Insulin sensitization early after menarche prevents progression from precocious pubarche to polycystic ovary syndrome

Girls with low birth weight (LBW) and with a history of precocious pubarche in childhood (PP) are at high risk of polycystic ovary syndrome (PCOS) in adolescence. In formerly LBW-PP girls, we examined whether initiation of insulin sensitization therapy early after menarche could prevent progression of PCOS features. Study design Twenty-four girls, small at term birth (mean weight, 2.4 kg), who presented with PP (at mean age 6.7 years) and were currently (mean age, 12.4 years) postmenarcheal, with hyperinsulinemic hyperandrogenemia but nonobese, were randomly assigned to receive metformin (850 mg/d) or no treatment for 12 months. Six-month fasting blood samples were collected, and body composition was assessed by dual-energy x-ray absorptiometry. In addition, overnight growth hormone (GH) and gonadotropin secretion was analyzed in 10 girls (6 treated; 4 untreated) at 0 and 6 months.

At baseline, compared with healthy control subjects, LBW-PP girls had dyslipidemia, excess truncal fat, reduced lean body mass, and increased insulin-like growth factor-I and GH levels. In untreated girls, insulin sensitivity, serum androgens, lipids, total and truncal fat mass, and lean body mass significantly diverged further from normal over 12 months. In metformin-treated girls, all these abnormalities significantly reversed within 6 months, and body composition continued to improve between 6 and 12 months.

Early metformin therapy prevents progression from PP to PCOS in a high-risk group of formerly LBW girls. This confirms the key role of hyperinsulinemic insulin resistance in the ontogeny of PCOS. Furthermore, normalization of body composition, lipid profiles, and GH secretion could reduce long-term cardiovascular risk.