Gender differences in hypothalamic-pituitary-adrenal (HPA) axis reactivity

The present study was designed to determine whether there are gender differences in hormonal response patterns to HPA axis activation. To this end, two methods of activating the HPA axis were employed: a standardized psychological stress test and a pharmacological challenge. Healthy subjects (mean age 23.4 years, SD 7.0 years) completed a naloxone challenge and/or the modified Trier Social Stress Test (TSST). For the naloxone challenge, two baseline blood samples were obtained. Placebo was then administered (0 min), followed by increasing doses of intravenous natoxone (50, 100, 200 and 400 mu g/kg) at 30-min intervals. Post-placebo blood samples were collected at 15-min intervals for 180 min. The TSST consisted of 5 min of public speaking followed by 5 min of mental arithmetic exercises. Three baseline and five post-TSST blood samples were drawn. Eighty subjects (53 mate, 27 female) underwent the TSST. Following the psychological stressor, adrenocorticotropin (ACTH) and cortisol responses were significantly greater in mate subjects compared to female subjects (z= -2.34, p = 0.019 and z= -2.12, p=0.034, respectively). Seventy-two subjects (52 mate, 20 female) underwent HPA axis activation induced by natoxone. In contrast to the TSST, cortisol responses to the natoxone challenge were significantly greater in female subjects compared to mate subjects (z=4.11, p < 0.001). Forty-one subjects (25 mate, 16 female) completed both the TSST and natoxone challenge. In this subset, ACTH and cortisol responses to the TSST did not differ significantly by gender, although the effect size was moderate to large. Adrenocorticotropin and cortisol responses to the naloxone challenge were significantly greater in female subjects compared to mate subjects (z=2.29, p=0.022 and z=4.34, p < 0.001, respectively). In summary, mate subjects had greater HPA axis responses to a psychological stressor than female subjects, and females had greater hormonal reactivity than mates to pharmacological stimulation with natoxone. Such differences are of interest as potential contributors to gender differences in health risks. (c) 2006 Elsevier Ltd. All rights reserved.