title: Early metformin therapy (age 8-12 years) in girls with precocious pubarche to reduce hirsutism, androgen excess, and oligomenorrhea in adolescence.
abstract: BACKGROUND
  Girls with a combined history of low(-normal) birth weight (LBW) and precocious pubarche (PP) are at high risk to develop polycystic ovary syndrome (PCOS).
  
  
  OBJECTIVE
  The objective of the study was to compare the capacity of early vs. late metformin treatment to prevent adolescent PCOS.
  
  
  METHODS
  This was a randomized, open-label study over 7 yr.
  
  
  METHODS
  The study was conducted at a university hospital.
  
  
  METHODS
  Thirty-eight LBW-PP girls were followed up from the mean age 8 until age 15 yr.
  
  
  METHODS
  Early metformin (study yr 1-4; age 8-12 yr) vs. late metformin (yr 6; age 13-14 yr).
  
  
  METHODS
  Measures included height; weight; hirsutism score; menstrual cycle; endocrine-metabolic screening (fasting; follicular phase); C-reactive protein; body composition (absorptiometry); abdominal fat partitioning (magnetic resonance imaging); ovarian morphology (ultrasound); PCOS (National Institutes of Health and Androgen Excess Society definitions) after yr 7 (all girls thus untreated for at least 1 yr).
  
  
  RESULTS
  None of the girls dropped out of the study. At age 15 yr, early-metformin girls were taller (4 cm), were in a less proinflammatory state, and had less central fat due to reductions in visceral and hepatic fat. Hirsutism, androgen excess, oligomenorrhea, and PCOS were between 2- and 8-fold more prevalent in late- than early-treated girls. Abdominal adiposity was the first variable to diverge (at age 8-10 yr) between girls without vs. with PCOS at age 15 yr.
  
  
  CONCLUSIONS
  In LBW-PP girls, early metformin therapy was found to prevent or delay the development of hirsutism, androgen excess, oligomenorrhea, and PCOS more effectively than late metformin. The time window of late childhood and early puberty may be more critical for the development, and thus for the prevention, of adolescent PCOS than the first years beyond menarche.
authors.affiliation: Department of Endocrinology, Hospital Sant Joan de Déu, University of Barcelona, 08950 Barcelona, Spain. libanez@hsjdbcn.org
authors.forename: Lourdes
authors.initials: L
authors.lastname: Ibáñez
authors.forename: Abel
authors.initials: A
authors.lastname: López-Bermejo
authors.forename: Marta
authors.initials: M
authors.lastname: Díaz
authors.forename: Maria Victoria
authors.initials: MV
authors.lastname: Marcos
authors.forename: Francis
authors.initials: F
authors.lastname: de Zegher
mesh_terms: D000293:Adolescent; D002648:Child; D005260:Female; D005500:Follow-Up Studies; D006628:Hirsutism / Q000188:drug therapy* / Q000453:epidemiology / Q000517:prevention & control; D006801:Humans; D017588:Hyperandrogenism / Q000188:drug therapy* / Q000453:epidemiology / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D008572:Menarche; D008687:Metformin / Q000008:administration & dosage*; D009839:Oligomenorrhea / Q000188:drug therapy* / Q000453:epidemiology / Q000517:prevention & control; D011085:Polycystic Ovary Syndrome / Q000453:epidemiology / Q000517:prevention & control*; D015995:Prevalence; D011629:Puberty, Precocious / Q000188:drug therapy* / Q000453:epidemiology; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin