title: 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: 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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  This was a randomized, open-label trial.
  
  
  METHODS
  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).
  
  
  METHODS
  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.
  
  
  METHODS
  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.
authors.affiliation: Endocrinology Unit, Hospital Sant Joan de Déu, University of Barcelona, Passeig de Sant Joan de Déu, 2, 08950 Esplugues, Barcelona, Spain. libanez@hsjdbcn.org
authors.forename: Lourdes
authors.initials: L
authors.lastname: Ibáñez
authors.forename: Marta
authors.initials: M
authors.lastname: Díaz
authors.forename: Giorgia
authors.initials: G
authors.lastname: Sebastiani
authors.forename: María Victoria
authors.initials: MV
authors.lastname: Marcos
authors.forename: Abel
authors.initials: A
authors.lastname: López-Bermejo
authors.forename: Francis
authors.initials: F
authors.lastname: de Zegher
mesh_terms: D050154:Adiposity / Q000187:drug effects; D000293:Adolescent; D041923:Adolescent Development / Q000187:drug effects; D000726:Androgen Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000032:analysis; D059168:Carotid Intima-Media Thickness; D003278:Contraceptives, Oral, Hormonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D017373:Cyproterone Acetate / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004338:Drug Combinations; D004997:Ethinyl Estradiol / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D017588:Hyperandrogenism / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D006946:Hyperinsulinism / Q000209:etiology / Q000517:prevention & control; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008599:Menstruation Disturbances / Q000209:etiology / Q000517:prevention & control*; D050177:Overweight / Q000209:etiology / Q000517:prevention & control*; D017539:Tunica Intima / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D014652:Vascular Diseases / Q000209:etiology / Q000517:prevention & control*
chemical_list: D000726:Androgen Antagonists; D003278:Contraceptives, Oral, Hormonal; D004338:Drug Combinations; D004997:Ethinyl Estradiol; D017373:Cyproterone Acetate; C032640:Cyproterone acetate, ethinyl estradiol drug combination; D002097:C-Reactive Protein