Pioglitazone reduces the adrenal androgen response to corticotropin-releasing factor without changes in ACTH release in hyperinsulinemic women with polycystic ovary syndrome

Objective: The hypothalamic-pituitary-adrenal (HPA) axis seems to hyperfunction at both central and peripheral levels in polycystic ovary syndrome (PCOS). Hyperinsulinemia is involved in the adrenal hyper-responsiveness to ACTH. The present study was performed to investigate the role of insulin in the derangement of the hypothalamic-pituitary compartment of the HPA axis in PCOS. Design: Prospective clinical study. Setting: Academic research center. Patient(s): Fifteen hyperinsulinemic PCOS women. Intervention(s): Hormonal and lipid assays, oral glucose tolerance test, and corticotropin-releasing factor (1 μg/kg CRF) test before and after 4 months of treatment with the insulin sensitizer pioglitazone (30 mg/day). Main Outcome Measure(s): Glycemic and insulinemic response to glucose load; pituitary and adrenal response to CRF. Result(s): We observed a significant reduction in insulin secretion after therapy. Pioglitazone administration did not modify ACTH and cortisol response to CRF. A significant reduction in the adrenal CRF-induced secretion of androstenedione (A) (area under the curve [AUC] 202.76 ± 78.68 ng/mL · 90 minutes to 147.05 ± 52.06 ng/mL · 90 minutes) and 17OH-progesterone (AUC 152.92 ± 59.56 ng/mL · 90 minutes to 117.10 ± 63.25 ng/mL · 90 minutes′) occurred after treatment. A trace response to CRF was observed for DHEAS and testosterone both before and after pioglitazone. Conclusion(s): In PCOS subjects, insulin may enhance adrenal steroidogenesis by acting directly on the peripheral gland, with no significant effects on the pituitary response to CRF stimulation. © 2007 American Society for Reproductive Medicine.