Psychological and endocrine responses to psychosocial stress and dexamethasone/corticotropin-releasing hormone in healthy postmenopausal women and young controls: The impact of age and a two-week estradiol treatment

In this placebo-controlled double-blind study, psychological and endocrine stress responses were investigated in healthy postmenopausal placebo-treate d women (n = 15; 60-75 years; placebo via transdermal patches), healthy pos tmenopausal estradiol-treated women (n = 13; 60-79 years; 0.1 mg 17 beta-es tradiol daily via transdermal patches) and young controls (n = 15; 20-31 ye ars; untreated). The aged subjects received estradiol or placebo treatment for 14 days. All subjects were then exposed to the 'Trier Social Stress Tes t' (TSST) and the dexamethasone (Dex)-human corticotropin-releasing hormone (hCRH) test (100 mu g hCRH after premedication with 1.5 mg Dex). Psycholog ical parameters including perceived stressfulness, mood and subjective well being were measured by visual analog scales, a mood questionnaire and a moo d diary, respectively. Results show that the TSST induced significant incre ases in adrenocorticotropin (ACTH), free salivary cortisol, total plasma co rtisol and heart rates (all p < 0.0001). Regardless of age, comparable horm onal response patterns were observed in the TSST as indicated by similar pe ak levels and recovery phases. Visual analog scales confirmed that the same amount of stress was experienced by young and elderly subjects. In both ag e groups, hCRH injection after Dex premedication provoked significant incre ases in ACTH, free salivary cortisol and total plasma cortisol (all p < 0.0 001). In contrast to the psychosocial stressor, elderly women were found to respond with a markedly enhanced cortisol response compared to young contr ols in the Dex-CRH test (p < 0.025). Additional investigation of morning co rtisol profiles could not reveal any age-related differences in basal hypot halamus-pituitary-adrenal (HPA) axis activity. Following estradiol treatmen t, estradiol levels significantly increased only in substituted postmenopau sal women (p < 0.001) reaching concentrations typically found in younger wo men during the follicular phase of the menstrual cycle. Corticosteroid-bind ing globulin levels did not differ significantly between groups. When confr onted with the TSST, no response differences emerged between the three grou ps. However, estradiol treatment appeared to blunt the total plasma cortiso l response in the Dex-CRH test, resulting in smaller increases in untreated premenopausal women and estradiol-treated postmenopausal women compared to placebo-treated postmenopausal women (p < 0.02). In sum, no response diffe rences were observed after confrontation with a psychosocial stress test in our sample of healthy elderly subjects. As shown with the Dex-CRH test, ou r data suggest that the negative feedback of the HPA axis in elderly women is altered. Moreover, the current data suggest that estradiol replacement m ay modulate HPA feedback sensitivity in humans. Copyright (C) 1999 S. Karge r AG, Basel.