The effect of short-term estrogen replacement therapy on cognition: A randomized, double-blind, cross-over trial in postmenopausal women

Abstract

Objective: To evaluate the effect of estrogen replacement therapy on cognitive functioning. Methods: The study consisted of two 3-month treatment periods, one with estrogen and one with the placebo, in random order, separated by a 1-month wash-out period. The study group comprised 70 healthy postmenopausal women, aged 47–65 years, with previous hysterectomy. Sixty-two women completed the study. Cognitive speed and accuracy, attention, and memory were evaluated. Serum estradiol (E2) and FSH levels were controlled at the end of the estrogen, placebo, and wash-out periods. Results: Most of the cognitive tests correlated with age: older women were slower and made more errors than younger women. Estrogen replacement therapy was not superior to the placebo in any test of cognitive performance. In two out of ten visual detection tasks, recognition thresholds were longer with estrogen than with the placebo ( P < .001 and P = .004). On the most demanding test of working memory, the reaction times ( P = .045) and error rates ( P = .043) differed between treatments, yet this finding proved to be an effect of learning rather than treatment. There was no correlation between cognitive performance and serum E2 levels. Conclusion: Cognitive performance decreased with age. Short-term estrogen replacement therapy did not provide any advantage over the placebo in terms of improving the performance.