Endometriosis is a disorder in which abnormal growths of tissue, histologically resembling the endometrium, are present in locations other than the uterine lining. Although endometriosis can occur very rarely in postmenopausal women, it is found almost exclusively in women of reproductive age. All other manifestations of endometriosis exhibit a wide spectrum of expression. The lesions are usually found on the peritoneal surfaces of the reproductive organs and adjacent structures of the pelvis, but they can occur anywhere in the body (Fig 40-1). The size of the individual lesions varies from microscopic to large invasive masses that erode into underlying organs and cause extensive adhesion formation. Similarly, women with endometriosis can be completely asymptomatic or may be crippled by pelvic pain and infertility.
Endometriosis is a common and important health problem of women. Its exact prevalence is unknown because surgery is required for its diagnosis, but it is estimated to be present in 3-10% of women in the reproductive age group and 25-35% of infertile women. It is seen in 1-2% of women undergoing sterilization or sterilization reversal, in 10% of hysterectomy surgeries, in 16-31% of laparoscopies, and in 53% of adolescents with pelvic pain severe enough to warrant surgical evaluation. Endometriosis is the commonest single gynecologic diagnosis responsible for hospitalization of women aged 15-44, being found in over 6% of patients.
Adenomyosis, also called endometriosis interna, is the presence of endometrial glands and stroma within the myometrium; it is generally thought to be unrelated to endometriosis.
The cause of endometriosis is unknown. The leading theories include retrograde menstruation with transport of endometrial cells, metaplasia of coelomic epithelium, and hematogenous or lymphatic spread of endometrial cells. A combination of these theories is likely to be responsible.
A theory of retrograde menstruation was proposed during the 1920s. It was postulated that endometriosis occurred because viable fragments of endometrium were shed at the time of menstruation and passed through the uterine tubes. Once in the pelvic cavity, the tissue became implanted on peritoneal surfaces and grew into endometriotic lesions. Subsequent observations have confirmed that some degree of retrograde menstruation normally occurs in women with patent tubes, that outflow tract obstructions (cervical stenosis, transverse vaginal septa) increase the incidence of endometriosis, and that intentional deposition of endometrium onto peritoneum can initiate endometriosis. Also, the risk of developing the disease is higher in women with prolonged menstrual flow and in those with short menstrual cycle lengths (more menses per year). This theory is simple, attractive, and easily explains why endometriosis is most commonly found on the peritoneal surfaces of the ovaries, cul-de-sac, and bladder and why lesions may develop in episiotomies and other incisions. However, it does not explain why all women do not develop endometriosis nor does it explain the rare cases of endometriosis in the lung, brain, or other soft tissues or in nonmenstruating subjects (women with Turner's syndrome or with absent uteri).
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Other workers proposed that endometrial tissue could be transported by lymphatic or hematogenous routes, and a theory of coelomic metaplasia was postulated. In the latter, peritoneum is induced to undergo metaplasia into endometrial tissue by some stimulus (menstrual fluid or other irritants, cyclic ovarian hormones, etc).
A role for the immune system in the origin of endometriosis was suggested by workers studying monkeys with spontaneous endometriosis that mounted a lesser immune response to endometrial antigens than control animals. The activity of peritoneal natural killer and T lymphocytes is suppressed in women with endometriosis, but whether these immunologic deviations are the cause or the result of endometriosis is still unclear. Endometriosis may occur when a deficiency in cellular immunity allows menstrual tissue to implant and grow on the peritoneum.
Genetic influences in the development of endometriosis have been described. Studies have found that 7-9% of endometriosis patients' first-degree female relatives are diagnosed with the disease - significantly greater than the control rate of 1-2%. Further investigation has revealed a possible role for the HLA-B7 allele. The expression of HLA-B7 has been shown to inhibit the cytotoxic activity of natural killerlike T lymphocytes, suggesting that the growth of ectopic endometrial cells might be under genetic control.
Treatment for endometriosis is preceded by careful confirmation and staging with laparoscopy or laparotomy. Factors to consider prior to treatment include the patient's age and desire for fertility, the severity of symptoms, and the extent, location, and severity of the disease. Even though there is no universally effective cure for this disorder, treatment options do exist that can provide relief of symptoms. The wide variety of treatments for endometriosis betray its poorly defined etiology and pathophysiology. Treatment includes expectant management, conservative surgical therapy, medical therapy, extensive surgery with castration, and superovulation therapies for infertility, such as in vitro fertilization or gamete intrafallopian tube transfer (GIFT). With more advanced endometriosis, there is a greater likelihood that surgical intervention will be required to treat the disease successfully. Surgical removal of both ovaries invariably induces remission of the disease but should be reserved for women with advanced endometriosis who are over 35 years of age and do not intend to become pregnant.
Expectant management, or watchful waiting, may be a reasonable management strategy for the younger woman who desires pregnancy and has mildly symptomatic endometriosis. Efforts can then be spent identifying and correcting any other infertility factors as necessary (see Evaluation of the Infertile Couple, below). This approach has been shown to produce pregnancy rates as high as those achieved with medical therapy or conservative surgery (50%).
Conservative surgery for endometriosis entails either laparoscopy or laparotomy and is indicated (1) for confirmation of diagnosis; (2) if fertility is desired, to determine tubal occlusion or peritubal, pelvic, or ovarian adhesions; (3) for aspiration of chocolate ovarian cysts; and (4) for evaluation of pelvic pain unrelieved by medical therapy. The initial treatment at the time of diagnostic laparoscopy can often be accomplished with electrocoagulation or laser ablation of implants through the laparoscope. Partial ovarian resection for endometriomas and lysis of adhesions are accomplished as necessary. Definitive surgery includes total hysterectomy and bilateral salpingo-oophorectomy and is indicated in women who do not desire pregnancy and for whom all previous medical and conservative surgical efforts have failed.
Medical management of endometriosis includes the use of danazol, progestins, oral contraceptives, and GnRH agonists. The goal of hormonal therapy is to control symptoms or improve fertility, or both. Most medical regimens involve treatment for at least 6 months, allowing for adequate regression of implants.
Endometriotic implants behave like normal endometrial tissue and are supported by ovarian hormones. The effectiveness of hormonal management takes advantage of the biologic response of endometriotic tissue to alterations of the hormonal environment. In either a hypoestrogenic or a hyperandrogenic environment, endometriotic implants become atrophic. Danazol (Danocrine), for instance, induces a hyperandrogenic state, and GnRH agonists produce a hypoestrogenic state. Both agents induce regression of endometriotic implants. Progesterone therapy such as medroxyprogesterone acetate (Cycrin, Provera) induces decidual or atrophic changes in endometriotic implants. Finally, administration of combined estrogen-progestogen contraceptives (pseudopregnancy regimen) produce an acyclic hormonal environment similar to that of pregnancy, which causes endometriotic implants to atrophy.
Severe endometriosis and infertility often require an organized treatment plan combining surgical and prolonged medical treatment. In a woman whose symptoms are consistent with endometriosis, empiric medical therapy may be tried prior to definitive surgical diagnosis. In a prospective study it was concluded that after failure of initial treatment with oral contraceptives and NSAIDs, empiric therapy with 3 months of a GnRH agonist is appropriate.
Infertility associated with endometriosis has now been treated with advanced reproductive techniques including administration of hyperstimulation gonadotropins, in vitro fertilization, and GIFT techniques. The family physician assumes a critical role in managing endometriosis by arranging for appropriate consultation, monitoring medical treatment protocols, and providing long-term emotional support to patients and families troubled by this chronic condition.
Family and Community Issues
Education regarding endometriosis ideally begins during early adolescence as part of comprehensive health education. Women should be encouraged to seek medical help for the symptoms of endometriosis. For many women endometriosis becomes a chronic affliction that requires ongoing education, treatment, and compassion. If the patient requests, the physician should meet with other members of the family to offer information and address questions or concerns. Patients and families may benefit from contacting the Endometriosis Association to obtain educational materials and information regarding support groups that deal with the impact of this chronic condition. Women with documented endometriosis who desire pregnancy should be counseled regarding its relation to infertility, so these desires and the timing of childbearing can be discussed. Effectively managing patients with endometriosis challenges the family physician to remain an informed patient advocate, as comprehensive care frequently involves referral and familiarity with long-term treatment modalities not routinely used by family physicians.