n e w e ng l a n d j o u r na l
m e dic i n e
Mechanisms of Disease
Serdar E. Bulun, M.D.
From the Division of Reproductive Biology Research, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago. Address reprint requests to Dr. Bulun at the Division of Reproductive Biology Research, Dept. ofObstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, 303 E. Superior St., Rm. 4-123, Chicago, IL 60611, or at firstname.lastname@example.org. N Engl J Med 2009;360:268-79.
Copyright © 2009 Massachusetts Medical Society.
ndometriosis is an estrogen-dependent inflammatory disease that affects 5 to 10% of women of reproductive age in the United States.1 Its defining feature isthe presence of endometrium-like tissue in sites outside the uterine cavity, primarily on the pelvic peritoneum and ovaries. The main clinical features are chronic pelvic pain, pain during intercourse, and infertility.1 Endometriosis can be the result of diverse anatomical or biochemical aberrations of uterine function. For example, endometriosis commonly develops in young women with vaginalobstruction of outflow, possibly because of large quantities of backwashed menstrual tissue that has become implanted on pelvic organs.2 In contrast, endometriosis can also involve mechanisms that are independent of anatomical abnormalities; for example, the incidence of endometriosis is increased in women who were exposed in utero to environmental toxins or potent estrogens such asdiethylstilbestrol.3 As cellular and molecular mechanisms involved in endometriosis are being uncovered, the disease’s classification is evolving from a local disorder to a complex, chronic systemic disease. Endometriosis can be inherited in a polygenic manner; its incidence in relatives of affected women is up to seven times the incidence in women without such a family history.4 There is evidence of linkage tochromosomes 7 and 10, but no relevant genes in these regions appear to have yet been identified.5,6 The three clinically distinct forms of endometriosis are endometriotic implants on the surface of the pelvic peritoneum and ovaries (peritoneal endometriosis), ovarian cysts lined by endometrioid mucosa (endometriomas), and a complex solid mass comprised of endometriotic tissue blended with adipose andfibromuscular tissue, residing between the rectum and the vagina (rectovaginal endometriotic nodule). All three types may be variants of the same pathologic process or they can be caused by different mechanisms.7,8 Their common histologic features are the presence of endometrial stromal or epithelial cells, chronic bleeding, and signs of inflammation. These lesions can occur singly or incombination and are associated with an increased risk of infertility or chronic pelvic pain.9,10 The inflammation involved in endometriosis can stimulate nerve endings in the pelvis and thereby cause pain, impair the function of uterine tubes, decrease receptivity of the endometrium, and hinder development of the oocyte and embryo.11,12 Endometriosis can also cause infertility by physically blocking thefallopian tubes.9,10 The treatment of infertility caused by endometriosis is surgical removal of endometriotic tissue or assisted reproductive technology, whereas the usual treatment of pain is a combination of medical suppression of ovulation and surgery. Peritoneal implants are resected or vaporized by means of an electric current or laser. Ovarian endometriomas and rectovaginal endometrioticnodules, however, can be removed effectively only with the use of full dissection. Epidemiologic and laboratory data suggest a link between ovarian endometriosis and distinct types of ovarian cancer.13,14 Clinical evidence clearly points to a deleterious effect of uninterrupted ovulatory cycles on the development and persistence of endometriosis.15,16 First, symptoms of endometriosis usually appear...
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