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Pioglitazone Treatment Increases Spontaneous Growth Hormone (GH) Secretion and Stimulated GH Levels in Polycystic Ovary Syndrome

Department of Endocrinology and Metabolism (D.G., R.K.S., C.H., A.P.H., M.A.), Odense University Hospital, DK-5000 Odense C, Denmark; Medical Research Laboratories (J.F., A.F.), Clinical Institute and Medical Department M (Diabetes and Endocrinology), Aarhus University Hospital, DK-8000 Aarhus, Denmark; and Division of Endocrinology and Metabolism (J.D.V.), Department of Internal Medicine, Mayo Clinical Research Center, Rochester, Minnesota 55905

Address all correspondence and requests for reprints to: Dorte Glintborg, Kløvervænget 6, Third Floor, DK-5000 Odense C, Denmark. E-mail: dorte.glintborg{at}dadlnet.dk.

Background: Low GH levels, probably due to insulin resistance and increased abdominal fat mass, are well described in polycystic ovary syndrome (PCOS). GH acts as an important ovarian cogonadotropin, and GH disturbances may be an additional pathogenic factor in PCOS. Decreased abdominal fat mass and improved insulin sensitivity during pioglitazone treatment may affect GH secretion.

Objective: The objective of the study was to investigate the effect of pioglitazone on GH levels in PCOS.

Design: Thirty insulin-resistant PCOS patients were randomized to either 16 wk pioglitazone (30 mg/d) or placebo treatment. Before and after intervention, levels of fasting insulin, GH, total IGF-I, free IGF-I, IGF binding protein-1, IGF-II, free fatty acids, testosterone, and SHBG were measured. Patients underwent whole-body dual x-ray absorptiometry scans, pyridostigmine-GHRH tests, and 24-h 20-min integrated blood sampling for measurement of GH.

Results: Peak GH and area under the curve for GH in pyridostigmine-GHRH tests and 24-h mean GH concentrations and pulsatile GH secretion significantly increased after pioglitazone treatment. No significant changes were observed in GH pulse frequency, pulse duration, approximate entropy levels, or basal GH release. Levels of IGF binding protein-1 significantly increased, whereas no significant differences were measured in total IGF-I and free IGF-I. Pioglitazone treatment significantly decreased fasting insulin and homeostasis model assessment levels. No significant changes were observed in Ferriman Gallwey score or androgen levels.

Conclusion: Pioglitazone treatment significantly increased GHRH-stimulated GH levels and 24-h pulsatile GH secretion, probably directly or indirectly due to improved insulin sensitivity.

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