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Endometriosis

By

James H. Liu

, MD, Case Western Reserve University School of Medicine

Last full review/revision Jul 2020| Content last modified Jul 2020
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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: Misplaced Tissue

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 Diagnosis 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... read more Diagnosis ). 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 chronic pelvic pain Pelvic Pain Pelvic pain is discomfort that occurs in the lowest part of the torso, the area below the abdomen and between the hipbones. It does not include pain that occurs externally in the genital area... read more (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:

  • Ovaries

  • Ligaments that support the uterus

  • The space between the rectum and vagina or cervix and the space between bladder and uterus

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

  • Started to menstruate earlier than usual or stopped menstruating later than usual

  • Have short menstrual cycles (less than 27 days long) with heavy periods that last more than 8 days

  • 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

  • Have used low-dose oral contraceptives for a long time

  • Exercise regularly (especially if they started before age 15, exercise more than 4 hours a week, or both)

Symptoms of Endometriosis

The main symptom of endometriosis is

The pain usually varies during the menstrual cycle Menstrual Cycle Menstruation is the shedding of the lining of the uterus (endometrium) accompanied by bleeding. It occurs in approximately monthly cycles throughout a woman's reproductive life, except during... read more , 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 cause inflammation. The misplaced tissue 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, diarrhea or 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 in 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

  • Sometimes a biopsy

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.

Ultrasonography or magnetic resonance imaging (MRI) may help doctors evaluate endometriosis in a noninvasive way (that is, no incision is required). Endometrial tissue has unique characteristics that can sometimes be detected with MRI.

However, to diagnose endometriosis, a doctor examines the abdominal cavity with a thin viewing tube (called a laparoscope) to be able to directly see whether endometrial tissue is present. 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. The abdominal cavity is then inflated with carbon dioxide gas, which distends it and makes the organs easier to see. The entire abdominal cavity is examined. Laparoscopy is done in a hospital and usually requires a general anesthetic. An overnight stay in the hospital is usually not required. Laparoscopy causes mild to moderate abdominal discomfort, but normal activities can usually be resumed in a few days.

If a doctor sees abnormal tissue and is not sure that it is endometrial tissue, a biopsy must be done. A sample of the tissue is removed, using instruments inserted through the laparoscope. The sample is then examined using a microscope. An overnight stay in the hospital is usually required only if a very large amount of abnormal tissue is removed.

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 Endoscopy Endoscopy is an examination of internal structures using a flexible viewing tube (endoscope). Endoscopy can also be used to treat many disorders because doctors are able to pass instruments... read more ) or bladder (cystoscopy Cystoscopy A doctor can diagnose some disorders of the bladder and urethra (for example, bladder tumors, stones in the bladder, benign prostatic enlargement) by looking through a flexible viewing tube... read more ). Occasionally, a larger incision in the abdomen (called laparotomy) is required.

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 Diagnosis The fallopian tube may be blocked or damaged, preventing the sperm from reaching the egg or preventing the egg or fertilized egg (zygote) from moving from the ovary to the uterus to be implanted... read more 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 location

  • 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 has been pregnant before

  • How well her reproductive organs are functioning

Treatment of Endometriosis

  • Nonsteroidal anti-inflammatory drugs 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 Nonsteroidal Anti-Inflammatory Drugs In some cases, treating the underlying disorder eliminates or minimizes the pain. For example, setting a broken bone in a cast or giving antibiotics for an infected joint helps reduce pain.... read more ) 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:

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)

  • Elagolix (a GnRH antagonist)

  • 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.

The GnRH antagonist elagolix, like GnRH agonists, suppresses estrogen production by the ovaries and, if it is taken for a long time, causes a decrease in bone density. If it is taken for more than 6 months, doctors may give women small doses of a progestin to minimize the decrease in bone density.

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.

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Endometriosis surgery

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 stage 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 In vitro (test tube) fertilization (IVF) Assisted reproductive techniques involve manipulating sperm and eggs or embryos in a laboratory (in vitro) with the goal of producing a pregnancy. (See also Overview of Infertility.) If treatment... read more In vitro (test tube) fertilization (IVF) .

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 Menopause Menopause is the permanent end of menstrual periods and thus of fertility. For up to several years before and just after menopause, estrogen levels fluctuate widely, periods become irregular... read more 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. 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 or who do not want to become pregnant again, want definitive treatment (to completely eliminate the disorder)

  • When endometriosis has recurred, often many times

Drugs Mentioned In This Article

Generic Name Select Brand Names
PROVERA
MIRENA, PLAN B
AYGESTIN, CAMILA
ACTONEL
FOSAMAX
BONIVA
LUPRON
SYNAREL
ZOLADEX
ESTRADERM, ESTROGEL, VIVELLE
Elagolix
No US brand name
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