SEX-DIFFERENCES IN ENDOCRINE AND PSYCHOLOGICAL RESPONSES TO PSYCHOSOCIAL STRESS IN HEALTHY ELDERLY SUBJECTS AND THE IMPACT OF A 2-WEEK DEHYDROEPIANDROSTERONE TREATMENT

Evidence from animal as well as human studies has suggested that signi ficant sex differences exist in hypothalamus-pituitary-adrenal axis (H PA) activity. As gonadal steroids could be important modulators of HPA sex differences, stress responses were investigated in subjects of ad vanced age after dehydroepiandrosterone (DHEA) or placebo treatment. A fter a 2-week treatment with 50 mg DHEA daily or placebo, 75 men and w omen (mean age, 67.6 yr) were exposed to the Trier Social Stress Test (TSST). The TSST is a brief psychosocial stress that consists of a fre e speech and mental arithmetic task in front of an audience. The resul ts show that the TSST induced significant increases in ACTH, salivary free cortisol, total plasma cortisol, norepinephrine, and heart rates (all P < 0.0001) as well as decreased positive affect in the elderly ( P = 0.0009). Men showed larger stress responses in ACTH (P = 0.004), s alivary free cortisol (P = 0.044), and plasma total cortisol (P = 0.07 6) compared to women. No sex differences were observed in norepinephri ne, epinephrine, or heart rate responses. In contrast to ACTH and cort isol response differences, women reported that they were significantly more stressed by the TSST than men (P = 0.0051). Women treated with D HEA showed ACTH stress responses similar to those of men, but signific antly enhanced compared to those of women taking placebos (P < 0.009). No other stress response differences emerged between DHEA and placebo groups. Finally, DHEA treatment did not result in an improvement of s ubjective well-being. We conclude that elderly men show larger HPA res ponses than women to psychosocial stress, as studied in the TSST. Estr ogen effects on hypothalamic CRF-producing neurons might be responsibl e for these sex differences.