Treatment with flutamide improves hyperinsulinemia in women with idiopathic hirsutism

Objective: To investigate insulin metabolism and its modifications induced by the administration of flutamide, a specific antiandrogen compound, in women with idiopathic hirsutism (IH) and in nonobese women with polycystic ovary syndrome (PCOS). Design: Prospective, randomized trial. Setting: Endocrinological Centre of the Department of Obstetrics and Gynecology, University of Caligari, Caligari, Italy. Patient(s): Thirty-two women with normal body mass index participated in the study: 11 with clinical and hormonal features of PCOS and 21 age- and weight-matched normally cycling women with IH (n = 11) and without IH (n = 10, controls). Intervention(s): Each subject with PCOS or IH was assigned randomly to receive either flutamide tablets (250 mg twice a day) or placebo for ≥5 months. Twelve subjects (6 with PCOS, 6 with IH) received flutamide and 10 (5 with PCOS, 5 with IH) received placebo. All subjects ingested 75 g of glucose and then underwent an oral glucose tolerance test (OGTT), 3–7 days after spontaneous or medroxyprogesterone acetate (5 mg daily for 5 days)–induced menses. In women with PCOS or IH, the OGTT was repeated at the fourth month of treatment. Main Outcome Measure(s): Fasting and OGTT-stimulated levels of glucose, insulin, and C peptide. Result(s): Both fasting and OGTT-stimulated levels of insulin and C peptide were significantly higher in women with PCOS and in those with IH than in controls. Placebo did not modify parameters of glucose metabolism. Flutamide was capable of significantly blunting fasting and OGTT-stimulated secretion of insulin only in women with IH. Conclusion(s): Hyperinsulinemia exists in women with IH as well as in nonobese women with PCOS. Treatment with flutamide can completely reverse hyperinsulinemia only in women with IH, which suggests that the efficacy of the drug is dependent on peripheral androgen hyperactivity.