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.

BACKGROUND

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.

AIM: 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.

DESIGN

This was a randomized, open-label trial.

STUDY POPULATION: 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).

INTERVENTIONS: 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.

MAIN OUTCOME MEASURES: 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.

RESULTS

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.

CONCLUSIONS

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.