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Original Article |
Endocrinology Unit (L.I., A.F., F.R.-H.), Hospital Sant Joan de Déu, University of Barcelona, 08950 Barcelona, Spain; Hormonal Laboratory (N.P.), Hospital Materno-Infantil Vall d’Hebron, 08035 Barcelona, Spain; Endocrinology Unit (M.V.M.), Consorci Hospitalari de Terrassa, 08227 Terrassa, Spain; and Department of Pediatrics (F.d.Z.), University of Leuven, 3000 Leuven, Belgium
Address all correspondence and requests for reprints to: Lourdes Ibáñez, M.D., Ph.D., Endocrinology Unit, Hospital Sant Joan de Déu, University of Barcelona, Passeig de Sant Joan de Déu, 2, 08950 Esplugues, Barcelona, Spain. E-mail: libanez{at}hsjdbcn.org.
Abstract
Adolescent girls born small for gestational age (SGA) are at risk for anovulation, hyperinsulinism, subclinical hyperandrogenism, dyslipidemia, and central adiposity. Hyperinsulinemic insulin resistance has been proposed as a key pathogenetic factor underpinning these associations.
We have tested this hypothesis in an intervention study by assessing the effects of insulin sensitization (metformin treatment, 850 mg/d for 3 months) in eumenorrheic, nonobese, anovulatory SGA adolescents [n = 13; mean birth weight, 2.3 kg; age, 15 yr; body mass index (BMI), 20.5 kg/m2; 
3 yr post-menarche] who were in a steady state (over 
6 months) for BMI, hyperinsulinism, subclinical hyperandrogenism, and dyslipidemia, and who presented a deficit of lean body mass and an excess of (truncal and abdominal) fat mass.
Metformin treatment was accompanied by a drop in fasting insulin and serum androgens and by a less atherogenic lipid profile (all P 
0.01). After 3 months on metformin, all identified aberrations in body composition were attenuated, the most marked changes (P < 0.0001) being a reduction of the excess in abdominal fat and of the deficit in lean body mass; BMI remained unaltered. Finally, 6 of 13 girls became ovulatory after about 6 wk on metformin, and 9 of 13 (69%) ovulated within 11 wk on metformin.
In conclusion, these observations corroborate the notion that anovulation, an excess of abdominal fat mass, and a deficit of lean mass in nonobese SGA adolescents are essentially underpinned by hyperinsulinemic insulin resistance, and that sensitization to insulin is an effective approach to correct these abnormalities and, conceivably, to prevent them.
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