HYPOTHALAMIC-PITUITARY-ADRENAL AXIS IN ABDOMINAL OBESITY - EFFECTS OFDEXFENFLURAMINE

OBJECTIVE Hyperactivity of the HPA axis is a possible mechanism underl ying abdominal obesity. We aimed to evaluate in premenopausal women wi th abdominal obesity, (i) the hypothalamic-pituitary-adrenal (HPA) axi s responses to direct pituitary stimulation with corticotrophin releas ing hormone (CRH) and to opioid blockade with naloxone, and (ii) the i nteraction between short-term serotoninergic activation with dexfenflu ramine (dF), a serotonin-release agonist, and these responses. DESIGN AND SUBJECTS Eight obese women (mean BMI, 35kg/m(2)) with waist to hip ratio (WHR) >0.85 were tested with CRH (1 mu g/kg i.v.) and naloxone (125 mu g/kg i.v.) before and at the end of two treatment periods with dF (15 mg twice dairy for 7 days) and placebo (washout 7 days) in a c ross-over design. Eight normal weight control women were tested with C RH and naloxone. RESULTS Prior to treatment, ACTH and cortisol respons es to naloxone (areas under the curve) were significantly higher in ob ese women then in control women (P = 0.027 and P = 0.035 respectively) . dF treatment resulted in significant (P < 0.05) reduction of ACTH an d cortisol increments. In contrast, ACTH and cortisol responses to CRH were not significantly different in obese and control subjects and we re unaffected by dF treatment. CONCLUSION We conclude that women with abdominal obesity have hyperreactivity of the HPA axis to opiod blocka ge and that dexfenfluramine treatment reduces this hyperreactivity.