The Role of the Adrenal Glands in the Hyperandrogenism Associated with Polycystic Ovarian Syndrome

Abstract

The magnitude of adrenal versus ovarian or peripheral contributions to the hyperandrogenemia of polycystic ovarian syndrome (PCOS) is controversial. Evidence for an adrenal origin of circulating androgens has been studied in prepubertal, adult, and postmenopausal women who will have, do have, or have had PCOS. Many girls who have premature adrenarche with increased circulating levels of adrenal steroid DHEA-S or those diagnosed with precocious puberty go on to develop PCOS in adolescence. Some adults with PCOS demonstrate increased DHEA and DHEA-S levels after ACTH stimulation test. Alternatively, or in addition, in many women with PCOS who have elevated DHEA or DHEA-S, these steroids may be suppressed by exogenous corticosteroid administration. In some PCOS women (20 %), long-term suppression of ovarian steroidogenesis to castrate levels with the use of GnRH agonists fails to suppress hyperandrogenemia, suggesting an adrenal source. Approximately 30–50 % of PCOS patients can be shown by these maneuvers to be producing excessive amounts of adrenal androgens. Increased activity of P450C17α can contribute to excessive production of both adrenal (DHEA) and ovarian (androstenedione) androgens. Alternatively, excess androgen production may occur as an ancillary phenomenon during processes that can result in cortisol overproduction (e.g., Cushing syndrome) or increased degradation of cortisol. The normal decline in adrenal androgen production with menopause is blunted in women who have PCOS and postmenopausal women with a history of PCOS demonstrate an exaggerated androgen response to exogenous ACTH. While the exact mechanisms remain unclear, these observations suggest that adrenal steroidogenesis may be under different control in women with PCOS.