Treatment of Androgen Excess in Adolescent Girls: Ethinylestradiol-Cyproteroneacetate Versus Low-Dose Pioglitazone-Flutamide-Metformin

Abstract Objective: The aim was to perform a first comparison between the effects of a classic therapy and those of a novel treatment for androgen excess in adolescent girls. Design and Setting: We conducted a randomized, open-labeled trial at a university hospital. Participants: Thirty-four adolescents with hyperinsulinemic androgen excess and without risk of pregnancy participated in the study. Interventions: Ethinyl estradiol-cyproterone acetate (EE-CA) vs. a low-dose combination of pioglitazone, flutamide, and metformin (PioFluMet) was administered for 6 months. Main Outcome Measures: We assessed hirsutism and acne scores; androgen excess; fasting insulin, lipid profile, C-reactive protein, high molecular-weight adiponectin, leptin, follistatin; carotid intima-media thickness; body composition (absorptiometry); and abdominal fat partitioning (magnetic resonance imaging). Results: EE-CA and PioFluMet attenuated the androgen excess comparably but had divergent effects on fasting insulinemia; on circulating cholesterol, triglycerides, C-reactive protein, high molecular-weight adiponectin, leptin, and follistatin; on carotid intima-media thickness; on lean mass; and on abdominal, visceral, and hepatic fat, with all these divergences pointing to a healthier condition on low-dose PioFluMet. Conclusion: Low-dose PioFluMet compared favorably to EE-CA in adolescents with androgen excess and without pregnancy risk. The efficacy and safety of low-dose PioFluMet remain to be studied over a longer term and in larger cohorts.