Endometriosis
Author
Robert L Barbieri, MD Section Editor
Robert L Barbieri, MD Deputy Editor
Leah K Moynihan, RNC, MSN
Vanessa A Barss, MD
ENDOMETRIOSIS OVERVIEW — The normal tissue that lines the uterus and bleeds during the menstrual period is called the endometrium (show figure 1
The most common locations for endometriosis are: the outer surface of the ovaries, peritoneum (the tissue that lines the abdomen) and peritoneal structures (the area behind the uterus and the various ligaments that hold the uterus in place), uterus, fallopian tubes, bowel, and bladder. Most women have endometriosis in more than one location.
ENDOMETRIOSIS RISK FACTORS — Risk factors for developing endometriosis include:
* No pregnancies resulting in the birth of an infant
* Endometriosis in a woman’s mother
* Short menstrual cycles (<27 days) with prolonged flow (>8 days)
* Partial or complete obstruction of normal menstrual flow (eg, from uterine abnormalities such as a tight cervical opening or vaginal septa [band of tissue] blocking the flow of menses)
* White or Asian race
Conditions that decrease the amount or frequency of menstrual bleeding lower the risk of endometriosis. Some examples are amenorrhea (absent menstrual periods), pregnancy, and prolonged use of birth control pills.
ENDOMETRIOSIS CAUSES — The cause of endometriosis is not known, but several theories have been suggested.
* Retrograde menstruation is a theory that menstrual blood and tissue flows backwards from the uterus, through the fallopian tubes and into the pelvis (show figure 1
* Endometrial tissue from the uterus may be transported through blood and lymphatic vessels to sites elsewhere in the body, including the pelvis.
* Changes in the immune system allow endometrial tissue outside of the uterus to grow and develop.
* Coelomic metaplasia is the concept that the cells from lining of the abdomen and surface of the ovaries can change into endometrial tissue with certain stimuli, such as irritation from retrograde menstruation or infection.
ENDOMETRIOSIS SYMPTOMS — Endometriosis may have no signs or symptoms. In those who do have symptoms, the intensity of the symptoms (eg, amount of pain and bleeding) does not always correlate with the severity or amount of endometriosis. For example, it is possible to have mild endometriosis with severe pelvic pain.
Pain — For many women, severe pelvic pain is the main symptom of endometriosis. Pelvic pain usually occurs just before or during menses or during or after sex. Other symptoms may include pain during bowel movements, spotting before the menstrual period, frequent or heavy uterine bleeding, and pain during urination. Painful periods may worsen over a period of years. (See “Patient information: Painful menstrual periods (dysmenorrhea)”).
Pelvic pain is probably the result of bleeding from areas of endometriosis and release of substances that cause pain (eg, prostaglandins). Endometriosis implants respond to the hormonal changes that occur during the menstrual cycle, similar to the normal endometrium. Thus, at the end of the menstrual cycle, small amounts of endometrial tissue are shed and bleeding occurs (show figure 2
Endometriomas (chocolate cysts) — Endometriomas are areas of endometriosis that are large enough to be considered a mass or growth. They are usually filled with old blood that resembles chocolate syrup; thus, they are sometimes called chocolate cysts. Endometriomas may be seen during a pelvic ultrasound, although only surgery can confirm that the mass is an endometrioma.
ENDOMETRIOSIS DIAGNOSIS — Endometriosis is rarely diagnosed before menarche (the first menstrual period of a woman’s life) and new cases are seldom diagnosed after menopause (the last menstrual period of a woman’s life).
Endometriosis may be suspected based upon a woman’s symptoms of pelvic pain and heavy menstrual periods. However, the diagnosis must be confirmed during surgery. There are no blood tests or imaging tests that can make a definitive diagnosis of endometriosis.
Surgical evaluation — Laparoscopy and laparotomy are surgical procedures that are commonly used to diagnose and treat endometriosis. Both procedures are usually done in an operating room after the woman has received general anesthesia to induce sleep and prevent pain. After laparoscopy most women go home the same day. After laparotomy most women go home after spending one to three nights in the hospital.
At surgery, endometriosis appears as small blue, purple, or red implants. Scar tissue (adhesions) and/or an ovarian cyst may also be noted. A biopsy (removal of a small piece of tissue) is usually done to confirm the diagnosis.
Staging — Surgery can help to determine the extent and location of disease (called staging) and treat the disorder. To stage the disease, the surgeon assigns points based upon the size, depth, and location of endometriosis implants (show figure 3
ENDOMETRIOSIS TREATMENT — There are several treatment options for women with endometriosis:
* No therapy
* Pain medication
* Birth control pills
* Other forms of hormonal therapy
* Surgery
* A combination of therapies
The treatment strategy depends upon whether the woman’s major concern is pain, infertility, or a pelvic mass.
Women with minimal disease or who are near menopause and have no troubling symptoms may choose to have no treatment. Near menopause, endometriosis may regress without treatment because the ovaries produce lower levels of estrogen, which decreases stimulation of the implants. Young women with minimal disease may consider taking a hormonal birth control treatment to prevent unplanned pregnancy and progression of disease.
Endometriosis progresses slowly, over years, and resolves after menopause. Most women with endometriosis will get relief of pain from a medication, after pregnancy, or after menopause; some women will be helped only by surgery. Removal of the ovaries almost always provides excellent pain relief, making this an option for women who do not wish to have children.
Some women with endometriosis will have difficulty becoming pregnant, especially those who have severe disease and extensive adhesions. However, most women can achieve pregnancy after medical or surgical therapy or with fertility enhancing drugs or procedures (eg, in vitro fertilization). ( See “Patient information: Evaluation of the infertile couple” and see “Patient information: Infertility treatment with clomiphene (Clomid® or Serophene®)”).
Pelvic pain — There are two options for treating pelvic pain caused by endometriosis: medications and surgery.
Nonsteroidal antiinflammatory drugs — Nonsteroidal antiinflammatory drugs (NSAIDs, eg, ibuprofen, naproxen sodium) may be useful in relieving mild pain. NSAIDs inhibit prostaglandins, one of the main chemicals responsible for pain during menses. NSAIDs do not shrink or prevent the growth of endometriosis implants, and pain often returns when the medication is stopped.
The recommended dose of ibuprofen is 400 to 600 mg by mouth every six hours, taken when pain starts or is expected. Other NSAIDs may also be used (show table 1
Serious side effects from NSAIDs, although uncommon, include gastrointestinal pain and bleeding, kidney problems, and worsening high blood pressure.
Hormonal birth control treatments — Birth control pills, patches, and the vaginal ring contain both estrogen and progestin, which cause the endometrial lining and endometriosis implants to shrink. There is no effect on scar tissue or endometriomas. These treatments are usually less effective than GnRH agonists and danazol (see below) for women with moderate or severe disease, but are a good choice for women with minimal or mild symptoms who do not want to become pregnant.
Hormonal birth control treatments work by reducing the number of menstrual cycles and volume of menstrual bleeding. Periods are usually less painful and worsening of endometriosis may be slowed. The most common side effects of hormonal birth control treatments include nausea, breast tenderness, and decreased libido, although these problems usually improve after using the treatment for several months. Serious side effects (eg, blood clots, stroke, heart attack) are rare in women who do not smoke and have no underlying blood vessel disease. (See “Patient information: Hormonal methods of birth control”).
Traditionally, hormonal birth control treatments are taken so that the woman has a monthly period. However, women who prefer NOT to have a monthly period and those who have severe pain with their period or heavy bleeding can take the treatment continuously to avoid or minimize pain associated with the menstrual period.
Gonadotropin releasing hormone agonists — Gonadotropin releasing hormone (GnRH) agonists (eg, nafarelin, leuprolide, goserelin) work by temporarily stopping the ovaries from producing estrogen, thereby causing a temporary menopause. The lack of estrogen causes the endometriosis implants to shrink and reduces pain in over 80 percent of women. The drugs may be given as a nasal spray, implant, or injection.
The full dose of a GnRH agonist may be taken for up to six months; a longer course is not usually recommended due to the risk of bone thinning. The average loss of bone density with full dose treatment for 6 months is between 2 and 7 percent. Bone strength recovers substantially after the drug is stopped.
Side effects of GnRH agonists can include headaches (in 20 percent of women, especially those with a history of migraine) and the signs and symptoms of menopause (lack of menstrual bleeding, hot flashes, vaginal dryness, decreased libido, insomnia, and loss of bone density). Many of these side effects can be minimized by giving estrogen or a bone strengthening drug along with the GnRH agonist.
Five years after completing GnRH agonist treatment, many women will again have pain (37 of women with mild disease and 74 percent of women with severe disease). Alternate dosing regimens that use lower doses of the GnRH agonist for longer than five years may be considered for some women; this reduces the amount of bone density lost, and may allow the woman to have better, long-lasting relief of pain compared to other treatments. Monitoring of bone density is usually recommended while GnRH agonists are used.
Progestins — Progestins (eg, medroxyprogesterone acetate (Depo Provera®) norethindrone acetate (Micronor®, NorQD®, Aygestin®) norgestrel acetate) may be recommended for women who do not get pain relief from or who cannot take a birth control pill (eg, smokers). These medications cause the endometrial lining and endometriosis implants to shrink, and usually cause the menstrual periods to temporarily stop. (See “Patient information: Long-term methods of birth control”).
Side effects are common and may include: bloating, weight gain, irregular uterine bleeding, and rarely, worsened depression. Women who take injections of long-acting medroxyprogesterone acetate (eg, Depo-Provera®) may not have a menstrual period for six to twelve months after stopping the treatment. Therefore, this drug may not be the best choice for women planning pregnancy in the near future.
Danazol — Danazol is a medication that increases the level of androgens (male type hormone) and decreases the level of estrogen. This temporarily stops the menstrual period by inhibiting ovulation and ovarian production of estrogen and by shrinking the endometrium.
The medication is taken by mouth for 6 months or more. Eighty percent of patients will have good pain relief and shrinkage of implants. However, there is a high (75 percent) incidence of one or more side effects, although only a small percentage of patients discontinue the drug because of them.
Side effects may include weight gain, edema, decreased breast size, acne, oily skin, hirsutism (male pattern hair growth), deepening of the voice, headache, hot flashes, changes in libido, and mood changes. All of these changes are reversible, except for voice changes; however, return to normal may take many months.
Danazol is not recommended for women with certain types of liver, kidney, and heart disease because these disorders may worsen. Women who could become pregnant must use a nonhormonal form of birth control (eg, condoms) while taking danazol because of a serious risk of birth defects if danazol is used during pregnancy. (See “Patient information: Barrier methods of birth control”).
Surgery — Surgery is an option when medications have failed to improve pain or if there is severe disease (scarring, endometriomas, involvement of the bowel or bladder) that is unlikely to respond to medications alone. The goal of surgery is to eliminate as many implants and adhesions as possible.
More than 80 percent of women who have surgery have relief of pain, although there is a 40 risk of recurrent pain within 10 years. Women who have surgery avoid the possible side effects of medication and may have improved fertility. However, surgery has some potential risks, including damage to pelvic organs, development of new adhesions (scar tissue), bleeding, and infection.
Surgery to “cure” endometriosis includes removal of the uterus (hysterectomy), ovaries, and endometrial implants; this eliminate as much of the disease as possible and creates a low estrogen state. This type of surgery may be recommended for women who are not planning pregnancy if severe symptoms remain after trying other less invasive treatments. Low dose hormone replacement therapy (eg, estrogen pills or a patch) is usually given after surgery to prevent menopausal symptoms and other complications of a low estrogen level; this treatment usually does not cause the pain to return. (See “Patient information: Abdominal hysterectomy” and see “Patient information: Vaginal hysterectomy”).
Pelvic mass — In a woman with endometriosis, a pelvic mass could be an endometrioma (chocolate cyst), a combination of scarring and normal pelvic organs, or a mass unrelated to the disease. Surgery is the best way to make a definite diagnosis and remove the mass. Medical therapy is not effective.
Infertility — Endometriosis sometimes interferes with the ability to become pregnant. Reduced fertility may develop because of adhesions that develop between the ovaries and fallopian tubes or as a result of substances produced by endometriosis implants, which impair normal ovulation, fertilization, and implantation. However, as many as 70 percent of women with minimal or mild endometriosis and infertility will conceive within three years without any therapy. If pregnancy occurs, endometriosis often regresses or resolves. Women with endometriosis who become pregnant have no increased risk of pregnancy complications.
The treatment of infertility caused by endometriosis includes a combination of observation, surgery, use of medications that enhance ovulation combined with intrauterine insemination, or in vitro fertilization (IVF). Medical treatments for endometriosis (eg, GnRH agonists) are of no benefit in improving fertility. (See “Patient information: Infertility treatment with clomiphene (Clomid® or Serophene®)”).
The ideal infertility treatment for women with mild to moderate endometriosis is surgical removal (burning or cutting) of endometriosis implants. Women with severe endometriosis have the greatest chance of becoming when they are treated with IVF.
ENDOMETRIOSIS PREVENTION — There is no proven way to prevent endometriosis. Reducing the number of periods and amount of bleeding during the menstrual period may reduce the risk. Having one or more pregnancies or using a hormonal birth control (eg, birth control pills) may be of benefit.
SUMMARY
* Endometriosis is a common condition in women. Its name is based on the endometrium, which is the tissue inside the uterus. During a woman’s monthly period, the endometrium sheds and bleeds (show figure 1
* The cause of endometriosis is not known. Women whose mother, sister, or aunt had endometriosis have a higher chance of developing it.
* The most common symptom of endometriosis is pain. Pain may occur in the abdomen, lower back, or pelvis, and is usually worst before and during a woman’s monthly period. Some women also have pain during sex.
* Surgery is needed to be certain of the diagnosis of endometriosis. Surgery is not always performed if endometriosis is likely and pain improves with medical treatment.
* There are many treatments for endometriosis. For most women, the first option is to use a medication to reduce pain and shrink the abnormal growths. Surgery may be the best choice for women with severe disease or pain that does not improve with medications.
* Endometriosis can cause difficulty becoming pregnant (infertility). If endometriosis is mild, surgery to remove the abnormal growths can treat infertility. Some women also need to use infertility medications or procedures to become pregnant (eg, in vitro fertilization or IVF).
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two people are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.uptodate.com/patients). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable.
* National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
* The Hormone Foundation
(www.hormone.org)
* The Endometriosis Association
(www.endo-online.org)
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REFERENCES
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2 Dlugi, AM, Miller, JD, Knittle, J, Lupron Study Group. Lupron depot (leuprolide acetate for depot suspension) in the treatment of endometriosis: A randomized, placebo-controlled, double-blind study. Fertil Steril 1990; 54:419.
3 Schlaff, WD, Carson, SA, Luciano, A, et al. Subcutaneous injection of depot medroxyprogesterone acetate compared with leuprolide acetate in the treatment of endometriosis-associated pain. Fertil Steril 2006; 85:314.
4 Porpora, MG, Koninckx, PR, Piazze, J, et al. Correlation between endometriosis and pelvic pain. J Am Assoc Gynecol Laparosc 1999; 6:429.
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