Effects of estradiol on cortisol response, working memory, and emotional memory during stress in young and post-menopausal women

2014-04-14Estradiol and the class of stress hormones called glucocorticoids exert contrasting effects on various systems throughout the body, including neural tissue and cognition. Evidence also exists showing that estradiol can mitigate the damaging effects of excessive glucocorticoid levels on neural tissue. Given the sharp decline in estradiol levels that characterize the menopausal transition in human females, it is important to understand if the loss of estradiol leaves post‐menopausal women at a higher risk of the negative effects of stress on neural tissue, and by extension the negative effects of stress on cognition. ❧ Studies do show that estradiol treatment after menopause can dampen the physiological stress response to a stressful event; however, it is less clear whether estradiol can dampen the effects of stress on cognition. The general aim of this dissertation was to examine whether, and to what extent, estradiol could blunt the stress response and the effects of stress on working memory and emotional memory in women. This was examined in a population of post‐menopausal women taking estradiol or placebo through the ELITE trial (Study 1) and in a population of young, spontaneously cycling, women during the low‐estradiol and high‐estradiol phases of the menstrual cycle (Study 2). ❧ Study 1 investigated the effects of estradiol treatment after menopause on the cortisol response to the cold pressor task and the effects of stress on working memory and emotional memory. It was revealed that higher estradiol levels, as a result of estradiol treatment after menopause, were associated with a blunted cortisol response to ice water exposure and protection against stress‐induced impairment of working memory. Although no effects of stress, estradiol, or interactions were found for emotional memory. ❧ Study 2 investigated the effects of estradiol fluctuations during the menstrual cycle in young, spontaneously cycling women on the cortisol response to the cold pressor task and the effects of stress on working memory and emotional memory. It was revealed that the late follicular, higher estradiol, phase of the menstrual cycle was associated with a larger cortisol response to ice water exposure, but still provided protection against stress‐induced impairment of working memory. Although no effects of stress, estradiol, or interactions were found for emotional memory. The potential mechanisms involved leading to the different patterns of results are discussed. ❧ Overall, this dissertation provides evidence that estradiol treatment after menopause can mitigate the effects of stress on cortisol release and working memory, and that the pattern of estradiol effects on stress may differ in young premenopausal women. The mechanisms that contribute to the differences may be related to the different physiological relationships between the stress response system and the estradiol system across the two age groups, and how this may influence the cortisol response and how estradiol and cortisol interact. These results can further inform the medical field on the effects of estradiol treatment after menopause, as well as help women understand their vulnerabilities to stress depending on their internal hormone milieu