The relationship between stress induced cortisol levels and memory differs between men and women.

Epidemiological as well as experimental studies in elderly subjects have suggested that postmenopausal women are more susceptible to the memory impairing effects of elevated cortisol levels than elderly men. Little is known however about gender differences in the susceptibility to acute stress in young subjects. In the present study a total of 58 healthy young subjects learned a word list, with recall being tested after a brief distraction task. Twenty-two subjects had to learn the list after exposure to a psychosocial stressor (Trier Social Stress Test: TSST), while the remaining subjects served as controls. Free cortisol was determined via saliva samples taken before and 10 minutes after stress. Subjects exposed to the stressor, did not show impaired memory performance per se when compared to the control group. However the cortisol increase in response to the stressor was negatively correlated (r=-0.43, P<0.05) with the memory performance within the stressed group (i.e., subjects showing a larger cortisol response recalling less words than subjects showing only a small cortisol increase). Additional analysis revealed, that this correlation was solely caused by the strong association observed in men (r=-0.82, P<0.05), while no association was observed in women (r=-0.05, P=ns). Our data suggests, that gender modulates the association between cortisol and memory after stress. Whether these differences reflect activational effects of sex steroids or developmentally-programmed sex differences awaits to be determined.

No evidence for a close relationship between personality traits and circadian cortisol rhythm or a single cortisol stress response.

Personality traits measured with the Eysenck Personality Questionnaire-Revised did not show associations with basal or stimulated concentrations of cortisol in a sample of 81 subjects. Cortisol responses to a single exposure to psychosocial stress as well as circadian salivary-free cortisol patterns did not distinguish between subjects with high or low scores on Extraversion, Neuroticism, or Psychoticism, respectively.

Sex differences in glucocorticoid sensitivity of proinflammatory cytokine production after psychosocial stress.

OBJECTIVE: Men and women show marked differences in susceptibility to disorders related to the immune system. These gender differences have been proposed to be mediated by functional interactions of the hypothalamus-pituitary-adrenal (HPA) and hypothalamus-pituitary-gonadal (HPG) axes. A potential mechanism involved in this interaction is the glucocorticoid (GC) sensitivity of relevant target tissues for GC. Therefore, the aim of the study reported here was to investigate the impact of psychosocial stress and HPA axis activation on the GC sensitivity of proinflammatory cytokine production in men and women. METHODS: A total of 45 healthy subjects were investigated. Eighteen women in the luteal phase of their menstrual cycle and 27 men were exposed to a psychosocial stress test (Trier Social Stress Test). Salivary free cortisol levels were measured repeatedly after exposure to the stressor. GC sensitivity was assessed in vitro by dexamethasone inhibition of lipopolysaccharide-stimulated production of interleukin-6 and tumor necrosis factor-alpha. RESULTS: The stress test induced significant increases in salivary free cortisol with no significant differences between men and women. In contrast, GC sensitivity and lipopolysaccharide-stimulated cytokine production showed large gender differences. In men GC sensitivity was markedly increased 1 hour after stress, whereas GC sensitivity decreased significantly in women. Similarly, lipopolysaccharide-induced cytokine production decreased in response to stress in men but increased in women. CONCLUSIONS: These results demonstrate that despite similar free cortisol responses of men and women (studied in the luteal phase) to psychosocial stress, gender may exert differential effects on the immune system by modulating GC sensitivity of proinflammatory cytokine production.

Impact of gender, menstrual cycle phase, and oral contraceptives on the activity of the hypothalamus-pituitary-adrenal axis.

OBJECTIVE: Results from animal and human studies suggest that disregulations of the hypothalamus-pituitary-adrenal (HPA) axis are involved in several behavioral, circulatory, endocrine, and immune disorders with clear-cut gender differences in disease prevalence. The aim of the present study was to investigate sex-specific HPA response patterns with a focus on the contribution of gonadal steroids as possible mediators. METHODS: A total of 81 healthy adults were investigated in the present study. Twenty men, 19 women in the follicular phase of the menstrual cycle, 21 women in the luteal phase, and 21 women using oral contraceptives (OC) were exposed to a brief psychosocial stress test (Trier Social Stress Test; TSST) and injected with 0.25 mg ACTH1-24 on consecutive days. Basal HPA activity was investigated by repeatedly measuring cortisol levels immediately after awakening, as well as in 30-minute intervals from 9:00 AM to 9:00 PM. Additionally, questionnaires were used to assess psychological state and trait parameters. RESULTS: Results show that the TSST induced significant increases in ACTH, salivary-free cortisol, total plasma cortisol, and heart rates, as well as increased wakefulness and reduced calmness in the total group. Significant group differences emerged for ACTH and salivary-free cortisol stress responses: Although men showed higher ACTH responses to the TSST compared with each of the three groups of women, salivary cortisol responses showed the following response pattern: Luteal = Men > Follicular = OC. The salivary cortisol responses to ACTH1-24 showed a similar response pattern: Luteal > Men > Follicular > OC. In contrast, total blood cortisol levels did not reveal any group difference between sexes or follicular versus luteal phase in either test. Although a similar salivary-free cortisol increase after awakening was found in the four groups, the circadian cortisol profile was significantly different throughout the first 4 hours of sampling. Questionnaire-derived psychological variables, as measured in the present study, could not explain the observed results. CONCLUSIONS: We conclude that gender, menstrual cycle phase, and OC use exert important effects on HPA responsiveness to psychosocial stress in healthy subjects. Although men seem to have a stronger hypothalamic drive in response to stressful stimulation than women, differences in salivary-free cortisol levels, at least in part, may be explained by estradiol-induced changes in corticosteroid-binding protein levels. ACTH and cortisol secretion is not affected by OC use per se but the amount of bioavailable unbound cortisol ("free") is greatly reduced in this group of women after stimulation. Inasmuch as none of these differences between the study groups emerged in total blood cortisol levels, we strongly advocate for the simultaneous measurement of free and total cortisol levels in future studies on HPA functioning.