James H. Liu, MD, Arthur H. Bill Professor and Chair, Departments of Obstetrics and Gynecology and Reproductive Biology;Professor, Obstetrics and Gynecology, UH Cleveland Medical Center, Case Western Reserve University;Case Western Reserve University School of Medicine
In endometriosis, patches of endometrial tissue—normally occurring only in the lining of the uterus (endometrium)—appear outside the uterus.
Why endometrial tissue appears outside the uterus is unknown.
Endometriosis can impair fertility and cause pain (particularly before and during menstrual periods and during sexual intercourse), but it may cause no symptoms.
Doctors check for endometrial tissue by inserting a thin viewing tube through a small incision near the navel (laparoscopy).
Drugs are used to relieve pain and to slow the growth of the misplaced tissue.
Surgery may be done to remove the endometrial tissue outside the uterus and sometimes to remove the uterus and the ovaries.
Endometriosis: Misplaced Tissue
In endometriosis, small or large patches of endometrial tissue, which is usually located only in the lining of the uterus (endometrium), appear in other parts of the body. How and why the tissue appears in other locations is unclear.
Common locations of misplaced endometrial tissue include the ovaries and ligaments supporting the uterus and, less commonly, the fallopian tubes. But the misplaced tissue may also appear in other locations in the pelvis and abdomen or, rarely, on the membranes that cover the lungs or heart.
The misplaced endometrial tissue can irritate nearby tissues, causing bands of scar tissue (adhesions) to form between structures in the abdomen. The misplaced tissue can also block the fallopian tubes, causing infertility.
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, typically laparoscopy). About 6 to 10% of all women have endometriosis. The percentage of women who have endometriosis is higher among women who are infertile (25 to 50%) and women who have pelvic pain (75 to 80%). The average age at diagnosis is 27, but endometriosis can develop in adolescents.
Common locations of misplaced endometrial tissue (called implants) include the following:
Ligaments that support the uterus
Space between the rectum and vagina or cervix
Less common locations include the fallopian tubes, 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.
Causes of Endometriosis
The cause of endometriosis is unclear, but there are several theories:
Small pieces of the lining of the uterus (endometrium) that are shed during menstruation may flow backward through the fallopian tubes toward the ovaries into the abdominal cavity, rather than flow through the vagina and out of the body with the menstrual period.
Cells from the endometrium (endometrial cells) may be transported through the blood or lymphatic vessels to another location.
Cells located outside the uterus may change into endometrial cells.
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 with the following characteristics:
Have their first baby after age 30
Have never had a baby
Have short menstrual cycles (less than 27 days) that are heavy and last a long time
Started to menstruate earlier than usual or stopped menstruating later than usual
Have certain structural abnormalities of the uterus
Have mothers who, when pregnant, took the drug diethylstilbestrol (DES), prescribed to prevent miscarriage (in 1971, the drug was banned in the United States)
Endometriosis seems to occur less often in women with the following characteristics:
Have had several pregnancies
Started to menstruate later than usual
Breastfeed a long time
Use low-dose oral contraceptives
Exercise regularly (especially if they started before age 15, exercise more than 4 hours a week, or both)
Symptoms of Endometriosis
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 endometriosis 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.
Symptoms also vary depending on where the endometrial tissue is located. Possible symptoms by location include
Large intestine: Abdominal bloating, pain during bowel movements, or diarrhea, constipation, or rectal bleeding during menstruation
Bladder: Pain above the pubic bone, pain during urination, urine that contains blood, and a frequent and urgent need to urinate
Ovaries: Formation of a blood-filled mass (endometrioma), which sometimes 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.
During pregnancy, endometriosis may become inactive (go into remission) temporarily or sometimes permanently. Endometriosis tends to become inactive after menopause because estrogen and progesterone levels decrease.
Diagnosis of Endometriosis
Laparoscopy to check for endometrial tissue
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 lump or mass of tissue behind the uterus or near the ovaries.
If endometriosis is suspected, a doctor examines the abdominal cavity with a thin viewing tube (called a laparoscope) to check for endometrial tissue. The laparoscope is inserted into the abdominal cavity (the space around the abdominal organs) through a small incision most often made just above or below the navel. Carbon dioxide gas is inserted into the abdominal cavity to distend it so that organs can be viewed more easily. The entire abdominal cavity is examined.
If a doctor sees abnormal tissue and is not sure that it is endometrial tissue, 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 abnormal tissue is removed. Laparoscopy causes mild to moderate abdominal discomfort, but normal activities can usually be resumed in a few days.
Depending on the location of the misplaced tissue, a biopsy may be done when the vagina is inspected during a pelvic examination or when a flexible viewing tube is inserted through the anus to examine the lower part of the large intestine, rectum, and anus (sigmoidoscopy) or bladder (cystoscopy).
Ultrasonography may be done to determine the extent of endometriosis and follow its course, but its usefulness for diagnosis is limited.
If a woman is infertile, tests may be done to determine whether the cause is endometriosis or another disorder, such as problems with the fallopian tubes.
Doctors classify endometriosis as minimal (stage I), mild (stage II), moderate (stage III), or severe (stage IV) based on the following:
The amount of misplaced tissue
Its depth (whether it is on the surface of or deep within an organ)
The presence and number of endometriomas and adhesions
Doctors may use the following to estimate what the chances of becoming pregnant are for a woman with endometriosis:
How severe the endometriosis is (its stage)
How old the woman is
How long she has been infertile
Whether she had been pregnant before
How well her reproductive organs are functioning
Treatment of Endometriosis
NSAIDs for pain
Drugs to suppress the activity of the ovaries
Surgery to remove or destroy the misplaced endometrial tissue
Sometimes surgery to remove only the uterus or the uterus and the ovaries
Endometriosis treatment depends on a woman's symptoms, pregnancy plans, and age, as well as the stage of endometriosis.
Drugs used to treat endometriosis
Usually, nonsteroidal anti-inflammatory drugs (NSAIDs) are used to relieve pain. They may be all that is needed if symptoms are mild and women do not plan to become pregnant.
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. The following drugs are commonly used:
Combination oral contraceptives (estrogen plus a progestin)
Other drugs that suppress the activity of the ovaries are usually used only when women cannot take combination oral contraceptives or when treatment with combination oral contraceptives is ineffective. They include
Progestins (such as medroxyprogesterone and norethindrone)
Gonadotropin-releasing hormone agonists (GnRH agonists—such as leuprolide and nafarelin)
Danazol (a synthetic male hormone, or androgen)
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 to completely and permanently stop the ovaries from functioning.
Combination 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 to try to slow progression of the disorder and to reduce pain. 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. Side effects of GnRH agonists include hot flashes, stiff joints, mood changes, and vaginal dryness. Continued use of GnRH agonists for more than 4 to 6 months causes a decrease in bone density and may lead to osteoporosis. To minimize the decrease in bone density, doctors may give women small doses of a progestin or a bisphosphonate (such as alendronate, ibandronate, or risedronate). If endometriosis recurs, women may need to be treated again.
Danazol inhibits release of an egg (ovulation). However, it has side effects including weight gain and the development of masculine characteristics (such as increased body hair, loss of hair from the head, reduced breast size, and lowering of the voice). These side effects limit its use.
After treatment with drugs, fertility rates range from 40 to 60%. Drugs do not change fertility rates in women with minimal or mild endometriosis.
Abdominal bloating, breast tenderness, increased appetite, ankle swelling, nausea, bleeding between periods (breakthrough bleeding), mood swings, and deep vein thrombosis
Rarely an increased risk of heart attack, stroke, and peripheral vascular disease
Oral contraceptives may be useful for women who wish to delay childbearing. They may be taken 3 weeks a month (cyclically) or every day (continuously), usually for 3–4 months. Then, they are stopped for 4 days and started again.
An intrauterine device (IUD) that releases the progestin levonorgestrel
Irregular menstrual bleeding and stopping of periods (after the IUD has been in place for a while)
These IUDs release levonorgestrel for 5 years. They must be inserted and removed by a doctor. They are appropriate for women who do not wish to become pregnant or who wish to delay pregnancy.
Bleeding between periods, mood swings, depression, weight gain, and atrophic vaginitis (drying and thinning of the vagina's lining)
Progestins are drugs that resemble the hormone progesterone. They can be given by mouth or by injection into a muscle.
Irregular menstrual bleeding, mood swings, depression, and weight gain
This drug is taken by mouth at bedtime.
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
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.
Hot flashes, atrophic vaginitis, a decrease in bone density, muscle and bone aches, stiff joints, mood swings, and a reduced sex drive
A GnRH agonist may be injected under the skin once a day, injected into a muscle once a month or once every 3 months, or used as a nasal spray. These drugs are often given with a progestin (sometimes combined with estrogen) 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.)
GnRH = gonadotropin-releasing hormone.
For most women with moderate to severe endometriosis, the most effective treatment is removing or destroying misplaced endometrial tissue and endometriomas. Usually, these surgical procedures are done through a laparoscope inserted into the abdomen through a small incision made near the navel. Such treatment may be needed in the following situations:
When drugs cannot relieve severe lower abdominal or pelvic pain
When adhesions in the lower abdomen or pelvis cause significant symptoms
When misplaced endometrial tissue blocks one or both fallopian tubes
When endometriomas are present
When endometriosis causes infertility and the woman wants to be able to become pregnant
When endometriosis causes pain during intercourse
Often, misplaced endometrial tissue can be removed or destroyed during laparoscopy when the diagnosis is made. Sometimes electrocautery (a device that uses an electrical current to produce heat) or a laser is used to destroy or remove endometrial tissue during laparoscopy. Sometimes abdominal surgery (involving an incision into the abdomen) is required to remove endometrial tissue.
Endometriomas are drained and removed whenever possible.
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 treated with a GnRH agonist. But whether this drug increases their chances of becoming pregnant is unclear. Some women who have endometriosis can become pregnant by using assisted reproductive techniques, such as in vitro fertilization.
Surgical removal of misplaced endometrial tissue is only a temporary measure. After the tissue is removed, endometriosis recurs in most women unless they take drugs to suppress the ovaries or the ovaries are removed.
Removal of the uterus but not the ovaries (hysterectomy without salpingo-oophorectomy) is often appropriate in women who do not plan to become pregnant, particularly when drugs do not relieve abdominal or pelvic pain.
Sometimes both ovaries must be removed, as well as the uterus. This procedure is called hysterectomy plus bilateral salpingo-oophorectomy. It has the same effects as menopause because it, like menopause, results in decreased estrogen levels. Thus, women under 50 may be given estrogen to reduce the severity of the menopausal symptoms that occur after this surgery. However, to help prevent endometriosis from recurring, doctors usually recommend that women wait 3 to 6 months after surgery before starting estrogen. Most of these women are also given a progestin. The progestin is included to help prevent any remaining misplaced endometrial tissue from growing. A progestin alone can be given to women over 50 to reduce symptoms that persist after the ovaries are removed.
Hysterectomy plus bilateral salpingo-oophorectomy may be done, for example, in the following situations:
When women, usually those who are near menopause, want definitive treatment (to completely eliminate the disorder)
The female reproductive system consists of the external and internal genital organs. Other parts of the body also affect the development and functioning of the reproductive system. Which of the following produces hormones that stimulate the ovaries?