SHORT-TERM ESTRADIOL TREATMENT ENHANCES PITUITARY-ADRENAL AXIS AND SYMPATHETIC RESPONSES TO PSYCHOSOCIAL STRESS IN HEALTHY-YOUNG MEN

Evidence from animal studies and clinical observations suggest that th e activity of the pituitary-adrenal axis is under significant influenc e of sex steroids. The present study investigated how a short term ele vation of estradiol levels affects ACTH, cortisol, norepinephrine, and heart rate responses to mental stress in healthy men. In a double bli nd study, 16 men received a patch delivering 0.1 mg estradiol/day tran sdermally, and age- and body mass index-matched control subjects recei ved a placebo patch. Twenty-four to 48 h later, they were exposed to a brief psychosocial stressor (free speech and mental arithmetic in fro nt of an audience). In response to the psychosocial stressor, ACTH, co rtisol, norepinephrine, and heart rate were increased in both experime ntal groups (all P < 0.0001). However, the estradiol-treated subjects showed exaggerated peak ACTH (P < 0.001) and cortisol (P < 0.002) resp onses compared to the placebo group. Also, the norepinephrine area und er the response curve was greater in the estradiol group (P < 0.05). A lthough heart rate response differences failed to reach statistical si gnificance, they, too, tended to be larger in the estradiol group. Nei ther mood ratings before or after the stressor, nor ratings of the per ception of the stressor could explain the observed endocrine response differences. In conclusion, short term estradiol administration result ed in hyperresponses of the pituitary-adrenal axis and norepinephrine to psychosocial stress in healthy young men independent of psychologic al effects, as assessed in this study.