Evidence of a disturbance of the hypothalamic-pituitary-adrenal axis in polycystic ovary syndrome: Effect of naloxone

DESIGN There are conflicting data on hypothalamic-pituitary-adrenal (HPA) axis function in women with polycystic ovary syndrome (PCOS). We have evaluated the HPA axis responses to naloxone in patients with PCOS compared to control subjects. PATIENTS Twenty PCOS patients and 10 control women participated in the study. MEASUREMENTS On days 5-6 of a spontaneous or progestin induced cycle each patient received an intravenous bolus (5 mg) of naloxone (time 0 min), followed by a 2-mg naloxone infusion in 100 ml of 0.9% saline over one hour. Samples were collected at -30, 0, 15, 30, 60, 90 and 120 minutes. ACTH and cortisol levels were measured in all plasma samples. RESULTS PCOS patients showed significantly greater response than controls to naloxone of ACTH (peak value 261 vs 172% of basal value) and cortisol (peak value 237 vs 165% of basal value); also, ACTH and cortisol incremental areas were higher in PCOS patients (P < 0.05 and P < 0.04 respectively). The cortisol/ACTH ratio of AUCs percentage increase was found to be near unity for all patients without significant difference between PCOS and control groups, suggesting a direct correspondence between ACTH circulating levels and adrenal cortisol production. CONCLUSIONS Polycystic ovary syndrome patients showed a hypothalamic-pituitary-adrenal axis hyperresponsiveness to naloxone infusion compared with control subjects. These data support the hypothesis that this disturbance could be central in origin.