Psychosocial stress and HPA functioning: no evidence for a reduced resilience in healthy elderly men.

In order to investigate if HPA functioning is altered with age, the present study was conducted. Fifteen healthy elderly men (60-76 years; mean age 66.5 +/- 1.48 yrs.) and 12 younger adults (20-29 years; mean age 25.6 +/- 0.77 yrs.) collected salivary free cortisol profiles after awakening for basal HPA activity. Then, all subjects were exposed to the "Trier Social Stress Test" (TSST). This psychosocial stress protocol consists of a free speech and a mental arithmetic task of 13 minutes duration performed in front of an audience. Beside the assessment of endocrine and cardiovascular responses to the stressful task ratings of depression, mood and perceived stressfulness were obtained. Results show that younger and elderly men had similar morning cortisol profiles after awakening with both groups showing the expected rise after awakening (P=0.004). The TSST induced significant increases in ACTH, total plasma cortisol, saliva free cortisol, and heart rates (all P<0.0001). Regardless of age, both age groups showed comparable endocrine response patterns when confronted with the stressor. However, cardiovascular responses were significantly higher in younger men compared to elderly men (P=0.03). Catecholamine data revealed significant norepinephrine and epinephrine increases due to the stressor (both P<0.0001) with a trend toward elevated norepinephrine levels in elderly men (P=0.058). In sum, the investigated basal and response parameters of HPA functioning neither support the idea of a reduced resilience in healthy aged humans nor do they appear to strengthen assumptions derived from the so called "glucocorticoid cascade hypothesis".

The cortisol response to awakening in relation to different challenge tests and a 12-hour cortisol rhythm.

Recent studies have shown that cortisol levels rapidly increase within the first 30 minutes after awakening. This response is rather robust over weeks or months and is altered by chronic stress and burnout. The present study investigated to what extent the cortisol response to awakening relates to responses following hCRH, ACTH(1-24), or psychosocial stress challenges in 22 healthy subjects. Furthermore, a 12-hour circadian cortisol profile was obtained to compare the morning response with cortisol levels obtained throughout the day. Results show that the morning cortisol response was of similar magnitude to that following injection of 1 microg/kg h-CRH or exposure to a brief psychosocial stressor (TSST). All of these were significantly smaller compared to maximal stimulation of the adrenal cortex by ACTH(1-24). Correlation analyses revealed that the morning cortisol response was closely related only to the cortisol response following 0.25 mg ACTH(1-24) (r=0.63, p=0.002). We conclude that the morning cortisol response to awakening can provide important information on the (re)activity of the HPA axis in addition to more 'traditional' methods like hCRH or Synacthen challenge tests. The sensitivity/capacity of the adrenal cortex appears to play a crucial role for the magnitude of cortisol responses observed after awakening.

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-treated women (n = 15; 60-75 years; placebo via transdermal patches), healthy postmenopausal estradiol-treated women (n = 13; 60-79 years; 0.1 mg 17beta-estradiol daily via transdermal patches) and young controls (n = 15; 20-31 years; untreated). The aged subjects received estradiol or placebo treatment for 14 days. All subjects were then exposed to the 'Trier Social Stress Test' (TSST) and the dexamethasone (Dex)-human corticotropin-releasing hormone (hCRH) test (100 microgram hCRH after premedication with 1.5 mg Dex). Psychological parameters including perceived stressfulness, mood and subjective well-being were measured by visual analog scales, a mood questionnaire and a mood diary, respectively. Results show that the TSST induced significant increases in adrenocorticotropin (ACTH), free salivary cortisol, total plasma cortisol and heart rates (all p < 0.0001). Regardless of age, comparable hormonal response patterns were observed in the TSST as indicated by similar peak levels and recovery phases. Visual analog scales confirmed that the same amount of stress was experienced by young and elderly subjects. In both age groups, hCRH injection after Dex premedication provoked significant increases in ACTH, free salivary cortisol and total plasma cortisol (all p < 0.0001). In contrast to the psychosocial stressor, elderly women were found to respond with a markedly enhanced cortisol response compared to young controls in the Dex-CRH test (p < 0.025). Additional investigation of morning cortisol profiles could not reveal any age-related differences in basal hypothalamus-pituitary-adrenal (HPA) axis activity. Following estradiol treatment, estradiol levels significantly increased only in substituted postmenopausal women (p < 0.001) reaching concentrations typically found in younger women during the follicular phase of the menstrual cycle. Corticosteroid-binding globulin levels did not differ significantly between groups. When confronted with the TSST, no response differences emerged between the three groups. However, estradiol treatment appeared to blunt the total plasma cortisol 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 differences were observed after confrontation with a psychosocial stress test in our sample of healthy elderly subjects. As shown with the Dex-CRH test, our data suggest that the negative feedback of the HPA axis in elderly women is altered. Moreover, the current data suggest that estradiol replacement may modulate HPA feedback sensitivity in humans.