14. Effects of gonadal steroids on the HPA axis response to stress

Abstract

The ability of gonadal steroids to modulate hypothalamic-pituitary-adrenal (HPA) axis function is not well established in humans, but may be of importance in understanding sexual dimorphisms in the stress response. To investigate these effects, we studied normal women (n = 8) and men (n = 5) during pharmacologically-induced hypogonadism and during gonadal steroid replacement. We measured the HPA axis response to three different stimuli: 1) treadmill exercise stress, 2) low-dose dexamethasone suppression test (DST), and 3) ovine corticotropin (oCRH) stimulation. Data were analyzed by analysis of variance with repeated measures (ANOVA-R) and post hoc Bonferroni t tests. Women exhibited a blunted cortisol response to exercise stress (p = 0.05) and increased dexamethasone suppression (p < 0.01) in the hypogonadal compared with the progesterone replaced condition. In men, however, there was no effect of hormonal condition on either the exercise stress or DST results. Exercise stimulated cortisol (p < 0.05) and ACTH (p < 0.01) were significantly increased in men compared with women during the hypogonadal condition. Finally, a significant (p < 0.05) increase in o-CRH stimulated ACTH was seen in men during testosterone replacement. Gonadal steroids appear to more actively regulate HPA axis function in women than men, and the appearance of dimorphic response to exercise under hypogonadal conditions may imply an organizational origin to these gender-related differences.