Objective: To test the hypothesis that ovarian hormones in women with hyperandrogenism alter adrenocortical steroidogenesis. Design: Combination of two prospective studies. Setting: Academic medical centers. Patient(s): Eighteen hyperandrogenic patients demonstrating hirsutism with either hyperandrogenemia, oligomenorrhea, or both. Eighteen healthy nonhirsute eumenorrheic untreated women served as controls. Interventions: Blood sampling basally and after acute adrenal stimulation with ACTH, before and after 20-24 weeks of leuprolide administration. Nine patients also received 0.625 mg/d of oral conjugated esterified estrogens and 10 mg of medroxyprogesterone acetate days 1-12 of the month (i.e., estrogen replacement therapy [ERT]), whereas the remaining nine did not. Main Outcome Measure(s): Before and after the administration of the GnRH agonist (GnRH- a), the basal concentrations of DHEAS; and the levels of androstenedione (A4), DHEA, androstenediol, 11β-hydroxyandrostenedione (11-OHA4), and cortisol before and 60 minutes after acute adrenal stimulation, were measured. Result(s): Levels of DHEAS, androstenediol, and 11-OHA4 decreased by 15%30%, regardless of whether patients initially had or did not have DHEAS excess. However, only hyperandrogenic patients with elevated levels of DHEAS showed a significant decrease in basal DHEA levels. No statistically significant difference in the response of either androgen to ACTH (1-24) stimulation was noted with ovarian suppression, regardless of initial DHEAS level or use of ERT. Conclusion(s): We found no evidence that ovarian hormone secretion affected adrenal steroidogenesis, and those women with the highest adrenal androgen levels had the least response to GnRH-a suppression. These findings further support the concept of an intrinsic, and possibly primary, abnormality of adrenocortical steroidogenesis in a subset of hyperandrogenic women that is independent of ovarian abnormalities.