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  • Title: Pioglitazone reduces the adrenal androgen response to corticotropin-releasing factor without changes in ACTH release in hyperinsulinemic women with polycystic ovary syndrome.
    Author: Romualdi D, Giuliani M, Draisci G, Costantini B, Cristello F, Lanzone A, Guido M.
    Journal: Fertil Steril; 2007 Jul; 88(1):131-8. PubMed ID: 17336978.
    Abstract:
    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 microg/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 x 90 minutes to 147.05 +/- 52.06 ng/mL x 90 minutes) and 17OH-progesterone (AUC 152.92 +/- 59.56 ng/mL x 90 minutes to 117.10 +/- 63.25 ng/mL x 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.
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