Endocrine Abstracts

Objective: To compare the effects of a classic therapy to those of a novel treatment for androgen excess in adolescent girls.

Study design: Randomized, open-labeled trial over 12 months.

Study participants: Adolescents (n=34; mean age 16 year, BMI 23 kg/m²) with hyperinsulinemic androgen excess and without risk of pregnancy.

Interventions: Ethinyl estradiol-cyproterone acetate (EE-CA; Diane 35 Diario) vs a low-dose combination of pioglitazone 7.5 mg/day, flutamide 62.5 mg/day, and metformin 850 mg/day (PioFluMet) for 12 months.

Main outcome measures: Hirsutism and acne scores; androgen excess; circulating C-reactive protein and high-molecular-weight adiponectin; carotid intima-media thickness; body composition (by absorptiometry); abdominal fat partitioning (by MRI); gene expression in consecutive biopsies of subcutaneous adipose tissue at the abdominal level.

Results: EE-CA and PioFluMet reduced the clinical and biochemical androgen excess comparably but had divergent effects on C-reactive protein and high-molecular-weight adiponectin; on carotid intima-media thickness; on lean mass; on abdominal and visceral fat; and on the expression of genes, for example, those related to macrophage activation and lipid storage in adipose tissue. All these divergences pointed to a healthier condition on low-dose PioFluMet.

Conclusion: Over 12 months, PioFluMet compared favorably to EE-CA in adolescents with androgen excess and without pregnancy risk. Further study of low-dose PioFluMet seems warranted, not only to strengthen its safety side over the longer term and in larger cohorts, but also to verify further whether the efficacy of this low-dose combination holds enough potential to allow it to become a first-choice therapy for the majority of young adolescents with androgen excess, namely those who are not at pregnancy risk and who are nowadays nevertheless exposed to supraphysiological doses of estro-progestagens.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.