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Endometriosis is a noncancerous disorder in which patches of endometrial tissue—normally occurring only in the lining of the uterus (endometrium)—appear outside the uterus.
Endometriosis is a chronic disorder that may be painful. Exactly how many women have endometriosis is unknown because it can usually be diagnosed only by directly viewing the endometrial tissue (which requires a surgical procedure). Endometriosis probably affects about 10 to 15% of menstruating women aged 25 to 44. It can also affect teenagers.
Endometriosis sometimes runs in families and is more common among first-degree relatives (mothers, sisters, and children) of women with endometriosis. It is more likely to occur in women who have their first baby after age 30, who have never had a baby, who have short menstrual cycles (less than 27 days), or who have certain structural abnormalities of the uterus. Endometriosis seems to occur less often in women who have had several pregnancies, who use low-dose oral contraceptives, or who exercise regularly (especially if they started before age 15, exercise more than 7 hours a week, or both).
The cause of endometriosis is unclear, but there are several theories:
Common locations of misplaced endometrial tissue (called implants) include the ovaries, the ligaments that support the uterus, the space between the rectum and vagina or cervix, and the fallopian tubes. Less common locations include the outer surface of the small and large intestines, the ureters (tubes leading from the kidneys to the bladder), the bladder, and the vagina. Rarely, endometrial tissue grows on the membranes covering the lungs (pleura), the sac that envelops the heart (pericardium), the vulva, the cervix, or surgical scars in the abdomen.
The misplaced endometrial tissue responds to hormones as normal endometrial tissue does. Thus, it can bleed and cause pain, particularly before and during menstrual periods. The severity of symptoms and the disorder's effects on fertility and on organ function vary greatly from woman to woman.
As the disorder progresses, the misplaced endometrial tissue tends to gradually increase in size. It may also spread to new locations. However, how much tissue is present and how quickly endometriosis progresses vary greatly. The tissue may remain on the surface of structures or may penetrate deeply (invade) and form nodules.
Symptoms
The main symptom is pain in the lower abdomen and pelvic area. The pain usually varies during the menstrual cycle, worsening before and during menstrual periods. Menstrual irregularities, such as heavy menstrual bleeding and spotting before menstrual periods, may occur. Misplaced endometrial tissue responds to the same hormones—estrogen and progesterone (produced by the ovaries)—as normal endometrial tissue in the uterus. Consequently, the misplaced tissue may bleed during menstruation and often causes cramps and pain.
The severity of symptoms does not depend on the amount of misplaced endometrial tissue. Some women with a large amount of tissue have no symptoms. Others, even some with a small amount, have incapacitating pain. In many women, endometriosis does not cause pain until it has been present for several years. For some women, sexual intercourse tends to be painful before or during menstruation.
Endometrial tissue attached to the large intestine may cause abdominal bloating, pain during bowel movements, or diarrhea, constipation, or rectal bleeding during menstruation. If the bladder is affected, women may feel pain above the pubic bone during urination, and urine may contain blood. Endometrial tissue may invade an ovary and form a blood-filled mass (endometrioma). Occasionally, an endometrioma ruptures or leaks, causing sudden, sharp abdominal pain.
The misplaced endometrial tissue and its bleeding may irritate nearby tissues. As a result, scar tissue may form, sometimes as bands of fibrous tissue (adhesions) between structures in the abdomen. The misplaced endometrial tissue and adhesions can interfere with the functioning of organs. Rarely, adhesions block the intestine.
Severe endometriosis may cause infertility when the misplaced tissue blocks the egg's passage from the ovary into the uterus. Mild endometriosis may also cause infertility, but how it does so is less clear. As many as 25 to 50% of infertile women have endometriosis.
During pregnancy, endometriosis may become inactive (go into remission) temporarily or sometimes permanently. Endometriosis tends to become inactive after menopause because estrogen levels decrease.
Diagnosis
A doctor may suspect endometriosis in a woman who has typical symptoms or unexplained infertility. Occasionally, during a pelvic examination, a woman may feel pain or tenderness, or a doctor may feel a mass of tissue behind the uterus or near the ovaries.
If endometriosis is suspected, a doctor examines the abdominal cavity with a thin, flexible viewing tube (called a laparoscope) to check for endometrial tissue. The laparoscope is inserted into the abdominal cavity through a small incision just above or below the navel. Carbon dioxide gas is injected into the abdominal cavity to distend it so that organs can be viewed more easily. The entire abdominal cavity is examined. If abnormal tissue is seen (particularly if the doctor is uncertain that the tissue is endometriosis), a biopsy may be done. A sample of the tissue is removed, using instruments inserted through the laparoscope. The sample is then examined using a microscope. Laparoscopy usually requires a general anesthetic, but an overnight stay in the hospital is usually required only if a very large amount of tissue is removed. Laparoscopy causes mild to moderate abdominal discomfort, but normal activities can usually be resumed in a few days.
Sometimes a biopsy is done during other procedures. A larger incision into the abdomen (laparotomy) may be required. Depending on the location of the misplaced tissue, the biopsy may be done when the vagina is inspected during a pelvic examination or when a flexible viewing tube is used to examine the lower part of the large intestine, rectum, and anus (sigmoidoscopy) or bladder (cystoscopy).
Other procedures may be used to determine the extent of endometriosis and follow its course, but their usefulness for diagnosis is limited. These tests include ultrasonography, x-rays taken after a barium enema, computed tomography (CT), and magnetic resonance imaging (MRI). Sometimes blood tests are done to measure levels of substances that increase when endometriosis is present. These substances (called markers) include cancer antigen 125 and antibodies to endometrial tissue. These markers cannot be used to confirm the diagnosis because they may be increased in several other disorders. Tests may be done to determine whether the endometriosis is affecting the woman's fertility (see Infertility: Diagnosis).
Doctors classify endometriosis as minimal (stage I), mild (stage II), moderate (stage III), or severe (stage IV) based on the amount, location, density, and size of misplaced tissue and on the presence of adhesions.
Treatment
Treatment depends on a woman's symptoms, pregnancy plans, and age, as well as the stage of endometriosis.
Drugs:
Usually, nonsteroidal anti-inflammatory drugs (NSAIDs—see Pain: Nonsteroidal Anti-Inflammatory Drugs) are used to relieve pain. They may be all that is needed if symptoms are mild and women do not plan to become pregnant.
Other drugs can be used to suppress the activity of the ovaries and thus slow the growth of the misplaced endometrial tissue and reduce bleeding and pain. However, these drugs may not eliminate endometriosis, and even if they do, endometriosis often recurs after the drugs are stopped unless more radical treatment is used. These drugs include combination oral contraceptives (estrogen plus a progestin), progestins (such as medroxyprogesterone), danazol (a synthetic male hormone, or androgen), and gonadotropin-releasing hormone agonists (GnRH agonists—such as goserelin, leuprolide, and nafarelin).
Oral contraceptives are used primarily in women who do not plan to become pregnant soon. Oral contraceptives may also be used after treatment with danazol or a GnRH agonist. The oral contraceptives can be taken continuously, especially if pain is worse during menstrual periods.
GnRH agonists turn off the brain's signal to the ovaries to produce estrogen and progesterone. As a result, production of these hormones decreases. Continued use of GnRH agonists causes a decrease in bone density and may lead to osteoporosis unless women also take small doses of oral contraceptives (estrogen plus a progestin or a progestin alone) or take a bisphosphonate (such as alendronate, ibandronate, or risedronate). Even when taken this way, GnRH agonists are not usually given for longer than 6 months.
New types of drugs, such as GnRH antagonists, antiprogestins, selective estrogen and progestin receptor modulators, aromatase inhibitors, and immune modulators (which stimulate the immune system) are being studied for the treatment of endometriosis.
Surgery:
Surgery beyond diagnostic laparoscopy may be needed in the following situations:
Often, misplaced endometrial tissue can be surgically removed during laparoscopy when the diagnosis is made. However, more extensive surgery requiring an incision into the abdomen (laparotomy) may be necessary.
If pain is persistent, the misplaced endometrial tissue may be removed, the nerve pathways that conduct pain sensation from the pelvis to the brain may be interrupted, or both may be done. Sometimes electrocautery (a device that uses an electrical current to produce heat), an argon beam coagulator (a device that uses argon gas to stop bleeding), an ultrasound device, or a laser is used to destroy or remove endometrial tissue during laparoscopic or abdominal surgery.
During surgery, doctors remove as much misplaced endometrial tissue as possible without damaging the ovaries. Thus, the woman's ability to have children may be preserved. Depending on the extent of the endometriosis, 40 to 70% of women who have surgery may become pregnant. If doctors cannot remove all of the tissue, women may be given an oral contraceptive or a GnRH agonist. This drug may increase their chances of becoming pregnant by further reducing the severity of endometriosis. Some women who have endometriosis can become pregnant by using assisted reproductive techniques, such as in vitro fertilization (see Infertility: In Vitro (Test Tube) Fertilization (IVF)).
Surgical removal of misplaced endometrial tissue is only a temporary measure. After treatment, endometriosis recurs in most women, although the use of oral contraceptives or other drugs may slow its progression. These drugs may be started immediately after surgery.
Removal of both ovaries and the uterus (oophorectomy plus hysterectomy) is appropriate only when drugs do not relieve abdominal or pelvic pain in women who do not plan to become pregnant. Removal of the ovaries and uterus has the same effects as menopause because both result in decreased estrogen levels (see Menopause). Thus, women may be given estrogen to reduce the severity of menopausal symptoms. Most women are also given a progestin. A combination oral contraceptive (estrogen plus a progestin) may be used in young women of premenopausal age. The progestin is included to help suppress the progression of endometriosis. Estrogen may be started after surgery. If a large amount of endometrial tissue remains, estrogen may be delayed 4 to 6 months because it may stimulate growth of the remaining endometrial tissue. The delay gives the endometrial tissue time to decrease in size or disappear. A progestin alone can be given to reduce symptoms and to help remaining endometrial tissue regress.
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Drugs Commonly Used to Treat Endometriosis
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Drug
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Some Side Effects
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Comments
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Combination estrogen-progestin oral contraceptives
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Ethinyl estradiol plus a progestin
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Abdominal bloating, breast tenderness, increased appetite, ankle swelling, nausea, bleeding between periods (breakthrough bleeding), and deep vein thrombosis
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Oral contraceptives may be useful for women who wish to delay childbearing. They may be taken 3 weeks a month (cyclically) or or every day (continuously).
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Possibly an increased risk of heart attack, stroke, and peripheral vascular disease
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Progestins
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Medroxyprogesterone acetate
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Bleeding between periods, mood swings, depression, and atrophic vaginitis (drying and thinning of the vagina's lining)
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Progestins are drugs that resemble the hormone progesterone. They can be given by mouth or by injection into a muscle.
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Possibly an increased risk of heart attack, stroke, and peripheral vascular disease
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Androgen
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Danazol
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Weight gain, acne, lowering of the voice, increased body hair, hot flashes, atrophic vaginitis, ankle swelling, muscle cramps, bleeding between periods, decreased breast size, mood swings, liver malfunction, carpal tunnel syndrome, and adverse effects on cholesterol levels in the blood
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Danazol, a synthetic hormone related to testosterone, inhibits the activity of estrogen and progesterone. It is taken by mouth. The usefulness of danazol may be limited by its side effects.
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GnRH agonists
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Goserelin
Leuprolide
Nafarelin
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Hot flashes, atrophic vaginitis, a decrease in bone density, and mood swings
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GnRH agonists may be injected under the skin or into a muscle once a month, used as a nasal spray, or implanted as a pellet under the skin. These drugs are often given with estrogen, a progestin, or both to reduce the effects of decreased estrogen levels, including decreased bone density. (This use of estrogen plus a progestin or of a progestin alone is called add-back therapy.)
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GnRH = gonadotropin-releasing hormone.
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Last full review/revision May 2007 by Robert W. Rebar, MD
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