OBJECTIVE: To conduct a review of the available clinical trials to determine whether sufficient evidence exists to support the conclusion that estrogen replacement therapy has a beneficial effect on cognitive performance in post-menopausal women and in women with Alzheimer's disease. Studies were identified through a MEDLINE search of all English-language publications between 1970 and 1996 in which the words estrogen and cognition or estrogen and memory appeared. DATA EXTRACTION: Data were extracted for each study, including features of subjects and eligibility criteria, duration of follow-up, and treatment regimen. Baseline characteristics were evaluated, including age; menopausal status; follicle-stimulating hormone, luteinizing hormone, and estradiol levels; mood; and measures of cognitive function. Psychological tests were evaluated for construct validity. RESULTS: Nineteen studies were reviewed, including 10 randomized trials of estrogen replacement therapy versus placebo. Extreme heterogeneity among subjects and variability in the use of cognitive measures across the studies precluded performing a quantitative summary. Of the 10 randomized trials, eight claimed therapeutic benefits for estrogen therapy, three of which reported significant improvements in memory and two of which showed improvements in attention. These studies did not control for potential confounds such as depression and vasomotor symptoms. Of the nine observational studies, five found a significant association between estrogen use and cognitive function. CONCLUSION: Although several observational studies provide encouraging evidence for the beneficial effect of estrogen on cognitive function, there is currently inadequate evidence available from randomized, controlled trials to support the conclusion that estrogen replacement therapy improves cognitive function in post-menopausal women or women with Alzheimer's dementia.
