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

• Published in: The journal of clinical endocrinology and metabolism Vol. 98; no. 5; pp. E902 - E907
• Main Authors: Ibáñez, Lourdes, Díaz, Marta, Sebastiani, Giorgia, Marcos, María Victoria, López-Bermejo, Abel, de Zegher, Francis
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.05.2013; Copyright by The Endocrine Society
• Subjects: Absorptiometry; Acne; Adipose tissue; Adiposity - drug effects; Adolescence; Adolescent; Adolescent Development - drug effects; Adolescents; Androgen Antagonists - administration & dosage; Androgen Antagonists - adverse effects; Androgen Antagonists - therapeutic use; Androgens; Birth control; Body composition; Body Mass Index; C-reactive protein; C-Reactive Protein - analysis; Carotid Intima-Media Thickness; Child development; Contraception; Contraceptives, Oral, Hormonal - administration & dosage; Contraceptives, Oral, Hormonal - adverse effects; Contraceptives, Oral, Hormonal - therapeutic use; Cyproterone Acetate - administration & dosage; Cyproterone Acetate - adverse effects; Cyproterone Acetate - therapeutic use; Drug Combinations; Ethinyl Estradiol - administration & dosage; Ethinyl Estradiol - adverse effects; Ethinyl Estradiol - therapeutic use; Ethinylestradiol; Female; Fertility; Flutamide; Girls; Hirsutism; Humans; Hyperandrogenism - drug therapy; Hyperandrogenism - immunology; Hyperandrogenism - pathology; Hyperandrogenism - physiopathology; Hyperinsulinism - etiology; Hyperinsulinism - prevention & control; Insulin; Insulin Resistance; Intra-Abdominal Fat - drug effects; Intra-Abdominal Fat - immunology; Intra-Abdominal Fat - pathology; Magnetic resonance imaging; Menstruation; Menstruation Disturbances - etiology; Menstruation Disturbances - prevention & control; Metformin; Oral contraceptives; Overweight - etiology; Overweight - prevention & control; Phenotypes; Pioglitazone; Population studies; Pregnancy; Protein composition; Proteins; Teenagers; Testosterone; Tunica Intima - drug effects; Tunica Intima - immunology; Tunica Intima - pathology; Vascular Diseases - etiology; Vascular Diseases - prevention & control
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/jc.2013-1041

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.