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

ObjectiveTo 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.DesignOpen-label, randomized study.SettingUniversity 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 ∼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.