Anovulation in Eumenorrheic, Nonobese Adolescent Girls Born Small for Gestational Age: Insulin Sensitization Induces Ovulation, Increases Lean Body Mass, and Reduces Abdominal Fat Excess, Dyslipidemia, and Subclinical Hyperandrogenism

Abstract

Adolescent girls who were small for gestational age when born are, even if not obese, at risk for numerous abnormalities, including hyperinsulinism, subnormal ovarian responsiveness to FSH, subclinical hyperandrogenism, areduced rate of ovulation, and abnormal blood lipids. Hyperinsulinemic insulin resistance has been suggested as an important pathogenetic factor. The authors tested this possibility by determining the effects of insulin sensitization in 13 such girls. They were not obese and had normal menses, but they did not ovulate and had central adiposity and dyslipidemia. In addition, subclinical hyperandrogenism was documented. All had weighed below 2 standard deviations at term birth and had a body mass index less than 25 kg/m 2 . The participants, 14 to 18 years of age at the time of study, had begun menstruating 3 to 6 years earlier. Metformin was given in a dose of 850 mg daily for 3 months. Blood levels of insulin, androgens, triglycerides, and FSH were elevated in these girls, but fasting insulin levels and androgens declined when metformin was given, and the lipid profile became less atherogenic in all cases. Initially the waist-to-hip ratio was high with excess fat, especially abdominally, and a reduced lean body mass. After 3 months on metformin, all of these abnormalities were less evident. The most marked changes were a reduction in abdominal fat mass and an increase in lean body mass (Fig. 1). Body weight remained unchanged. Six of the 13 girls (46%) began ovulating about 6 weeks after the start of treatment, and within 11 weeks, 69% were ovulating. The increase in lean body mass that followed from metformin therapy raises the question of whether it reduces growth hormone secretion in adolescent girls with hyperinsulinemic hyperandrogenism. If so, this would reinforce the importance of insulin sensitivity in maintaining a normal body shape and ovulatory function.