Early metformin therapy to delay menarche and augment height in girls with precocious pubarche

Objective: To study the effects of early metformin treatment on menarche, height, and polycystic ovary syndrome (PCOS) markers. Low-birthweight (LBW) girls with precocious pubarche (PP) are at risk for an early menarche (< 12 years), an adult stature below target level, and PCOS. Hyperinsulinemic insulin resistance is thought to be a key factor. Design: Open-label, randomized study. Setting: University hospital. Patient(s): Thirty-eight LBW-PP girls. Intervention(s): At age 8 years, girls were randomly assigned to remain untreated or to receive metformin for 4 years; subsequently, both subgroups were followed without treatment until each girl was postmenarcheal. Main Outcome Measure(s): Age at menarche, height, weight, endocrine-metabolic state (fasting blood), body composition (by absorptiometry), abdominal fat (subcutaneous vs. visceral), and hepatic adiposity (by magnetic resonance imaging). Result(s): At last assessment, girls in each subgroup were on average 2 years beyond menarche; the mean growth velocity was below 2 cm/years. Age at menarche was 11.4 +/- 0.1 years in untreated girls and 12.5 +/- 0.2 years in metformin-treated girls; the latter girls were taller and much leaner (with less visceral and hepatic fat) and had more favorable levels of circulating insulin, androgens, and lipids. Conclusion(s): Early metformin therapy (age similar to 8-12 years) suffices to delay menarche; to augment postmenarcheal height; to reduce total, visceral, and hepatic adiposity; and to curb the endocrine-metabolic course of LBW-PP girls away from adolescent PCOS. (Fertil Steril(R) 2011;95:727-30. (C) 2011 by American Society for Reproductive Medicine.)