Hypothalamic-pituitary-adrenal axis in abdominal obesity: effects of dexfenfluramine

Hyperactivity of the HPA axis is a possible mechanism underlying abdominal obesity. We aimed to evaluate in premenopausal women with abdominal obesity, (i) the hypothalamic-pituitary-adrenal (HPA) axis responses to direct pituitary stimulation with corticotrophin releasing hormone (CRH) and to opioid blockade with naloxone, and (ii) the interaction between short-term serotoninergic activation with dexfenfluramine (dF), a serotonin-release agonist, and these responses.

Eight obese women (mean BMI, 35 kg/m2) with waist to hip ratio (WHR) > 0.85 were tested with CRH (1 microgram/kg i.v.) and naloxone (125 micrograms/kg i.v.) before and at the end of two treatment periods with dF (15 mg twice daily for 7 days) and placebo (washout 7 days) in a cross-over design. Eight normal weight control women were tested with CRH and naloxone.

Prior to treatment, ACTH and cortisol responses to naloxone (areas under the curve) were significantly higher in obese women then in control women (P = 0.027 and P = 0.035 respectively) dF treatment resulted in significant (P < 0.05) reduction of ACTH and cortisol increments. In contrast, ACTH and cortisol responses to CRH were not significantly different in obese and control subjects and were unaffected by dF treatment.

We conclude that women with abdominal obesity have hyperreactivity of the HPA axis to opiod blockage and that dexfenfluramine treatment reduces this hyperactivity.