Adrenal and Ovarian Contributions to the Elevated Free Plasma Androgen Levels in Hirsute Women

Abstract

Hirsute women have been studied to explore the possibility that overproduction of androgens by the ovary might be more directly associated with amenorrhea than overproduction by the adrenal. Dexamethasone was administered in order to suppress ACTH secretion, and hence, ACTH-dependent androgen production by the adrenal. Human chorionic gonadotropin was administered in order to stimulate ovarian androgen production. Androgen production was evaluated by measuring indexes of free (unbound) plasma androgen levels and several intermediates in androgen metabolism. Following dexamethasone administration, the levels of free androgens were significantly higher (p < 0.01) in hirsute women with amenorrhea than in other hirsute or normal women. The failure of dexamethasone to suppress plasma free androgens to normal levels in amenorrheic, hirsute women is probably due to overproduction of androgen by the ovaries of such subjects. This conclusion was supported by the finding that gonadotropin reproduced the androgenic abnormality in the latter group. Total and free androgen plasma levels in amenorrheic, hirsute women were partially suppressed by dexamethasone administration, however. The finding that dexamethasone suppressed androgen levels by comparable absolute amounts in normal and amenorrheic, hirsute women seems to indicate that ACTH-dependent androgen production is normal in hirsute, amenorrheic women. These data suggest that normal adrenal androgen production may be superimposed upon overproduction of androgen by the ovary. It is proposed that adrenal androgen production is normal in amenorrheic, hirsute women because it is not finely regulated in a negative feedback fashion by the level of free plasma androgens. Rather, adrenal androgen secretion appears to be determined by those factors which regulate ACTH secretion. The additional finding of high free androgen levels in some fertile women suggests that androgens exert a relatively weak influence on the female gonadotropin-releasing mechanism.