Progesterone resistance in endometriosis: Link to failure to metabolize estradiol

摘要: Endometriosis is the most common cause of pelvic pain and affects an estimated 5 million women in US. The biologically active estrogen estradiol (E2) best-defined mitogen for growth inflammation processes ectopic endometriotic tissue that commonly resides on organs. Progesterone progestins may relieve by limiting endometriosis but a portion patients with do not respond to treatment progestins. Moreover, progesterone-induced molecular changes eutopic (intrauterine) endometrial are either blunted or undetectable. These vivo observations indicative resistance progesterone action endometriosis. basis be related overall reduction levels receptors (PRs) lack PR isoform named receptor B (PR-B). In normal endometrium, acts stromal cells induce secretion paracrine factor(s). unknown factor(s) act neighboring epithelial expression enzyme 17beta-hydroxysteroid dehydrogenase type 2 (17beta-HSD-2), which metabolizes E2 estrone (E1). tissue, does 17beta-HSD-2 due defect cells. inability produce factors stimulate PR-B very low A (PR-A) observed tissue. end result deficient metabolism giving rise high local concentrations this mitogen. cellular mechanisms underlying failure metabolize reviewed.