widespread since 1980, multiple births have significantly increased. About 35% of all ART births are multiple ones, with 4.3% being triplets or more. Multiple births increase the risk of complications, for both the mother and the child.

Assisted reproductive technology (ART), and multiple births, increase the risks for pregnancy complications. According to a 2005 study, the type of complications may depend on the infertility treatment:

Fertility drugs. Increase risks of the placenta becoming detached from the uterus (“placental abruption”), third trimester miscarriage, and gestational diabetes.
In vitro fertilization. Increase risks of placental abruption, the placenta developing in the lower section of the uterus (“placenta previa”), dangerously high blood pressure during pregnancy (“pre-eclampsia”), and Caesarean sections.

Multiple births can also increase the risk of pregnancy death. A 2006 study indicated that women who carry multiple fetuses have a 3.6 times greater risk of dying from pregnancy complications than women with singleton pregnancies. The leading causes of death were blood clot (embolism), high blood pressure complications, excessive bleeding (hemorrhage), and infections.

The main risks for children conceived with assisted reproductive technology (ART) are complications associated with pregnancy problems and multiple births. Children conceived with ART are more likely to be born premature and to have extremely low birth weight. These conditions increase the risk for heart and lung problems, as well as learning and developmental disabilities. Premature delivery is also associated with cerebral palsy, a brain injury condition that affects muscle coordination. A 2006 study indicated that children born after in vitro fertilization have an increased risk for cerebral palsy.

However, studies suggest that ART does not increase the risk for chromosomal damage or other major birth defects. Couples undergoing ART may have other factors, such as older age or genetic predispositions, which make complications more likely. Infertility itself, even without ART, can pose a risk factor for birth defects. Children conceived naturally by couples with infertility problems tended to have more disorders of the nervous system, digestive system, and musculoskeletal system than children born to fertile couples, according to a 2006 study in the British Medical Journal. Children born to couples treated for infertility with ART may also have a slightly increased risk for these problems, as well as genital organ malformations, but the overall risk for birth defects appears to be very small.

ART remains a good option for many infertile couples. The likelihood of having a healthy single child of normal birth weight using ART is about 94%. The likelihood of having a child free of major birth defects is about 91%. Frozen eggs do not appear to pose any higher risk for developmental problems.

Preimplantation genetic diagnosis (PGD) is now available in some fertility centers. It can help identify genetic defects in the offspring and may help parents determine future problems. Such testing, however, also raises significant emotional issues that should be addressed beforehand.

Given the hazards of multiple births, parents must make some hard decisions if the treatment produces multiple embryos. The choices are limited:

Carry all of them to term, which increases health risks for both the mother and the developing fetuses
Complete abortion
Embryo reduction, in which the doctor removes one or more embryos (possibly endangering the remaining embryos)

At this time, the best approach is to limit the number of implanted embryos in the first place. Researchers are attempting to develop methods to reduce the risk for multiple births:

Most centers now implant two to three embryos at a time, and the remainder can be frozen for future use. (Frozen eggs do not appear to pose a risk for developmental problems in children conceived using them.) This limits the chance for success, but implanting more than three embryos only increases success rates very slightly, whereas the risk for multiple births increases significantly.
Reducing the dosage of fertility drugs also reduces the risk for multiple births, but not significantly, and it also reduces the chance for successful outcome.
Blastocyst transfer may help reduce the chances for multiple births.

Resources

www.resolve.org -- National Infertility Association
www.asrm.org -- American Society for Reproductive Medicine
www.theafa.org -- American Fertility Association
www.endometriosisassn.org -- The Endometriosis Association
www.acog.org -- American College of Obstetricians and Gynecologists
www.endo-society.org -- The Endocrine Society
www.aace.com -- American Association of Clinical Endocrinologists
www.cdc.gov/reproductivehealth/index.htm -- Centers for Disease Control: Assisted Reproductive Technology Reports

References

Boomsma CM, Keay SD, Macklon NS. Peri-implantation glucocorticoid administration for assisted reproductive technology cycles. Cochrane Database Syst Rev. 2007 Jan 24;(1):CD005996.

Chavarro JE, Rich-Edwards JW, Rosner BA, Willett WC. Iron intake and risk of ovulatory infertility. Obstet Gynecol. 2006 Nov;108(5):1145-52.

Dieterle S, Ying G, Hatzmann W, Neuer A. Effect of acupuncture on the outcome of in vitro fertilization and intracytoplasmic sperm injection: a randomized, prospective, controlled clinical study. Fertil Steril. 2006 May;85(5):1347-51.

Hvidtjorn D, Grove J, Schendel DE, Vaeth M, Ernst E, Nielsen LF, et al. Cerebral palsy among children born after in vitro fertilization: the role of preterm delivery--a population-based, cohort study. Pediatrics. 2006 Aug;118(2):475-82.

Jain T, Gupta RS. Trends in the use of intracytoplasmic sperm injection in the United States. N Engl J Med. 2007 Jul 19;357(3):251-7.

Jensen A, Sharif H, Svare EI, Frederiksen K, Kjaer SK. Risk of breast cancer after exposure to fertility drugs: results from a large Danish cohort study. Cancer Epidemiol Biomarkers Prev. 2007 Jul;16(7):1400-7. Epub 2007 Jun 21.

Lee SJ, Schover LR, Partridge AH, Patrizio P, Wallace WH, Hagerty K, et al. American Society of Clinical Oncology recommendations on fertility preservation in cancer patients. J Clin Oncol. 2006 Jun 20;24(18):2917-31.

Legro RS, Barnhart HX, Schlaff WD, Carr BR, Diamond MP, Carson SA, et al. Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome. N Engl J Med. 2007 Feb 8;356(6):551-66.

Mackay AP, Berg CJ, King JC, Duran C, Chang J. Pregnancy-Related Mortality Among Women With Multifetal Pregnancies. Obstet Gynecol. 2006 Mar;107(3):563-568.

Ombelet W, Martens G, De Sutter P, Gerris J, Bosmans E, Ruyssinck G, et al. Perinatal outcome of 12,021 singleton and 3108 twin births after non-IVF-assisted reproduction: a cohort study. Hum Reprod. 2006 Apr;21(4):1025-32.

Sallam HN, Garcia-Velasco JA, Dias S, Arici A. Long-term pituitary down-regulation before in vitro fertilization (IVF) for women with endometriosis. Cochrane Database Syst Rev. 2006 Jan 25;(1):CD004635.

Shevell T, Malone FD, Vidaver J, Porter TF, Luthy DA, Comstock CH, et al. Assisted reproductive technology and pregnancy outcome. Obstet Gynecol. 2005 Nov;106(5 Pt 1):1039-45.

Smith C, Coyle M, Norman RJ. Influence of acupuncture stimulation on pregnancy rates for women undergoing embryo transfer. Fertil Steril. 2006 May;85(5):1352-8.

Terry KL, Willett WC, Rich-Edwards JW, Michels KB. A prospective study of infertility due to ovulatory disorders, ovulation induction, and incidence of breast cancer. Arch Intern Med. 2006 Dec 11-25;166(22):2484-9.

Tulandi T, Martin J, Al-Fadhli R, Kabli N, Forman R, Hitkari J, et al. Congenital malformations among 911 newborns conceived after infertility treatment with letrozole or clomiphene citrate. Fertil Steril. 2006 Jun;85(6):1761-5.

Westergaard LG, Mao Q, Krogslund M, Sandrini S, Lenz S, Grinsted J. Acupuncture on the day of embryo transfer significantly improves the reproductive outcome in infertile women: a prospective, randomized trial. Fertil Steril. 2006 May;85(5):1341-6.

Zhu JL, Basso O, Obel C, Bille C, Olsen J. Infertility, infertility treatment, and congenital malformations: Danish national birth cohort. BMJ. 2006 Sep 30;333(7570):679. Epub 2006 Aug 7.

Review Date:
10/29/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Retroversion of the uterus

admin — Thu, 04 Sep 2008 18:46:55 -0700

Overview

Definition
Alternative Names
Causes, incidence, and risk factors
Symptoms
Signs and tests
Treatment
Expectations (prognosis)
Complications
Calling your health care provider
Prevention

Illustrations

Female reproductive anatomy

Uterus

HEALTH GUIDE REFERENCE FROM A.D.A.M

Definition

Retroversion of the uterus is a normal variation of female pelvic anatomy in which the body of the uterus is tipped toward the back rather than forward.

Alternative Names

Uterus retroversion; Malposition of the uterus; Tipped uterus

Causes, incidence, and risk factors

Retroversion of the uterus is common and is found to be the normal uterine position in about 20% of all women. Laxness of the supporting pelvic ligaments associated with menopause may cause retroversion in women who previously did not have a retroverted uterus.

Enlargement of the uterus, either as the result of a pregnancy or a tumor, may also change the relative position of the uterus within the pelvis. Pelvic adhesions (scar tissue that forms in the pelvis) resulting from salpingitis, pelvic inflammatory disease, or endometriosis have also been associated with holding the uterus in a retroflexed position.

Symptoms

Uterine retroversion by itself almost never causes any symptoms.
Rarely, retroversion of the uterus caused by an enlarging pregnancy or tumor may cause pelvic pain or discomfort.
Retroversion of the uterus resulting from other causes such as endometriosis may be associated with the symptoms of the underlying disorder.

Signs and tests

A pelvic examination reveals the position of the uterus. However, a tipped uterus can sometimes be mistaken for a pelvic mass or an enlarging fibroid. A rectovaginal exam may be used to distinguish between a mass and a retroverted uterus.

An ultrasound examination can be used to determine the exact position of the uterus, if necessary.

Treatment

Treatment is usually not necessary. Any underlying disorders (such as endometriosis or adhesions) may be treated as needed.

Expectations (prognosis)

Usually this condition does not cause problems.

Complications

Atypical positioning of the uterus may be caused by endometriosis, salpingitis, or pressure from a growing tumor. These conditions should be ruled out in a patient with pain or other symptoms.

Calling your health care provider

Call your health care provider if you develop persistent pelvic pain or discomfort.

Prevention

There is no known prevention. However, early treatment of PID or endometriosis may reduce the chances of a change in the position of the uterus.

Review Date: 11/8/2006

Reviewed By: Audra Robertson, MD, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, MA. Review provided by VeriMed Healthcare Network.

A.D.A.M. Copyright

adam.com

Source Doc: 1_001506

What to Expect at Your Postpartum Checkup

LilSugar — Tue, 21 Jul 2009 15:00:00 -0700

Mamas wait for what seems like an eternity for their babies, so when they finally arrive it's a big relief. There's another wonderful thing that comes with holding the warm bundle of joy, clearing your calendar of prenatal appointments! But, before women can pencil in other activities, they need to go in for their six week postpartum checkup. Here's what to expect during the visit:

A thorough pelvic exam, including a pap smear, an examination of any episiotomy, vaginal tear, or C-section scar healing and a check of the uterus's return to its prepregnancy size.
A breast exam including a breast cancer screening and checks for infections and abscess that may result from breastfeeding.
Blood work to check for anemia or thyroid issues.
A mental health evaluation to screen for postpartum depression and determine the mother's overall well-being.
A discussion about birth control options. Depending on a woman's breastfeeding goals and her plans for subsequent children, her contraceptive options may vary from her prepregnancy ones. Be sure to discuss all options with your doctor.
Clearance for postpartum sexual activity. Many husbands view the six-week postpartum checkup as the green light for resuming sexual activity. If your doctor does say it is OK to proceed, discuss any tips she might have to get you started again.

Ovarian cancer

FitSugar — Wed, 08 Oct 2008 17:34:58 -0700

In This Report

Highlights
Introduction
Symptoms
Causes
Prevention
Diagnosis
Prognosis
Treatment
Surgery
Medications
Radiation Therapy
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Ovarian Cancer Symptoms

Even early-stage ovarian cancer can produce symptoms, according to a 2007 consensus statement issued by the American Cancer Society, the Gynecologic Cancer Foundation, and the Society of Gynecologic Oncologists. Because ovarian cancer can grow very rapidly, early detection is extremely important. Contact your doctor (preferably a gynecologist) if you experience these symptoms on a daily basis for more than a few weeks:

Bloating
Pelvic or abdominal pain
Difficulty eating or feeling full quickly
Urgent or frequent urination

Hormone Replacement Therapy (HRT) Increases Ovarian Cancer Risk

Post-menopausal women who use hormone replacement therapy (HRT) for more than 5 years are 20% more likely to develop ovarian cancer than women who do not use HRT, suggests a 2007 study in the Lancet. Researchers analyzed data from more than 1 million women.
A similar association between HRT use and ovarian cancer, especially for women who have not had a hysterectomy, was reported in a 2006 study in the Journal of the National Cancer Institute.

Surgery

About 1 in 3 women with ovarian cancer fail to receive recommended surgical treatment, according to a 2007 study in Cancer. The study found that women who are poor, African-American or Hispanic, or over age 70 are least likely to receive adequate care. Another Cancer study suggested that although experienced cancer centers may cost more than other facilities, they are more cost-effective over the long term than less experienced medical facilities.
For optimal ovarian cancer treatment, it is best to seek care from an experienced gynecologic oncologist and specialized cancer center.

Investigational Drugs

Aflibercept (VEGF-TRAP), an experimental anti-angiogenesis drug, may benefit patients with epithelial ovarian cancer who have not been helped by platinum-based chemotherapy, according to interim results of a Phase II study presented at the 2007 annual meeting of the American Society of Clinical Oncology. Anti-angiogenesis drugs prevent tumors from growing and spreading by starving them of their blood supply.

Introduction

The ovaries are two small, almond-shaped organs located on either side of the uterus. They are key components of a woman's reproductive system:

Ovaries store 200,000 - 400,000 follicles, tiny sacs that are present from birth, that nurture immature eggs (ova).
During each normal (usually monthly) reproductive cycle, a follicle in one ovary bursts and releases a mature or "ripened" egg. The egg travels down the fallopian tube into the uterus, where it either is fertilized by a man's sperm or, if unfertilized, breaks down and is excreted as part of the menstrual cycle.
Ovaries also secrete the important reproductive hormones estrogen and progesterone.

The uterus, commonly called the womb, is a hollow muscular organ located in the female pelvis between the bladder and rectum. The ovaries produce the eggs that travel through the fallopian tubes. Once the egg has left the ovary it can be fertilized and implant itself in the lining of the uterus. The main function of the uterus is to nourish the developing fetus prior to birth.

Ovarian cancers are potentially life-threatening malignancies that develop in one or both ovaries. Malignant ovarian tumors generally fall into three primary classes:

Epithelial tumors
Germ cell tumors
Stromal tumors

Epithelial Tumors. Epithelial tumors account for up to 90% of all ovarian cancers and therefore are the primary focus of this report. These cancers develop in a layer of cube-shaped cells known as the germinal epithelium, which surrounds the outside of the ovaries.

Germ Cell Tumors. Germ cell tumors, which account for about 3% of all ovarian cancers, are found in the egg-maturation cells of the ovary. They occur most often in teenagers and young women. Although they progress rapidly, they are very sensitive to treatments. About 90% of patients with germ cell malignancies can be cured, often preserving fertility.

Stromal Tumors. Stromal tumors, which account for 6% of all ovarian cancers, develop from connective tissue cells that hold the ovary together and that produce the female hormones, estrogen and progesterone. Stromal tumors do not usually spread, in which case the prognosis is good. If they spread, however, they can be more difficult to treat than others.

Click the icon to see an image of ovarian cancer.

Ovarian cancer is called the silent killer because it progress almost silently, with vague symptoms. By the time symptoms do appear, the ovarian tumor may have grown large enough to shed cancer cells throughout the abdomen. At such an advanced stage, the cancer is more difficult to cure.

Ovarian cancer cells that have spread outside the ovaries are referred to as metastatic ovarian cancers. Ovarian tumors tend to spread to the following locations:

Diaphragm
Intestine
Omentum (a fatty layer that covers and pads organs in the abdomen)

Cancer cells can also spread to other organs through lymph channels and the bloodstream.

Not all ovarian tumors are malignant. Benign cysts, dermoid tumors, and borderline malignant tumors all are distinct from ovarian cancer.

Benign Cysts. Benign cysts are common. They typically develop in one of two ways:

Follicular Cysts. During normal ovulation, follicles (the little sacs in the ovary) expel eggs. If the egg is not expelled, fluids and other substances can build up inside the follicle, forming a follicular cyst.
Corpus Luteum Cysts. Benign cysts may form when an egg has been released, but the emptied follicle (now called the corpus luteum) does not break down normally, instead filling with blood from nearby blood vessels.

Both follicular cysts and corpus luteum cysts are normal parts of the menstrual cycle and nearly always resolve within one or two cycles without treatment.

Dermoid Tumors. Dermoid tumors are benign growths that occur when an egg begins to develop without fertilization by a sperm; they can contain hair, teeth, and cartilage. They are easily removed by surgery.

Borderline Ovarian Tumors. About 15% of ovarian tumors are referred to as "borderline" because their appearance and behavior under the microscope is between benign and malignant. These tumors are often referred to as carcinomas of low malignant potential because they rarely metastasize or cause death. Even when borderline carcinomas do spread outside the ovary, only 10 - 20% are fatal.

Symptoms

Ovarian cancer used to be considered a “silent killer." Symptoms were thought to appear only when the cancer was in an advanced stage. Now, experts know this is not true -- even early-stage ovarian cancer can produce symptoms.

In June 2007, the Gynecologic Cancer Foundation, the Society of Gynecologic Oncologists, and the American Cancer Society released a consensus statement concerning ovarian cancer symptoms. If you have the following symptoms on a daily basis for more than a few weeks, you should see your doctor (preferably a gynecologist):

Bloating
Pelvic or abdominal pain
Difficulty eating or feeling full quickly

Ovarian cancer grows quickly and can progress from early to advanced stages within a year. Paying attention to symptoms can help improve a woman's chances of being diagnosed and treated promptly. Detecting cancer while it is still in its earliest stages can help improve prognosis. Even a few months delay in detection may affect survival.

Other symptoms are also sometimes associated with ovarian cancer. These symptoms include fatigue, indigestion, back pain, pain during intercourse, constipation, and menstrual irregularities. However, according to experts, these symptoms are not as useful in diagnosing ovarian cancer, because they are also commonly experienced by women who do not have cancer.

Based on the symptoms and physical examination, the doctor may order pelvic imaging tests or a CA-125 blood test. If these tests reveal signs of cancer, patients should be referred to a gynecologic oncologist or a surgeon who specializes in female reproductive system cancers.

Causes

About 22,430 new cases of ovarian cancer are expected in the United States in 2007. Evidence suggests that the incidence of ovarian cancer is declining. The average age for the onset of ovarian cancer is about 60, although ovarian cancer can develop in women from the ages of 20 - 90. The lifetime risk of ovarian cancer in women with no family history of the disease is approximately one in 70 (1.4%).

Women with a history of ovarian cancer in one first-degree relative (mother or sister) have an overall 5% risk of developing the disease, but it may be higher in women with specific genetic factors. The majority of women with ovarian cancer have no family history of the disease, however, meaning that genetic inheritance is not the only risk factor.

Genetic mutations causing abnormal cell growth and differentiation are the basis for all cancer. The great majority of genetic defects that cause cancer are due to unknown causes. Most likely overexposure to environmental assaults, or errors that occur during cell division, play a role in many cases.

Several circumstances that create hormonal changes may increase the risk of ovarian cancer.

Number of Ovulations. Risk of ovarian cancer is directly related to the number of times a woman ovulates, which is indicated by the total number of menstrual periods she has had. A lower number of ovulations occur when the menstrual periods are shut off (as in pregnancy), so the risk of developing ovarian cancer is reduced.

The following women have a lower risk for ovarian cancer:

Women with a history of multiple pregnancies.
Women who took birth control pills (these shut off the menstrual period).
Women who breast-fed. (The body usually does not release eggs while a woman is breast-feeding.)

Some researchers theorize that ovarian cancer develops in women with a higher number of ovulations because of persistent damage to the epithelial cells as the egg passes through during ovulation. Researchers postulate that the recurring cell division needed to heal these tiny wounds to the ovaries, month after month and year after year, creates opportunities for errors in cell reproduction that lead to the formation of cancerous cells. Therefore, the more ovulations, the more risk of ovarian cancer. Ovulation temporarily ceases during pregnancy, breast-feeding, and birth control pill use.

Gonadotropins and Fertility Drugs. Gonadotropins are hormones produced in the pituitary gland that stimulate the ovaries to secrete estrogen and cause the follicles to produce and release eggs.

The pituitary is a gland attached to the base of the brain which secretes hormones that govern the onset of puberty, sexual development and reproductive function.

In a few studies, elevated levels of gonadotropins have been associated with an increased risk for ovarian cancer. These hormones are the basis for many fertility drugs, including human menopausal gonadotropin (Pergonal, Repronal, Metrodin) and clomiphene (Clomid, Serophene). Although there has been concern about an increased risk for ovarian cancers in women, a growing body of evidence is finding no higher risk from the drugs themselves. Instead, evidence suggests that ovarian cancers are most likely caused by factors contributing to the infertility -- not the drugs used to treat it.

Hormone Replacement Therapy. Hormone replacement therapy (HRT) appears to increase the risk for ovarian cancer. A 2007 UK study of nearly 1 million women found that women who used HRT for more than 5 years were 20% more likely to develop and die from ovarian cancer than women who had never taken HRT. Another important study, from the U.S. National Cancer Institute, indicated that 5 or more years of combination HRT (estrogen and progestin) increases the risk of ovarian cancer for women who have not had a hysterectomy.

Family history plays a role in 5 - 10% of women who have ovarian cancer. Certain genes are being investigated and identified that are responsible for some of these cases. Depending on the particular genetic type, the lifetime risk for ovarian cancer in women who carry these genes ranges from 16 - 65%.

BRCA1 and 2 Genes. Inherited mutations in genes known as BRCA1 or BRCA2 are now believed to be responsible for 30 - 50% of breast cancers, ovarian cancers, or both in patients with a strong family history of these cancers.

According to some studies, the risks are as follows:

Studies indicate that about 25 - 40% of women who carry the abnormal BRCA1 gene may develop ovarian cancer.
The risk for women with the BRCA2 gene mutation is generally believed to be lower, about 9 - 15%.

The mutated genes are linked to an even higher risk for developing breast cancer. These mutations are present in only about 0.5% of the U.S. population overall but occur in about 2.5% of all Jewish women of Eastern European (Ashkenazi) descent. These mutations are not restricted to the Ashkenazi population and may occur in women of any ethnicity, including women of Asian and African descent.

Either a mother or father can pass down BRCA mutations to the daughter. These mutations may also occur in 5 - 10% of ovarian cancer patients who have no family history of breast or ovarian cancer. A number of studies have suggested that women with BRCA-mutated ovarian cancers tend to have better survival rates than other women.

A 2005 study in the Journal of the National Cancer Institute indicated that women who have a family history of breast cancer, but no history of BRCA genetic mutations, are not at increased risk for ovarian cancer.

Other Genetic Mutations. Women who carry the hereditary nonpolyposis colorectal cancer (HNPCC) gene have about a 9% chance of developing ovarian cancer.

Risk Factors for Inherited Ovarian Cancer. Women are considered at high risk for ovarian cancer if they have:

A first-degree relative (mother, sister, or daughter) with ovarian cancer at any age. The risk increases with the number of affected first-degree relatives.
A first-degree relative (or two second-degree relatives on the same side) with early onset breast cancer (occurring before age 50).
A family member with both breast and ovarian cancer.
A family history of male breast cancer (which might indicate a BRCA2 mutation).
A family history of hereditary nonpolyposis colorectal cancer.

When a woman describes her family history to her doctor, she should include the history of cancer in women on both the mother's and the father's side. Both are significant.

Screening High-Risk Women. It is now possible to test for genetic mutations in the BRCA1 and BRCA2 genes and for hereditary nonpolyposis colorectal cancer (HNPCC) and Peutz-Jeghers syndrome in high-risk women. Any positive result raises difficult issues:

The presence of a mutation in any of these genes does not predict with absolute certainty that either breast cancer or ovarian cancer will occur. The lifetime risk for BRCA1, for example, is significantly higher (up to 40%) than for BRCA2 (about 10 - 15%).
Surgical preventive strategies, which can involve both mastectomy and removal of the ovaries, do not completely eliminate the risk for cancer, since malignant cells may occur in nearby regions. Removal of the ovaries will reduce ovarian cancer risk, however, and may also reduce breast cancer risk in mutation carriers.

Screening Guidelines for BRCA Genes. In 2005, the U.S. Preventive Services Task Force (USPSTF) released updated guidelines for BRCA testing. While women at high risk should be tested, the USPSTF does not recommend routine genetic counseling or testing for BRCA genes in low-risk women (no family history of BRCA1 or BRCA2 genetic mutations).

Most ovarian cancers are the result of genetic mutations that are not inherited but occur from environmental or other factors that cause damage to genetic material over time. Such genetic changes are referred to as sporadic (as opposed to inherited). Genetic alterations that have been observed in ovarian cancers involve the p53 tumor suppressor gene, the HER2/neu gene, and the PIC3KA gene.

Some research indicates that ovarian cancer occurs more often in North America and Northern Europe and among middle-to-upper socioeconomic class women from highly industrialized countries. Ovarian cancer is also much more common in Caucasian women than in African-American women. Japan has a low, but rising, number of ovarian cancer cases. One study observed that when Japanese women immigrate to the United States, they and their daughters have an incidence of ovarian cancer that approaches that of Caucasian women, although another study did not support such findings.

Pregnancy. Women who have never had children are more likely to develop ovarian cancer than women who have had children. The more children a woman has had, the lower her risk for ovarian cancer.

Obesity. Obesity may increase the risk of developing more aggressive types of ovarian tumors. A 2006 study indicated that a higher body mass index was associated with poorer survival.

Endometriosis. Women with endometriosis may have some higher risk for ovarian cancer. However, endometriosis is very common and ovarian cancer is not, so the risk is still very low. Some research suggests that ovarian cancer associated with endometriosis may differ from most ovarian cancer cases and, in fact, have a better outlook.

Click the icon to see an image of endometriosis.

Fat Intake. Fats have been under scrutiny for some time for putting some women at higher risk for ovarian cancer. A review study reported an association between a high intake in animal fats and a greater risk. However, other studies on this subject have found no correlation between fat intake and ovarian cancer.

Prevention

No specific lifestyle factors are proven to protect against ovarian cancer, although the following study results suggest some lower or higher risk:

Some studies have suggested a lower rate of ovarian cancer in women who eat a diet rich in vegetables. The American Cancer Society recommends that women eat 5 servings of fruits and vegetables a day, and limit consumption of high-fat red meat.
A 2005 study of more than 61,000 women suggested that tea consumption may reduce the risk of ovarian cancer. Women in the study who drank at least 2 cups of tea a day (mainly black tea) had a lower risk of ovarian cancer than women who did not drink tea.
Exercise, which protects against many diseases and even some cancers, appears to have no effect on ovarian cancer. However, obesity is associated with poorer ovarian cancer survival. Women who are obese also have a higher risk for breast cancer. Regular exercise is a good idea in any case.
Smokers should quit. Although evidence of an association with ovarian cancer is weak, it is always wise to stop smoking.

In general, factors or behaviors that limit stimulation of the ovaries or inhibit ovulation appear to be protective.

Pregnancy. The more times a woman has been pregnant the less likely she is to develop ovarian cancer. One study indicated that ovarian cancer was reduced by 40% with one pregnancy and by an additional 14% with each subsequent pregnancy.

Breast-feeding. Breast-feeding, even for only 1 - 2 months, may also reduce the risk for ovarian cancer by as much as 40%. A longer duration of breast-feeding does not appear to increase its protective benefits.

Oral Contraceptives and Progestin. Studies have suggested that routine use of birth control pills that contain the female hormones estrogen and progestin, even low-dose forms, reduces a woman's risk of ovarian cancer by about 50% when compared to women who have never taken oral contraceptives. The longer a woman takes oral contraceptives the greater the protection and the longer protection lasts after stopping oral contraceptives.

Click the icon to see an illustrated series detailing the birth control pill.

Pregnant women or women with breast cancer should not take birth control pills. Other conditions that may preclude taking oral contraceptives include:

Liver disease
Migraines
Coronary artery disease and any risk factors for heart disease or stroke (particularly smoking, obesity, high blood pressure, blood clotting disorders, or diabetes)

Tubal Ligation. Tubal ligation, a method of sterilization that ties off the fallopian tubes, has been associated with a decreased risk for ovarian cancer in some -- but not all -- studies.

Click the icon to see an image of tubal ligation.

Surgical removal of the ovaries, called oophorectomy, significantly reduces the risk for ovarian cancer. When it is used to specifically prevent ovarian cancer in high-risk women, the procedure is called a prophylactic oophorectomy. Prophylactic oophorectomy is approximately 95% protective against ovarian cancer. It is sometimes recommended for women at high risk for ovarian cancer. These women generally have the BRCA1 or BRCA2 genetic mutation, or have two or more first-degree relatives who have had ovarian cancer.

Bilateral oophorectomy is the removal of both ovaries. Bilateral salpingo-oophorectomy is the removal of both fallopian tubes plus both ovaries. Several recent studies indicate that salpingo-oophorectomy is very effective in reducing risk for ovarian cancer in women who carry the BRCA1 or BRCA2 mutation.

A 2006 Journal of the American Medical Association study reported that bilateral salpingo-oophorectomy reduces ovarian cancer risk by 80% for women with certain mutations in the BRCA1 and BRCA2 genes. A study presented at the 2006 meeting of the American Society of Clinical Oncology (ASCO) indicated that this procedure is most effective for reducing ovarian cancer risk in women with the BRCA1 gene mutation. For women with BRCA2 gene mutation, the procedure was better at reducing the risk for breast cancer.

Even after oophorectomy, women in high-risk groups for ovarian cancer still have a risk for the development of cancer in the peritoneum (the sac inside the abdomen that holds the intestines, uterus, and ovaries).

Premenopausal women should realize that oophorectomy causes immediate menopause, which poses a risk for several health problems, including osteoporosis, heart disease, and reduction in muscle tone. Estrogen replacement can help offset these problems. Women who have a bilateral oophorectomy and do not receive hormone replacement therapy may experience more severe hot flashes than women who enter menopause naturally.

Diagnosis

Up to 95% of women diagnosed with ovarian cancer will survive longer than 5 years if their cancers are treated before they have spread beyond the ovaries. Unfortunately, there are no screening tests for ovarian cancer that are the equivalent to mammography for early detection of breast cancer. Therefore, only about 25% of ovarian cancer cases are diagnosed at such early stages. It is possible to perform genetic screening in high-risk women, but this raises some complex issues.

Every woman should have a regular annual examination with her doctor that includes:

Pelvic examination. Routine exams called bimanual pelvic examinations are a reasonable precaution, although they are not perfect screening methods due to their low sensitivity. This exam can be performed two ways. In the more common method, the doctor inserts two fingers into the vagina while palpating the abdomen with the other hand. The other method, called a bimanual rectovaginal exam, involves the insertion of one finger into the vagina and another into the rectum.

Either exam enables the doctor to assess the size of the ovaries as well as the contour and mobility of the uterus and to feel for masses and growths. The rectovaginal exam may reveal rectal lesions that may otherwise go unnoticed and is particularly important for women over 50. A mass felt on pelvic exam often requires further evaluation by ultrasound and sometimes requires surgery to make a definitive diagnosis.

Pap smear. This test is specifically designed to detect cervical cancer. In very rare instances, however, it may reveal abnormal ovarian cells, which might indicate the presence of an ovarian cancer.

Click the icon to see an image of a pap smear.

Unfortunately, ovarian cancer rarely produces changes that are detectable during a regular checkup.

An estimated 290,000 women are hospitalized each year in the United States because of ovarian growths or lesions. Many more women find out about some ovarian abnormality during their annual Ob/Gyn check up. The vast majority of conditions are noncancerous. They include:

Benign functional ovarian cysts
Abscesses and infection
Fibroids

Click the icon to see an image of a fibroid tumor.

Endometriosis
Polycystic ovaries

Click the icon to see an image of a polycystic ovary.

Ectopic pregnancies

Click the icon to see an image of an ectopic pregnancy.

Meig syndrome (which involves a benign ovarian growth associated with fluid buildup in the abdomen and around the lungs)
Ovarian hyperstimulation syndrome following fertility treatments.

Once a growth is detected, additional tests [below] may help the doctor gauge the risk for it being cancerous.

Ultrasound. Ultrasound is a noninvasive diagnostic tool that can evaluate tumors and masses discovered during the rectovaginal exam:

Typically, a probe is placed in the vagina and emits sound waves (ultrasound). The sound waves bounce off tissues, organs, and masses in the pelvic cavity. These echoes are collected and converted into a picture of the area called a sonogram.

Click the icon to see an image of transvaginal ultrasound.

The ultrasound probe may also be placed on abdominal walls above the ovaries (transabdominal ultrasound), but it does not provide as clear a picture of the ovaries. Healthy tissue, fluid-filled cysts, and solid tumors produce different sound waves.

Ultrasound is not helpful for identifying early-stage ovarian cancer in high-risk women. (Researchers hope that blood tests for protein markers may eventually provide a better method for diagnosing early-stage ovarian cancer.) In addition, ultrasound does not provide enough specific information to reliably determine which abnormal masses are cancerous or noncancerous.

Studies suggest that small so-called simple cysts (fluid-filled without an associated mass) are usually noncancerous, particularly when they appear in premenopausal women whose blood tests for the protein CA-125 are normal. Such women are sometimes given oral contraceptives and observed for a few months to see if the cyst goes away.
Postmenopausal women with small simple cysts and normal CA-125 levels may sometimes be observed for a time if they have no other risk factors or symptoms of ovarian cancer.
In contrast, a "complex" cyst (one that shows a mass or other abnormalities) is often surgically removed, since it has a higher chance of being malignant. Only a small percentage of these cysts turn out to be cancerous. (In one study 6% of complex cysts were actually cancerous.)

Click the icon to see an image of an ovarian cyst.

Other Imaging Techniques. Other imaging techniques are less common for the diagnosis or evaluation of suspected ovarian cancer but may help determine if cancer has spread to other parts of the body:

Computed tomography (CT). Computed tomography records x-ray absorption rates of tissue and bone. These data is converted into clear images on a screen. CT scans help determine if cancer has spread to the lymph nodes, abdominal organs, abdominal fluid, and the liver.

Click the icon to see an image of a CT scan.

Magnetic resonance imaging (MRI). MRI creates multiple cross-sectional images of the pelvis and abdominal organs, which are assembled into three-dimensional images. An MRI is not usually used to diagnose ovarian cancer, but may help determine if cancer has spread to the brain or spinal cord.

Click the icon to see an image of a MRI scan.

Chest x-rays. Find cancer that has spread to the lungs.

Click the icon to see an image of an x-ray machine.

CA-125 is a protein that is secreted by ovarian cancer cells and is elevated in over 80% of patients with ovarian cancer. The CA-125 blood test is not approved for screening in the general population. Oncologists will usually only obtain a blood test for this protein if ovarian cancer is strongly suspected or has been diagnosed. In general, a CA-125 level is considered to be normal if it is less than 35 U/mL (microns per milliliter). The test may also be useful for evaluating tumor growth and predicting survival in patients with recurrent cancer who have been treated with topotecan or paclitaxel-carboplatin chemotherapy regimens.

The test is not useful for diagnosis or early screening, however. In about half of women with very early ovarian cancer, CA-125 levels are not elevated above the normal standard at all. Furthermore, an elevated level can be caused by a number of other conditions including:

Endometriosis (which may be a risk factor for ovarian cancer)
Fibroids
Noncancerous ovarian cysts
Pregnancy
Pelvic inflammatory disease
Liver diseases
Other tumors, such as breast, colon, lung, and pancreatic cancers
Age and menstrual status can also affect the levels of CA-125

Research is under way to find better tests that will detect this cancer in early stages.

Proteomics. A promising new approach relies on a technique called proteomics. Proteomics is the analysis of certain proteins. In this approach, researchers are looking at a unique pattern of proteins produced by ovarian cancer cells. Studies suggest this set of proteins serves as an early biomarker for detecting ovarian cancer. Scientists at the National Cancer Institute (NCI) and Food and Drug Administration (FDA) have developed a blood test to check for the presence of these abnormal proteins. In one study, the proteomics tool identified 100% of patients with ovarian cancer and incorrectly diagnosed cancer in only 3 out of 66 of women who were actually cancer-free. A clinical trial is now under way comparing the proteomics test to the CA-125 test. OvaCheck, another investigational ovarian cancer blood test, is based on principles similar to the NCI and FDA platform, but is being developed independently by a private corporation.

Osteopontin. Scientists are also looking into the possibility that the protein osteopontin may be a biomarker for ovarian cancer. Studies have shown that osteopontin is overexpressed in tumors and serum of women with ovarian cancer.

Other Biomarkers. Researchers have also had preliminary success with a blood test that measures osteopontin along with three additional protein markers in blood: leptin, prolactin, and insulin-like growth factor-II. In early trials, prolactin and osteopontin levels were significantly elevated in women with early ovarian cancer. The other two proteins were greatly reduced. When measured collectively, these four proteins completely distinguished between healthy women and those with early ovarian cancer, according to the results published in the May 2005 journal of the Proceedings of the National Academy of Sciences.

An exploratory surgical procedure called laparotomy generally is required for the definitive diagnosis of ovarian cancer. Laparotomy involves the following steps:

It requires general anesthesia and employs standard surgical techniques to make a vertical, midline incision from the pubic bone to the navel.
Such an incision ensures careful evaluation of the entire abdominal area. After the incision is made, the surgeon assesses the fluid and cells in the abdominal cavity.
During this procedure, cysts or other suspicious areas will be removed and biopsied (tested for cancer).
If the lesion is cancerous, the surgeon continues with a process called surgical staging to find out how far the cancerous tumor has spread and to remove the ovaries and any cancerous tissue.

Investigators are also studying laparoscopy -- instead of more invasive surgery -- for initial surgical evaluation (staging).

Click the icon to see an image of pelvic laparoscopy.

Prognosis

Ovarian cancer ranks behind lung, breast, and colorectal cancer as the fourth most common cause of female cancer death in this country. About 15,280 American women are expected to die from ovarian cancer in 2007.

In general, overall 5-year survival rates (all stages combined) increased from 37% in 1974 to greater than 50% currently. Survival rates vary depending on different factors, including age and the stage at which it is detected.

The survival rate also varies according to the cancer stage:

Five-year survival rates are over 90% if the cancer is still confined to the ovary at diagnosis. However, only 19% of ovarian cancers are found at this stage.
If the cancer has spread to nearby regions in the pelvis, the survival rate drops to 60 - 80%.
If the cancer has spread to sites outside the pelvis, the 5-year survival rates are only 10 - 30%.

Unfortunately, most patients with ovarian cancer are not diagnosed until the disease is advanced. This usually means the cancer has spread to the upper abdomen. In order to establish a prognosis and determine treatment, the doctor needs to know the cell type, stage, and grade of the disease.

About 90% of ovarian epithelial cancers fall into one of four major subtypes based on their origin and shape as viewed under a microscope:

Serous. (This is the most common type.)
Endometrioid. (This is sometimes associated with endometriosis and tends to have a more favorable outlook.)
Mucinous. (The presence of malignant mucinous cells indicates a poorer outlook if the disease is advanced.)
Clear cell. (Clear cell carcinomas are the most difficult to treat even when the malignancy is still confined to the ovary.)

The remaining 10% of common epithelial cancers are referred to as undifferentiated, because their exact cell of origin cannot be determined microscopically. These epithelial ovarian carcinomas tend to grow and spread quickly.

Cancers are staged (I through IV) according to whether they are still localized (remaining in the ovary) or have spread beyond the original site.

Tumors are also graded according to how well or poorly organized they are (their differentiation). Ovarian tumors are graded on a scale of 1, 2, or 3. Grade 1 tends to closely resemble normal tissue and has a better prognosis than grade 3, which indicates very abnormal, poorly defined tissue.

Age. In general, younger women have a better prognosis than older women although stage and grade of tumor also are important to the prognosis.

BRCA Carriers. Some studies have reported that women who carry mutated BRCA genes may have better survival rates than non-carriers. The survival advantages may be due to having a slower course or being more responsive to therapies than sporadic ovarian cancers, although this is controversial.

Angiogenesis. Experimentally, the level of biochemicals stimulating the formation of new blood vessels that support tumor growth (angiogenesis) appears to correlate with prognosis. The more angiogenic factors present in a tumor population, the more new blood vessels will form, encouraging both tumor growth and metastasis.

Overexpression of p53 Mutations. High levels of a defective p53 gene (which regulates cell growth) are associated with a poorer outlook.

Women who survive ovarian cancer have a high risk for psychological stress. Support groups can be very helpful.

Treatment

In general, the course of treatment is determined by the stage of the cancer. Stages range from I to IV based on the cancer's specific characteristics, such as whether it has spread beyond the ovaries.

In stage I, the cancer has not spread. It is confined to one ovary (stage IA) or both ovaries (stage IB). In stages IA and IB, the ovarian capsules are intact, and there are no tumors on the surface. Stage IC can affect one or both ovaries, but the tumors are on the surface, or the capsule is ruptured, or there is evidence of tumor cells in abdominal fluid (ascites). The overall 5-year survival rate for stage IA or IB can be as high as 90%, but the presence of other factors may affect this rate. For example, non-clear-cell well-differentiated cancer cells or borderline tumors have a favorable prognosis. Clear cells or those that are more poorly differentiated have a worse outlook. Stage IC has a poorer outlook than the earlier stages. It is very important that women receive an accurate staging assessment, including a pathologic review conducted by a gynecologic pathologist.

Treatment Options: Treatment for most women with stage IA and IB includes surgical removal of the uterus and both ovaries and fallopian tubes (total hysterectomy and bilateral salpingo-oophorectomy), partial removal of the omentum (the fatty layer that covers and pads organs in the abdomen), and surgical staging of the lymph nodes and other tissues in the pelvis and abdomen. (Carefully selected premenopausal women in Stage I with the lowest-grade tumors in one ovary may sometimes be treated only with the removal of the diseased ovary and tube in order to preserve fertility.) Patients with stage IA or B disease, grade 1 (or sometimes grade 2), usually do not need further therapy after surgery. However, higher risk patients (stage IC, stage I/grade 3) are usually treated with platinum-based chemotherapy to reduce their risk of subsequent relapse.

A 2005 study suggested that adjuvant platinum-based chemotherapy (chemotherapy added to surgical treatment) can improve survival and reduce cancer recurrence. With the considerable adverse effects of chemotherapy, more research is needed to determine which stage 1 patients would benefit most from this adjuvant treatment.

Click the icon to see an illustrated series detailing hysterectomy.

In stage II, the cancer has spread to other areas in the pelvis. It may have advanced to the uterus or fallopian tubes (stage IIA), or other areas within the pelvis (stage IIB), but is still limited to the pelvic area. Stage IIC indicates capsular involvement, rupture, or positive washings (that is, they contain malignant cells). The 5-year survival rate for stage II is about 60 - 80%.

Treatment Options: Surgical management for most women in this stage is total hysterectomy, bilateral salpingo-oophorectomy, and removal of as much cancer in the pelvic area as possible (tumor debulking). Surgical staging should be performed.

After the operation, treatment with chemotherapy is usually necessary in an attempt to eradicate residual cancer and decrease the chance for relapse.

In stage III, one or both of the following are present: (1) The cancer has spread beyond the pelvis to the omentum (the fatty layer that covers and pads organs in the abdomen) and other areas within the abdomen, such as the surface of the liver or intestine. (2) The cancer has spread to the lymph nodes. The average 5-year survival rate for this stage is 20%.

Click the icon to see an image of the lymph system located near the ovaries.

Treatment Options: Surgical management for most women in this stage is total hysterectomy and bilateral salpingo-oophorectomy and removal of as much cancer as possible (tumor debulking).

Following surgery, chemotherapy is usually needed for any remaining cancer cells. Several approaches are under investigation for reducing high rates of recurrence (about 80%). These approaches include the following:

Experimental chemotherapy drugs
Anti-angiogenic therapies
Gene and biological therapies
Intraperitoneally administered high-dose chemotherapy
Neoadjuvant therapy (chemotherapy before surgery)
High-dose chemotherapy
Peripheral blood stem cell transplantation (to date this approach has proven to be very toxic with no convincing improvement in survival)

Stage IV is the most advanced cancer stage. The cancer may have spread to the inside of the liver or spleen. There may be distant spreading of the cancer, such as ovarian cancer cells in the fluid around the lungs. The average 5-year survival rate for this stage is less than 10%.

Treatment Options: Tumor debulking may be performed before chemotherapy.

Although not standard practice in the United States, a surgical procedure called retroperitoneal lymphadenectomy is sometimes performed. This procedure involves removal of aortic and pelvic lymph nodes from the rear of the abdomen. Results from a 2005 randomized controlled trial suggest that while retroperitoneal lymphadenectomy does help reduce cancer progression, it does not prolong survival.

Treatment Options: If ovarian cancer returns, chemotherapy is the mainstay of treatment, although it is not generally curative in the setting of relapsed disease.

If the interval between the last platinum-containing chemotherapy (carboplatin or cisplatin) and relapse is long (greater than 6 months), it is reasonable to attempt a repeat trial of platinum-based chemotherapy, with or without paclitaxel.

If the interval is short, or if these drugs fail to control the tumor, other second-line drugs may be useful in achieving a response. They include topotecan, liposomal doxorubicin, etoposide, docetaxel, gemcitabine, or tamoxifen. There is no evidence that second-line drug combinations are any more effective than single drugs, although they are generally more toxic.

Clinical trials using various investigative approaches are under way. It is not clear if there is a role of a second debulking surgical procedure. A 2004 study published in the New England Journal of Medicine found that additional debulking did not prevent cancer progression or prolong survival.

Surgery

Surgery for ovarian cancer uses laparotomy, a major abdominal operation. It is the primary diagnostic tool for ovarian cancer and also plays a role in treatment. Complete surgical intervention includes the following:

Surgical staging (examining all tissues and organs in the pelvic cavity for accurate assessment of the disease stage).
Debulking (removal of as much of the cancerous tissue as possible). This is an important component of ovarian cancer management and should be performed by a surgeon trained in cancer surgery techniques.

Patients with ovarian cancer should see a qualified gynecologic oncologist (a surgical specialist in female reproductive cancers) and a qualified medical oncologist with special expertise in the chemotherapeutic management of gynecologic cancer. Studies indicate that it is best for patients, especially those with advanced-stage ovarian cancer, to receive care at medical centers that specialize in cancer treatment and surgery.

According to a 2007 study, 1 in 3 patients with ovarian cancer fails to receive recommended surgical treatment. Women over age 70, poor patients, and African-American or Hispanic patients were least likely to receive proper treatment. Women who were not treated by gynecologic oncologists were also less likely to receive optimal surgical care.

Surgical staging includes biopsies of the following:

The undersurface of the diaphragm
The omentum (the fatty layer that covers and pads organs in the abdomen)
Sometimes lymph nodes along the abdominal aorta

An abdominal wash is performed by injecting a salt solution into the abdominal cavity to facilitate microscopic detection of cancerous cells not visible to the naked eye. The surgeon then evaluates the pelvis and abdomen and removes suspected cancer tissue. The entire affected ovary is usually removed (oophorectomy) during surgical staging if the surgeon believes it might be cancerous. The tissue is sent to a laboratory for an immediate evaluation called a frozen section diagnosis. The doctor will also examine the bowel and bladder for cancer invasion.

If the tumor is in an early stage on one ovary and a young woman wants to retain her ability to have children, the surgeon may be able to remove only the affected ovary and perform surgical staging. Chemotherapy follows in selected patients. Studies indicate that in carefully selected young patients, many can expect normal fertility afterward. However, most women with ovarian cancer are not candidates for this procedure.

The goal of surgery is to remove as much of the tumor as possible (called debulking or cytoreductive surgery) for improving symptoms and increasing the effectiveness of chemotherapy. The surgery itself is typically performed as follows:

In premenopausal women in later stages, and in all postmenopausal women, the surgeon usually removes the uterus (a hysterectomy) and both ovaries and fallopian tubes (a bilateral salpingo-oophorectomy).
In addition, the surgeon usually removes the omentum (omentectomy), any growths on the diaphragm and intestine, and possibly certain lymph nodes (lymphadenectomy).

If surgical staging reveals that the cancer has invaded the bowel, a portion of the intestine may have to be removed as well.

Postoperative Care. If possible, a patient should ask a family member or friend to help out for the first few days at home. The following are some of the precautions and tips for postoperative care:

For 1 - 2 days after surgery, the patient is given medications to prevent nausea and painkillers to relieve pain at the incision site.
As soon as the doctor recommends it, usually within a day of the operation, the patient should get up and walk in order to help prevent pneumonia, reduce the risk of blood-clot formation, and to hasten recovery.
Walking and slow, deep breathing exercises may help to relieve gas pains, which can cause major distress for the first few days.
Coughing can cause pain, which may be reduced by holding a pillow over a surgical abdominal wound or by crossing the legs after vaginal surgery.
Patients are advised not to lift heavy objects (including small children), not to douche or take baths, and not to climb stairs or drive for several weeks.
For the first few days after surgery, many women weep frequently and unexpectedly. These mood swings may be due to depression from the loss of reproductive capabilities and form abrupt changes in hormones, particularly if the ovaries have been removed.

The patient should talk to their doctor about when they can start exercise programs that are more intense than walking. The abdominal muscles are important for supporting the upper body, and recovering strength may take a long time. Even after the wound has healed, the patient may experience an on-going feeling of overall weakness, which can be demoralizing, particularly in women used to physical health. Some women do not feel completely well for as long as a year. Others may recover in only a few weeks.

Complications Following the Procedure. Minor complications after hysterectomy are very common:

Women may develop minor and treatable urinary tract infections.
There is usually light vaginal bleeding and pain after the operation, which can be well-controlled with pain medications.

More serious complications are uncommon but patients should be aware of their symptoms and call the doctor immediately if they occur:

Infection occurs in 10 - 15% of patients, with the risk being higher with abdominal than with vaginal surgery. Symptoms might include continuing or increasingly severe pain, fever, heavy discharge, or bleeding. Antibiotics given at the time of surgery help to reduce this risk. Other risk factors for infection include obesity, a longer than normal operative time, and low socioeconomic status.
There is a slight risk for small blood clots, usually in veins of the legs (thrombophlebitis). A sudden swelling or discoloration in the leg can indicate this condition and requires immediate medical attention.

This picture shows a red and swollen thigh and leg caused by a blood clot (thrombus) in the deep veins in the groin (iliofemoral veins), preventing normal return of blood from the leg to the heart.

Other serious and even life-threatening complications, though rare, include pulmonary embolism (blood clots that travel to the lung), abscesses, perforation of the bowel, fistulas (a passage that bores from an organ to the skin or to another organ), or dehiscence (the opening of the surgical wound).

Treating Menopausal Symptoms and Premature Menopause after Hysterectomy. After hysterectomy, premenopausal women usually have hot flashes, a symptom of menopause. Symptoms come on abruptly and may be more intense than those of natural menopause. Symptoms include hot flashes, vaginal dryness and irritation, and insomnia. A significant number of women gain weight.

The most important complications that occur in women who have had their ovaries removed are due to estrogen loss, which places women at risk for osteoporosis (loss of bone density) and a possible increase in risks for heart disease. Women have typically taken hormone replacement therapy (HRT) after surgery if their ovaries have been removed. There have been concerns however about health risks, including the risk for breast cancer and stroke, that have now limited its use. Risks in premenopausal women who have had a hysterectomy have not yet been clarified. Several nonhormonal drugs, however, can help protect both bones and heart.

After chemotherapy is completed, surgeons used to perform an exploratory procedure called second-look laparotomy. Although this procedure is the most sensitive way of detecting residual cancer that remains after chemotherapy, it has no proven impact on patient survival. Its use is restricted to patients being treated in clinical trials.

Bowel obstruction is common in ovarian cancer. Surgery can be very helpful for selected patients with this problem.

Medications

Following surgery, patients (other than those with early-stage, low-grade disease) usually have chemotherapy. Unlike surgery and radiation, which treat the cancerous tumor and the area surrounding it, drug therapy destroys rapidly dividing cells throughout the body, so it is as systemic therapy.

Ovarian cancers are very sensitive to chemotherapy and often respond well initially. Unfortunately, in most cases, ovarian cancer recurs. With treatment advances, however, more than half of women now survive 5 years or longer. Doctors are now approaching this disease as a chronic and potentially long-term illness that requires the following:

Identifying the disease recurrence as soon as possible
Administering treatments that are as effective as possible without causing suffering
Partnering with the patient in determining her own best course

Standard Chemotherapy. The standard initial chemotherapy uses a combination of:

A platinum-based drug, such as carboplatin (Paraplatin) or cisplatin (Platinol). Carboplatin is preferred over cisplatin in the combination. Carboplatin works as well as cisplatin but is less toxic and can be administered in a more convenient, outpatient regimen.
A taxane, such as paclitaxel (Taxol) or docetaxel (Taxotere). Currently paclitaxel is the drug most often used as initial therapy in combination with a platinum drug. Docetaxel, however, is less toxic to the nervous system (but has more adverse effects on blood cell production). Taxotere is now commonly substituted for Taxol.

Paclitaxel-carboplatin chemotherapy will reduce tumor size in about 70% of women. Older women (over age 60) may benefit as much as younger ones from this regimen.

Other drugs that may prove to be useful first-line treatments are gemcitabine (Gemzar) and doxorubicin (Doxil). A third drug, topotecan (Hycamtin), is not helpful for first-line treatment for advanced ovarian cancer, according to recent studies. In an important 2006 study, topotecan following paclitaxel-carboplatin therapy did not help prolong survival, and it caused many serious side effects, including anemia and infections.

Chemotherapy Drugs Studied for Relapsed or Refractory Cancer. Unfortunately, some ovarian tumors are resistant to platinum drugs. Even in patients who respond, the disease eventually becomes resistant to the first-line drugs, and the cancer returns. Various approaches for increasing responsiveness to these drugs are being investigated. Investigators are studying two approaches for preventing relapse after remission:

Developing more effective drug combination regimens to increase initial response rates and duration of the response.
Developing maintenance drugs to prevent or delay relapse.

Once cancer recurs or continues to progress, several second-line chemotherapies are available or under investigation. The following lists some drugs that are being used, usually as single drugs, for relapsed or refractory cancers:

Nucleoside analogs, including gemcitabine (Gemzar). In 2006, gemcitabine was approved as a treatment for recurrent ovarian cancer. It is used in combination with carboplatin for women with advanced ovarian cancer that has relapsed at least 6 months after initial therapy.
Paclitaxel or carboplatin alone or in combination. A landmark study published in the July 2003 Journal of Clinical Oncology, found that additional cycles of paclitaxel significantly delayed disease progression in women with advanced ovarian cancer.
Pegylated liposomal doxorubicin (Doxil) is a form of standard doxorubicin (Adriamycin) that remains in the bloodstream longer, tends to spare the bone marrow, and moves selectively through the tumor. It is showing promise in clinical trials and also may have fewer toxic effects than standard doxorubicin and other drugs used for ovarian cancer. Studies show that peglyated liposomal doxorubicin is very well tolerated, with a total response rate of about 20 - 30% in patients with recurrent cancer. This compares favorably with other drugs, such as topotecan, carboplatin, and taxol.
Topoisomerase I inhibitors, including topotecan (Hycamtin) and irinotecan (Campto).
Topoisomerase II alpha inhibitors, including etoposide (VePesid).
Alkaloids, including vinorelbine (Navelbine).
Hormonal drugs: tamoxifen (Nolvadex) or anastrozole (Arimidex).
Valspodar and capecitabine (Xeloda) are oral drugs that may help improve response to other drugs, although data are preliminary.

In addition to studying individual drugs in different combinations, investigators are looking for the optimal sequence, dosages and timing of administering them. In general, the typical regimen is as follows:

Paclitaxel and carboplatin are administered in an outpatient clinic within several weeks of the surgery.
Each treatment takes about 4 - 5 hours to complete.
It is repeated every 3 weeks for a total of six times. (Each 3-week interval is known as a cycle of chemotherapy.)

Such chemotherapy is usually administered intravenously (by vein). However, an important 2006 study in the New England Journal of Medicine found that patients with Stage III ovarian cancer who received intraperitoneal chemotherapy had a significant survival advantage compared with patients who received standard intravenous chemotherapy. (Intraperitoneal chemotherapy involves administering the drugs directly into the abdominal cavity.) Patients in the intraperitoneal group did have more severe side effects than those who had intravenous chemotherapy. Researchers are continuing to investigate ways to reduce these side effects. Another 2006 study noted that intraperitoneal chemotherapy requires careful catheter insertion and maintenance, and that doctors need to be well trained to perform this procedure.

Side effects occur with all chemotherapeutic drugs. They are more severe with higher doses and increase over the course of treatment. Some may be long-lasting. In one study of ovarian cancer survivors, 20% had long-term treatment side effects, such as gynecologic and abdominal problems. Even so, most enjoyed a high quality of life that was comparable to other cancer survivors and peers without a history of cancer.

Common side effects include:

Nausea and vomiting. Drugs known as serotonin antagonists, especially ondansetron (Zofran), can relieve these side effects in nearly all patients given moderate drugs and most patients who take more powerful drugs.
Diarrhea
Temporary hair loss
Weight loss
Fatigue
Depression

Serious short- and long-term complications can also occur and may vary depending on the specific drugs used. The following list includes some of these complications and a few of their treatments:

Anemia. Erythropoietin stimulates red blood cell production and can help reduce or prevent this side effect. It is available as epoetin alfa (Epogen, Procrit) and darbepoetin alfa (Aranesp). Aranesp stays in the blood longer than epoetin alfa, so fewer injections are needed.
Increased chance for infection from severe reduction in white blood cells (neutropenia). The addition of a drug called granulocyte colony-stimulating factor (filgrastim and lenograstim) is very helpful in reducing the risk for severe infection in selected patients.
Liver and kidney damage.
Abnormal bleeding (thrombocytopenia).
Allergic reaction, particularly to platinum-based drugs.
Rarely, secondary cancers such as leukemia.
Between a quarter and a third of women report problems in concentration, motor function, and memory. These problems may be long-term and may be due to reductions in estrogen levels after treatments.
Cumulative doses of anthracyclines can damage heart muscles over time and increase the risk for heart failure. An encapsulated form doxorubicin (Myocet, Doxil) may reduce the risk for toxic effects on the heart.
Taxanes can cause a drop in white blood cells and possible problems in the heart and central nervous system. Allergic reactions can occur. Talking a corticosteroid before taxane administration can help prevent such reactions. Taxane therapy may also cause severe joint and muscle pain in some patients, which is relievable with corticosteroids.

Physical Exam and CA-125 Blood Test. During treatment, the effectiveness of the chemotherapy is evaluated primarily with a physical examination and the CA-125 blood test. Falling CA-125 levels indicate effective treatment and persistently elevated levels indicate resistance to the chemotherapy.

Second Look Laparotomy. Second-look laparotomy is sometimes considered after completion of chemotherapy for patients who are participating in clinical trials.

Comparative Computed Tomography Scans. Another method for evaluating the success of chemotherapy is to compare computed tomography (CT) scans of the pelvis and abdomen before and after chemotherapy to check the size of any residual tumors that persisted after the original surgery. CT scanning is not always required, however.

Positron Emission Tomography ). Positron emission tomography (PET) scans have no proven role in the management of patients with ovarian cancer. More study is needed to determine their utility in diagnosing relapsed disease.

Any patient with ovarian cancer is a candidate for clinical trials. In addition to testing high-dose or combinations of chemotherapy, drugs with unique actions are being investigated.

Anti-angiogenesis drugs. Angiogenesis, the formation of new blood vessels that feed the growth of a cancerous tumor, is a critical process in the spread of ovarian cancer. Drugs that block this process are under investigation for ovarian cancer. Some of these drugs target vascular endothelial growth factor (VEGF), a protein involved in tumor cell growth. Results of a phase II study, presented at the 2007 meeting of the American Society of Clinical Oncology, indicated that the anti-angiogenesis drug aflibercept (VEGF-TRAP) may benefit patients with epithelial ovarian cancer who are resistant to platinum-based chemotherapy. Such drugs include thalidomide, gefinitib (Iressa), and carboxyamido-triazole (CAI).

Aromatase inhibitors. Aromatase inhibitors block aromatase, an enzyme that is a major source of estrogen in many body tissues. Aromatase inhibitors are used for treatment of estrogen-sensitive breast cancer. These drugs include anastrozole (Arimidex) and letrozole (Femara). Studies indicate that they may provide an alternative to chemotherapy for types of ovarian cancers that are responsive to anti-estrogen hormonal therapy.

Multiple signal transduction regulators. Phenoxodiol is an multiple signla transduction regulator that is being developed as a broad-spectrum anti-cancer drug. It is currently being evaluated in phase III clinical trials, in combination with other drugs, such as carboplatin, for its ability to shrink tumors or stop tumor growth in women with ovarian or fallopian cancer who have failed other forms of chemotherapy.

HER Dimerization Inihibitors. Pertuzumab (Omnitarg) is the first of a new class of drugs called HER dimerization inhibitors. It is designed to inhibit tumor growth for tumors that express the HER2 receptor protein. Pertuzumab is currently in phase II trials in combination with gemcitabine for women with platinum-resistant ovarian, peritoneal, or fallopian cancer.

Immunotherapy. Several therapies under investigation use the body's immune response to attack ovarian cancer cells. Experimental immunotherapies include vaccines designed to treat -- not prevent -- cancer. Some of these vaccines use specially designed antibodies (called monoclonal antibodies, or MAbs) to boost the immune responses against tumor-associated factors, such as CA125 or HER-2/neu. Vaccine therapy is still in early-stage clinical research and is being studied in combination with various chemotherapy drugs.

Epothilones. Epothilones are a new class of anti-cancer drugs that are similar to taxanes (paclitaxel) but are more potent. One of these drugs, ixabepilone (BMS-247550), is being studied for ovarian cancer.

Radiation Therapy

Radiation therapy is not typically used in ovarian cancer. This is because radiation would need to be given to the entire abdomen and pelvis, increasing its toxicity. Radiation is sometimes useful to treat isolated areas of tumor that are causing pain and are no longer responsive to chemotherapy.

Resources

www.cancer.gov -- National Cancer Institute
www.cancer.org -- American Cancer Society
www.aacr.org -- American Association for Cancer Research
www.asco.org -- American Society of Clinical Oncology
www.plwc.org -- People Living with Cancer
www.ovarian.org -- National Ovarian Cancer Coalition
www.ovariancancer.org -- Ovarian Cancer National Alliance
www.sgo.org -- Society of Gynecologic Oncologists
www.wcn.org -- Women's Cancer Network
www.ovariancancer.com -- The Gilda Radner Familial Ovarian Cancer Registry
www.cancer.gov/clinicaltrials -- Find clinical trials

References

Beral V; Million Women Study Collaborators; Bull D, Green J, Reeves G. Ovarian cancer and hormone replacement therapy in the Million Women Study. Lancet. 2007 May 19;369(9574):1703-10.

Bristow RE, Santillan A, Diaz-Montes TP, Gardner GJ, Giuntoli RL 2nd, Meisner BC, et al. Centralization of care for patients with advanced-stage ovarian cancer: a cost-effectiveness analysis. Cancer. 2007 Apr 15;109(:1513-22.

Goff BA, Mandel LS, Drescher CW, Urban N, Gough S, Schurman KM, et al. Development of an ovarian cancer symptom index: possibilities for earlier detection. Cancer. 2007 Jan 15;109(2):221-7.

Goff BA, Matthews BJ, Larson EH, Andrilla CH, Wynn M, Lishner DM, et al. Predictors of comprehensive surgical treatment in patients with ovarian cancer. Cancer. 2007 May 15;109(10):2031-42.

Lacey JV Jr, Brinton LA, Leitzmann MF, Mouw T, Hollenbeck A, Schatzkin A, et al. Menopausal hormone therapy and ovarian cancer risk in the National Institutes of Health-AARP Diet and Health Study Cohort. J Natl Cancer Inst. 2006 Oct 4;98(19):1397-405.

[No authors listed] An experiment in earlier detection of ovarian cancer. Lancet. 2007 Jun 23;369(9579):2051.

Smyth JF, Gourley C, Walker G, MacKean MJ, Stevenson A, Williams AR, et al. Antiestrogen therapy is active in selected ovarian cancer cases: the use of letrozole in estrogen receptor-positive patients. Clin Cancer Res. 2007 Jun 15;13(12):3617-22.

Review Date:
10/16/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Infertility in men

FitSugar — Wed, 08 Oct 2008 17:35:50 -0700

In This Report

Highlights
Introduction
Male Reproductive System...
Sperm Abnormalities
Causes
Diagnosis
Treatment
Assisted Reproductive Techn...
Complications of Assisted R...
Other Treatments
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

New At-Home Fertility Test Kit

Fertell, the first at-home fertility test kit, became commercially available in June 2007. The Fertell kit contains tests to screen for both male and female infertility. Men can test their semen for concentrations of motile sperm, while women can test their urine for levels of follicle-stimulating hormone (a marker for egg quality). Results are available in fewer than 90 minutes and, according to the test kit's manufacturer, are 95% accurate. However, Fertell does not screen for all types of infertility problems and should not be used as a replacement for a complete evaluation by a doctor.

Intracytoplasmic Sperm Injection May Be Overused

Use of intracytoplasmic sperm injection (ICSI), in combination with in vitro fertilization (IVF), has increased 5-fold over the past decade, even though the proportion of men treated for male infertility has remained the same. This increase suggests that doctors are now using ICSI to treat problems other than male infertility, according to a 2007 study in the New England Journal of Medicine. Some doctors recommend ICSI for women who have failed IVF cycles or who have few or poor-quality eggs. According to the Society for Assisted Reproductive Technology, there is little evidence that ICSI can help couples conceive when male infertility is not a factor.

Infertility and Birth Defects

Although there has been concern that assisted reproductive technologies (ART) may increase the risk for birth defects, infertility itself may be a risk factor, regardless of whether ART is used. Even children born to infertile couples who do not use ART have a slightly increased risk for birth defects, indicates a 2006 study in the British Medical Journal.

Varicocele Embolization

Varicocele embolization, a minimally invasive surgical approach to varicocele repair, can help improve sperm count and motility, according to research presented at the 2006 annual meeting of the Radiological Society of North America. Varicoceles (varicose veins in the testicles) are often linked to male infertility.

Introduction

Infertility is the failure of a couple to become pregnant after one year of regular, unprotected intercourse. In both men and women the fertility process is complex. Even under ideal circumstances, the probability that a woman will get pregnant during a single menstrual cycle is only about 30%. And, when conception does occur, only 50 - 60% of pregnancies advance beyond week 20. In many cases, infertility is caused by a combination of problems in both partners that conspire to prevent conception from occurring.

About 8 - 10% of couples of reproductive age experience infertility, and in around 40% of these cases male infertility is the major factor. Another 40% of infertility problems are caused by abnormalities of the woman's reproductive system, and the remaining 20% involve couples who both suffer reproductive difficulties.

Infertility affects one in 25 American men. More than 90% of male infertility cases are due to low sperm counts, poor sperm quality, or both. Whether sperm counts are declining overall in industrialized countries is a controversial issue. However, over the last few years the number of assisted reproductive procedures that target male infertility have increased, while female procedures have declined.

The male reproductive system creates sperm that is manufactured in the seminiferous tubules within each testicle. The head of the sperm contains the DNA, which when combined with the egg's DNA, will create a new individual. The tip of the sperm head is the portion called the acrosome, which enables the sperm to penetrate the egg. The midpiece contains the mitochondria which supplies the energy the tail needs to move. The tail moves with whip-like movements back and forth to propel the sperm towards the egg. The sperm have to reach the uterus and the fallopian tube in order to fertilize a woman's egg.

Male Reproductive System

Male fertility depends on the proper function of a complex system of organs and hormones:

The process begins in the area of the brain called the hypothalamus-pituitary axis, a system of glands, hormones, and chemical messengers called neurotransmitters, all of which are critical for reproduction.
The first step in fertility is the production of gonadotropin-releasing hormone (GnRH) in the hypothalamus, which prompts the pituitary gland to manufacture follicle-stimulating hormone (FSH) and luteinizing hormone (LH).
FSH maintains sperm production, and LH stimulates the production of the male hormone testosterone.
Both sperm and testosterone production occurs in the two testicles, or testes, which are contained in the scrotal sac (the scrotum). (This sac develops on the outside of the body because normal body temperature is too high to allow sperm production.)

The male reproductive structures include the penis, the scrotum, the seminal vesicles, and the prostate.

Sperm are manufactured in several hundred microscopic tubes, known as seminiferous tubules, which make-up most of the testicles.

Surrounding these tubules are clumps of tissue containing so-called Leydig cells. Here, testosterone is manufactured.

Sperm Development. The life cycle of sperm consists of a remarkable journey that depends on hormonal signals combined with a mechanical process. It takes about 74 days:

Sperm begin partially embedded in nurturing amoebae-like cells known as Sertoli cells, which are located in the lower parts of the seminiferous tubules.
As they mature and move along, they are stored in the upper part of the tubules. Young sperm cells are known as spermatids.
When the sperm has completed the development of its head and tail, it is released from the cell into the epididymis. This remarkable C-shaped tube is 1/300 of an inch in diameter and about 20 feet long. It loops back and forth on itself within a space that is only about one and a half inches long. The sperm's journey through the epididymis takes about 3 weeks.
The fluid in which the sperm is transported contains sugar in the form of fructose, which provides energy as the sperm matures. In the early stages of its passage, the sperm cannot swim in a forward direction and can only vibrate its tail weakly. By the time the sperm reaches the end of the epididymis, however, it is mature and looks like a microscopic squirming tadpole.
At maturity, each healthy sperm consists of a head that contains the man's genetic material, his DNA, and a tail that lashes back and forth at great speed to propel the head forward at about four times its own length every second. The ability of a sperm to move forward rapidly and straight is probably the most significant determinant of male fertility.

Ejaculation. When a man experiences sexual excitement, nerves stimulate the muscles in the epididymis to contract, which forces the sperm out through the penis:

In the penis, the sperm first pass into one of two rigid and wire-like muscular channels, called the vasa deferentia. (A single channel is called a vas deferens.)
Muscle contractions in the vas deferens from sexual activity propel the sperm along past the seminal vesicles. These are clusters of tissue that contribute fluid, called seminal fluid, to the sperm. The vas deferens also collects fluid from the nearby prostate gland. This mixture of various fluids and sperm is the semen.
Each vas deferens then joins together to form the ejaculatory duct. This duct, which now contains the sperm-containing semen, passes down through the urethra. (The urethra is the same channel in the penis through which a man urinates, but during orgasm, the prostate closes off the bladder so urine cannot enter the urethra.)
The semen is forced through the urethra during ejaculation, the final stage of orgasm when the sperm is literally shot out of the penis.

Click the icon to see an image of the vas deferens.

Semen. In addition to providing the fluid that transports the sperm, semen also has other benefits:

It provides a very short-lived alkaline environment to protect sperm from the harsh acidity of the female vagina. (If the sperm do not reach the woman's cervix within several hours, the semen itself becomes toxic to sperm and they die.)
It contains a gelatin-like substance that prevents it from draining from the vagina too quickly.
It contains sugar in the form of fructose to provide instant energy for sperm locomotion.

The Path to the Egg. The sperm's passage to the egg is a perilous journey.

Usually about 100 - 300 million sperm are delivered into the ejaculate at any given time. Even under normal conditions, however only about 15% of these millions of sperm are sound enough to fertilize an egg.
To compound the problem, after the stress of ejaculation, only about 400 sperm survive the orgasm to complete the journey.
Out of this number, a mere 40 or so sperm survive the toxicity of the semen and the hostile environment of the vagina to reach the vicinity of the egg. Normally, the cervical mucus forms an impenetrable barrier to sperm. However, when a woman ovulates (releases her egg, the oocyte), the mucous lining thins to allow sperm penetration.
Sperm that manage to reach the mucous lining in the woman's cervix (the lower part of her uterus) must survive about four more days to reach the woman's fallopian tubes. (Here, the egg is positioned for fertilization for only 12 hours each month.)
The few remaining sperm that penetrate the cervical mucus and are able to reach the fallopian tubes become capacitated.
Capacitation is a one-time explosion of energy that completes the sperm's journey. It boosts the motion of the sperm and triggers the actions of the acrosome, a membrane that covers the head of the sperm and resembles a warhead. The acrosome is dissolved, and enzymes contained within it are released to allow the sperm to drill a hole through the tough outer coating of the egg.
In the end, only one sperm gets through to fertilize the egg.

Click the icon to see an image of the uterus.

Sperm Abnormalities

More than 90% of male infertility cases are due to low sperm counts, poor sperm quality, or both. In 30 - 40% of cases of sperm abnormalities, the cause is unknown. It may be the end result of one or more factors that include chronic illness, malnutrition, genetic defects, structural abnormalities, and environmental factors. Partial obstruction anywhere in the long passages through which sperm pass can reduce sperm counts. In one study, obstruction was believed to be a contributing factor in over 60% of low sperm count cases. Obstruction itself can be caused by many factors.

Sperm abnormalities are categorized by whether they affect sperm count, sperm quality, or sperm shape.

In the past, a sperm count of less than 40 million/mL in the ejaculate was believed to cause infertility. Now, however, if the woman is fertile and young, a count as low as 10 million can often accomplish conception over time, even without treatment. In fertilization clinics, men with low sperm counts report fertilization rates of about 30%, while those with average sperm counts have rates between 60 - 80%. Sperm count varies widely over time, and temporary low counts are common. Therefore, a single test that reports a low count may not be a representative result.

Sperm motility is the sperm's ability to move. If movement is slow, not in a straight line, or both, the sperm have difficulty invading the cervical mucous or penetrating the hard outer shell of the egg. If 60% or more of sperm have normal motility, the sperm is at least average in quality. If less than 40% of sperm are able to move in a straight line, the condition is considered abnormal. Sperm that move sluggishly may also have genetic or other defects that render them incapable of fertilizing the egg. An important 2001 study identified a protein in the tail of the sperm called CatSper, which might play a central role in the ability of the sperm to swim and penetrate the egg.

Morphology refers to the shape and structure of an object. Morphology may be even more important than count or motility in determining potential fertility. Abnormally shaped sperm cannot fertilize an egg. About 60% of the sperm should be normal in size and shape for adequate fertility.

The perfect structure is an oval head and long tail. Abnormally shaped sperm may include a number of variations:

A very large round head. (In one study, if 14% or more of sperm had round enlarged heads, the chances for pregnancy fell to about 20%. Such an abnormality indicates early unraveling of genetic material.)
An extremely small pinpoint head
A tapered head
A crooked head
Two heads
A tail with kinks and curls

Sperm carry half the genetic material necessary to make a complete human being. (The egg holds the other half.) Genes are contained in the rod-like structures called chromosomes. The genes themselves are made up of chains of molecules called DNA, which carry the information that defines a human. Genetically fragile sperm are important factors in male infertility. Such sperm have fragmented DNA chains, which make them less capable of fertilization and may also contribute to low quality.

Causes

In one study, the causes of infertility in men seeking to conceive included:

Vasectomy. In the study, 56% of men were seeking a reversal of this procedure. Thirty years ago, this was a factor in only 5% of men seeking help for fertility.
Varicocele (14%). A network of veins carries blood away from the testicles and back up into the body. If these veins become enlarged, twisted, and swollen (similar to varicose veins in the leg), this condition is termed a varicocele. Varicoceles can impair testicular function and fertility.
Unknown infertility (8%).
Absence of sperm (6%). There are many biologic and environmental factors that can lead to low sperm count. For instance, abnormalities in production or obstruction of the tubes that carry sperm can reduce sperm levels. A condition called Sertoli cell-only syndrome is one in which the cells that produce sperm (the Sertoli cells) are absent. This can be a congenital problem that a man is born with or caused by infection, injury, medication, radiation, or genetics. In addition, other conditions may cause infertility in men.

The effect of aging on male fertility is not totally clear. However, growing evidence suggests that it may be a factor (although not to the extent that it is in women). This evidence indicates that age-related sperm changes in men are not abrupt, but are a gradual process. Aging can adversely affect sperm counts and sperm motility (the sperm's ability to swim quickly and move in a straight line). A 2006 study also suggested that the genetic quality of sperm declines as a man ages. The researchers found that poor sperm motility was associated with DNA fragmentation. This led to some older men having an increased risk of passing on gene mutations that cause dwarfism and possibly other genetic diseases.

Nearly any major physical or mental stress can temporarily reduce sperm count. Some common conditions that lower sperm count, temporarily in nearly all cases, include:

Emotional Stress. Stress may interfere with the hormone GnRH and reduce sperm counts.

Sexual Issues. In fewer than 1% of cases, impotence, premature ejaculation, or psychological or relationship problems contribute to male infertility, although these conditions are usually very treatable. Lubricants used with condoms, including spermicides, oils, and Vaseline, can affect fertility. Astroglide, Replens, or mineral oil may not be as harmful to sperm. However, oil-based lubricants can damage latex condoms and should be avoided.

Testicular Overheating. Overheating, such as from high fevers, saunas, and hot tubs, may temporarily lower sperm count. Persistent exposure to high temperatures during work may impair fertility. Several studies have found no negative effects on fertility from wearing tight trousers, briefs, or athletic supports, even every day.

Substance Abuse. Cocaine or heavy marijuana use appears to temporarily reduce the number and quality of sperm by as much as 50%. Sperm actually have receptors for certain compounds in marijuana that may impair the sperm's ability to swim and also inhibit their ability to penetrate the egg. Alcohol does not appear to affect fertility, unless it is so abused that it causes liver damage.

Smoking. Smoking impairs sperm motility, reduces sperm lifespan, and may cause genetic changes that affect the offspring. One study found that men or women who smoke have lower success rates with assisted reproductive technologies. Another study reported that men who smoke also have lower sex drives and less frequent sex.

Malnutrition and Nutrient Deficiencies. Deficiencies in certain nutrients, such as vitamin E, vitamin C, selenium, zinc, and folate, may be particular risk factors for infertility

Obesity. Obesity may be a risk factor for male infertility. A 2006 epidemiological study found that a 20-pound increase in a man's weight increased the chance for infertility by about 10%.

Bicycling. Bicycling has been linked to impotence in men and also may affect fertility. Pressure from the bike seat may damage blood vessels and nerves that are responsible for erections. Mountain biking, which involves riding on off-road terrain, exposes the perineum (the region between the scrotum and the anus) to more extreme shocks and vibrations and increases the risk for injuries to the scrotum. One study found that men who mountain bike are far more likely to have scrotal abnormalities, including calcium deposits, cysts, and twisted veins. Men who cycle can reduce such risks by:

Taking frequent rests while biking
Wearing padded bike shorts
Using a padded or specially contoured bike seat that is raised high enough and sits at the proper angle

Problems in the genes that regulate male fertility and in the genetic material of sperm itself are important contributors to infertility problems in men. In fact, even in men with no known fertility problems, 19% of the sperm are genetically defective. Certain inherited medical conditions also contribute to male infertility. Defective genes themselves can be inherited, produced by environmental assaults (such radiation exposure), or both. Of some concern is the possibility that these mutations will be passed to offspring in men who undergo fertilization techniques that retrieve sperm and directly fertilize the egg. (Under natural conditions, genetically abnormal sperm would be very unlikely to reach and fertilize the egg.)

Defective Genetic Material. Sperm carry half the genetic material necessary to make a human being. Infertile men have been reported to have a relatively high percentage of sperm with broken or damaged DNA (the molecular chain that makes up a gene).

Genetic Factors Specifically Affecting Sperm Production or Quality. Abnormalities in genes that specifically regulate sperm production and quality are major factors in male infertility. Some research suggests that about 10% of cases of male infertility may be due to problems, most likely genetic, in the acrosome. The acrosome is the enzyme-filled membrane cap on the sperm -- its warhead -- that is critical for piercing the egg. In one study, pregnancy was impaired if 7% or more of sperm had abnormalities in the acrosome.

Inherited Disorders that Affect Fertility. Certain inherited disorders can impair fertility. Examples include:

Cystic fibrosis patients often have missing or obstructed vas deferens (the tubes that carry sperm). In fact, men whose infertility is caused by an inborn missing vas deferens have a 60% chance that they carry the gene for cystic fibrosis (even if they don't have the disease itself).
Klinefelter syndrome patients carry two X and one Y chromosomes (the norm is one X and one Y), which leads to the destruction of the lining of the seminiferous tubules in the testicles during puberty, although most other male physical attributes are unimpaired.
Kartagener syndrome, a rare disorder that is associated with a reversed position of the major organs, also includes immotile cilia (hair-like cells in lungs and sinuses that have a structure similar to the tails of sperm). Sperm motility may also be impaired by this condition.
Polycystic kidney disease, a relatively common genetic disorder that causes large cysts to form on the kidneys and other organs during adulthood, may cause infertility as the first symptom if cysts develop in the reproductive tract.

Exposure to toxins, chemicals, or infections may reduce sperm count by either affecting testicular function or altering hormone systems. The extent of the impact and specific environmental assaults involved, however, are often controversial. Some researchers believe environmental toxins are contributing to a general worldwide decline in male fertility. Data indicate that testosterone levels in American men may have declined over the last several decades. The reasons for this decline have not yet been determined. However, even if testosterone levels are declining, the proportion of men treated for fertility problems has not changed much over the past decade.

Free Radicals (Oxidants). The primary suspects in the link between environmental assaults and infertility are free radicals, also called oxidants. These are unstable molecules, usually containing oxygen, that are released as a by-product of many natural chemical processes in the body. Infections, chemicals, and other environmental assaults can produce high levels of these particles. High levels may even affect the genetic material in cells. Sperm are particularly vulnerable to the damaging effects of this oxidation process. There have been reports that significant levels of oxidants occur in the semen of about 25% of infertile men.

Exposure to Estrogen-Like and Hormone-Disrupting Chemicals. European studies have increasingly reported a worsening in male reproductive health and an increase in testicular and prostate cancers. Many investigators strongly suspect environmental causes, particularly excessive chemicals that disrupt hormones, as a major cause for both these events. Estrogen-like chemicals found in pesticides and other chemicals are of particular concern. Overexposure to estrogen in male animals reduces the number of Sertoli cells (the cells necessary for the initial development of sperm). Some hormone-disrupting chemicals under investigation include:

Treatment of prostate cancer varies depending on the stage of the cancer and may include surgical removal, radiation, chemotherapy, hormonal manipulation or a combination of these treatments.

Bisphenol A is a widely used chemical found in plastic food containers and bottles that has provoked concern. It has potent estrogen-like effects in low dose. Use of the chemical in female rats has produced prostate abnormalities in their male offspring.
Phthalates, chemicals used to soften plastics, are under particular scrutiny for their ability to disrupt hormones. Specific phylates of special concern include dibutyl phthalate (DBP), which is found in many products, including cosmetics and clay products sold to children (Fimo, Sculpey). Animals exposed to phylates have significantly impaired sperm count and abnormalities in their reproductive structures, such as the testes. In addition, there is some concern that exposure in pregnant women may affect the offspring,
Organochlorines are compounds that combine chlorine and organic substances -- usually petrochemicals. Many have estrogen-like effects, including those previously used to make plastics (PCBs) and pesticides (DDT and p,p-DDE). Some, such as dioxins and furans, are byproducts of many chemical processes. Fortunately, most of these chemicals have been banned, but they were heavily used in manufacturing before 1970 and are still widespread in the environment. Studies report that when men had a history of moderate or high on-the-job exposure to pesticides containing organochlorines, their fertility rates were lower than men without such exposures. Studies have found a strong correlation between high levels of polychlorinated biphenyls (PCBs) or p,p-DDE with reduced sperm quality and quantity. In one of the studies, even men with healthy sperm with high organochlorine levels had a lower sperm count than those with lower levels of these compounds.

Most evidence on the hormone of chemical estrogens has occurred in animals and birds. Tests of single chemicals containing estrogen have reported little danger for people. Some studies suggest, however, that exposure to more than one of these chemicals may be very harmful. At this time, there is no strong evidence supporting a serious harmful effect in people who have normal exposure to these chemicals. Major efforts are underway to determine the extent of any possible harm from these chemicals.

Exposure to Heavy Metals. Chronic exposure to heavy metals such as lead, cadmium, or arsenic may affect sperm quality. Trace amounts of these metals in semen seem to inhibit the function of enzymes contained in the acrosome, the membrane that covers the head of the sperm.

Radiation Treatments. X-rays and other forms of radiation affect any rapidly dividing cell, so cells that produce sperm are quite sensitive to radiation damage. Cells exposed to significant levels of radiation may take up to 2 years to resume normal sperm production and, in severe circumstances, may never recover.

Men with fertility problems because of low semen levels when they ejaculate may have a structural abnormality in the tubes transporting the sperm. (A normal amount of semen is 2.5 - 5 mL, or about 1/2 - 1 teaspoon.)

A varicocele is an abnormally enlarged and twisted (varicose) vein in the spermatic cord that connects to the testicle. Varicoceles are found in 15 - 20% of all men and in 25 - 40% of infertile men, although it is not clear how or even if they affect fertility. They tend to occur more commonly (85%) on the left side. Some theories supporting their possible effect on infertility include:

Click the icon to see an image of a varicocele.

Varicoceles may partially obstruct the passages through which sperm pass.
Varicoceles may elevate temperature in the testes.
Varicoceles may produce higher levels of nitric oxide, a substance that has beneficial effects on blood flow and other functions but which might, in excess, injure sperm.
Varicoceles may block oxygen supply to the sperm.
Varicoceles have been associated with abnormalities in cellular material in the sperm. One study suggested that some men with fertility problems may have genetic defects that cause both varicoceles and impaired sperm.

Some reports indicate that only varicoceles that are large enough to be felt (or palpable) may impact fertility. On the other hand, however, an 8-year study of men with and without varicoceles found no differences in sperm quality or in the ability to conceive. Furthermore, the few well-conducted studies on repair of varicoceles suggest that the procedure does not improve pregnancy rates. Their effect on fertility remains unclear.

Hypogonadism is the general name for a severe deficiency in gonadotropin-releasing hormone (GnRH), the primary hormone that signals the process leading to the release of testosterone and other important reproductive hormones. Low levels of testosterone from any cause may result in defective sperm production.

Hypogonadism is uncommon and is most often present at the time of birth, usually the result of rare genetic diseases affecting the pituitary gland that may include selective deficiencies of the hormones FSH and LH, Kallman syndrome, or panhypopituitarism, in which the pituitary gland fails to make almost all hormones. It can also develop later in life from brain or pituitary gland tumors or as a result of radiation treatments. Defects in the gene on the X chromosome that regulates receptors that bind to androgens (male hormone) may also prove to be very important causes of male infertility.

Click the icon to see an image of the pituitary gland.

Autoimmunity is a condition in which antibodies of the immune system attack specific cells in the body, mistaking them for foreign microinvaders. In the case of male infertility, these so-called autoantibodies ("self" antibodies) target the sperm. Antibodies bind to specific parts of the sperm, such as the head or tail and, depending on the site of attachment, cause various problems:

Sperm may stick together (agglutinate)
They may fail to interact with cervical mucous
They may be unable to penetrate the egg

Some experts believe that in most cases the presence of these antibodies will not prevent conception unless a large percentage of sperm are affected.

Vasectomy and Anti-Sperm Antibodies. Vasectomy, the primary sterility procedure in men, is the most common cause of sperm autoantibodies (also called anti-sperm antibodies). Their typical development may be as follows:

Vasectomy works by severing the vas deferens, the tube that carries sperm from the testicles to the urethra (which leads out of the penis).
After vasectomy, sperm continue to be produced but, instead of being confined to the reproductive passages, they leak out into the body.
Here, the immune system may perceive them as foreign invaders and develop antibodies to attack them.

Such antibodies often persist, even if a man restores sperm flow by a successful reversal procedure (vasovasostomy). The persistence of anti-sperm antibodies may result in infertility.

Click the icon to see an illustrated series detailing vasectomy.

Other Causes of Autoantibodies. Antibodies to sperm can also appear in men without previous vasectomies and have been reported to be present in 10% of all men with fertility problems. They may be linked to genital infections or injury, although the cause is usually not known.

Retrograde ejaculation occurs when the muscles of the urethra do not pump properly during orgasm and sperm are forced backward into the bladder instead of forward out of the urethra. Sperm quality is often impaired.

Retrograde ejaculation can be the consequence of several conditions:

Surgery to the lower part of the bladder or prostate (the most common cause of retrograde ejaculation)
Diabetes
Multiple sclerosis
Back surgery
Spinal cord injury

Medications such as tranquilizers, certain antipsychotics, or hypertension medications also may cause temporary retrograde ejaculation.

Any structural abnormalities that affect the testes, tubes, or other reproductive structures can have a profound effect on fertility.

Testicular Dysgenesis Syndrome. Testicular dysgenesis syndrome is a recently observed occurrence of three conditions -- impaired sperm production and quality, testicular cancer, and genital tract abnormalities. Environmental factors that increase damage from oxidants are believed to be responsible.

The genital abnormalities identified with this syndrome are undescended testes and hypospadias, each of which is associated with infertility:

Undescended Testes (Cryptorchidism). In some cases, there is a failure of the testes to descend from the abdomen into the scrotum during fetal life. Cryptorchidism is associated with mild to severe impairment of sperm production. In one survey, 38% of men who as youngsters had two undescended testicles and 10% of men with one undescended testicle were infertile, compared with 5% of men who had normal testes. Even one undescended testicle may impair fertility. In cryptorchidism, the testes are exposed to the higher internal body heat, but this may not totally explain the damage in sperm production that can occur. (Men who suffer from this condition should be aware that even if the testicle is surgically moved to the scrotum, their risk of testicular cancer is significantly increased, warranting careful self-exams and regular follow-up with a doctor.)
Hypospadias. This is a birth defect in which the urinary opening is on the underside of the penis, can prevent sperm from reaching the cervix if not surgically corrected.

Click the icon to see an image of an undescended testicle.

Click the icon to see an image of hypospadias.

Blockage in the Tubes that Transport Sperm. Some men are born with a blockage in the epididymis or ejaculatory ducts or other problems that later affect fertility. One center reported that 2% of men seeking treatment had no vas deferens.

Anorchia. In the very rare condition known as anorchia, a man is born without any testes.

Syringomyelia. This is a disease of the spinal cord that results in no ejaculate at all (aspermia).

Birth rates among cancer survivors are only 40 - 85% of normal rates. Certain cancers, particularly testicular cancer, impair sperm production, often severely. Cancer treatments such as chemotherapy and radiation can damage sperm quality and quantity, causing infertility. The closer radiation treatments are to reproductive organs, the higher the risk for infertility. Fortunately, while men may fail to produce sperm for as long as 5 years after radiation therapy, many men eventually recover their sperm production ability. Chemotherapy with drugs that harm reproductive function tends to affect fertility more severely in men than in women. New drug regimens are helping to improve fertility rates.

Adolescents and adult men undergoing cancer treatments who may want to father children should consider banking and freezing their sperm for later use in assisted reproductive therapies. This technique is called sperm cryopreservation. Sperm cryopreservation is recommended by the American Society of Clinical Oncology as the method with the highest likelihood of success for male cancer survivors. However, these banking methods are not appropriate for pre-adolescent boys being treated for childhood cancers such as leukemia. Researchers are investigating ways that stem cell transplantation may someday help these children regain their fertility while avoiding leukemia relapse.

There is some controversy over the effect of infections on infertility. Simply detecting the presence of an infection in infertile men does not necessarily mean that it has any relationship to the infertility itself. The immune response to some infections may release inflammatory factors and oxidants, chemically unstable particles that can damage sperm. The exact impact of this process on sperm is unclear, however. Infections may alter the liquidity of semen and sperm motility, although these are likely to be temporary effects. Among the infections most implicated in infertility are:

Sexually Transmitted Diseases. Repeated Chlamydia trachomatis or gonorrhea infections are most often associated with male infertility. Such infections can cause scarring and block sperm passage. Human papilloma viruses, the cause of genital warts, may also impair sperm function.

Mycoplasma. Mycoplasma is an infectious organism that appears to fasten itself to sperm cells and render them less motile.

Mumps. When mumps develops after puberty, it damages the testicles in 25% of men afflicted with the disease. (Interferon, an anti-viral drug, may help prevent infertility in adult males with active mumps, but the drug is highly toxic and caution is essential.)

Glandular Infections in the Urinary Tract or Genitals. Glandular infections that may affect fertility include prostatitis (in the prostate gland), orchitis (in the testicle), semino-vesculitis (in the glands that produce semen), or urethritis (in the urethra), perhaps by altering sperm motility. Even after successful antibiotic treatment, infections in the testes may leave scar tissue that blocks the epididymis.

Medical Conditions. Other medical conditions that can affect male fertility include any severe injury or major surgery, diabetes, HIV, thyroid disease, Cushing syndrome, heart attack, liver or kidney failure, and chronic anemia.

The effects of medications on sperm quality and count have not been rigorously studied, and many medicines are commonly prescribed without knowing whether they impair fertility. Anabolic steroids (which are often abused by weight lifters and other athletes) deserve special notice because they are known to severely impair sperm production. Among the other drugs that can affect male fertility are cimetidine (Tagamet), sulfasalazine (Azulfidine), salazopyrine, colchicine, methadone, methotrexate (Folex), phenytoin (Dilantin), corticosteroids, spironolactone (Aldactone), thioridazine (Mellaril), and calcium channel blockers.

Diagnosis

In any fertility work-up, both male and female partners are tested if pregnancy fails to occur after a year of regular unprotected sexual intercourse. It should be done earlier if a woman is over age 35 or if either partner has known risk factors for infertility. A work-up can not only uncover the causes of infertility but also detect other potentially serious medical problems as well, including genetic mutations, cancer, or diabetes.

The patients will provide the doctor with a detailed history of any medical or sexual factors that might affect fertility:

Frequency and timing of sexual intercourse
Duration of infertility and any previous fertility events
Childhood illnesses and any problems in development
Any serious illness (diabetes, respiratory infections, cancer, previous surgeries)
Sexual history, including any sexually transmitted diseases
Any exposure to toxins, such as chemicals or radiation
History of any medications and allergies
Any family history of reproductive problems

A fertility specialist, usually a urologist, will perform a physical examination. A physical examination of the scrotum, including the testes, is essential for any male fertility work-up. It is useful for detecting large varicoceles, undescended testes, absence of vas deferens, cysts, or other physical abnormalities.

Varicoceles large enough to possibly interfere with fertility can be felt during examination of the scrotum. In such cases, they are described as feeling like "a bag of worms." They disappear or are greatly reduced when the patient lies down, so the patient should be examined for varicocele while standing.
Checking the size of the testicles is helpful. Smaller-sized and softer testicles along with tests that show low sperm count are strongly associated with problems in sperm formation. Normal testicles accompanied by a low sperm count, however, suggest possible obstruction. The doctor may also take the temperature of the scrotum with a test called scrotal thermography.
The doctor will also check the prostate gland for abnormalities.
The penis is checked for warts, discharge from the urinary tract, and hypospadias (incorrect location of the urethra opening).

A urine sample to detect sperm after ejaculation may rule out or indicate retrograde ejaculation. It also may be used to test for infections.

The basic test to evaluate a man's fertility is a semen analysis. The sperm collection test for men who can produce semen involves the following steps:

A man should abstain from ejaculation for several days before the test because each ejaculation can reduce the number of sperm by as much as a third. To ensure an accurate sample, most doctors recommend abstaining from ejaculation for at least 2 days, but not more than 5 days, prior to semen collection.
A man collects a sample of his semen in a collection jar during masturbation either at home or at the doctor's office. Proper collection procedure is important, since the highest concentration of sperm is contained in the initial portion of the ejaculate. Specially designed condoms are also available that enable collection of a sample during sexual intercourse. (Regular condoms are not useful, since they often contain substances that kill sperm.)
The sample should be kept at body temperature and delivered promptly. If the sperm are not analyzed within 2 hours or kept reasonably warm, a large proportion may die or lose motility.
A semen analysis should be repeated at least three times over several months.

The sperm count test is performed if a man's fertility is in question. It is helpful in determining if there is a problem in sperm production or quality of the sperm as a cause of infertility. The test may also be used after a vasectomy to make sure there are no sperm in the semen.

The man and woman should both be present when the doctor discusses the results of this analysis so that both partners understand the implications. The analysis report should contain results of any abnormalities in sperm count, motility, and morphology as well as any problem in the semen. However, semen analysis alone is not necessarily a definitive indicator of either infertility or fertility.

In June 2007, the first at-home fertility test kit became commercially available. Fertell includes both male and female tests that allow couples to test sperm motility (for men) and follicle-stimulating hormone (for women). Results are available in less than 90 minutes, and are 95% accurate. The test is available on-line and at some pharmacies. It does not require a prescription. However, Fertell does not screen for all types of fertility problems and should not be used as a substitute for a professional evaluation by a doctor.

Sperm Count. A low sperm count should not be viewed as a definitive diagnosis of infertility but rather as one indicator of a fertility problem. Although in a large analysis sperm counts below 13.5 million were considered a strong indication of infertility, pregnancy was possible so long as any motile sperm were present. If there are no sperm cells at all in the semen, the doctor checks for obstruction in the tubes or for Sertoli cell-only syndrome, in which there are no sperm-producing cells in the testes. An at-home test (FertilMARQ) is now available to help gauge sperm quantity.

Sperm Motility. Motility (the speed and quality of movement) is graded on a 1 - 4 ranking system. For fertility, motility should be greater than 2.

Grade 1 sperm wriggle sluggishly and make little forward progress. (Sperm that, in fact, clump together may indicate that antibodies to the sperm are present.)
Grade 2 sperm move forward, but they are either very slow or do not move in a straight line.
Grade 3 sperm move in a straight line at a reasonable speed and can home in on an egg accurately.
Grade 4 sperm are as accurate as Grade 3 sperm, but move at terrific speed.

More than 63% of sperm should be motile for normal fertility, but even men whose motile sperm constitutes only about a third of the total sperm count should not rule out conception. Testing for sperm motility is particularly valuable for predicting the success of artificial insemination and which men might be candidates for the intracytoplasmic sperm injection (ICSI) fertilization technique, in which the sperm is inserted directly into the egg and motility plays almost no role.

Sperm Morphology. Morphology is the shape and structure of the sperm and, of the three main sperm values, may be the best predictor of fertility. Older reports indicated that about 60% of the sperm should be normal in size and shape for adequate fertility. However, one major analysis used a much broader range of criteria for sperm morphology and concluded that values over 12% were good predictors of fertility. Determining the morphology of the sperm is particularly important for the success of the fertility treatments in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI).

Seminal Fluid. The seminal fluid (semen) itself is analyzed for abnormalities. The color is checked and should be whitish-gray.

The amount of semen is important. Most men ejaculate 2.5 - 5 milliliters (mL) or cubic centimeters (cc) (1/2 - 1 teaspoon) of semen. Either significantly higher or lower amounts can be a sign of trouble:

Amounts greater than 1 cc but lower than 2.5 cc may indicate prostate problems or frequent intercourse.
A semen sample that is less than 1 cc could indicate a blockage of the ejaculatory ducts or other tubular abnormalities.
No ejaculate at all may signal retrograde ejaculation.
High amounts of ejaculate may, in some cases, also contribute to infertility.

The semen will be tested for how liquid it is. (Normal semen is liquefied within 20 minutes after adding certain enzymes.) Abnormal results suggest the following:

Overly sticky fluid suggests problems in the prostate gland (which adds fluid to sperm)
Overly watery fluid suggests lack of sperm

The amount of sugar (fructose) in sperm will be measured:

Since fructose is added to the semen in the epididymis, an absence of fructose indicates that an obstruction has occurred either in the vas deferens or the epididymis.
Conversely, if there is fructose in the semen but no sperm, then the channel from the epididymis is open but there is a defect in sperm production.

Other factors may also be measured:

White blood cell counts are taken to detect infection.
Low levels of a substance called inhibin B, which appears to be produced only in the testes, may indicate blockage or other defects in the seminiferous tubules.
Low levels of another compound, alpha-glucosidase, may also indicate blockage in the epididymis.

Blood tests are used for measuring several factors that might affect fertility:

Hormonal Levels. Tests for certain hormone levels are indicated if semen analysis is abnormal (especially if sperm concentration is less than 10 million per milliliter) or there are other indications of hormonal disorders.

Blood tests for testosterone and follicle-stimulating hormone (FSH) levels are usually taken first.
If testosterone levels are low, then luteinizing hormone (LH) are measured.

Low levels of FSH, LH, and testosterone indicate a diagnosis of hypogonadotropic hypogonadism. Very high FSH levels with normal levels of other hormones indicate abnormalities in initial sperm production. Usually this occurs only if the testicles are severely defective, causing Sertoli cell-only syndrome, in which sperm-manufacturing cells are absent. Other hormones, such as prolactin, estrogen, or stress hormones may be measured if there are symptoms of other problems, such as low sexual drive or the presence of breasts.

Infections. Blood tests can also determine the presence of any infections that might affect fertility, including HIV, hepatitis, and Chlamydia.

The postcoital test, also known as the cervical mucus penetration test, is designed to evaluate the effect of a woman's cervical mucus on a man's sperm. Typically, a woman is asked to come into the doctor's office within 2 - 24 hours after intercourse at mid-cycle (when ovulation should occur). A small sample of her cervical mucus is examined under a microscope. If the doctor observes no surviving sperm or no sperm at all, the cervical mucus should then be cultured for the presence of infection. The test cannot evaluate sperm movement from the cervix into the fallopian tubes or the sperm's ability to fertilize an egg.

If a man has had a vasectomy reversed and still cannot conceive or if semen analysis shows sperm clumping together, blood tests for anti-sperm antibodies will be conducted. Anti-sperm antibodies may also develop after genital infection or injury to the testes. The primary negative effect of these antibodies is to bind the sperm to the woman's cervical mucus, preventing the sperm from swimming further up.

Occasionally, a testicle biopsy may be performed, particularly for the following:

If Sertoli cell-only syndrome is suspected, in which sperm-producing cells in the testes are absent. It should be noted that specific cellular patterns can determine whether this condition is congenital (inborn) or caused by some later injury. This distinction is important in predicting the potential success of later sperm retrieval procedures.
For detecting obstruction in the transport system when sperm production looks normal but the count is low.

The standard biopsy procedure requires incisions (called an open approach) under anesthesia. It can be painful afterward. More than one biopsy may be needed in the case of suspected Sertoli cell-only syndrome, since one area may not have cell-producing cells, but other regions may contain normal sperm. Biopsies of both testes are more accurate than one. (Doctors must be careful to avoid the epididymis during a biopsy, since it is a continuous tiny tube and would be destroyed.) Patients may consider freezing any sperm retrieved during biopsy for later use.

Ultrasound imaging may be used to accurately determine the size of the testes or to detect cysts, tumors, abnormal blood flow, or varicoceles that are too small for physical detection (although such small veins may have little or no effect on fertility). It also can detect testicular cancer, which some experts believe make it worthwhile as a routine procedure for any male infertility work-up.

Click the icon to see an image of testicular ultrasound.

Genetic testing may be warranted in men who are severely deficient in sperm and who show no evidence of obstruction, particularly in men undergoing the intracytoplasmic sperm injection (ICSI) procedure. One study of men attending a fertility clinic showed that a third had genetic defects. If genetic abnormalities are suspected in either partner, counseling is recommended. Researchers are testing techniques such as preimplantation genetic diagnosis (PGD) that can examine all the chromosomes in a human embryo and detect defective genes, such as those for cystic fibrosis, at the very earliest stages. If it proves useful, it may help identify numerous abnormalities that increase the risk for infertility, treatment failures, or genetic defects in the offspring. In fact, a 2003 study suggested that performing an initial genetic analysis to determine DNA fragmentation in sperm may be a better way of predicting whether conception will succeed than analyzing semen.

In men who wish to undergo fertility treatments, certain tests will help determine the right strategies.

The Hamster Test. The hamster test, or micro-penetration assay test, uses the sperm sample to fertilize hamster eggs that have had their covering removed to allow penetration. If fewer than 5 - 20% of the eggs are fertilized, infertility is diagnosed. It may be useful for determining the best assisted reproductive treatment options for men with infertility.

The Human Zona Penetration Test. The human zona penetration test uses sperm to fertilize dead human eggs, which are usually obtained from an ovary that was removed for medical purposes. (Like the hamster test, the procedure cannot result in a living embryo.) Results may provide the same information as the hamster test and also indicate whether the sperm can penetrate the outer coating of an egg.

Acrosome Reaction Test. Tests that induce the ability of the sperm's enzyme-rich covering (acrosome) to dissolve can be very useful.

Other Tests. Additional advanced laboratory tests to measure sperm function, such as computer-aided sperm motility analysis, may also be performed. Some of these tests assess such factors as level of cell-damaging oxidants.

Treatment

Many men diagnosed with infertility in the past would be considered treatable now, even some men with spinal cord injuries. Unless a man produces no sperm at all, recent developments in treatment have made fertility possible for many men willing to undergo treatment and bear the expense. Before undergoing more advanced procedures, most couples trying to conceive should attempt some simple lifestyle changes.

Both male and female hormone levels fluctuate according to the time of day, and they also vary from day to day and month to month. Some timing tips might be helpful.

Male Hormone Levels and Sexual Activity. Male hormone levels are highest in the morning. In one study of men, their sexual activity was highest in October, when conception rates were also high.

Hormone Monitoring Systems for Women. A device called a saliva fertility monitor (Fertility Tracker) uses a microscope to view slides containing saliva and monitors estrogen levels. Home test kits that monitor reproductive hormone levels in the urine are also available. They are less costly than the saliva test but are messier. Monitoring hormone levels helps to determine when a woman is ovulating.

Frequency of Intercourse. The question of how often a couple should have intercourse is in debate. Some experts say that having sex more than 2 days a week adds no benefits. And, in fact, frequent sexual activity lowers sperm count per ejaculation. Some studies have indicated, however, that having intercourse every day, or even several times a day, before and during ovulation, improves pregnancy rates. Although sperm count per ejaculation is low, a constantly replenished semen supply is more likely to result in a fertilized egg.

Everyone should eat a healthy diet rich in fresh fruits, vegetables, and whole grains. Replace animal fats with monounsaturated oils, such as olive oil. Fish is also a good choice, and fish oils may have benefits for men with infertility. Certain specific nutrients, vitamins and minerals may also improve fertility.

Higher antioxidant intakes of vitamin C, vitamin E, and beta-carotene may help improve sperm numbers and motility, according to a 2005 study. The study included both food and supplement sources.
Vitamins C and E may also help repair DNA damage to sperm. According to a 2005 study, men who took 1 gram per day of these vitamins significantly reduced their percentage of DNA sperm fragmentation within 2 months.
The dietary supplements L-carnitine and L-acetylcarnitine may help improve sperm motility, according to several recent clinical trials.

A man who wants to increase his sperm count should also pursue a healthy lifestyle.

Avoid cigarettes and any drugs that may affect sperm count or reduce sexual function.
Overweight men should try to reduce their weight.
Get sufficient rest, and exercise moderately but regularly. (Those who exercise excessively might cut back, but not stop altogether.)
Stress may contribute to reduced sperm quality. It is not known if stress reduction techniques can improve fertility, but they may help couples endure the difficult processes involved in fertility treatments.
Although studies now indicate that tight underwear and pants pose no threat to male fertility, there is no harm in wearing looser clothing.
To prevent overheating of the testes, men should avoid hot baths, showers, and steam rooms.

The fertility process is a roller coaster of emotions that are present throughout both failure and success. There are almost no sure ways to predict which couples will eventually conceive. Some couples with multiple problems will overcome great odds, while other seemingly fertile couples fail to conceive. Many of the new treatments are remarkable, but a live birth is never guaranteed. The emotional burden on the couple is considerable, and some planning is helpful.

Planning for Emotional Turmoil.

Decide in advance how many and what kind of procedures will be emotionally and financially acceptable and attempt to determine a final limit. Fertility treatments are expensive.
Determine alternatives (adoption, donor sperm or egg, or having no children) as early as possible in the fertility process. This can reduce anxiety during treatments and feelings of hopelessness in case conception does not occur.

Managing Emotional Stress During the Process. Managing negative emotions in both men and women can be viewed as important as medical treatment. The process of fertility evaluation can be very difficult for many men. In a 2003 study, over 10% of men who required a second semen sample were unable to collect a semen sample using masturbation. Such men had had no problems with a first collection, but after being asked for additional samples they suffered severe anxiety during both masturbation in the fertility clinic and during regular sexual activity at home. Numerous studies reported a significant association between psychologic factors, particularly anxiety, and fertility treatment failure in women.

Managing the Emotional Effects of the Outcome. After enduring the process of fertility evaluation, the couple must face the outcome, and even a positive outcome has emotional repercussions.

Effects of Failure. Needless to say, the emotional stress of failure can be devastating even on the most loving and affectionate relationships and even in those who have prepared for the possibility of failure. Neither the male nor female partner should hesitate to seek professional help if the emotional burdens are too heavy.
Effects of Genetic Testing. As advanced technologies allow testing and greater genetic information at the earliest stage, potential parents will have to learn to deal with the uncertainties of possible chromosomal abnormalities, which may or may not be significant.
Effects of Multiple Births. A successful pregnancy that results in a multiple birth introduces new complexities and emotional problems. One study reported a very high rate of depression in women with triplets, particularly if they had little help from others, and especially if their husbands weren't involved.
Effects on Parenting. Once the fertility treatment-assisted child arrives, parents (both men and women) are more likely to be anxious and to have less confidence than those who conceive naturally.

Assisted Reproductive Technologies

Assisted reproductive technologies (ART) are medical techniques that help couples conceive. These procedures involve either:

A couple's own eggs or sperm
Donor eggs, sperm, or embryos

Fertilization may occur either in the laboratory or in the uterus. In the U.S., the number of live birth deliveries from ART increased by 128% from 1996 - 2002. More than 45,000 babies are now born in the U.S. each year using assisted reproductive technologies.

ART includes fertility drug treatments, artificial insemination (AI), in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), and other procedures.

Choosing a good fertility clinic is important. The government does not always regulate centers offering assisted reproductive techniques, and abuses have been reported, including lack of informed consent, unauthorized use of embryos, and failure to routinely screen donors for disease.

The clinic should always provide the following information:

The live-birth rate (not just pregnancy success rate) for other couples with similar infertility problems. (Multiple births, such as twins or triplets, are counted as one live birth.)
Such statistics should include high-risk women, such as those who are older or fail to produce eggs. (Some disreputable clinics give success percentages that exclude high-risk women from their total, thereby making the percentage of success much higher.)

Advanced fertility procedures and medications are extremely expensive and often not covered by insurance. Couples should be cautious about offers of rebates in the event of failure. The clinics offering them are often significantly more expensive than those that don't.

Artificial insemination it is the least complex of the assisted reproductive technologies and is often tried first in uncomplicated cases of infertility. Artificial insemination either involves placing the sperm directly in the cervix (called intracervical insemination) or into the uterus (called intrauterine insemination, or IUI). IUI is the standard artificial insemination procedure.

It is useful under the following circumstances:

When the woman's cervical mucus is unreceptive.
When donor sperm are required.
If the man's sperm count is very low (although it is preferable if at least 5 million per milliliter are motile).
When unexplained infertility exists in both partners.

Those in whom artificial insemination fails, couples with specific fertility defects, or older women may be candidates for more advanced reproductive technologies.

Researchers in one study suggested IUI as a reasonable first option for many women under age 43. It is less expensive and poses less risk for multiple births than the more advanced assisted reproductive technologies (ART), such as in vitro fertilization. Although in vitro fertilization procedures are more effective per cycle, couples tend to be able to afford more IUI cycles, so the pregnancy rates over time are very similar.

The Artificial Insemination Procedure. The artificial insemination procedure is as follows:

A woman usually (but not always) takes fertility drugs in advance.
The man must produce sperm at the time the woman is ovulating.
The sperm are subjected to certain so-called "washing" procedures. They are then inserted into the uterine cavity through a long, thin catheter.

The administration of fertility drugs and sperm retrieval is timed so that the process can coincide with time of ovulation. One study suggested that women who lay quietly for 10 minutes after sperm were implanted had a significantly higher rate of pregnancy than those who got up immediately.

Intracytoplasmic sperm injection (ICSI) is an assisted reproductive technology used for couples when male infertility is the main factor. It involves injecting a single sperm into an egg obtained from in vitro fertilization (IVF). The procedure is very simple:

A tiny glass tube (called a holding pipet) stabilizes the egg.
A second glass tube (called the injection pipet) is used to penetrate the egg's membrane and deposit a single sperm into the egg.
The egg is released into a drop of cultured medium.
If fertilized, the egg is allowed to develop for 1 - 2 days and then is either frozen or implanted.

The greatest concern with this procedure has been whether it increases the risk for birth defects. However, several studies have reported no higher risks of birth defects in children born using ICSI procedures. While other studies have shown a higher number of birth defects in children conceived with ICSI, the results may have more to do with the genetic background of the parents than ICSI itself. A 2006 study of 8-year-old children conceived with ICSI, meanwhile, found no important differences between these children and children who were conceived naturally.

While ICSI is an important assisted reproductive technology for male infertility, it may be overused. Some doctors recommend ICSI for women who have failed prior IVF attempts or who have few or poor-quality eggs, even if their male partners have normal semen measurements. There is little evidence that ICSI helps improve pregnancy success for couples who do not have a problem with male factor infertility, according to the Society for Assisted Reproductive Technology.

About 71% of ART procedures now use in vitro fertilization (IVF) with the woman's own eggs. An in vitro procedure is one that is performed in the laboratory. Advances in these procedures have dramatically increased the rate of live births.

The doctor first induces superovulation using fertility drugs so that several eggs can be harvested from the ovary before they have been released from the follicles. Higher doses of fertility drugs for subsequent cycles do not appear to add any advantage in women who have a poor response the first time.
To harvest eggs, the doctor generally inserts a probe into the vagina and is guided by ultrasound. A needle is then used to drain the liquid from the follicles, and several eggs are retrieved.
The eggs and sperm are combined in a Petri dish. Between 48 - 72 hours later the eggs are fertilized.
The resulting embryos (the first stage toward the development of the fetus) are reimplanted into the woman's uterus.
It takes about 2 weeks to determine if the process is successful.

IVF success rates for the first three cycles of treatment are about equal. They then decline modestly for the fourth cycle and drop significantly after the fifth cycle.

GIFT: The procedure is as follows:

The eggs are harvested as in IVF.
They are mixed with the sperm but not actively fertilized.
They are immediately injected back into the woman. Laparoscopy, a technique that employs a miniature viewing device, is used with this procedure to guide the placement of the embryos or egg through a long, thin catheter into the fallopian tubes.
The sperm and egg are placed exactly where they would be in natural fertilization.

ZIFT: The procedure is as follows.

The eggs are harvested as in IVF.
They are then mixed with the sperm and, in this case, are fertilized in the laboratory.
They are then implanted in the fallopian tubes as in GIFT. (The advantage of this procedure over GIFT is that the doctor and couple are assured that fertilization has taken place and the eggs can be examined for defects before implantation.)

Success rates have increased in all age groups (although they are still considerably lower in older than in younger women). Chances for assisted reproductive technology success are also greater among women who do not have uterine abnormalities and have had previous successful pregnancies.

Success rates are also higher or lower depending on whether the woman uses her own eggs or whether they are donated and also whether the eggs are fresh or frozen. The highest live birth rates are with donated fresh eggs (an average of 50% per transfer) and the lowest rates are when a woman uses her own frozen eggs (an average of 29% per transfer). However, using frozen eggs is less expensive than fresh eggs, so a couple may be able to afford more cycles with frozen eggs.

Use of Donor Eggs. Older women are more likely to use donor eggs. In one study, success rates were the same for women who used donors with an age range of 20 - 40. There were also no differences in delivery rates for recipients up to age 45. Women over age 45, however, increasingly had problems with implantation, pregnancy, and delivery.

Use of Frozen Eggs. Frozen eggs tend to have lower success rates because of toxins released by cells damaged in the freezing and thawing tissues.

In Vitro Maturation. A new technique called in vitro maturation allows fertilization without the use of fertility drugs. In this process, follicles are harvested a few days before ovulation. In such cases, up to 50 have already begun to mature. About 15 of these maturing follicles can be removed, out of which 2 or 3 can produce healthy embryos.

Before fertilization using intrauterine insemination (IUI) or advanced assisted reproductive technologies (ART) can take place, the sperm must be collected and prepared for optimal chances for success.

Retrieval Procedures

When a man has no available sperm in the ejaculate (usually from blockage, vasectomy, or lack of vas deferens), the sperm must be retrieved from the testes or the epididymis. Various microsurgical techniques are now available for retrieval. The procedure may be done under local or general anesthesia, using a spring-loaded biopsy device, a thin needle, incisions, or microsurgical techniques.

Surgical Biopsy. In men without obstruction, sperm can be retrieved using a surgical testicular biopsy.

Testicular Fine Needle Aspiration. With testicular fine needle aspiration (TFNA), the surgeon uses a fine needle to remove sperm. This can be performed with local anesthetic and by surgeons who do not have to be experienced in microsurgeries.

Microsurgical Epididymal Sperm Aspiration. Microsurgical epididymal sperm aspiration (MESA) uses microsurgical techniques to collect sperm that are close to blocked portions of the epididymis. It involves an open incision and may be done under general or spinal anesthesia in a hospital setting, although the patient can often go home the same day. The doctor accesses the epididymis and retrieves sperm with an extremely fine needle-like device. It has the advantage that it can retrieve the largest number of sperm compared to other procedures. However, as with any invasive procedure, it carries some risks of complications, such as bleeding or infection.

Percutaneous Epididymal Sperm Aspiration. Percutaneious epididymal sperm aspiration (PESA) uses a needle to obtain mature sperm from areas in the upper parts of the epididymis (the coiled tube where sperm are stored before ejaculation). It is done under local anesthesia, sometimes in the doctor's office, is less expensive than other techniques, and recovery is fairly painless. However, it has less of a chance of achieving sufficient sperm than MESA, and there is also a chance of hitting a blood vessel, causing bleeding.

Testicular Sperm Extraction. Testicular sperm extraction (TESE) is a microsurgery that removes a small amount of tissue from one or more areas of the testes using incisions and microsurgery techniques. The tissue is placed in a culture and chopped into tiny pieces. Sperm are liberated from the tiny tubes and extracted. It is a complex process, however. This is the second best method for men with vasectomies, according to some experts. It is more painful than PESA, however. In addition, if the procedure is repeated too often, it can cause permanent alterations in testicular function that may even reduce male hormone levels.

Testicular Sperm Aspiration. Testicular sperm aspiration (TESA) uses a needle-like biopsy device to draw a small sample of testicular tissue. Multiple attempts are sometimes required to retrieve sperm, and it is not as effective or as safe as TESE, although imaging techniques using ultrasound may improve results.

Sperm Washing

A sperm's energy output is 20 times greater once it is removed from the seminal fluid. Methods for washing sperm can have a dramatic effect on the ability of sperm to move towards the egg. The simplest method involves:

The sperm is mixed with a nutrient-rich fluid (or culture media) in a test tube.
They are then centrifuged (spun very rapidly) for about 5 minutes.
The sperm, which are heavy, settle on the bottom, forming a dense button of millions of pure sperm. The fluid left on top is siphoned off.
This procedure may be repeated.

This simple method of sperm washing, however, does not eliminate heavy debris, such as dead sperm, white blood cells, or bacteria, which may impair fertility. Scientists are developing new techniques, such as adding a substance called platelet-activating factor during the sperm washing process, which may enhance pregnancy rates.

Swim-Up Technique

The swim-up technique is not only a useful diagnostic procedure for testing the ability of sperm to escape from the semen into the cervical mucus, but it also achieves the goal of removing sperm from semen.

A specially prepared semen sample is placed in a tube.
A culture media (a nutrient-rich substance in which cells thrive) is placed on top of the sample.
The medium is a hospitable environment for sperm, and those that are healthy will swim up to it.
After an hour or more, the culture is examined, and the number of sperm that have reached the medium is compared to the number still remaining in the semen.

The result gives a fair estimation of the number of sperm potentially capable of fertilization. It is superior to sperm washing because the live sperm will swim up to the culture media, leaving behind most of the debris, although some may float up into the medium. There is also some evidence that such sperm may have fewer genetic abnormalities than those retrieved through sperm washing. The strongest sperm, which are those at the top of the medium, can be collected for in vitro fertilization or artificial insemination. A good swim test yields about half a million very active sperm.

Freezing Sperm

Sperm can be fresh or frozen in advance. Studies are reporting that frozen sperm provide excellent results and can be used confidently for fertilization procedures. Fresh sperm, however, are preferred by some centers for cases when low sperm count is not caused by obstruction.

Complications of Assisted Reproductive Technology

Fertility drugs. Increase risks of the placenta becoming detached from the uterus (placental abruption), third trimester miscarriage, and gestational diabetes.
IVF. Increase risks of placental abruption, the placenta developing in the lower section of the uterus (placenta previa), dangerously high blood pressure during pregnancy (pre-eclampsia), and Caesarean sections.

However, unlike earlier research, recent studies suggest that ART does not increase the risk for chromosomal damage or other major birth defects. Couples undergoing ART may have other factors, such as older age or genetic predispositions, which make complications more likely. Infertility itself, even without ART, can pose a risk factor for birth defects. Children conceived naturally by couples with fertility problems tended to have more disorders of the nervous system, digestive system, and musculoskeletal system than children born to fertile couples, according to a 2006 study in the British Medical Journal. Children born to couples treated for infertility with ART may also have a slightly increased risk for these problems, as well as genital organ malformations, but the overall risk for birth defects appears to be very small.

Preimplantation genetic diagnosis (PGD) is now available in a few fertility centers. It can help identify genetic defects in the offspring and may help parents determine future problems. Such testing, however, also raises significant emotional issues that should be addressed beforehand.

Given the hazards of multiple births, parents must make some hard decisions if the treatment produces multiple embryos. The choices are limited:

Carry all of them to term, which increases health risks for both the mother and the developing fetuses
Complete abortion
Embryo reduction, in which the doctor removes one or more embryos (possibly endangering the remaining embryos)

At this time, the best approach is to limit the number of implanted embryos in the first place. Experts are attempting to develop methods to reduce the risk for multiple births:

Most centers now implant two to three embryos at a time, and the remainder can be frozen for future use. (Frozen eggs do not appear to pose a risk for developmental problems in children conceived using them.) This limits the chance for success, but implanting more than three embryos only increases success rates very slightly, whereas the risk for multiple births increases significantly.
Reducing the dosage of fertility drugs also reduces the risk for multiple births, but not significantly and it too reduces the chance for successful outcome.
Blastocyst transfer may help reduce the chances for multiple births.

Other Treatments

Hormone therapy has been effective for women with infertility problems, but has been disappointing in men except in a few specific cases:

Gonadotropin-releasing hormone (GnRH) is often very helpful in restoring fertility in men with gonadotropin deficiency and hypogonadism.
GnRH may be useful for restoring sperm production after chemotherapy treatments.
Sperm production occasionally responds to low doses of estrogen and testosterone or testosterone alone, menotropins (Pergonal, Repronal), clomiphene citrate (Clomid), human chorionic gonadotropin (hCG), or human follicle-stimulating hormone (r-hFSH, Gonal-F).
Prolonged treatment with follicle-stimulating hormone (FSH) prior to intracytoplasmic sperm injection (ICSI) may improve implantation rates.
Aromatase inhibitors block aromatase, an enzyme that is a major source of estrogen in many major body tissues. These drugs include anastrozole (Arimidex) and letrozole. (Femara). They may be helpful for specific men whose infertility is associated with abnormal testosterone-to-estrogen ratios.

Bromocriptine. Bromocriptine (Parlodel) is used in men whose infertility is related to excess prolactin manufactured by the pituitary.

Antibiotics. Infections interfering with fertility may be successfully treated with antibiotics.

Mast Cell Blocking Antihistamines. Studies report that certain antihistamines that block mast cells may be beneficial for some men with low sperm counts. Mast cells are inflammatory immune factors that may play a role in lower sperm quality. Studies have reported that two such drugs used overseas, ebastine and tranilast, improved pregnancy rates. Similar antihistamines in the U.S. are fexofenadine (Allegra), loratadine (Claritin), and cetirizine (Zyrtec).

Repair of a varicocele (varicocelectomy) in men with infertility problems is a common surgical practice. Nevertheless, although many urologists favor varicocele repair, the few well-conducted studies on this procedure suggest that it does not improve the chances for a successful pregnancy. Some experts argue that such studies were not using the most advanced techniques, which may be more effective. Some studies report that repair may improve the success rate of assisted reproductive technologies, such as intrauterine insemination (IUI). Still, the overall benefits remain uncertain, and additional rigorous trials are needed. In any case, the procedure does not appear to be beneficial for improving fertility in men whose varicoceles are very small.

Varicocele repair for fertility is sometimes considered when the following conditions are met:

When the varicocele can be felt during a physical examination.
Surgical treatment of varicoceles may be important in boys and adolescents to prevent later testicular damage.
When the male partner with varicoceles has abnormal semen quality or abnormal sperm function test results.
When the couple has known infertility, and the man has varicoceles but the woman is either fertile or can be treated for her infertility.

Varicocelectomy. Varicocelectomy, the standard repair procedure, involves tying off the swollen and twisted veins. Recovery takes 6 days, and most men cannot resume full activity for about 3 weeks. This technique eliminates 90% of varicoceles.

Recent surgical techniques use laparoscopy, which only requires tiny incisions (less than an inch). This approach allows for quicker recovery, although the procedure itself takes longer. It also has a higher rate of complications than the standard approach.

Varicocele Embolization. A nonsurgical technique called varicocele embolization may eventually prove to be an effective and less painful treatment for varicoceles, including those in young boys. It involves inserting a narrow tube (catheter) through a small incision in the neck or leg. Tiny steel plugs are passed through the catheter to block off the affected veins. The procedure takes 15 - 45 minutes to perform and uses local anesthetic. Some studies suggest that recurrence occurs in more than 10% of men, often requiring conventional surgery. This procedure is not yet widely available, and it may not be appropriate for some men.

Men with retrograde ejaculation and failure of emission caused by surgery, severe disease, or spinal cord injury are treated with various methods.

Drugs known as alpha-adrenergic agonists, including pseudoephedrine (Sudafed, Actifed), stimulate muscle contraction and help ejaculation. The tricyclic antidepressant imipramine (Tofranil) has similar effects, and in one analysis of 35 studies was more effective than pseudoephedrine. Promising investigational drugs include amezinium, which increases blood pressure.
If drugs are not effective, a technique called electrovibration (or electrical stimulation) is often beneficial. (Drugs in any case are not helpful for men with complete failure of emission.)

With any of these methods, the sperm can be collected for intrauterine insemination or assisted reproductive techniques. Spontaneous conception is possible, but not common, even with these treatments.

To prepare sperm for in vitro fertilization (IVF), men with retrograde ejaculation typically use sodium bicarbonate four times a day to reduce the acidity of the urine. After ejaculation, the man urinates or has a catheter (a tube) inserted to withdraw urine, which is then submitted for washing techniques to separate out the sperm.

Procedures that assist ejaculation are helping men with spinal cord injury conceive children. Vibratory or electronic stimulation is proving to be very beneficial for many of these men. The sperm retrieved using these methods are inserted into the women using self-insemination, intrauterine insemination, in vitro fertilizaiton, or intracytoplasmic sperm injection. Nearly a third of couples achieve pregnancy, a success rate that approaches natural conception.

Vasovasostomy. For men who wish to conceive after vasectomy, reversal surgery (vasovasostomy) may restore fertility. In vasovasostomy the severed ends of the vas deferens (which were cut during vasectomy) are reconnected to reestablish the flow of sperm. The reversal procedure is difficult. It involves sewing together the two ends of both tubes, each with pinhead sized openings. [See In-Depth Report #37: Vasectomy and vasovasostomy.]

Pregnancy Rates After Vasovasostomy. An Australian study reported that pregnancy rates in the late 1990s after reversal surgery were nearly four times higher than they were in the early 1980s. Pregnancy rates of over 50% are now being reported after a vasovasostomy. One study indicated that when successful conception occurs, it does at an average of 1 year after the surgery.

A successful reversal is more likely if the following conditions are present:

The section removed during vasectomy was not long
The original procedure was performed on straight sections of the vas deferens
The pieces joined during the vasovasostomy are of equal size

The closer in time the vasovasostomy is to the original vasectomy, the better. In one large study, the pregnancy rates were 76% for those who had vasectomy less than 3 years before reversal surgery, but decreased to 30% for those men who had a vasectomy more than 15 years earlier. The decrease in rates as time goes by is probably due to an increase in the chance for obstruction of the epididymis and the development of anti-sperm antibodies. Success rates, according to some studies, are slightly better if the male partner does not change female partners after the procedure. Other studies suggest that it makes no difference if the man has a new female partner. The age of the woman is an important factor, and the chances of achieving pregnancy are best for women younger than age 35. Some research suggests that men who have a vasectomy reversal may have a greater rate of sperm chromosomal abnormalities than normal fertile men.

Reversal Versus Assisted Reproductive Technologies. Even though newer techniques such as ICSI are improving pregnancy rates after vasectomy, vasovasostomy is still a better choice than assisted reproductive technologies (ART) for most men who want children.

Success rates with reversal surgeries are improving, and the costs are lower than with ART. In addition, a vasovasostomy does not pose a risk for multiple births. In one study, the pregnancy rate for vasovasostomy was 52%, whereas success after intracytoplasmic sperm injection (ICSI) was 25 - 30% (ICSI is the ART treatment of choice for men who have had vasectomy). Even for men who have failed vasovasostomy, a repeat procedure appears to be less expensive than embarking on fertility treatments at that time.

ART may, however, be a better approach than reversal for men with evidence of anti-sperm autoantibodies due to vasectomy. ICSI may also be more effective than reversal surgeries in men whose vasectomy was conducted at least 15 years or more beforehand.

Surgical Treatment of Obstructions. Obstructions in the area of the ejaculatory ducts have been successfully treated by excising or scraping the area where the prostate gland surrounds the urethra and by reconstructing the ducts.

Correcting Undescended Testicles. Undescended testicles of young boys may be repositioned surgically to prevent later infertility. It is important to perform the operation before 15 - 18 months of age to prevent the destruction of most of the sperm-producing cells, which occurs if the testicles remain in the abdomen.

Stem Cells. Researchers are investigating using sperm stem cells to treat male infertility. The research is still in its earliest stages. In 2004, researchers announced that they had successfully grown sperm progenitor cells in the laboratory. These types of cells could potentially develop into sperm cells capable of fertilizing an egg. This discovery was an important first step for developing stem cell infertility treatments.

Resources

www.resolve.org -- National Infertility Association
www.asrm.org -- American Society for Reproductive Medicine
www.urologyhealth.org -- American Urological Association
www.afafamilymatters.com -- American Fertility Association
www.ssmr.org -- Society for the Study of Male Reproduction
www.sart.org -- Society for Assisted Reproductive Technology
www.cdc.gov/ART/index.htm -- Centers for Disease Control: Assisted Reproductive Technology Report

References

Jain T, Gupta RS. Trends in the use of intracytoplasmic sperm injection in the United States. N Engl J Med. 2007 Jul 19;357(3):251-7.

Travison TG, Araujo AB, O'Donnell AB, Kupelian V, McKinlay JB. A population-level decline in serum testosterone levels in American men. J Clin Endocrinol Metab. 2007 Jan;92(1):196-202. Epub 2006 Oct 24.

Zhu JL, Basso O, Obel C, Bille C, Olsen J. Infertility, infertility treatment, and congenital malformations: Danish national birth cohort. BMJ. 2006 Sep 30;333(7570):679. Epub 2006 Aug 7.

Review Date:
10/17/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Urinary incontinence

FitSugar — Wed, 08 Oct 2008 17:34:59 -0700

In This Report

Highlights
Introduction
Stress Incontinence
Urge Incontinence
Overflow Incontinence
Functional Incontinence
Risk Factors
Diagnosis
Prognosis
Treatment
Lifestyle Changes
Other Treatments
Behavioral Treatments
Medications
Surgery
Other Procedures
Catheters and Collection De...
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Sling Procedure Versus Burch Colposuspension

The sling procedure is better than Burch colposuspension in treating stress incontinence but may cause more post-operative urinary complications, according to results from an important 2007 New England Journal of Medicine study. In the first large-scale clinical trial to directly compare these two types of surgery, 47% of women who underwent the sling procedure had no urinary incontinence 2 years after surgery, compared with 38% of women who received the Burch procedure. However, 63% of women who had the sling procedure (and 47% of women who underwent the Burch procedure) experienced urinary tract infections following surgery.

Oxybutynin May Cause Hallucinations

In 2007, the FDA investigated reports that oxybutynin (Detrol) may cause hallucinations, especially in children and older adults. Out of 202 reports of oxybutynin-related central nervous system side effects, hallucinations occurred in 27% of cases involving children and 25% of cases involving adults age 60 years and older. The FDA is considering adding stronger cautions about these risks to oxybutynin’s prescribing label.

Tamsulosin and Tolterodine Combination Treatment

For men with moderate-to-severe lower urinary tract symptoms, including overactive bladder, a combination of tamsulosin (Flomax) and tolterodine (Detrol) works better than either drug alone, according to a study published in 2006 in the Journal of the American Medical Association.

Researchers Investigating Stem Cell Treatment for Stress Incontinence

Muscle stem cell injections may eventually prove to be an effective treatment for stress incontinence, indicate several small studies. Doctors took tissue biopsies from patients’ arm muscles, then isolated and injected the muscle stem cells into areas surrounding the urethra. The injections helped strengthen sphincter muscles and improved bladder control. Researchers presented results of these studies at the 2007 American Urological Association annual meeting and the 2006 Radiological Society of North America annual meeting.

Introduction

Urinary incontinence is the inability to control urination. It may be temporary or permanent, and can result from a variety of problems in the urinary tract. Urinary incontinence is generally divided into four groups, according to the problem involved:

Stress incontinence
Urge incontinence
Overflow incontinence
Functional incontinence

Often, more than one type of incontinence is present, with about 40% of all cases falling into more than one category.

Because incontinence is a symptom, rather than a disease, it is often hard to determine the cause. In addition, a variety of conditions may be the cause.

The urinary system helps to maintain proper water and salt balance throughout the body:

The process of urination begins in the two kidneys, which process fluids and dissolve waste matter to produce urine.
Urine flows out of the kidneys into the bladder through two long tubes called ureters.
The bladder is a sac that acts as a reservoir for urine. It is covered with a membrane and enclosed in a powerful muscle called the detrusor. The bladder rests on top of the pelvic floor. This is a muscular structure similar to a sling running between the pubic bone in front to the base of the spine.
The bladder stores the urine until it is eliminated from the body via a tube called the urethra, which is the lowest part of the urinary tract. (In men it is enclosed in the penis. In women it leads directly out.)
The connection between the bladder and the urethra is called the bladder neck. Strong muscles called sphincter muscles encircle the bladder neck (the smooth internal sphincter muscles) and urethra (the fibrous external sphincter muscles).

Click the icon to see an animation about urination.

The Process of Urination

The process of urination is a combination of automatic and conscious muscle actions. There are two phases: the emptying phase and the filling and storage phase.

The Filling and Storage Phase. When a person has completed urination, the bladder is empty. This triggers the filling and storage phase, which includes both automatic and conscious actions.

Automatic Actions. The automatic signaling process in the brain relies on a pathway of nerve cells and chemical messengers (neurotransmitters) called the cholinergic and adrenergic systems. Important neurotransmitters include serotonin and noradrenaline. This pathway signals the detrusor muscle surrounding the bladder to relax. As the muscles relax, the bladder expands and allows urine to flow into it from the kidney. As the bladder fills to its capacity (about 8 - 16 oz of fluid) the nerves in the bladder send back signals of fullness to the spinal cord and the brain.
Conscious Actions. As the bladder swells, the person becomes conscious of a sensation of fullness. In response, the individual holds the urine back by voluntarily contracting the external sphincter muscles, the muscle group surrounding the urethra. These are the muscles that children learn to control during the toilet training process.

When the need to urinate becomes greater than one's ability to control it, urination (the emptying phase) begins.

The Emptying Phase. This phase also involves automatic and conscious actions.

Automatic Actions. When a person is ready to urinate, the nervous system initiates the voiding reflex. The nerves in the spinal cord (not the brain) signal the detrusor muscles to contract. At the same time, nerves are also telling the involuntary internal sphincter (a strong muscle encircling the bladder neck) to relax. With the bladder neck now open, the urine flows out of the bladder into the urethra.
Conscious Actions. Once the urine enters the urethra, a person consciously relaxes the external sphincter muscles, which allows urine to completely drain out from the bladder.

The female and male urinary tracts are relatively the same except for the length of the urethra.

Stress Incontinence

The primary symptom of stress incontinence is leakage due to activities that apply pressure to a full bladder. High-impact exercise poses the greatest risk for leaking. But stress incontinence can occur with even minor activities, such as:

Coughing
Sneezing
Laughing
Running (sometimes even standing can produce leakage)
Lifting

Leakage stops when the activity stops. If the condition persists, it is more likely to be urge incontinence.

Stress incontinence occurs because the internal sphincter does not close completely. In both men and women, the aging process causes a general weakening of the sphincter muscles and a decrease in bladder capacity. Causes of stress incontinence, however, may differ between men and women.

In women, stress incontinence is nearly always due to one or both of the following:

The urethra fails to close and becomes overly movable (urethral hypermobility).
The muscles around the bladder neck weaken (intrinsic sphincteric deficiency or ISD). Some experts believe that this problem is present to some degree in nearly all women with stress incontinence. (ISD can also occur in anyone from an inborn disorder or injury from surgery or radiation.)

Many women are prone to one or both of these problems, which can occur under the following circumstances:

Having had many children through vaginal deliveries. In such cases, pregnancy and childbirth strain the muscles of the pelvic floor. Prolapsed uterus, in which the uterus protrudes into the vagina, occurs in about half of all women who have given birth. This condition can often cause incontinence.
Menopause. Estrogen deficiencies after menopause can cause the urethra to thin out so that it may not close properly.

Urethral Hypermobility. In urethral hypermobility the urethra does not close properly, allowing it to move too much (hypermobile). This condition typically occurs when the pelvic floor muscles in women become weak, and the following events occur:

The weakened pelvic floor muscles stretch.
This allows the bladder to sag downward within the abdomen.
The sagging bladder pulls on the muscles surrounding the bladder neck (internal sphincter), which are connected to the urethra.

Stress incontinence associated with urethral hypermobility is sometimes categorized as type 1 or type 2.

Type 1 is the less severe form, and the bladder neck and urethra remain incompletely closed.
In type 2, the angle of the bladder neck shifts. In such cases cystocele may occur, in which the bladder muscles bulge (herniate) into the vaginal wall.

Intrinsic sphincteric deficiency (ISD). Intrinsic sphincter deficiency (sometimes called type 3) is the other major cause of stress incontinence in women. It occurs when the bladder neck muscles are damaged or weakened. The result is twofold:

The bladder neck is open during filling.
The closing pressure around the urethra is low.

This is the most severe stress incontinence in women and usually occurs after previous surgeries for incontinence.

Prostate treatments can impair the sphincter muscles. Such treatments are the major causes of stress incontinence in men. They include the following:

Surgery or radiation for prostate cancer. Incontinence occurs in nearly all male patients for the first 3 - 6 months after radical prostatectomy. After a year of the procedure, most men retain continence, although leakage can occur.

Surgery for benign prostatic hyperplasia. Stress incontinence occurs in 1 - 5% of men after transurethral resection of the prostate (TURP), the standard treatment for severe benign prostatic hyperplasia.

Click the icon to see an illustrated series detailing TURP surgery.

Incontinence after prostate procedures is often a combination of urge and stress. Because studies often combine the two types of incontinence, it is not always clear which predominates.

Urge Incontinence

The main symptom of urge incontinence (also called hyperactive, irritable, or overactive bladder) is the need to urinate frequently. Patients may go to the bathroom more than 8 times over 24 hours, including 2 or more times a night, and have subsequent leakage. However, most people (60%) with overactive bladder experience only urgency and frequency. In some cases, urge incontinence occurs only at night. This is called nocturnal enuresis.

All cases of urge incontinence involve an overactive bladder. This occurs when the detrusor muscle, which surrounds the bladder, contracts inappropriately during the filling stage. When this occurs, the urge to urinate cannot be voluntarily suppressed, even temporarily. There is usually one of two types:

Idiopathic Detrusor Overactivity (formerly called Detrusor Instability). In this type, the nerves serving the bladder have signaled the brain appropriately that the bladder is full, but the detrusor muscles are unable to be suppressed. The actual cause, however, is not known.
Neurogenic Detrusor Overactivity (formerly called Detrusor Hyperreflexia). With this type, a known neurologic abnormality impairs the signaling systems between the bladder and the central nervous system, and the brain is unable to inhibit the detrusor muscles controlling urination.

Very often, the cause of detrusor instability and bladder hyperactivity is unknown. Some conditions that can produce the disorders leading to urge incontinence include the following:

Benign prostatic hyperplasia (BPH). Detrusor instability occurs in about 75% of men with BPH and causes frequency, urgency, and urination during the night (although incontinence itself occurs only in very severe cases). Urge incontinence only at night can be a sign of severe obstruction in the urinary tract.

Benign prostatic hypertrophy (BPH) is a non-cancerous enlargement of the prostate gland, commonly found in men over the age of 50.

Prostate surgical procedures. Either prostatectomy for prostate cancer or transurethral resection of the prostate (TURP) for BPH can cause detrusor instability. As with stress incontinence, prostatectomy poses a much higher rate than with TURP, which is very low.
Hysterectomy. Complications of this operation, which removes the uterus, are associated with a higher risk for urge incontinence. In one study, for example, incontinence developed or worsened after hysterectomy in about 16% of women who had only mild or no incontinence before surgery. However, hysterectomies can also significantly improve urinary incontinence in many women who have an existing condition before the procedure. In the same study, 30% of women had severe urinary incontinence before hysterectomy, which declined to 20% afterward and was sustained for at least 2 years.

Click the icon to see an image about hysterectomy.

Damage to the central nervous system. Certain neurologic disorders or injuries can disrupt the passage of nerve messages between the urinary tract and central nervous system. These neurological conditions include stroke, multiple sclerosis, spinal cord or disk injury, and Parkinson's disease.
Infections.
The aging process.
Emotional disorders. Anxiety and possibly even depression have been associated with urge incontinence.
Medications, including some sleeping pills.
Genetic factors may play a role in some cases.

Overflow Incontinence

Overflow incontinence happens when the normal flow of urine is blocked and the bladder cannot empty completely. Overflow incontinence can be due to a number of conditions:

A partial obstruction. In this case the urine cannot flow completely out of the bladder, so it never fully empties.
An inactive bladder muscle. In contrast to urge incontinence, the bladder is less active than normal, not more. It cannot empty properly and so becomes distended, or swells. Eventually this distention stretches the internal sphincter until it opens partially and leakage occurs.

The causes of the conditions leading to overflow incontinence include:

Tumors
Certain medications (anticholinergics, antidepressants, antipsychotics, sedatives, narcotics, alpha-adrenergic agonists, beta-adrenergic agonists, calcium channel blockers)
Benign prostatic hyperplasia (enlarged prostate)
Scar tissue
Nerve damage. In such cases, nerves in the bladder are damaged so that the body cannot feel when the bladder is full, and the bladder does not contract. Such damage can be caused by spinal cord injuries, previous surgery in the colon or rectum, and pelvic fractures. Diabetes, multiple sclerosis, and shingles also can cause this problem.

Functional Incontinence

Patients with functional incontinence have mental or physical disabilities that keep them from urinating, although the urinary system itself is normal. Conditions that can lead to function incontinence include:

Parkinson's disease.
Alzheimer's disease and other forms of dementia. Mental confusion may prevent both recognition of the need to void and locating a bathroom.
Severe depression. In such cases, people may become incontinent because they are indifferent to self-control.

Risk Factors

About 13 million adults experience incontinence at some time. The number, however, may actually be higher because most patients are reluctant to discuss incontinence with their doctors. In fact, research indicates that many patients will not admit to having the problem even when questioned directly. Although a third of American men and women age 30 - 70 have experienced at least some loss of bladder control, most have not been diagnosed by a doctor.

A 2004 survey of more than 1,400 Americans found that despite the prevalence of bladder control loss, an alarming 64% of those experiencing symptoms are not currently taking measures to manage their condition. The survey, sponsored by the National Association for Continence, also found that adults waited an average of 6 years before discussing their symptoms with a doctor. A 2006 study reported that only half of women with urinary incontinence have discussed their condition with a doctor, while only a third had received any treatment.

Incontinence is uncommon in children 5 years and older. However, it may still occur in:

10% of 5 year-olds
5% of 10 year-olds
1% of 18 year-olds

Incontinence that occurs before puberty is twice as common in boys as in girls. Most young people who experience nighttime wetting do not have any serious physical or emotional disorders. It is often difficult to diagnose incontinence in children. Many cases result from a combination of factors, including:

Birth defects or inborn conditions that cause problems in the urinary tract
Slower physical development
An overproduction of urine at night
A lack of ability to recognize bladder filling when asleep
Anxiety
Inherited factors (indicated by a strong family history of bedwetting)

Bedwetting in children is not considered incontinence. However, bedwetting and other urinary problems in childhood may predict the later development of adult urinary incontinence. According to a 2006 study, women who experienced childhood bedwetting, as well as frequent daytime and nighttime urination, had an increased risk of developing adult urge incontinence.

All older adults are susceptible to incontinence. One in 10 people over age 65 have some type of bladder control loss. About 12% of women ages 60 - 64 and 21% of women age 85 and over experience daily urinary incontinence. About half of the elderly who are housebound or in nursing homes experience incontinence.

Urinary incontinence is far more common among women than men. Between 15 - 50% of women experience urinary incontinence during their lifetimes, with the highest rates occurring in women who have had children. Severe urinary continence affects 7 – 10% of women. About 10% of women undergo surgery for urinary incontinence or pelvic organ prolapse.

Birth Conditions. Pregnancy and childbirth may increase the risk for urinary incontinence. The risk is highest with the first child, and there is an increased risk in women who have their first child over age 30. Some studies suggest that women who used the drug oxytocin for inducing labor are at higher risk for developing urinary incontinence. Such medically induced labor tends to subject the muscles and nerves in the pelvis to greater force than does natural labor.

Studies indicate that the method of birth can affect risk later in life. For example, a major 2003 study reported that women who had a cesarean section had a much lower risk for stress incontinence before age 50 than women who had vaginal delivery. However, a 2006 study contradicted many assumptions by suggesting that vaginal delivery is not associated with later development of urinary incontinence in postmenopausal women. The study compared sisters who had either given birth vaginally or had never had children. Researchers found no difference in rates of urinary incontinence. The study suggested that cesarean delivery may not make much difference in preventing urinary incontinence.

Another 2006 study found that episiotomy does not help prevent urinary incontinence. Episiotomy is a surgical incision that is made during childbirth to the perineum, the muscle between the vagina and the rectum. Doctors commonly perform this procedure to help widen the vaginal opening and prevent tearing. The study found that episiotomy does not have many benefits, and may later cause pain during intercourse.

Vaginal birth can cause pelvic prolapse, a condition in which pelvic muscles weaken and the pelvic organs (bladder, uterus) slip into the vaginal canal. Pelvic prolapse, and the surgery used to correct it, can cause incontinence. Sacrocolpopexy is the standard surgical procedure for repairing pelvic prolapse. A 2006 study found that performing a urinary incontinence surgical procedure (Burch colposuspension) at the same time as sacrocolpopexy can help prevent stress incontinence. [See Surgery section.]

High-Impact Exercise. Women who engage in high-impact exercise are susceptible to urinary leakage, particularly women with a low foot arch. Shock to the pelvic area is increased as the foot makes impact with hard surfaces. Those at highest risk for urinary leakage are gymnasts, followed by softball, volleyball, and basketball players.

Smokers. Studies have reported a higher risk for incontinence, notably mixed incontinence, in women who are current or former heavy smokers (more than a pack a day).

Obesity. Being overweight is a major risk factor for all types of incontinence. The more a woman weighs, the greater her risk.

Medical Factors in Older Women. Urge incontinence is more common among postmenopausal women who have a history of:

Diabetes
Higher body mass index (heavier weight)
Hysterectomy
Two or more urinary tract infections within the past year

The rate of incontinence in men (about 1.5 - 5%) is much lower than in women. The risk for urinary incontinence increases with age. In the United States, about 17% of men over age 60 have urinary incontinence. In older men, prostate problems and their treatments are the most common factors that affect the urinary tract. Up to 30% of men who have had surgery to remove their prostate gland experience some degree of urinary incontinence.

Urinary incontinence varies by race and ethnicity. It is most common in non-Hispanic white women. Among men, African-Americans are at highest risk. Some studies suggest that the greatest disparity is with stress incontinence. African-American and Asian American women have a much lower risk for stress incontinence than Caucasian and Hispanic women.

A number of conditions can cause temporary incontinence in anyone:

Urinary tract infections
Excess fluid intake
Constipation
Severe depression
Restricted mobility

Drugs. Drugs are most often the cause of temporary incontinence.

Drugs that affect the adrenergic system (a nerve-cell and hormonal pathway that regulates the sphincter muscle) are common causes of incontinence. For example, alpha-adrenergic blockers, such as terazosin (Hytrin), used for benign prostatic hypertrophy, can cause incontinence by over-relaxing the muscles. On the other hand, men with enlarged prostates who suffer from urinary problems may be helped by the increase of urine flow after using terazosin.
Alpha-adrenergic agonists, such as pseudoephedrine (found in some oral decongestants) strengthen the muscles and may cause overflow incontinence in susceptible people.
Beta-adrenergic blockers, such as propranolol (Inderal), prescribed for hypertension and angina, relax the sphincter.
Diuretics, used for high blood pressure, often rapidly introduce high urine volumes into the bladder.
Calcium-channel blockers can cause overflow incontinence by relaxing the bladder detrusor muscles.
Colchicine, a drug used for gout, can cause urge incontinence.
Other medications and substances that increase the risk for incontinence are caffeine, sedatives, antidepressants, antipsychotics, and antihistamines.

Diagnosis

Fewer than half of the patients who have urinary incontinence tell their doctor about the problem. In many cases, patients simply feel that incontinence is part of the aging process. And, in spite of the commonness of this problem, two-thirds of doctors never ask their older patients if they experience incontinence.

It is important, however, for both the doctor and the patient to raise the issue.

The first step in the diagnosis of incontinence is a detailed history. The doctor should ask questions about the patient's present and past medical conditions and patterns of urination. Patients should tell the doctor the following information:

When the problem began
Frequency of urination
Amount of daily fluid intake
Use of caffeine or alcohol
Frequency and description of leakage or urine loss, including activity at the time, sensation of urge to urinate, and approximate volume of urine lost
Frequency of urination during the night
Whether the bladder feels empty after urinating
Pain or burning during urination
Problems starting or stopping the flow of urine
Forcefulness of the urine stream
Presence of blood, unusual odor or color in the urine
A list of major surgeries with their dates, including pregnancies and deliveries, and other medical conditions
Any medications being taken

A 2006 study suggested a simpler way of diagnosing incontinence using a test that asks 3 questions:

During the last 3 months, have you leaked urine (even a small amount)?
When did you leak urine? (During physical activity; when you could not reach the bathroom quickly enough; without physical activity or bladder urge.)
When did you leak urine most often? (Physical activity; bladder urge; without or about equally with physical activity or bladder urge.)

Based on the patient’s answers, the “3IQ” test may help a doctor distinguish between urge and stress urinary incontinence.

Voiding Diary. The patient might find it helpful to keep a diary for 3 to 4 days before the office visit. This diary, sometimes referred to as a voiding diary or log, should be a detailed record of:

Daily eating and drinking habits
The times and amounts of normal urination

For each incident of incontinence, the log should also detail:

The amount of urine lost (the patient is often asked to catch and measure urine in a measuring cup during a 24-hour period)
Whether the urge to urinate was present
Whether the patient was involved in physical activity at the time

The office visit should consist of a thorough physical examination, checking for abnormalities or enlargements in the rectal, genital, and abdominal areas that may cause or contribute to the problem.

One of the important measurements for urinary incontinence is the postvoid residual urine volume (PVR). This is the amount of urine left in the bladder after urination:

Normally, about 50 mL or less of urine is left
More than 100 mL suggests an abnormality and requires further tests
More than 200 mL is a definite sign of abnormalities

Use of a Catheter. The most common method for measuring PVR uses a catheter, which is inserted into the urethra after a few minutes of urination. The advantage of the catheter is that it can also collect urine for analysis.

Ultrasound. Ultrasound is useful in determining the volume of urine.

Cystometry measures the bladder's ability to retain urine at different capacities and pressures. It uses a catheter and can be performed at the same time as the PVR test.

Subtraction Cystometry. Although procedures vary, the basic steps for the technique are as follows:

The patient empties the bladder as much as possible.
Two catheters are inserted into the urethra until they reach the bladder. One is used to fill the bladder with water. The other is used to measure pressure. Another catheter is inserted into the rectum or vagina, which is used to measure abdominal pressure.
While water is instilled through the tube into the bladder, the pressure in the bladder and abdomen are measured and the results are recorded in a computing device.
During the process, the patient informs the doctor about any changes in the need to urinate, including the initial need to urinate, a normal desire to urinate, and a strong need to urinate.
Often during this process, the patient is asked to cough, bounce up and down, or even walk in place. The patient may also be asked to strain as if he or she is having a bowel movement. This is called the Valsalva maneuver. The point at which leakage occurs during this action is called the Valsalva leak point pressure, which might be a useful measurement for determining treatment.
When the urge to urinate is strong, the doctor stops this portion of the test.
A calculation is then made using bladder and abdominal pressure measurements as well as volume and flow rate of the urine. The result provides the doctor with an assessment of detrusor contractions.

The detrusor muscles of a normal bladder will not contract during bladder filling. Severe contractions at low amounts of administered fluid (less than 200 mL) indicate urge incontinence. Stress incontinence is suspected when there is no significant increase in bladder pressure or detrusor muscle contractions during filling, but the patient experiences leakage if abdominal pressure increases.

Video Cystometry. Video cystometry combines a computer reading of bladder pressures and pictures of the bladder itself. It is most useful in cases where the more standard tests have not yielded satisfactory results.

To determine whether the bladder is obstructed, the speed of urine flow is measured electronically using a test called uroflowmetry. The test involves the following steps:

Patients are instructed not to urinate for several hours before the test and to drink plenty of fluids so they have a full bladder and a strong urge to urinate.
To perform this test, a patient urinates into a special toilet equipped with a uroflowmeter.
It is important that patients remain still while urinating to help ensure accuracy, and that they urinate normally and do not exert strain to empty their bladder or attempt to retard their urine flow.

Many factors can affect urine flow (such as straining or holding back because of self-consciousness) so experts recommend that the test be repeated at least twice.

Q[max]. The rate of urine flow is calculated as milliliters of urine passed per second (mL/s). At its peak, the flow rate measurement is recorded and referred to as the Q[max]. The higher the Q[max], the better the patient's flow rate. Men with a Q[max] of less than 12 mL/s have four times the risk for urinary retention than men with a stronger urinary flow.

The Q[max] measurement is sometimes used as the basis for determining the severity of obstruction and for judging the success of treatments. It is not very accurate, however, for a number of reasons:

Urine flow varies widely among individuals as well as from test to test.
The patient's age must be considered. Flow rate normally decreases as men age, so the Q[max] typically ranges from more than 25 mL/s in young men to less than 10 mL/s in elderly men.

The Q[max] level does not necessarily coincide with a patient's perceptions of the severity of his own symptoms.

Urethrocystoscopy. Urethrocystoscopy, also called cystourethroscopy or cystoscopy, detects structural abnormalities, inflammation of the bladder wall, or masses that might not show up on x-ray.

The patient is given a light anesthetic, and the bladder is filled with water.
Next, a thin flexible tube called a cystoscope is inserted through the urethra into the bladder.
The end of the cystoscope contains a tiny microscope-like instrument.
The doctor uses the cystoscope to look for abnormalities in the interior of the bladder.

Cystoscopy is a procedure that uses a flexible fiber optic scope, which is inserted through the urethra into the urinary bladder. The doctor fills the bladder with water and inspects the interior of the bladder. The image seen through the cystoscope may also be viewed on a color monitor and recorded on videotape for later evaluation.

The procedure has some risks. Complications are uncommon, but can include allergic response to the anesthetic, urinary tract infection, bleeding, and urine retention.

Intravenous Pyelogram. Intravenous pyelogram (IVP) may be used to diagnose urge incontinence. It is performed as follows:

A dye is injected into the patient's vein and is processed by the kidneys.
A series of x-ray pictures are taken of the kidneys, ureter, and bladder as the dye passes through them. This provides a dynamic picture of the relationship between the patient's urinary system and urinary functioning.

Click the icon to see an image of an intravenous pyelogram.

IVPs can detect structural abnormalities, urethral narrowing, or incomplete emptying of the bladder. This test should not be used on pregnant women or patients with kidney failure. There is a risk for an allergic reaction to standard dyes, although newer, less allergenic ones are becoming available.

Ultrasound. Ultrasound plays a role in many cases of incontinence. For example, it is useful for men with prostate problems. It is helpful in measuring urine volume in the bladder. Ultrasound may also be useful in many cases of female stress incontinence, by identifying abnormalities in the bladder neck, and in assessing the urinary tract before and after surgery. It also may eventually be useful in diagnosing detrusor instability.

Chain Cystogram. In cases of stress incontinence, a chain cystogram may also be performed. With this procedure, a beaded chain is positioned in the bladder and urethra. The x-ray image of the chain reveals the angle of the bladder neck. This test should not be performed on pregnant women.

Electrophysiologic sphincter testing, also referred to as electromyography (EMG), evaluates two important factors:

The function of the nerves serving the sphincter and pelvic floor muscles.
The patient's ability to control these muscles.

Using a technique similar to that of an electrocardiogram, the doctor places electrodes on the affected areas to observe electrical activity in the muscles.

Urethral pressure profile is used to investigate urethral blockage. A probe is placed in the urethra to determine pressure at different points along this pathway during urination and the exact location of any obstruction in the urethra.

Prognosis

Incontinence is rarely life threatening. In most cases, if treated promptly, physical complications are not serious.

Urinary incontinence can have severe emotional effects. Depression is very common in women with incontinence. For example, in a 2003 study, 82% of women with severe incontinence and 41% of those with moderate incontinence reported at least 2 weeks of depression during the preceding year. Incontinence also has emotional effects on men. A number of studies of prostate cancer patients suggest that incontinence is a much more distressing side effect for men than impotence (also a side effect of prostate cancer treatment).

Other negative emotional effects reported include:

Loneliness and humiliation. Because little public attention has been paid to this problem, the incontinent person often feels alone and humiliated. Many people with incontinence do not even seek medical advice for the problem. In one survey of doctors, nearly all of them reported that a patient's embarrassment and reluctance to discuss bladder problems is a major barrier to successful treatment.
Shame. Many people experience a sense of personal failure.
Helplessness. Patients often feel helpless and angry.
Introversion. Patients may eventually curtail social activities, or even give them up entirely.
Lack of confidence. Many people with incontinence believe that they are unemployable.

To prevent humiliation due to wetness or odors, people with incontinence may have to alter their way of life.

Errands become very difficult and need advanced planning.
Public bathrooms may difficult to locate or unavailable. The problem is particularly severe for those with urge incontinence who have little time to reach a bathroom and have large volume spills.

Incontinence is particularly serious in older adults:

Older adults who are otherwise healthy may stop exercising because of leakage, which can increase their impairment.
Incontinence can result in loss of independence and quality of life.
It is a major reason for nursing home placement.
Severe incontinence may require catheterization. This is the insertion of a tube that allows urine to continually pass into an external collecting bag. In such cases, complications are common, particularly infections.
There is a strong association between urge incontinence and falls and injuries. In one large study, over half of women who reported incontinence experienced at least one fall over a 3-year period. This high incidence of falls may be due in part to the rush to the toilet in the middle of the night. Keeping a pan or portable commode near the bed may prevent injuries as well as improve sleep and general convenience.

Treatment

The treatment for temporary incontinence can be rapid, simple, and effective. If urinary tract infections are the cause, they can be treated with antibiotics. Any related incontinence will often clear up in a short time. Medications that cause incontinence can be discontinued or changed to halt episodes.

Chronic incontinence may require a variety of treatments, depending on the cause. Treatment options are listed below in the order in which they are usually tried, from least-to-most invasive:

Behavioral techniques, which include Kegel exercises and bladder training, are sometimes all a person needs for achieving continence. A number of devices can also be used to strengthen muscles and prevent urine leakage. Bladder training is useful for urge incontinence.
Medications are tried next. These may include anticholinergics and antispasmodics. Estrogen or estrogen plus progesterone used to be recommended, but recent research has shown that these hormone treatments can actually make urinary incontinence worse.
Surgery. Surgery is the last resort; there are many effective procedures available for stress incontinence.

Lifestyle techniques to improve quality of life and improve hygiene are part of all treatments.

Lifestyle measures, including dietary recommendations, bladder training, and continent aids, are useful for anyone with incontinence. Other treatments vary depending on whether the patient has stress or urge incontinence. In people who have both, the treatment usually is aimed at the predominant form.

Treating Stress Incontinence. The general goal for women with stress incontinence is to strengthen the pelvic muscles. Typical steps for treating women with type 1 stress incontinence are:

Devices and continent aids for blocking urine in the urethra (vaginal pessaries, adhesive pads, and others).
Behavioral techniques and noninvasive devices, including Kegel exercises, weighted vaginal cones, and biofeedback.
Medications. Alpha-adrenergic agonists and possibly tricyclic antidepressants.
Surgery is a reasonable option if symptoms do not improve with noninvasive methods. Many are available, and most are designed to restore the bladder neck and urethra to their anatomically correct positions.

Treating Urge Incontinence. The goal of most treatments for urge incontinence is to reduce the hyperactivity of the bladder. The following methods may be helpful:

Behavioral methods
Medications (anticholinergics, anti-spasmodics, and alpha blockers)
Procedures that stimulate the pelvic floor or nerves in the tailbone (the sacral nerves), which help retrain the bladder

Lifestyle Changes

Many products are now available that help patients avoid embarrassment and, in some cases, prevent leakage. With recent improvements in paper technology, pads are now thin enough to be worn undetected, and a spare can be hidden in a purse or pocket. Proper hygiene is also essential for patients with incontinence.

Keeping Skin Clean. To avoid skin irritation and infection associated with incontinence, keep the area around the urethra clean. The following tips may be helpful:

After a urinary accident, clean any affected areas right away.
When bathing, use warm water and don't scrub forcefully; hot water and scrubbing can injure the skin.
A number of cleansers are available that are specially created for incontinence and allow frequent cleansing without over-drying or causing irritation to the skin. Most do not have to be rinsed off; the area is simply wiped with a cloth.
After bathing, a moisturizer plus a barrier cream should be applied. Barrier creams include petroleum jelly, zinc oxide, cocoa butter, kaolin, lanolin, or paraffin. These products are water repellent and protect the skin from urine.
Anti-fungal creams that contain miconazole nitrate are used for yeast infections.

Preventing or Reducing Odor. Certain methods may help reduce odor from accidents. They include:

Deodorizing tablets, such as Derifil, Nullo, Devrom, and Chlorofresh can be taken by mouth or used in appliances. Most contain chlorophyll.
Taking an alfalfa pill four times a day may reduce odor, and is not believed to interfere with any other medications. Alfalfa is a common grass, and some people with seasonal allergies may experience an allergic reaction. Talk to your doctor before taking any type of supplement.
Drinking more water, not less, will also reduce odors. Drinking more water may actually help reduce leakage, too.
To remove odors from mattresses, some experts recommend a solution of equal parts vinegar to water. Once the mattress has dried, baking soda can be applied on the stain, rubbed in, and then vacuumed off.

Weight Control. In women, pelvic floor muscle tone weakens with significant weight gain, so women are urged to eat healthy foods in moderation and to exercise regularly.

Fluid Intake. A common misconception among people with incontinence is that drinking less water will prevent accidents. In reality, limiting fluid intake has the following effects:

The lining of the urethra and bladder becomes irritated, which may actually increase leakage.
Concentrated urine also has a stronger pungency, so drinking plenty of fluids can help reduce odor.

Some experts recommend drinking two to three quarts a day.

Drinking plenty of cranberry juice may be particularly helpful. It is known to help prevent urinary tract infections. (Low calorie juices are available.)

People with incontinence, however, should stop drinking beverages 2 - 4 hours before going to bed, particularly those who experience leakage or accidents during the night.

Fiber-Rich Foods. Constipation can worsen urinary incontinence, so diets should be high in fiber, fruits, and vegetables.

Fluid and Food Restrictions. A number of foods and beverages may increase incontinence. Some experts suggest that people who eat or drink the following items should try eliminating one a day over a 10-day period and check to see if removing them improves continence:

Caffeinated beverages. (In one major 2003 study, tea drinking -- but not coffee drinking -- was associated with incontinence. In general, however, it might be useful to try avoiding coffee as well, including decaf coffee.)
Carbonated beverages such as soda
Alcoholic beverages
Citrus fruits and juices
Tomatoes and tomato-based foods
Spicy foods
Chocolate
Sugars and honey
Artificial sweeteners
Milk and milk products

Some otherwise healthy adults stop exercising because of leakage. There are a number of methods for preventing or stopping leakage during exercise. The following are some tips:

Limit fluid intake before exercising (but be sure not to become dehydrated)
Urinate frequently, including right before exercise
Women can try wearing pads or urethral inserts

A variety of absorbent pads and undergarments are quite effective in catching spills and leaks. Many undergarments developed for incontinence are almost indistinguishable from regular briefs and underpants.

For women, the following are available:

Normal and even attractive looking washable underwear that contains waterproof panels is available for women. Even stomach-control panties are available for women with incontinence.

For men, the following are available:

Drip collectors are available which can be worn under briefs and are not noticeable under normal clothing. Lined with absorbent material, the pouch-like collector surrounds the penis or scrotum and is fastened with a belt or pins.
Washable briefs made from polyester have a fully functional fly and waterproof panel and look and feel like normal underwear. Boxer shorts are also available that look regular but have a protective pouch.

Even for men and women with severe incontinence, disposable undergarments can be purchased that have a normal look to them.

All absorbent undergarments should be changed when wet to limit problems of chafing or infection.

A specially shaped plastic urinal (Feminal) is available for women. It avoids the use of a bedpan, and can be used while the woman is lying down, seated, or even standing.

Urinals for men are available that attach to athletic-like supporters.

Other Treatments

Foam pads (Miniguard, UroMed, Impress, Softpatch) with an adhesive coating have been developed for women with stress incontinence. They work as follows:

The pad is placed over the opening of the urethra where it creates a seal, preventing leakage.
It is removed before urinating and replaced with a new one afterwards.
The pad can be worn up to 5 hours a day and through the night.
It can be used during physical activity, although it may change position during vigorous exercise.
It should not be worn during sexual intercourse.

In one study of women who used these products, the average number of leaks per week dropped from 14 to 5. Women with more severe incontinence (an average of 34 leaks a week) had only 10 events, and when leakage occurred, it was slight.

Adhesive pads should not be used by women with the following conditions:

Urinary tract or vaginal infections
Urge or other forms of nonstress incontinence
A history of surgery for incontinence

Urethral Shields. Shields or caps (CapSure, Bard Cap Sure, FemAssist) that fit over the urethral opening are safe and effective in managing many forms of incontinence.

In a study of patients with stress incontinence, CapSure reduced urine loss by 96% within a week, and 82% of patients were completely dry. Side effects include irritation and urinary tract infections, although they are not severe.
In another study, 47% of women who used FemAssist reported complete continence, and 33% of the women reported continence was improved by more than half. FemAssist offered equal benefits for women with stress, urge, or mixed incontinence.

Urethral Tubes or Sleeves. Tubes or sleeves (Reliance Urinary Control Device, FemSoft) that fit into the urethra are also available for female incontinence.

The Reliance Urinary Control Device for women is a small tube inserted into the urethra using a reusable syringe. The device must be prescribed by a doctor, who measures the woman's urethra to determine the right size. The tip of the tube contains a balloon that is inflated against the urethra and blocks urine, preventing leakage. Every time a woman urinates, she pulls a string that deflates the balloon, then throws the old device away and replaces it with a new one. It is effective, but carries a high risk for urinary tract infections and most women report discomfort and irritation.
FemSoft is a silicone tube insert surrounded by a liquid-filled sleeve. When the tube is inserted into the urethra, the sleeve conforms to its shape and creates a seal at the bladder neck, preventing leakage. It is intended for one-time use and is replaced after voiding. This is a relatively new product and information is lacking on its comfort and risk for urinary tract infections.

Vaginal Devices. Devices that support the vaginal wall also help support the urethra that is located next to it:

Tampons. Mild stress incontinence in women, particularly when induced by exercise, may be managed by using a tampon. Specially designed tampons (such as the Contrelle Continence Tampon) are available, but even simple menstrual tampons may be helpful. (Keep in mind that tampons can only be worn for a few hours.) As tampons push on the vaginal wall, it compresses the urethra. In one study, 86% of women with mild incontinence remained continent during exercise sessions when using tampons. Out of this group, however, only 29% with severe incontinence remained dry.
Vaginal Pessaries. Vaginal pessaries are devices inserted into the vagina that support the inside of the vaginal walls. Pessaries are usually made of silicon and come in various forms, including donut or cube-shapes. They must be fitted by a health professional and are effective for vaginal prolapse or other vaginal structural problems. Serious complications are rare but can occur if the pessary is not replaced periodically.
Introl Bladder Neck Support. The Introl bladder neck support prosthesis is a flexible ring that is inserted into the vagina and has two ridges that press against the walls, supporting the urethra. Sizing the Introl is difficult, but success rates of 83% have been reported in women with stress incontinence. It can be left in during urination but must be removed and cleaned afterward. Introl can cause vaginal or urethral infections and may also be uncomfortable.

Behavioral Treatments

With the exception of functional incontinence, most cases of incontinence will almost always improve with behavioral techniques. There are a variety of methods, but the focus is usually on strengthening or retraining the bladder. Studies indicate that such exercises are very effective, even for men recovering from surgery for prostate cancer.

To enhance bladder training for incontinent patients who are in nursing rooms, nurses may need to check patients for dryness and regularly remind them to urinate. As an extra tip for older people with severe incontinence, keeping a pan or portable commode near the bed may prevent injuries from falling as well as improve general convenience.

Perhaps the best first-line approach for any form of incontinence is a combination of Kegel exercises and bladder training. In one study, women who used this combination approach experienced an average 50% reduction in incontinence episodes, with nearly 40% of them achieving complete continence. It was equally effective for urge, stress, or mixed incontinence.

Studies also report that between 50 - 75% of patients who perform only Kegel exercises experience a substantial improvement in their symptoms, including elderly people who have had the problem for years. A 2006 review suggested that Kegel exercises are especially helpful for women in their 40s and 50s who suffer from stress incontinence. The women participated in a supervised Kegel exercise program for at least 3 months.

Pelvic Floor Muscle (Kegel) Exercises. Kegel exercises are designed to strengthen the muscles of the pelvic floor that support the bladder and close the sphincters.

Stress incontinence is an involuntary loss of control of urine that occurs at the same time abdominal pressure is increased as in coughing or sneezing. It develops when the muscles of the pelvic floor have become weak.

Dr. Kegel first developed these exercises to assist women before and after childbirth, but they are very useful in helping to improve continence for both men and women. Kegel exercises are particularly useful for the following conditions:

Stress incontinence. Some experts believe that Kegel exercises should be the primary treatment for stress incontinence.
Urge incontinence. They can also be helpful for urge incontinence in cases that are not caused by nerve damage. In one study, 85% of women reported satisfaction with this program.

The general approach for learning and practicing Kegel exercises is as follows:

Since the muscles are sometimes difficult to isolate, the best method is to first learn while urinating. The patient begins to urinate and then contracts the muscle in the pelvic area with intention of slowing or stopping the flow of urine. Women should contract the vaginal muscles as well. They can detect this by inserting a finger inside the vagina. When the vaginal walls tighten, the pelvic muscles are being correctly contracted.
An alternate approach is to isolate the muscles used in Kegel contractions by sensing then squeezing and lifting the muscles in the rectum that are used in passing gas. (Again, women should contract the vaginal muscles as well.)
Patients should place their hands on their abdomen, thighs, and buttocks to make sure there is no movement in these areas while exercising.
In order to achieve success, some experts recommend performing two exercises that have different timing for the hold and release of the contraction. Both should be done regularly.
The first method is used for strengthening the pelvic floor muscles. The patient slowly contracts and lifts the muscles and holds for 5 seconds, then releases them. There is a rest of 10 seconds between contractions.
The second method is simply a quick contraction and release. The object of this exercise is to learn to shut off the urine flow rapidly.
In general, patients should perform 5 - 15 contractions, three to five times daily.

Some notes of caution:

Once learned, Kegel exercises should not be performed while urinating more than about twice a month, since this practice may eventually weaken the muscles.
In women, incorrect or overly vigorous exercises may cause vaginal muscles to tighten excessively, resulting in pain during sexual intercourse.
Over-exercise can also tire muscles and cause more leakage.
Incontinence will return to its original severity if these exercises are discontinued, so commitment to the program must be high and possibly life-long.
It may be several months before the patient sees significant improvement.

Bladder Training. Bladder training involves a specific, graduated schedule for increasing the time between urinations:

Patients start by planning short intervals between urinations, then gradually progressing with a goal of voiding every 3 - 4 hours.
If the urge to urinate arises between scheduled voidings, patients should remain in place until the urge subsides. At the time, the patient moves slowly to a bathroom. (In a small study, 73% of women with stress incontinence were helped by an absurdly simple and obvious movement: crossing the legs whenever a cough or sneeze was coming on.)

This system uses a set of weights to improve pelvic floor muscle control. The cones are inexpensive, relatively simple to use, and evidence suggests that they are as effective as Kegel exercises or electrostimulation:

The typical set includes five cones of graduated weights ranging from 20 grams (less than 1 ounce) to 65 grams (slightly over 2 ounces).
Starting with the lightest, the woman places the cone in her vagina while standing and attempts to prevent the cone from falling out. The muscles used to hold the cone are the same ones needed to improve continence.

As with standard Kegel exercises, frequent repetition is required, but most women will eventually be able to use the heavier weights and build up the ability to prevent stress and urge incontinence.

Women who are unable to learn Kegel muscle contraction and release with verbal instructions can be helped with the use of biofeedback:

Biofeedback uses a vaginal or rectal probe inserted by the patient that relays information to monitoring equipment.
The patient isolates the pelvic floor and bladder muscles and performs Kegel exercises.
The monitor emits auditory or visual signals that indicate how strongly the patient is contracting the proper pelvic floor muscles and how effectively the bladder muscles are being released.
The apparatus is designed for home use.

As with any Kegel exercise regimen, biofeedback must be used for several months before it is effective. In one major study, 75% of women with urge incontinence reported satisfaction with biofeedback, although women who were simply given verbal cues were even more satisfied (85%). A 2005 study of older women found that biofeedback worked better than oxybutynin (Ditropan) in controlling nighttime urge incontinence. Biofeedback that teaches control of pelvic muscles may even be very helpful in children who have daytime wetting, frequent urinary tract infections, or both.

A treatment called extracorporeal magnetic innervation therapy stimulates pelvic muscles to automatically perform Kegel exercises:

The patients stay fully dressed and sit on a special chair during the treatment.
Highly focused magnetic fields penetrate the pelvic area to stimulate the nerves.
Sessions are twice a week for about 6 weeks, although it may take more than 8 weeks to build up the muscles.

Studies report that patients experience fewer leaks, need fewer pads, and have fewer voiding episodes throughout the day and night. Comparison studies of magnetic therapy and sham (or "dummy") treatments are mixed, however, with some reporting no differences. More studies are needed to determine whether extracorporeal magnetic innervation therapy has any value.

Electrical stimulation of the pelvic floor muscles has been a common treatment for years. The procedure uses a probe inserted into the anus or vagina, which produces a contraction in the pelvic floor muscles. Success rates range from 50 - 90% for urge incontinence. (It may also be useful for some patients with stress incontinence.) A recent study regarding patient-adjusted intermittent electrostimulation in women with stress or mixed urinary incontinence using a new implanted stimulator found the concept promising. Researchers, however, encouraged further investigation regarding the effectiveness and safety of the technique. The procedure requires frequent visits, and it takes 2 - 3 months before the patient feels the benefits. It is often not covered by insurance. Side effects can be distressing and include abdominal cramps, diarrhea, bleeding, and infection.

Medications

A number of medications are available that increase sphincter or pelvic muscle strength or relax the bladder, improving the ability to hold more urine. Medications are prescribed for all kinds of incontinence, but they are generally most helpful for urge incontinence.

Anticholinergics. Anticholinergics work in the following ways:

Inhibit the involuntary contractions of the bladder
Increase capacity of the bladder
Delay the initial urge to void

A major 2003 analysis reported that these drugs produce small but significant improvements. However, the medications have not been rigorously compared with behavioral methods, such as bladder training and Kegel exercises, which are very effective for most cases of urge incontinence. Anticholinergics can have distressing side effects, notably dry mouth.

Anticholinergics include:

Propantheline (ProBanthine). This drug used to be the most commonly prescribed anticholinergic, but has been largely replaced by newer anticholinergics with fewer side effects.
Oxybutynin (Ditropan, Oxytrol)
Tolterodine (Detrol)
Hyoscyamine (Levbid, Cystospaz)

Extended-release versions of oxybutynin (Ditropan XL) and tolterodine (Detrol LA) are proving to be especially effective. They improve continence and have fewer adverse effects than short-acting forms. In a major 2003 comparison study of the extended release drugs, oxybutynin was slightly better than tolterodine, but dry mouth was reported more often. A skin patch form of oxybutynin (Oxytrol) is now available. It appears to work better and have fewer side effects, such as dry mouth and constipation, than the pill form.

Oxybutynin may cause more severe central nervous side effects than previously thought, especially for children and older adults. In 2007, the FDA reviewed 202 cases of oxybutynin-related central nervous system problems. Hallucinations were reported in 27% of pediatric cases and 25% of cases involving adults age 60 and older. Eleven percent of adults age 17 – 59 years experienced hallucinations. The FDA recommends that doctors monitor patients for these symptoms.

According to one study of tolterodine, the drug also improved quality of life. A 2006 study reported that tolterodine is helpful for men with overactive bladder and urge urinary incontinence. A 2006 study, published in the Journal of the American Medical Association, suggested that a combination of tolterodine and the alpha-blocker drug tamsulosin (Flomax) may work better than either drug alone for men with lower urinary tract symptoms, including overactive bladder.

Overactive Bladder Treatments for Children

Oxybutynin (Ditropan X) is approved for pediatric use in children ages 6 and older. The recommended dose is 5 mg once a day. A 2006 study suggested that children who have fewer episodes of daytime wetting may benefit most from this drug.
A 2004 analysis found that tolterodine is also effective and well tolerated in children with urinary symptoms due to overactive bladder.

Side effects of anticholinergic drugs include:

Dry eyes (a particular problem for people who wear contact lenses; patients who wear contacts may wish to start with low doses of medication and gradually build up)
Dry mouth
Headache
Constipation
Rapid heart rate
Confusion, forgetfulness, and possible worsening of mental function, particularly in older people with dementia, such as those with Alzheimer's disease
Hallucinations, possibly, especially for children and older adults
Glaucoma, in rare cases

Antispasmodics. Antispasmodic drugs help relax the bladder muscle and are used for urge incontinence. Before bladder relaxants are prescribed, a thorough evaluation for obstructions in the ureter must be performed to avoid excessive urine retention.

Flavoxate (Urispas) and dicyclomine (Bentyl), the most common antispasmodics, have been used for years, although studies suggest that Urispas has very little benefit for the majority of patients with urge incontinence. The drugs also have anticholinergic properties. In May 2004, the FDA approved a new antispasmodic, trospium chloride (Sanctura), for the treatment of overactive bladder with symptoms or urge incontinence.

Possible side effects reported with use of antispasmodic drugs include:

Weakness
Dizziness
Drowsiness
Hallucinations
Insomnia
Dry mouth
Impotence
Restlessness

M3 selective receptor antagonists. In 2004, the FDA approved darifenacin (Enablex) for treatment of urge incontinence and overactive bladder. Some clinical trials suggested that darifenacin could help reduce weekly incontinence episodes by 83%. The drug’s most common side effects are dry mouth and constipation. For elderly patients, darifenacin may have less negative effects on memory than oxybutynin.

Capsaicin and Analogs. Studies have reported beneficial effects from instillation of capsaicin, a component of hot red chili peppers, into the bladder of people with hyperactive and hypersensitive bladders. Temporary adverse effects, however, can be distressing. A capsaicin analog called resiniferatoxin may be more effective than capsaicin and have fewer side effects.

Alpha-Blockers. Alpha-blockers are drugs that relax smooth muscles and improve urine flow. They are useful for men with benign prostatic hyperplasia who also have urge incontinence. They include terazosin (Hytrin), doxazosin (Cardura), tamsulosin (Flomax), and alfuzosin (Xatral). Tamsulosin may be particularly beneficial. A 2006 study published in the Journal of the American Medical Association reported that the combination of tamsulosin and tolterodine works better than either drug alone for men with moderate-to-severe lower urinary tract symptoms, including overactive bladder. Men in the study were age 40 years and older and had symptoms related to overactive bladder and benign prostatic hyperplasia.

Alpha-Adrenergic Agonists. Alpha-adrenergic agonists are used to strengthen the smooth muscle that opens and closes the internal sphincter. They include ephedrine and pseudoephedrine, which are common ingredients in numerous over-the-counter decongestants and appetite suppressants.

Such drugs may be helpful for patients with mild stress incontinence not caused by nerve damage, although evidence on their benefits is weak. They also can have significant side effects, particularly ephedrine. In fact, products containing a similar drug, phenylpropanolamine (PPA), have been taken off the market because of reports of a higher risk for stroke in some women who took it.

Side effects may include agitation, insomnia, and anxiety. They may have adverse effects on the heart in people with existing heart problems. People with glaucoma, diabetes, hyperthyroidism, heart disease, or high blood pressure should avoid alpha-adrenergic agonists.

Nitrovasolidators. Deficiencies in nitric oxide, a gas that keeps blood vessels open, have been associated with many disorders, including incontinence. Drugs that release nitric oxide, such as nitroflurbiprofen, are being investigated for urinary incontinence.

Evidence indicates that both urge and stress incontinence are affected, in part, by central nervous system processes, particularly signal transmission. Investigators are particularly interested in serotonin and noradrenaline, which are chemical messengers (called neurotransmitters) that affect pathways involved with urination. (These neurotransmitters are also important for many other emotional and physical functions.) Antidepressants targeting one or both of these neurotransmitters are sometimes used for urge incontinence and may also be helpful for some people with stress incontinence.

Tricyclic Antidepressants. Tricyclic antidepressants include imipramine (Janimine, Tofranil), doxepin (Sinequan), desipramine (Norpramin), and nortriptyline (Pamelor). They provide multiple benefits for both urge and stress incontinence. They act as anticholinergic drugs and relax the bladder. They also strengthen the internal sphincter. These drugs should be used carefully. They pose some risk for adverse effects on the heart and possibly the lungs, and they have other severe side effects in older adults. These antidepressants produce side effects similar to anticholinergic drugs, and may cause drowsiness. They may also backfire and actually cause overflow incontinence in some people.
Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs). SNRIs are specially designed antidepressants that are similar to tricyclics but do not have the same side effects. The neurotransmitters serotonin and norepinephrine are thought to play key roles in the normal action of bladder muscles and nerves. Increased neurotransmitter activity stimulates the nerve that controls the urethral sphincter. The SNRI duloxetine (Cymbalta) is approved in Europe for treatment of stress urinary incontinence. (It is approved in the U.S. for other conditions, but not stress urinary incontinence.) In 2005, the manufacturer of duloxetine withdrew its drug application after a small number of women in duloxetine urinary incontinence trials tried to commit suicide. The FDA is investigating whether duloxetine can cause suicidal behavior.

Desmopressin. Studies have reported that desmopressin (DDAVP), a drug used for bedwetting in children, may be helpful in treating adults with urinary incontinence that occurs during sleep. The drug affects sodium levels, and there is a slight risk for water intoxication with this drug.

Botulinum (Botox). Botulinum, the deadly toxin that sometimes contaminates improperly cooked foods, is also a powerful muscle-relaxant. Tiny injected amounts of a purified form (Botox) can relax the muscles and may help control overactive bladder that causes urge incontinence. It may also help relieve urinary retention that might occur after incontinence surgeries.

Stem Cells. Researchers are investigating muscle stem cell injections as a treatment for stress incontinence. Several small studies have indicated promising results. In these experiments, a doctor took a biopsy of skeletal muscle tissue from a patient’s arm. Stem cells were cultured and isolated from the biopsy sample. The doctor then injected the muscle-derived stem cells into the area surrounding the patient’s urethra that is close to the damaged sphincter muscle. In research results presented at the 2007 American Urological Association annual meeting and the 2006 Radiological Association of North American Meeting, patients experienced sustained improvements in bladder control and quality of life.

Surgery

There are nearly 200 procedures for incontinence. Most are designed to restore the bladder neck and urethra to their anatomically correct positions in patients with stress incontinence.

The American Urological Association suggests that surgery should actually be considered as initial therapy for women with severe stress incontinence. It is an effective and safe alternative when conservative treatments fail. Many of the procedures are safe even for women up to 80 years old who do not have serious medical conditions. Potential complications of all procedures include obstruction of the outlet from the bladder, causing difficulty in urination and irritation.

Deciding which procedure to choose is difficult and often depends on the factors causing the incontinence and whether anatomical abnormalities are involved. It should be noted that although hysterectomy has been shown to improve incontinence, it must not be performed only as a cure for incontinence.

In general, patients should weigh all options carefully. They should discuss the situation with their doctor, and ask about their surgeon's experience. As a general rule, the more times a surgeon has successfully performed a procedure, the better.

Retropubic Colposuspension Surgery. Retropubic colposuspension using standard "open" surgery is an effective treatment for stress incontinence, especially over the long term. ("Open" surgery implies the use of a wide incision in order to "open" the area.) Long-term continence rates can range from 85 - 90%.

The goal of colposuspension is to correct the position of the bladder and urethra by sewing the bladder neck and urethra directly to the surrounding pelvic bone or nearby structures. There are many variants, but, in general, they are effective only for women with urethral hypermobility. Most procedures require a general or spinal anesthetic and a 2-day hospital stay.

Burch colposuspension (sometimes called colpocystourethropexy) is a standard approach. It requires a wide abdominal incision and is often performed during abdominal surgeries such as hysterectomy or hernia operations. It is also performed along with sacrocolpopexy, a surgical procedure used to repair pelvic organ prolapse. (Pelvic organ prolapse occurs when the uterus or bladder slips from the pelvic cavity into the vagina. It is often due to pelvic muscle weakness that develops after childbirth.) Prolapse can lead to stress incontinence. However, prolapse surgery itself sometimes causes incontinence. A 2006 study suggested that a Burch colposuspension performed at the same time as sacrolpopexy can help reduce postsurgical stress incontinence.

The surgeon secures the urethra and bladder neck with lateral (sideways) sutures that pass through thick bands of muscle tissue running along the pubic bones. Unlike an older suspension procedure, this procedure poses a much lower risk for obstruction of the urethra. It is more effective in premenopausal than postmenopausal women and may not be appropriate for all women.

A rigorous 2007 study published in the New England Journal of Medicine compared the effectiveness of the Burch colposuspension to the sling procedure, another type of surgical treatment for stress incontinence. The study found that the sling procedure had better results for achieving dryness. However, more women who had the sling procedure had post-operative urinary problems, especially urinary tract infections. Overall, women were satisfied with the outcomes of both procedures. Eighty-six percent of women who had a sling procedure and 78% of women who had a Burch colposuspension reported satisfaction with their treatment.

Marshall-Marchetti-Krantz (MMK). The MMK approach requires a wide abdominal incision. The surgeon then elevates the urethra and bladder neck using sutures. These structures are then secured and anchored in nearby cartilage. This approach is one of the most reliable, but is used less often because of the risk for scarring and because the incision limits the surgeon's ability to correct any potential hernias (cystoceles).

Click the icon to see an illustrated series detailing bladder neck surgery.

Laparoscopy. Other less invasive procedures use laparoscopy, which requires only one or two small incisions over the pubic bone. Evidence suggests that laparoscopy, performed by an experienced surgeon, works just as well as standard surgery. While laparoscopy has a higher complication rate, it also has a faster recovery time and less postoperative pain. Still, well-conducted long-term studies are needed for an accurate comparison with standard colposuspension.

Needle Suspension. Needle suspensions include a number of approaches, including the Pereyra, Stamey, Raz, and Gittes procedures. The basic approach places stitches on either side of the bladder and ties them to muscle tissue or the pubic bone. Some of these procedures use transvaginal suspension, which requires only a small abdominal incision or no incision at all. In this case, the surgeon works through the vagina and places sutures through the vaginal walls. Transvaginal suspension works only if the walls of the vagina are strong enough to withstand the procedure. Some studies report poor long-term results, particularly compared to colposuspension. In one study, only 35% of patients who had transvaginal suspension reported success after 6 years. In another study, the failure rate was 83% after 4 - 5 years. Additional research has indicated that 20% of women have worse sexual function after the procedure.

Postoperative Considerations for Most Procedures. Following most standard procedures, patients usually leave the hospital on the second or third day, but need a urinary catheter for about 10 days. Newer procedures may require shorter stays and less intensive postoperative care.

Complications after surgery include:

Some risk of damage to the surrounding nerves or vessel. This can result in internal sphincter deficiency. (In some cases it may already have been present before the operation.)
Difficulty in urinating from surgical overcorrection. (This may require additional surgery.)
Poor wound healing.
Adhesions (scar tissue) that obstruct the urethra. This complication is higher with older standard procedures.
Vaginal abnormalities (prolapsed vagina).

A sling procedure may be a good option for severe stress incontinence in women who have either intrinsic sphincter deficiency or urethral hypermobility. The method is even proving to help women with mild-to-moderate incontinence and young girls with severe incontinence. It may also be useful for managing female urge incontinence. Sling procedures are also available for men who experience incontinence after prostatectomy.

Until recently, there were few clinical trials that directly compared the sling procedure with Burch colposuspension. In 2007, the New England Journal of Medicine published the results of the largest and most rigorous clinical trial conducted on these two types of surgery. In this study of 655 women with stress incontinence, half of the women underwent the sling procedure and half had open surgery with the Burch colposuspension.

Two years after surgery, success rates were highest for women who had the sling procedure. Forty-seven percent of women who had the sling procedure reported no urinary incontinence (either stress or urge) compared to 38% of women who had the Burch procedure. For stress-only incontinence, 66% of women who had the sling procedure and 49% of women who had the Burch procedure were dry. Eighty-six percent of women who had the sling procedure and 78% of the Burch group reported satisfaction with their treatment.

However, women who had the sling procedure did experience more post-operative urinary problems. The most common complication was urinary tract infections, which affected 63% of women who had a sling procedure compared with 47% of women who had the Burch procedure. A small number of women who had a sling procedure also reported difficulty voiding and urge incontinence.

The Percutaneous Sling Procedure for Women. The procedure generally works as follows:

The surgeon makes an incision above the pubic bone and removes a layer of abdominal fasci (tissue that covers muscle fibers). This muscle strip is set aside and later serves as the sling. (The uses of fasci taken from a cadaver or synthetic slings are also being investigated. However, the natural muscle strip may last longer than some of the common synthetic materials.)
The surgeon makes an incision in the vaginal wall. The piece of muscle fiber or material is attached under the urethra and bladder neck, somewhat like a hammock, and secured to the abdominal wall and pelvic bone.
This sling then compresses the urethra back to its original position. The sling must be supportive without being too tense, which can cause urinary obstruction.

Complications can include infection, bleeding, and the formation of fistulas (holes that form and are usually infected).

Vaginal Sling and Tape Procedures for Women. Newer outpatient procedures do not use abdominal incisions. Instead, they are performed through a small incision in the vagina. Typically, two small tacks are placed in the pubic bone. A sling is inserted into the vagina and is attached to the tack.

The tension-free vaginal tape (TVT) procedure uses a special gauze tape covered by a polypropylene coating, which is attached on each side of the urethra. The patient remains conscious and is asked to cough during the procedure so that the surgeon can determine if the tape is secure. Small early studies showed that the procedure worked as well as colposuspension (the standard suspension procedure), with stress incontinence cure rates of 84 - 100%. According to a 2005 study, the benefits of TVT can last for up to 8 years for women with stress incontinence. However, women with mixed incontinence (a combination of stress and urge) did not fare as well. Women with mixed incontinence had a 60% cure rate during the first 4 years following surgery, but the cure rate declined to 30% within 4 - 8 years post-surgery.

Sling Procedures in Men. For some men who have prostatectomy-induced incontinence, sling procedures may be a good option. Researchers have reported an 80% success rate, the same as an artificial urinary sphincter, which is the standard surgical treatment for such patients. The sling procedure has been less effective in men who have had radiation therapy, although improved techniques are making this approach useful even for these patients. Minimally invasive procedures are also being tested.

Artificial Sphincter. In cases of sphincter incompetence, or complete lack of sphincter function, an artificial internal sphincter may be implanted. This procedure is useful for appropriate male and female candidates of any age, including children. It is particularly helpful for men after radical prostatectomy. Studies have found poor results for patients with incontinence due to radiation therapies, although a 2001 study of men with prostatectomy indicated that it was useful regardless of previous radiation therapy.

Click the icon to see an illustrated series detailing artificial sphincter surgery.

This device uses a balloon reservoir and a cuff around the urethra that is controlled with a pump. The patient opens the cuff manually by activating the pump. The urethra opens and the bladder empties. The cuff closes automatically several minutes later. The two major drawbacks of the internal sphincter implant are:

Malfunction. If the implant malfunctions, the surgery must be performed again.
Infection. Infection is more serious as it can cause erosion of the urethra or bladder neck underneath the implant. Such infections not only require removal of the device, but also may worsen the incontinence. Fortunately, techniques have improved so that infection is uncommon.

In a 2001 study, after an average of 7 years, 70% of female patients with stress incontinence had either the original implant or a replacement, and 82% had urination properly restored. (Only 37% still had the original implant, however.) Studies on men have reported similar findings, although newer devices that use narrow cuffs may significantly improve re-implantation rates. Nearly all patients still need to use pads for leakage.

Injections of materials, such as collagen, that provide bulk to help support the urethra are proving to be beneficial for the following patients:

Women (even the elderly) with severe stress incontinence who cannot or do not wish to have surgery that involves anesthesia.
Men who have slight incontinence caused by prostate surgery. Men who have bulking injections after TURP (transurethral resection of the prostate) have a continence rate that is equal to the rate in women. After radical prostatectomy (removal of the prostate gland in prostate cancer), collagen injections can achieve some level of continence in up to nearly half of men. (Collagen injections are not beneficial after radiation therapy for prostate cancer.)

The Procedure.

First, bladder instability or hyperactivity should be medically treated and managed to control muscle activity before having the procedure. Otherwise it is likely to fail.
The basic procedure involves injecting bulking material into the tissue surrounding the urethra.
The material used is usually animal or human collagen. (Collagen is the basic protein in bones, muscles, and all connective tissue.) Synthetic bulking materials, such as carbon-coated beads, are also being used.
The doctor passes the collagen-containing needle through a cystoscope, a tube that has been inserted into the urethra. The collagen can also be injected into the skin next to the sphincter.
The injected collagen tightens the seal of the sphincter by adding bulk to the surrounding tissue.
The procedure takes about 20 - 40 minutes, and most people can go home immediately afterward.
Two or three additional injections may be needed to achieve satisfactory results.

Postoperative Care. People may experience immediate improvement followed by a temporary relapse after a week or so. Patients must be taught to use a catheter tube for withdrawing urine for a few days following the procedure. In general, it takes about a month for the full benefits to be apparent.

Complications.

There is a risk for infection and urinary retention, although these conditions are temporary.
An increase in autoimmune disease has been reported in a small number of cases.
The procedure may not be appropriate for patients with certain cardiac conditions.

Duration of Effectiveness. Collagen is absorbed over time, so injections generally need to be repeated every 6 - 18 months. According to one study, however, after a year 44% of women who had the implants still experienced the same level of improvement. (Synthetic materials may last longer than collagen from other sources, but they pose a risk for rejection as well as migration to the lymph nodes and other parts of the body.)

Anterior vaginal repair procedures that correct a prolapsed (fallen) uterus or vagina can often correct incontinence in women who have these conditions. The anterior vaginal repair (also called a bladder tuck) requires an incision to be made through the vagina. This releases part of the anterior (front) vaginal wall, which is attached to the base of the bladder. The pubocervical fascia (the supportive tissue between the vagina and bladder) is folded and stitched to bring the bladder and urethra into proper position. Several variations on this procedure may be necessary, depending on the severity of the prolapse. It is not as effective as retropubic suspension procedures, however, and should not be used as the primary method for correcting incontinence.

An interesting investigative approach uses radiofrequency energy to shrink tissue that supports the bladder neck and reduces hypermobility. Early studies are promising. In one, for example, the cure rate was nearly 80% at the end of a year, and 83% of patients reported satisfaction with the procedure.

Other Procedures

The sacral nerves, located in the tail bone, appear to play an important role in regulating bladder control. A sacral nerve stimulation system (InterStim) is now available for patients with urge incontinence. The system sends electrical pulses to the sacral nerves to help retrain them. InterStim is reserved for the treatment of urinary retention and the symptoms of overactive bladder in patients who have failed or cannot tolerate less invasive treatments. The system works as follows:

A stopwatch-size device is implanted under the skin in the abdomen.
A wire connected to it runs to the sacral nerves in the lower back.
The device, a battery-operated generator, produces electrical pulses.
The pulses are sent to the sacral nerves and reduce the hyperactivity of the bladder.
The sensation of the electrical pulse is similar to a slight pulling sensation in the pelvic area. Sometimes it can cause a small jolt or shock if the patient changes posture quickly. It should not cause pain. (If it does, something is wrong with the device.)

Complications include infection, lower back pain, and pain at the implant site. The system, however, does not cause nerve damage and can be removed at any time.

Patients have reported improvement in the frequency and volume of urination, as well as the intensity of urgency and their quality of life. Studies report complete dryness in nearly half of patients, with about 75% of patients experiencing relief from heavy leaking.

Transcutaneous Neuromodulation. The use of electrodes on the surface of the skin, called transcutaneous neuromodulation, may prove to be beneficial and particularly attractive for children.

Percutaneous Stoller Afferent Nerve Stimulation. The percutaneous stoller afferent nerve system (PerQ SANS System) has also been approved for urge incontinence.

In this therapy, a very thin needle is inserted a short distance above the ankle bone.
The needle is applied to the tibial nerve in the ankle, which connects with the sacral nerve complex.
Low-frequency electrical stimulation is applied for 30 minutes once a week for about 3 months.
After that, depending on the patient's response, treatments are given every week to every other week.
Short-term results are promising, but more research is needed.

Catheters and Collection Devices

A catheter is a slim flexible tube inserted into the urethra. They are mainly used for cases of severe urge incontinence.

A catheter (a hollow tube) may be inserted into the urinary bladder when there is a urinary obstruction, following surgical procedures to the urethra, in unconscious patients (due to surgical anesthesia, coma, etc.), or for any other problem in which the bladder needs to be kept empty (decompressed) and urinary flow assured.

Click the icon to see an image of male bladder catheterization.

Temporary Catheterization. For people who are still active, catheterization is often very distressing. If possible, temporary, also called intermittent, catheterization is usually the best choice. Patients insert the catheter tube into their urethras, generally every 3 - 4 hours. This type of catheterization carries few risks and empties the bladder completely. Some patients report that they can maintain an active life with no significantly increased risk for infection with some simple precautions:

Sterilize catheters at home.
Use a Zip Lock plastic bag for carrying them when leaving home.
Use another plastic bag for antiseptic cleansing solution.
When using public bathrooms, wash before and after catheterization. Touch as few places in the bathroom as possible.

Permanent Catheterization. People who are mentally or physically incapable of self-catheterization may need permanent catheterization.

The permanent catheter is inserted by a doctor or nurse into the opening of the bladder and a cuff is inflated to hold the tube in place.
Urine drains to an external collection device, which is generally strapped to the leg and must be emptied periodically.

The procedure is not painful, but there is a substantial increased risk of infection. Many experts feel that the catheter is overused, especially in the elderly.

Condom Catheters. Condom catheters are much more satisfactory than standard catheters for many male patients, although there is more spillage.

The condom is worn all day.
At night it is removed and washed for reuse the next day.

Collection Devices Attached to the Leg. For chronic or severe incontinence, collective devices drain urine into a bag that is attached to the lower leg and emptied periodically. These are generally more successful for men. Urine can be funneled into the tube by a pouch surrounding the penis. The positioning of the collecting device is difficult for women, and more accidents occur. For both men and women, irritation of the area around the urethral opening is a problem, since urine is in contact with the area for long periods.

Resources

www.nafc.org -- National Association for Continence
www.simonfoundation.org -- The Simon Foundation for Continence
www.niddk.nih.gov -- National Kidney and Urologic Diseases Information
www.acog.org -- American College of Obstetricians and Gynecologists
www.augs.org -- American Urogynecologic Society
www.kegel-exercises.com -- Information on Kegel Exercises
www.urologyhealthy.org -- Urology Health from the American Urological Association

References

Albo ME, Richter HE, Brubaker L, et al. Burch colposuspension versus fascial sling to reduce urinary stress incontinence. N Engl J Med. 2007 May 24;356(21):2143-2155. Epub 2007 May 21.

Harris SS, Link CL, Tennstedt SL, Kusek JW, McKinlay JB. Care seeking and treatment for urinary incontinence in a diverse population. J Urol. 2007 Feb;177(2):680-4.

Kaplan SA, Roehrborn CG, Rovner ES, Carlsson M, Bavendam T, Guan Z. Tolterodine and tamsulosin for treatment of men with lower urinary tract symptoms and overactive bladder: a randomized controlled trial. JAMA. 2006 Nov 15;296(19):2319-28.

Litwin MS, Saigal CS, editors. Urologic Diseases in America. US Department of Health and Human Services, Public Health Service, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. Washington, DC: US Government Printing Office, 2007; NIH Publication No. 07–5512.

Review Date:
6/15/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

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