Hyperandrogenic anovulation (the polycystic ovary syndrome)--back to the ovary?

Hyperandrogenic anovulation is characterized by polycystic appearance of the ovaries, elevated free serum testosterone with decreased concentrations of serum sex hormone binding globulin, an increased ratio of luteinizing hormone to follicle stimulating hormone and varying degrees of insulin resistance. We hypothesize that this is the result of variably increased 'ovarian androgenic insulin responsiveness' acting in combination with body mass. Women who develop hyperandrogenism and anovulation when lean (having normal serum insulin concentrations) represent the more severely affected individuals, whereas those who can resume ovulation by losing weight (and lowering their elevated serum insulin) represent a milder form. The tendency of these women to develop ovarian hyperstimulation syndrome despite hypophyseal desensitization suggests a primary ovarian defect which is apparently more pronounced in lean subjects. The unique ability of surgical damage to the ovary to induce ovulation, raises the possibility that inflammatory-like tissue remodelling has a major role in rescuing follicles from androgen-induced atresia. Approaches that may facilitate the study of this possible mechanism may include examination of in-vitro perfused, post-surgery mammalian ovaries and the elucidation of signal transduction mechanism(s) of insulin in the ovary, with special reference to cells emanating from affected women.