Oral Contraception vs Insulin Sensitization for 18 Months in Nonobese Adolescents With Androgen Excess: Posttreatment Differences in C-Reactive Protein, Intima-Media Thickness, Visceral Adiposity, Insulin Sensitivity, and Menstrual Regularity

Abstract

An oral estro-progestagen is the standard medication given to adolescent girls with androgen excess, even when those girls are not at risk of pregnancy. The aim of this study was to compare on-treatment and post-treatment effects of intervention with an oral contraceptive vs an insulin-sensitizing treatment for androgen excess in nonobese adolescents. This was a randomized, open-label trial. Subjects were nonobese adolescent girls with hyperinsulinemic androgen excess and without risk of pregnancy (mean age, 16 years; body mass index, 23 kg/m²; n = 34). The effects of treatment with ethinylestradiol-cyproteroneacetate (EE-CA) vs a low-dose combination of pioglitazone (7.5 mg/d), flutamide (62.5 mg/d), and metformin (850 mg/d) (PioFluMet) for 18 months were studied. Posttreatment follow-up was for 6 months. Androgen excess (hirsutism and acne scores and serum testosterone), glucose-stimulated insulinemia, circulating C-reactive protein, carotid intima media thickness, body composition (absorptiometry), abdominal fat partitioning (magnetic resonance imaging), and menstrual regularity were measured. EE-CA and PioFluMet attenuated androgen excess similarly but had divergent, and even opposing, effects on other outcomes. Six months posttreatment, the PioFluMet-treated girls had a lower glucose-induced insulinemia, a lower C-reactive protein level, and a thinner intima media than the EE-CA-treated girls, and they were viscerally less adipose, had a higher lean mass, and were more likely to have regular cycles. The on-treatment and post-treatment effects of PioFluMet compared favorably with those of oral contraception in nonobese adolescents with androgen excess. The intervention whereby androgen excess is reduced in adolescence influences the post-treatment phenotype. PioFluMet-like interventions in adolescence may thus hold the potential to prevent part of the androgen-excess phenotype in adulthood, including adiposity and subfertility.