Endometriosis is a common condition in which implants of endometrial tissue appear outside of the uterine cavity, usually within the pelvis. It is a frequent cause of dysmenorrhea and pelvic pain, and it may cause infertility. The pathogenesis is unknown but is thought to be associated with retrograde menstruation, in which menstrual tissue flows through the fallopian tubes and into the pelvic and abdominal peritoneum. Other hypotheses suggest the condition may result from displacement of endometrial tissue through surgical processes (e. g., cesarean section, episiotomy), transport of cells through blood or lymph to distant locations, and differentiation of peritoneal cells to become endometrial cells.
Endometriosis is largely dependent upon active menstruation. The disease rarely occurs prior to menarche or after menopause. The most commonly involved locations are the peritoneal surface of the ovaries, anterior and posterior cul-de-sac, and the pelvic ligaments. In the gastrointestinal tract, the sigmoid colon and the appendix are most commonly affected. In some cases, the vagina and urinary system can be involved.
The severity of the condition varies greatly. It can be asymptomatic, or severe and even debilitating. Symptoms are often nonspecific and do not always correlate with the severity of disease. Common symptoms include pelvic, abdominal, or low-back pain occurring in the premenstrual or perimenstrual period; abnormal uterine bleeding; dyspareunia; and infertility. Further symptoms occur based on the location of ectopic endometrial tissue (e.g., rectal bleeding or pain with defecation if colonic lesions are present, suprapubic pain upon urination if bladder lesions are present). Many women with endometriosis have no symptoms, and some women with severe pain have minimal visible endometriosis, suggesting that the body’s response to the implants is more important than the presence of the implants themselves.
The risk factors for endometriosis are not well understood. It is most commonly diagnosed in women in their late 20s and early 30s. Other associated factors include nulliparity, early menarche/late menopause, short menstrual cycles, prolonged menses, and müllerian anomalies.
Conversely, multiparity, long lactation periods, and late menarche (after age 14 years) seem to decrease the risk.
Dietary factors may play a role and are discussed in Nutritional Considerations below.
Endometriosis is usually suspected from the history, although tender nodules and masses may be palpable or visible on the vagina or cervix during pelvic examination.
Pelvic ultrasound may be helpful and is typically indicated in the evaluation of undifferentiated pelvic pain. Visualization of an ovarian endometrioma on ultrasound can be diagnostic. Endoscopy of the colon or cystoscopy of the bladder may be necessary if deep seeded implants are suspected in these organs.
Laparoscopy is performed to confirm a diagnosis and visual identification is typically satisfactory. Endometrial implants may appear in various colors (black, red, yellow, white, blue, or clear). If a visual diagnosis is in question, a biopsy that reveals endometrial glands and stroma is considered diagnostic. Many women with typical endometriosis symptoms have no visible disease but occult microscopic implants are possible. Pathology specimens may reveal evidence of endometrial tissue in women with typical symptoms, but grossly normal appearing pelvic structures.
In some cases, history and physical examination that exclude other likely diagnoses are enough to justify the initiation of low-risk treatment (NSAIDs, oral contraceptive pills). However, any degree of response to treatment should not be taken as confirmation of diagnosis. If treatment options are considered that carry more than minimal risk, laparoscopic visualization is recommended.
Elevated serum CA-125 concentration suggests the presence of the condition (but is not specific), and higher values may correspond with advanced disease. This test is not typically used for the evaluation of endometriosis in clinical practice.
Treatment aims to address pelvic pain, pelvic mass, or infertility. The treatment strategy depends upon the severity and extent of disease, proximity to menopause, and whether the patient hopes to become pregnant. After menopause, symptoms will likely improve dramatically, even in severe disease.
Watchful waiting is always an option for minimally symptomatic patients or patients who wish to avoid more risky treatment options.
For mild to moderate pain, analgesics (e. g., NSAIDs) and oral contraceptive pills can be used. Oral contraceptives may also reduce the risk of ovarian cancer, a diagnosis which has been associated with endometriosis.
Gonadotropin-releasing hormone (GnRH) analogues, danazol, or progestins (e. g., norethindrone acetate, intrauterine levonorgestrel) may be very helpful, particularly in severe cases. GnRH analogs (e. g., leuprolide injections, goserelin implants) decrease ovarian estrogen production, preventing the pain-inducing stimulation of ectopic endometrial tissue. Treatment usually lasts at least 6 months. GnRH analogues cause a temporary decrease in bone density that has not been shown to be clinically important. Supplemental estrogen or norethindrone acetate may minimize the side effects of hot flashes and bone mineral loss. Bone loss has also been associated with the use of long-acting progesterone, medroxyprogesterone acetate. This is likely reversible with cessation of medication and return of ovulatory function.
Aromatase inhibitors are under investigation.
Medical therapy affords some relief in 80-90% of patients, but does not address cases complicated by pelvic mass or adhesions nor does it improve fertility. Surgery is often used for severe disease or complicated cases. Laser ablation or electrocautery of endometrial implants and adhesions may treat the pain, decrease the rate of recurrence, and restore fertility. If there is no desire for future pregnancy, definitive treatment is total abdominal hysterectomy with bilateral salpingo-oophorectomy. However, most patients can be managed effectively without such extreme measures.
Exercise. Observational data suggest a decreased incidence of endometriosis in women who exercise regularly with sufficient intensity. Moreover, exercise appears to significantly improve pain in women with dysmenorrhea, a finding which can likely applied to those with endometriosis.
Endometriosis is an estrogen-dependent disorder, and some studies have suggested that oxidative stress may also contribute to the disease process. These observations may explain the apparent value of diet and exercise interventions, which can improve both hormone levels and antioxidant status. Alcohol may increase the risk for endometriosis, perhaps through its tendency to increase both estrogen levels and oxidative stress. Aberrations in vitamin A metabolism may also contribute. The following diet changes may reduce the risk for endometriosis and its progression:
A high-fiber, plant-based diet. Although research on the effectiveness of dietary approaches is limited, several lines of evidence support the use of plant-based diets.
Case-control studies have suggested that frequent red meat consumption is associated with endometriosis risk, while fruit and vegetable intake appears to be protective. In an Italian population including 504 cases and an equal number of matched controls, women who ate at least 7 servings of red meat per week had twice the risk of endometriosis compared with those who ate fewer than 3 servings of red meat weekly. Women having 13 or more servings per week of green vegetables had a 70% lower risk of endometriosis compared with those who ate fewer than 6 servings per week. And those eating 14 or more servings of fruit per week had a 20% lower risk compared with women having fewer than 6 servings per week.
Western diets are associated with higher levels of estradiol and lower levels of sex hormone- binding globulin (SHBG). In contrast, plant-based diets tend to reduce blood estrogen concentrations and increase SHBG concentration, effects that may be attributable to an increase in fiber intake (fiber interrupts the enterohepatic circulation of hormones, such that a portion of the hormone load is excreted with the feces), or the weight loss that typically results from these diet changes. , , Endometrial tissue can convert cholesterol to estradiol, raising concerns about elevated plasma cholesterol levels and the food components (saturated fat and dietary cholesterol) that tend to increase plasma cholesterol levels. Also see the Dysmenorrhea chapter.
The higher fiber content of plant-based diets can also lower blood insulin levels. This is important due to insulin’s agonistic effects for estrogen production and endometrial cell proliferation.
Avoiding alcohol. Some evidence suggests that greater alcohol intake may be associated with increased risk of endometriosis.
What to Tell the Family
Endometriosis is a painful disorder that will often respond to available medical therapies. Regular exercise may improve symptoms. Alcohol consumption should be minimized. A low-fat, vegan diet, which has been shown to be helpful for functional menstrual pain, has not been tested for endometriosis. To the extent patients seek to make lifestyle changes, family members can help by supporting these changes.
- Missmer SA, Hankinson SE, Spiegelman D, et al. Reproductive history and endometriosis among premenopausal women. Obstet Gynecol. 2004;104(5 Pt 1):965-74. [PMID:15516386]
- Balasch J, Creus M, Fábregues F, et al. Visible and non-visible endometriosis at laparoscopy in fertile and infertile women and in patients with chronic pelvic pain: a prospective study. Hum Reprod. 1996;11(2):387-91. [PMID:8671229]
- Carvalho LF, Samadder AN, Agarwal A, et al. Oxidative stress biomarkers in patients with endometriosis: systematic review. Arch Gynecol Obstet. 2012;286(4):1033-40. [PMID:22791380]
- Bonocher CM, Montenegro ML, Rosa E Silva JC, et al. Endometriosis and physical exercises: a systematic review. Reprod Biol Endocrinol. 2014;12:4. [PMID:24393293]
- Brown J, Brown S. Exercise for dysmenorrhoea. Cochrane Database Syst Rev. 2010. [PMID:20166071]
- Parazzini F, Chiaffarino F, Surace M, et al. Selected food intake and risk of endometriosis. Hum Reprod. 2004;19(8):1755-9. [PMID:15254009]
- Fung TT, Hu FB, Barbieri RL, et al. Dietary patterns, the Alternate Healthy Eating Index and plasma sex hormone concentrations in postmenopausal women. Int J Cancer. 2007;121(4):803-9. [PMID:17455249]
- Goldin BR, Woods MN, Spiegelman DL, et al. The effect of dietary fat and fiber on serum estrogen concentrations in premenopausal women under controlled dietary conditions. Cancer. 1994;74(3 Suppl):1125-31. [PMID:8039147]
- Bagga D, Ashley JM, Geffrey SP, et al. Effects of a very low fat, high fiber diet on serum hormones and menstrual function: implications for breast cancer prevention. Cancer . 1995;76:2491-2496.
- Barnard ND, Scialli AR, Hurlock D, et al. Diet and sex-hormone binding globulin, dysmenorrhea, and premenstrual symptoms. Obstet Gynecol. 2000;95(2):245-50. [PMID:10674588]
- Sofo V, Götte M, Laganà AS, et al. Correlation between dioxin and endometriosis: an epigenetic route to unravel the pathogenesis of the disease. Arch Gynecol Obstet. 2015;292(5):973-86. [PMID:25920525]
- McAuley K, Mann J. Thematic review series: patient-oriented research. Nutritional determinants of insulin resistance. J Lipid Res. 2006;47(8):1668-76. [PMID:16720893]
- Mendez-Figueroa H, Dahlke JD, Vrees RA, et al. Trauma in pregnancy: an updated systematic review. Am J Obstet Gynecol. 2013;209(1):1-10. [PMID:23333541]