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

Abstract

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 17β-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 µg 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.

Sex, trauma, stress hormones and depression

“…32 Furthermore, oral contraceptives profoundly decrease the free cortisol response to this stressor. 33 We have similar data confirming large menstrual cycle difference in free (saliva) cortisol response to the TSST in normal women, as well as a markedly blunted response in oral contraceptive users (Young, unpublished data).…”

“…41 Estradiol administered to postmenopausal women had no effect on the response to the stressor, TSST, but it did decrease the response to the dex-CRH challenge. 33 In a clever study design in normally menstruating women, Roca et al 42,43 analyzed women treated with Lupron, which leads to a loss of all gonadal steroids, followed by estradiol or progesterone add-back phases. They examined the response to exercise stress and found that the exercise stress response was increased during the progesterone 'add-back' phase but not during the estrogen 'add-back' phase.…”

Assessment of the Dexamethasone/CRH Test as a State-Dependent Marker for Hypothalamic-Pituitary-Adrenal (HPA) Axis Abnormalities in Major Depressive Episode: A Multicenter Study

“…In line with this, Kudielka et al (1999) found that healthy elderly women (60-75 years) exhibited a markedly enhanced cortisol response to the DEX/CRH test compared to young controls (20-31 years). In contrast, a more recent study found no significant effect of age on hormonal responses to the DEX/ CRH test in acutely depressed inpatients (Kunzel et al, 2003).…”

Estrogen Administration Negatively Alters Mood Following Monoaminergic Depletion and Psychosocial Stress in Postmenopausal Women

“…Komesaroff et al (1999) found that 8 weeks of E2 supplementation produce a similar reduction of physiological responses to mental stress. In a low dose, short duration transdermal estrogen study in PMW, the TSST was not found to provoke a differential effect on physiological measures in estrogentreated women (Kudielka et al, 1999). In an extensive review, Kajantie and Phillips (2006) conclude that there is an increase in sympathoadrenal responsiveness after menopause which is attenuated during oral hormone therapy and that sex differences in sympathoadrenal responses are likely the result of estrogen.…”

“…Prior studies of the effects of hormone treatment in PMW on experimentally induced psychological or psychosocial stress have generally focused on physiological reactivity such as blood pressure and hormonal responses (Burleson et al, 1998;Ceresini et al, 2000;Komesaroff et al, 1999;Kudielka et al, 1999;Lindheim et al, 1992b;Matthews et al, 2005). However, there has not been an experimental study that has focused on the effects of estrogen treatment in PMW on mood reactivity to psychosocial stress and examining whether hormonal effects interact with levels of brain monoamine neurotransmitters.…”