Pathogenesis of hyperandrogenism in polycystic ovary syndrome

Androgen excess (AE) is an important, even essential feature of the polycystic ovary syndrome (PCOS), and arises primarily from ovarian AE, although a hyperactivity of adrenocortical function and adrenal androgen (AA) excess are present in a significant number of patients. Increased ovarian theca cell function, and possibly number, and augmented expression of steroidogenic enzymes have been demonstrated in PCOS. Increased LH stimulation of thecal androgen biosynthesis also appears to be an important, early event in PCOS. Abnormalities in other intrinsic ovarian factors such as inhibin, activin, and follistatin appear to modulate ovarian LH response. Granulosa cell dysfunction may also contribute, with PCOS women demonstrating arrested granulose development and increased 5 alpha-reductase expression. Adrenal AE, possibly arising from generalized adrenocortical hyper-responsivity, is a relatively common feature of PCOS. Finally, the metabolic consequences of obesity and insulin resistance appear to potentiate excess androgen production in adolescent and adult PCOS patients. In short, the hyperandrogenism of PCOS appears to be aptly multifactorial, consistent with the complex nature of the syndrome itself.