Adrenal androgen production in polycystic ovary syndrome

Abstract

Secondary PCOS may occur in association with disorders characterized by adrenal androgen excess, e.g. congenital adrenal hyperplasia. Primary PCOS is associated frequently with more subtle abnormalities in adrenal androgen status. However, it has not been established that the mild adrenal androgen occurring in PCOS is causally involved in the development of PCOS, although adrenal hyperresponsiveness to stimulation appears to be characteristic of PCOS. It remains to be clarified whether this is due to excess stimulation of the adrenal by the putative CASH, which with ACTH probably coordinates adrenal androgen steroidogenesis, or whether adrenal hyperresponsiveness occurs as a consequence of increased cortisol clearance with compensatory hypersecretion of ACTH, which is associated with excessive adrenal androgen production. The possibility also exists that the enzyme system responsible for 17-hydroxyprogesterone production and its conversion to androgens is excessively active and may occur as a common defect in the adrenal and ovaries as a consequence of a congenital disorder. For at least some patients, treatment with a nocturnal low-dose glucocorticoid is an effective form of treatment. Indeed, this is the only hormonal form of treatment for hirsutism that also facilitates fertility and pregnancy. It is possible that PCOS may occur as a consequence of any disorder in which anovulation is associated with normal or elevated oestrogen levels. For some patients with PCOS, mild adrenal androgen excess is probably primary to development of the disorder. Thus, a trial of treatment with low-dose glucocorticoid at night appears to be a reasonable option in susceptible patients who can probably be recognized by demonstration of an excessive androgen response to ACTH or metyrapone.