Endometriosis is a gynecological condition that occurs when cells from the lining of the womb (uterus) grow in other areas of the body.
Endometriosis symptoms vary widely, and some women with the condition have no symptoms. The most common symptom of endometriosis is chronic pelvic pain. Other symptoms can include:
Infertility and Endometriosis
Endometriosis rarely causes a complete inability to conceive, but it can contribute to reduced fertility.
Treatment options for endometriosis include:
Endometriosis is a condition in which the cells that line the uterus grow outside of the uterus in other areas, such as the ovaries or in the pelvis. The condition can interfere with a woman's ability to become pregnant. Endometriosis can also cause severe pelvic pain, especially during menstruation.
Endometriosis is a common gynecological condition and common cause of chronic pelvic pain, affecting more than 10% of women of reproductive age. It is chronic and may be a painful and progressive disease. However, the causes of endometriosis are unknown, it is widely variable in symptoms and severity, and it can only be diagnosed definitively with surgery (usually laparoscopy). The average time to endometriosis diagnosis in the United States is currently over 10 years. There is a high probability that endometriosis is the likely cause for the majority of initial visits by young women to physician's offices for severe dysmenorrhea (painful menses).
Endometriosis occurs when cells from the tissue layer lining the uterus (endometrium) form implants that attach, grow, and function outside the cavity of the uterus, often in the pelvic region. The endometriosis implants contain both glands (an epithelial tissue) and stroma (a connective tissue) from the endometrial layer.
A related condition is adenomyosis, in which endometrial glands are found deep within the muscle walls of the uterus. Adenomyosis can also cause pelvic pain similar to that caused by endometriosis. More information regarding adenomyosis is given below.
Endometrial cells contain receptors that respond to the female hormones estrogen and progesterone, which promote uterine lining growth and thickening. When these cells become implanted in organs and structures outside the uterus, these hormonal activities continue to occur, causing bleeding, inflammation, and scarring.
Endometriosis is a condition in which cells that normally line the uterus (endometrium) grow on other areas of the body, causing pain and abnormal bleeding.
Endometrial implants vary widely in size, shape, and color. Over the years, they may diminish in size or disappear, or they may grow.
Location of Implants
Implants can form in many areas, most commonly in the following locations in the pelvis:
Rarely, remote sites of endometriosis may include the spinal column, brain, nose, umbilicus, lungs, pelvic lymph nodes, the forearm, and the thigh.
Process of Endometriosis
The process of endometriosis mimics the stages of the menstrual cycle:
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 and bind together nearby pelvic organs, causing pain, inflammation, and sometimes infertility. Endometriosis pain may also be due to innervation to the endometrial implants, and to implant production of inflammatory molecules called prostaglandins. While very uncommon, endometriotic lesions may rarely become cancerous.
Doctors do not know the exact cause of endometriosis. A combination of genetic, biologic, and environmental factors may work together to trigger the initial process, produce implantation, and cause subsequent reseeding and spreading of the implants.
Theories of the cause of endometriosis include:
Endometriosis can develop in teenagers and adult women of all ages, but it is most typically diagnosed in women ages 25 to 50 years.
A family history of endometriosis, especially in a mother or sister, increases a woman's likelihood of developing it herself.
Not Having Had Children
Pregnancy appears to protect against endometriosis, while never having had children is associated with increased risk. However, endometriosis can still occur in women who have had children.
Some studies suggest that consumption of red meat and trans fats may increase the risk of developing endometriosis, while consumption of fruits, green leafy vegetables, and omega-3 fatty acids (found in fish) may be protective. Other studies have not verified this association.
Women at increased risk for endometriosis tend to have more problems with menstruation. They often have a shorter than normal cycle, heavier periods, and longer periods. They may also have begun menstruating at a younger than average age.
The inflammatory response due to endometriosis causes pelvic pain. It is often more severe near or during menses. Adhesions can also cause significant pain. They are dense, web-like structures of scar tissue that can attach to nearby organs and cause damage to tissues and scarring, damage to nerves, or damage to the blood supply of different organs. Pelvic pain is the most common complaint for women with endometriosis, and it can significantly impair the quality of life, including work and social activities. The pelvic pain associated with endometriosis is usually chronic (lasting more than 6 months). Pain may also occur in the abdomen and back.
Infertility is another main complication of endometriosis. More severe endometriosis is very likely to lead to infertility. Endometriosis rarely causes an absolute inability to conceive, but it can reduce fertility both directly and indirectly:
Effects on Other Parts of the Pelvic Region
Implants can also occur in the bladder (although less commonly) and cause pain and even bleeding during urination. Implants also sometimes form in the intestine and cause painful bowel movements, constipation, or diarrhea.
Not all women with endometriosis have symptoms. When symptoms occur, pain is the main one.
Many women with endometriosis have chronic pain in the pelvic area (the lower part of the trunk of the body). Chronic pelvic pain lasts more than 6 months and is not necessarily related to menstruation. 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. The pain may be continuous or it may come and go. Pain tends to worsen over time.
The severity of the pain 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 some women with extensive endometriosis may have very few signs of the disorder except for infertility. Large cysts (endometriomas) can rupture or leak and cause very severe pain at any time.
Pain caused by endometriosis may be associated with:
Because endometriosis symptoms do not always appear, or may be caused by other conditions, a diagnosis cannot be based on symptoms alone. Laparoscopy, an invasive diagnostic procedure, is the only definitive method for diagnosing endometriosis. However, a trial using a hormonal drug may be used to confirm or rule out endometriosis.
After collecting your symptom report and medical history, the doctor will perform a physical and pelvic exam. During the pelvic exam, the doctor will evaluate the size and position of the ovaries and check for tender masses or nodules behind the cervix.
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, cysts that are usually located on the ovaries and filled with thick dark blood. Ultrasound can pick up cysts larger than 1 cm (about 1/3 inch), but it will miss smaller cysts, or small and shallow endometrial implants on the surface of ovaries or on the peritoneum (lining of the pelvis). Other imaging techniques, such as computed tomography (CT) scanning or magnetic resonance imaging (MRI), may occasionally be used.
Diagnostic laparoscopy is used to confirm a suspected diagnosis of endometriosis and to evaluate the severity of the condition. It may also be used to treat endometriosis. During laparoscopy, the surgeon determines the number, size, and location of endometrial implants and adhesions. This information can help in staging endometriosis and in making treatment decisions.
The procedure involves the doctor making a small incision in the abdomen and inserting a thin flexible fiber-optic tube (the laparoscope). The laparoscope is equipped with a small telescopic lens, which enables the doctor view the uterus, ovaries, tubes, and peritoneum (lining of the pelvis) on a video monitor. Laparoscopy normally requires a general anesthetic, although the patient can go home the same day. [For more information on laparoscopy, see the "Conservative Surgery" section of this report.]
A number of blood and urine tests called biomarkers have been evaluated alone or in combination with imaging tests. None have appeared to be helpful in improving the diagnosis of endometriosis without invasive procedures such as laparoscopy.
Ruling out Conditions with Similar Symptoms
Many conditions cause pelvic pain. In many cases, the cause is unknown, and the condition often resolves on its own. However, some causes of pelvic pain can be serious and should be ruled out during a work-up for endometriosis.
Primary dysmenorrhea is recurrent pelvic pain associated with menstruation. Dysmenorrhea is common in many women.
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. It typically occurs in women who have uterine fibroids, women age 40 to 50, and women who have had children. Women, who have had surgery for endometriosis, yet continue to suffer from menstrual and pelvic pain may actually have adenomyosis.
Other Causes of Pelvic Pain
Many conditions cause pelvic pain that may or may not be related to menstruation. Some causes of pelvic pain that can be serious and should be ruled out include:
Conditions that may mimic symptoms of endometriosis, but which are unrelated to problems in the reproductive organs include:
Treatment of endometriosis is often managed by different specialists. A multidisciplinary team may include specialists in gynecology, reproductive endocrinology and infertility, urology, general surgery, immunology, psychology, pain management, and others.
There is no perfect way of managing endometriosis. The three basic treatment approaches are:
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.
Delaying treatment may be most appropriate for women with mild endometriosis or those who are approaching the age of menopause.
Women may also use lifestyle modifications, such as exercise and relaxation, to cope with their pain. Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (Advil, Motrin, generic) and naproxen (Aleve, generic), or acetaminophen (Tylenol, generic), can help provide some pain relief.
Hormonal therapies are used to mimic states in which ovulation does not occur (pregnancy or menopause) or to directly block ovulation. These hormonal treatments actually suppress natural hormone production and are the preferred and most effective treatment option for treating symptoms of endometriosis and minimizing the progression of the disease.
Hormonal drugs include oral contraceptives (a first-line treatment), progestins, GnRH agonists, and (rarely) danazol. They can be very effective in relieving endometriosis symptoms, especially pain. Some of these drugs may also be used after surgery to help prevent recurrence of endometriosis. Downsides of these drugs include:
Surgery is an option for women who:
There are two basic surgical approaches for endometriosis:
In choosing between hysterectomy (with or without removal of the ovaries) and conservative surgeries, age and the desire for children are important factors.
Nerve Surgery for Pelvic Pain
Laparoscopic uterine nerve ablation (LUNA) and laparoscopic presacral neurectomy (LPSN) are procedures that aim to reduce chronic pelvic pain by destroying or interrupting the nerves that attach the uterus to the pelvic bone. Some small studies have shown more benefit for LPSN than for LUNA.
LPSN appears to work best when combined with laparoscopic ablation of endometrial implants (conservative surgery). Stronger evidence is needed before these procedure scan be recommended for women with chronic pelvic pain associated with endometriosis. Many insurance companies consider these procedures experimental and will not pay for them.
Treating Infertility in Patients with Endometriosis
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, generally do not help fertility. If surgery fails, fertility drugs and assisted reproductive technologies, such as in vitro fertilization, are options. Women with endometriosis who are trying to conceive should discuss all treatment options with a fertility specialist.
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. They do not improve fertility rates and in some cases may delay conception.
Specific hormonal drugs may have different effects for women with endometriosis:
Most 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 birth control pills or "the Pill," contain combinations of an estrogen and a progestin. Combined oral contraceptives are a first-line treatment for endometriosis pain. They are generally used along with nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen.
Oral contraceptives may be used either before surgery or after laparoscopic removal of endometrial tissue to prevent current symptoms.
When used throughout a menstrual cycle, OCs suppresses the actions of other reproductive hormones (luteinizing hormone [LH] and follicle stimulating hormone [FSH]) and prevents 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 better than 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. Women with severe pain who have not been helped by standard combination OCs may benefit from switching to continuous-dosing combination OCs. Continuous-dosing 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 progestin levonorgestrel; the hormonally active pills are taken continuously without a break.
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, particularly in older women who smoke.
Progestin alone may be helpful for women whose pain has not been relieved with combination estrogen-progestin oral contraceptives. Some doctors recommend progestins as the first choice for women with endometriosis who do not want to become pregnant.
Progestins can prevent ovulation and reduce the risk for endometriosis in the following ways:
Progestins are available in various forms. They include:
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. The most common side effects include:
Gonadotropin releasing hormone (GnRH) agonists are effective hormone treatments for endometriosis. They 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 to 10 weeks after stopping the drug. The specific length of time depends on the type of GnRH agonist used.
Prescribing low dose of hormones in the form of birth control pills along with GnRH agonists can help relieve some of the menopausal-type side symptoms and help prevent osteoporosis, without reducing the effectiveness of GnRH treatment. This approach is called add-back therapy.
Specific GnRH Agonists
GnRH agonists include the implant goserelin (Zoladex), a monthly injection of leuprolide (Lupron, Depot, generic), the nasal spray nafarelin (Synarel), and most recently elagolix (Orilissa).
Side Effects and Complications
Common side effects (which can be severe in some women) include menopause-like symptoms, including hot flashes, night sweats, vaginal dryness, 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. To help protect the bones, doctors may prescribe "add-back therapy," with a supplement of combination estrogen-progestin. Because of estrogen loss side effects, doctors generally recommend that women not take GnRH agonists alone for more than 6 months. If add-back therapy is prescribed, the GnRH agonist may be prescribed for a longer period.
GnRH treatments can increase the 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.
Other Drug Treatments
Danazol (Danocrine, generic) is a synthetic drug that resembles a male hormone (androgen). It suppresses the pathway leading to ovulation. Danzol is rarely used for endometriosis therapy nowadays. Many women stop taking this drug because of its adverse side effects, which include:
Danazol can also cause male characteristics, such as growth of facial hair, reduced breasts, and deepening of the voice. Because GnRh agonists cause far fewer side effects, danazol is not a first-line choice for endometriosis treatment.
Aromatase inhibitors (AIs) are a class of drugs that stop the body from making estrogen in tissues such as fat and skin. However, these drugs do not prevent the ovaries from making estrogen. AIs are primarily used for more severe pain caused by endometriosis where other treatments have not worked, and include:
The goal of conservative surgery is to remove as many endometrial implants and cysts as possible without causing surgical scarring or subsequent adhesions that could cause fertility problems. Surgery can help improve fertility in women with severe endometriosis. Whether it offers any advantage in pregnancy rates in women with mild-to-moderate endometriosis is unclear. Conservative surgery can also help relieve pain caused by implants. It may, however, miss microscopic implants that could continue to cause pain and other symptoms after the procedure.
The two conservative surgical procedures are:
A laparoscopy is performed, usually under general anesthesia, as follows:
People may 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.
Even with successful surgery, endometriosis may recur within several months to several years.
Hysterectomy is the surgical removal of the uterus. Removal of the uterus and ovaries is considered in women who do not respond well to conservative approaches and who do not wish to become pregnant. Endometriosis accounts for a significant percentage of hysterectomies. Hysterectomy does not, however, necessarily cure endometriosis.
A woman cannot become pregnant after having a hysterectomy. Women should realize that hysterectomy causes immediate menopause if the ovaries are also removed.
Types of Hysterectomies
Once a decision for a hysterectomy has been made, the patient should discuss with her doctor what will be removed. The common choices are:
Hysterectomy is surgical removal of the uterus, resulting in inability to become pregnant. This surgery may be done for a variety of reasons, including chronic pelvic inflammatory disease, uterine fibroids, and cancer. A hysterectomy may be done through an abdominal or a vaginal incision.
Removal of the ovaries (oophorectomy) along with hysterectomy significantly reduces the likelihood that endometriosis will recur. However, there is still a small chance that recurrence can happen.
Types of Hysterectomy Procedures
Hysterectomies may be performed abdominally (through an incision in the abdomen) or vaginally (through a vaginal incision). A variation of the vaginal approach is called laparoscopic-assisted vaginal hysterectomy (LAVH). There are other laparoscopic approaches as well, including total laparoscopic hysterectomy (TLH) and robotic assisted laparoscopy. Recovery times for vaginal hysterectomy and laparoscopic procedures are shorter than those for abdominal hysterectomy.
The ovaries are the main source of production of estrogen. In premenopausal woman, the removal of both ovaries causes immediate menopause. After a hysterectomy with bilateral oophorectomy, women may have hot flashes and other symptoms of menopause, including vaginal dryness, insomnia, and weight gain. Prescribed hormone replacement will typically ameliorate these symptoms. Women who have surgical removal of both ovaries, and who do not receive hormone replacement therapy, tend to have more severe hot flashes than women who enter menopause naturally. The lack of estrogen is also associated with increased risk for cardiovascular and metabolic diseases.
If hormone therapy is recommended after hysterectomy, it is given as estrogen-only therapy (ET). Women who do not have a uterus do not need to take combination estrogen-progesterone therapy.
After a total hysterectomy, in which the cervix has been removed, a woman may not need annual Pap smears of the cervix depending on her medical/gynecological history. However, she still should get regular pelvic and breast exams.
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