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The Journal of Clinical Endocrinology & Metabolism Vol. 86, No. 8 3595-3598
Copyright © 2001 by The Endocrine Society

Endocrine Care

Sensitization to Insulin Induces Ovulation in Nonobese Adolescents with Anovulatory Hyperandrogenism

Lourdes Ibáñez, Carme Valls, Angela Ferrer, Maria Victoria Marcos, Francisco Rodriguez-Hierro and Francis de Zegher

Endocrinology Unit (L.I., A.F., F.R-H.) and Hormonal Laboratory (C.V.), Hospital Sant Joan de Déu, University of Barcelona, 08950 Esplugues, Barcelona, Spain; Endocrinology Unit (M.V.M.), Consorci Hospitalari de Terrassa, 08227 Terrassa, Spain; and Department of Paediatrics (F.d.Z.), University of Leuven, 3000 Leuven, Belgium

Address all correspondence and requests for reprints to: Lourdes Ibáñez, M.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

In nonobese girls with an adolescent variant of polycystic ovary syndrome, insulin-sensitizing treatment reduces hyperinsulinism, dyslipidemia, and hyperandrogenism and restores eumenorrhea; however, the effect on anovulation is unknown. We assessed whether metformin treatment is capable of inducing ovulation in nonobese adolescents with anovulatory hyperandrogenism after precocious pubarche.

The study population consisted of 18 adolescents (mean age, 16 yr; body mass index, 21.4 kg/m2; 3–7 yr beyond menarche) with hyperinsulinemic hyperandrogenism. All girls received metformin for 6 months in a daily dose of 1275 mg. Before inclusion, persistent anovulation was documented by weekly serum progesterone measurements less than 4 ng/ml (months -3 and -1); the ovulation rate was assessed similarly after 2, 4 and 6 months on metformin; a premenstrual progesterone level greater than 8 ng/ml was used as ovulation marker.

Regular menses were reported by 16 of 18 girls within 4 months on metformin, and all girls were eumenorrheic after 6 months on metformin. Of the 18 girls, 1 (6%) ovulated after 2 months on metformin, 7 (39%) after 4 months, and 14 (78%) after 6 months; ovulation induction failed in the girls with the lowest birth weight or most severe hyperandrogenism. Metformin treatment was well tolerated.

In conclusion, sensitization to insulin was found to be an effective approach to induce ovulation in nonobese adolescents with anovulatory hyperandrogenism.




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