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Retinol-Binding Protein 4 in Polycystic Ovary Syndrome—Association with Steroid Hormones and Response to Pioglitazone Treatment

Department of Internal Medicine (E.A., F.H., C.D.), General Hospital Oberndorf, 5110 Oberndorf, Austria; Departments of Laboratory Medicine (K.K., W.P.) and Gynecology and Obstetrics (N.B.), Paracelsus Medical University Salzburg, 5020 Salzburg, Austria; and Division of Gynecological Endocrinology and Reproductive Medicine (C.D.G.), Women’s Hospital, University of Basel, CH-4031 Basel, Switzerland

Address all correspondence and requests for reprints to: Christian Datz, M.D., Department of Internal Medicine, General Hospital Oberndorf/Salzburg; Paracelsusstrasse 37, 5110 Oberndorf, Austria. E-mail: c.datz{at}kh-obdf.salzburg.at.

Context: Polycystic ovary syndrome (PCOS) is frequently associated with insulin resistance.

Objective: The aim of the study was to investigate a putative role of the adipokines retinol-binding protein 4 (RBP4), adiponectin, and visfatin in a cohort of patients with PCOS and their response to treatment with pioglitazone.

Design and Setting: We conducted a randomized, controlled, double-blind study at a tertiary referral center.

Patients and Interventions: Forty premenopausal women with PCOS were allocated to receive treatment with either pioglitazone (30 mg/d) or a placebo for a period of 3 months.

Main Outcome Measures: Serum concentrations of RBP4, adiponectin, and visfatin were determined along with metabolic and hormonal parameters before and after treatment.

Results: Serum adiponectin concentrations were higher after treatment with pioglitazone (P = 0.003), whereas RBP4 levels tended to decrease (P = 0.06), and visfatin concentrations remained unchanged. We found RBP4 serum concentrations at baseline to be positively correlated with serum levels of testosterone (R = 0.446; P = 0.005), 17-OH progesterone (R = 0.345, P = 0.037), and dehydroepiandrosterone sulfate (R = 0.347; P = 0.041). However, these correlations were abolished after treatment with pioglitazone. Patients with high RBP4 levels had significantly higher hirsutism scores (P = 0.038 before and P = 0.034 after treatment). In contrast, serum adiponectin concentrations were related to parameters of impaired glucose metabolism, and no significant associations were detected for visfatin.

Conclusions: Our results suggest that RBP4 may contribute to endocrine changes and to the phenotypic manifestation of patients with PCOS because higher RBP4 concentrations are associated with higher androgen levels and higher clinical hirsutism scores independently of pioglitazone treatment. The molecular involvement of RBP4 in human steroid metabolism requires further clarification.