The pathogenesis of polycystic ovary syndrome: lessons from ovarian stimulation studies.
In polycystic ovary syndrome (PCOS) the ovary produces markedly increased amounts of both androgens and estrogens in response to gonadotropin stimulation. Distinctive responses of 17-hydroxyprogesterone and androstenedione to ovarian stimulation testing suggest that ovarian hyperandrogenism is a result of dysregulation of theca cell androgen production which is intrinsic to the ovary. The occurrence of hyperestrogenism together with hyperandrogenism in PCOS suggests that whatever the abnormality of local regulatory factors of steroidogenesis, it affects granulosa as well as theca cells. Dysregulation is often associated with an increase in the number of follicles which evade atresia and reach the 2-8 mm stage of development. Autocrine/paracrine factors, especially those which are FSH-dependent, likely play an important role in the pathogenesis of the ovarian abnormality. Both LH and insulin hypersecretion probably play a secondary role in PCOS by amplifying the preexisting ovarian dysregulation. Because FSH secretion is under tight long-loop negative-feedback control and LH is not, hyperandrogenism is the primary clinical manifestation of dysregulation of steroid production in PCOS. However, anovulation in PCOS is most likely a result of excessive estrogen and inhibin production by multiple, small follicles which inhibit FSH secretory dynamics sufficiently to prevent selection of a dominant follicle.
Barnes
R B
RB
Department of Obstetrics and Gynecology (M/C 2050), The University of Chicago, IL 60637, USA.
D000728:Androgens / Q000096:biosynthesis*; D004967:Estrogens / Q000096:biosynthesis*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists; D006107:Granulosa Cells / Q000378:metabolism; D006801:Humans; D006946:Hyperinsulinism; D007986:Luteinizing Hormone / Q000502:physiology; D010053:Ovary / Q000378:metabolism*; D011085:Polycystic Ovary Syndrome / Q000209:etiology*; D013799:Theca Cells / Q000378:metabolism
D000728:Androgens; D004967:Estrogens; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone