Estrogen production in endometriosis and use of aromatase inhibitors to treat endometriosis

Estrogen is the most important known factor that stimulates the growth of e ndometriosis. Estrogen delivery to endometriotic implants was classically v iewed to be only via the circulating blood in an endocrine fashion. We rece ntly uncovered an autocrine positive feedback mechanism, which favored the continuous production of estrogen and prostaglandin (PG)E-2 in the endometr iotic stromal cells. The enzyme, aromatase, is aberrantly expressed in endo metriotic stromal cells and catalyzes the conversion of C-19 steroids to es trogens, which then stimulate cyclooxygenase-2 to increase the levels of PG E(2), PGE(2), in turn, is a potent inducer of aromatase activity in endomet riotic stromal cells. Aromatase is not expressed in the eutopic endometrium . Aromatase expression in endometriosis and its inhibition in eutopic endom etrium are controlled by the competitive binding of a stimulatory transcrip tion factor, steroidogenic factor-1, and an inhibitory factor, chicken oval bumin upstream promoter-transcription factor to a regulatory element in the aromatase P450 gene promoter. In addition, we find that endometriotic tiss ue is deficient in 17 beta-hydroxysteroid dehydrogenase type 2, which is no rmally expressed in eutopic endometrial glandular cells and inactivates est radiol-17 beta to estrone. This deficiency is another aberration that favor s higher levels of estradiol-17 beta in endometriotic tissues in comparison with the eutopic endometrium. The clinical relevance of local aromatase ex pression in endometriosis was exemplified by the successful treatment of an unusually aggressive form of recurrent endometriosis in a postmenopausal w oman using an aromatase inhibitor.