PCOS is usually a form of FOH. The magnitude of the local androgen concentration resulting from intraovarian androgen excess would seem to account for the high frequency of anovulatory symptoms in ovarian as compared with the adrenal disorders resulting in similar, moderately elevated plasma androgen levels. Although ovarian hyperandrogenism can be caused by primary disturbances that promote the process of follicular atresia, extraovarian virilizing disorders and steroidogenic blocks, the vast majority of cases appear to be due to dysregulation of androgen secretion. The primary nature of this abnormality is suggested by its appearance in perimenarcheal adolescent girls. We propose that FOH represents a flaw in the intraovarian processes that normally coordinate ovarian androgen and estrogen secretion. The data indicate generalized overactivity of the entire steroidogenic cascade involved in androgen secretion, most prominent in the Δ4-pathway. The overstimulation of steroidogenesis may be manifest as FOH alone (PCOS and hyperthecosis), functional adrenal hyperandrogenism alone (17-ketosteroid hyperresponsiveness to ACTH), or both con currently. The fundamental ovarian abnormality often involves LH excess, but this is the situation in only about half the cases and there appears to be escape from the normal LH-steroid dose-response characteristics. There is evidence that the insulin/IGF system can suffice to cause the steroidogenic abnormalities, acting for the most part in synergism with LH. The ovary functions as if it were responding to the hyperinsulinemic state in spite of the resistance to the effects of insulin on glucose metabolism. This paradox remains lobe resolved. Finally, in addition to the nearly universal finding of insulin resistance among women with FOH, a subset appears to have evidence of β-cell secretory dysfunction, which may indicate a relationship of the disorder to NIDDM.
|Number of pages
|Published - Jan 1 1995
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism