THE PATHOGENESIS OF POLYCYSTIC-OVARY-SYNDROME - LESSONS FROM OVARIAN STIMULATION STUDIES

In polycystic ovary syndrome (PCOS) the ovary produces markedly increa sed amounts of both androgens and estrogens in response to gonadotropi n stimulation. Distinctive responses of 17-hydroxyprogesterone and and rostenedione to ovarian stimulation testing suggest that ovarian hyper androgenism is a result of dysregulation of theca cell androgen produc tion which is intrinsic to the ovary. The occurrence of hyperestrogeni sm together with hyperandrogenism in PCOS suggests that whatever the a bnormality of local regulatory factors of steroidogenesis, it affects granulosa as well as theca cells. Dysregulation is often associated wi th an increase in the number of follicles which evade atresia and reac h the 2-8 mm stage of development. Autocrine/paracrine factors, especi ally those which are FSH-dependent, likely play an important role in t he pathogenesis of the ovarian abnormality. Both LH and insulin hypers ecretion probably play a secondary role in PCOS by amplifying the pree xisting ovarian dysregulation. Because FSH secretion is under tight lo ng-loop negative-feedback control and LH is not, hyperandrogenism is t he primary clinical manifestation of dysregulation of steroid producti on in PCOS. However, anovulation in PCOS is most likely a result of ex cessive estrogen and inhibin production by multiple, small follicles w hich inhibit FSH secretory dynamics sufficiently to prevent selection of a dominant follicle. (J. Endocrinol. Invest. 21: 567-579, 1998) (C) 1998, Editrice Kurtis.