The Adrenals as a Source of Androgens in the PCOS
The evaluation of the role of the adrenal androgens in the pathophysiology of hyperandrogenism in PCOS is beyond the scope of this article. Numerous studies have clearly demonstrated that, in a subset of affected women, the adrenals may participate in determining androgen excess, which implies the possibility that a common regulation by specific enzymatic pathways may be responsible for combined ovarian and adrenal overproduction of androgens in women with PCOS. These aspects have been extensively summarized in previous review articles, to which the reader may refer to for a more comprehensive understanding.[7,8]
Of patients with PCOS, 20–30% do in fact have adrenal androgen excess, detectable primarily by elevated dehydroepiandrosterone sulfate (DHEAS) levels. In these patients, a generalized hypersecretion of adrenocortical products, in the basal state or in response to adrenocorticotropic hormone (ACTH) 1–24 stimulation, has been suggested; however, whether cortisol hypersecretion follows that of adrenal androgens is still a matter of debate. The mechanisms responsible for these abnormalities are partially unclear although adrenal androgen excess in PCOS is probably a complex trait, modulated by both intrinsic and acquired factors, as partially discussed in the paper. The production of adrenal androgens in basal conditions or in response to ACTH appears to be closely related to altered enzyme regulation, which may depend on various specific mechanisms, including insulin, obesity and other signals. Importantly, DHEAS levels and the response of adrenal androgens to stimulatory factors, and particularly to ACTH, seem to be relatively constant over time and are closely correlated between PCOS patients and their siblings, suggesting that this abnormality is an inherited trait in PCOS. Thus, this may explain the heterogeneity among individuals in the factors determining adrenal androgen excess in women with PCOS.
Expert Rev Endocrinol Metab. 2012;7(5):555-566. © 2012 Expert Reviews Ltd.