Abstract
CONTEXT: Postmenopausal estradiol therapy (ET) can reduce the stress response. However, it remains unclear whether such reductions can mitigate effects of stress on cognition. OBJECTIVE: Investigate effects of ET on cortisol response to a physical stressor, cold pressor test (CPT), and whether ET attenuates stress effects on working memory. DESIGN: Women completed the CPT or control condition across two sessions and subsequently completed a sentence span task. SETTING: General community: Participants were recruited from the Early vs Late Intervention Trial with Estradiol (ELITE). PARTICIPANTS: ELITE participants (mean age = 66, standard deviation age = 6.8) in this study did not suffer from any major chronic illness or use medications known to affect the stress response or cognition. INTERVENTIONS: Participants had received a median of randomized 4.7 years of estradiol (n = 21) or placebo (n = 21) treatment at time of participation in this study. MAIN OUTCOME MEASURES: Salivary cortisol and sentence span task performance. RESULTS: Women assigned to estradiol exhibited blunted cortisol responses to CPT compared with placebo (P = 0.017) and lesser negative effects of stress on working memory (P = 0.048). CONCLUSIONS: We present evidence suggesting ET may protect certain types of cognition in the presence of stress. Such estrogenic protection against stress hormone exposure may prove beneficial to both cognition and the neural circuitry that maintains and propagates cognitive faculties.