Adrenal Function in Hirsutism. II. Effect of an Oral Contraceptive*

Fifteen preovulatory hirsute woman were studied before and at the completionof one cycle (21 days) of an oral contraceptive that contained norethindrone (2 mg) and mestranol (0.1 mg; N + M). A 3-day protocol included a diurnal study, followed by overnight dexamethasone suppression and ACTH stimulation. Plasma A4-androstenedione (A), testosterone (T), and dehydroepiandrosterone sulfate (DHEAS) and plasma cortisol (F) were meDHEAS was reduced 28%, and F was increased 176% with therapy. A exhibiteda diurnal rhythm synchronouswith F across all of the time periods, but T and DHEAS did not. ACTH dependency of A was determined by measuring the magnitude of changein A between the timeof the F peak and the F nadir in the diurnal study. In the diurnal study, both themean concentration of A as wellas the net change in plasma A concentration from the time of theF peak to the F nadir correlated significantly with the mean DHEAS concentration during N+ M treatment. The responsiveness of A and F to 0.5 U ACTH iv was determined afterdexamethasone (mg)had beengiven the night before. On treatment, dexamethasone-suppressed mean F values wer higher and mean A levels were lower. The incremental increase above the dexamethasone-suppressedlevels was significantly decreased for A,but was significantly increased fo F during N + M treatment. The responsiveness of A and F to 0.5 U ACTH iv was determined after dexamethasone (1 mg) had been given the night before. On treatment, dexamethasone-suppressed mean F values were higher and mean A levels were lower. The incremental increase above the dexamethasone-suppressed levels was significantly decreased for A, but was significantly increased for F during N + M treatment. The response of A to ACTH correlated significantly with the mean concentration of DHEAS during but not before treatment. The significant reduction in plasma A and T by N + M noted in this study confirms the usefulness of this agent in reducing androgen levels in hirsute women. The data ofthis study document that N + M reducesadrenal androgen activity as evidenced by 1 a reduction of the magnitude of the diurnalchange in A synchronous with F, 2) a reductionof the A response to exogenous ACTH, and 3) a reduction in the circulating concentration of DHEAS. DHEAS correlated significantly with the mean and the difference in the peak to nadiaconcentration in the diurnal study and with the A response to ACTH during N + M. This suggests that this relatively simple assay can serve as an indicator of the magnitud ofadrenal androgen secretion in hirsute females.