Could estradiol therapy soften stress’s effect on working memory after menopause?

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Postmenopausal estradiol therapy can reduce the stress response, but it was unclear whether that reduction could lessen stress’s effects on cognition. Researchers investigated how estradiol therapy affected cortisol responses to a physical stressor, the cold pressor test (CPT), and whether it reduced stress’s effects on working memory.

Women completed the CPT or a control condition across two sessions, then completed a sentence span task. The researchers measured salivary cortisol and sentence span task performance.

Participants were recruited from the Early vs Late Intervention Trial with Estradiol (ELITE) in the general community. Their mean age was 66 years (standard deviation 6.8); they had no major chronic illness and did not use medications known to affect stress responses or cognition. At the time of the study, they had received a median of 4.7 years of randomized estradiol treatment (n = 21) or placebo (n = 21).

Compared with the placebo group, women assigned to estradiol had a blunted cortisol response to the CPT (P = 0.017) and experienced less negative effect of stress on working memory (P = 0.048). The researchers said the evidence suggests estradiol therapy may protect certain types of cognition in the presence of stress. They proposed that estrogenic protection against stress hormone exposure might benefit cognition and the neural circuitry that maintains and propagates cognitive faculties.