The effects of estrogen replacement therapy on neuropsychological functioning in postmenopausal women with and without dementia: a critical and theoretical review

We review 42 studies examining the effects of estrogen replacement therapy (ERT) on memory and cognition in nondemented postmenopausal women. Although there are an appreciable number of nonsignificant findings, the number of significant findings favoring ERT users considerably outnumbers the rare findings of better performance in controls. Experimental studies demonstrate a consistent beneficial effect on verbal memory, but these are short-term studies of the more acute effects of ERT. The observational studies suggest that there may be a long-lasting effect of continued ERT on cognitive functioning, but these studies need to be interpreted with caution because of the lack of random assignment and a possible "healthy user bias." We also summarize findings from studies on the effects of ERT on Alzheimer's disease (AD). ERT is associated with a decreased risk for dementia, but there is little evidence for a positive effect on cognition in women with AD. Definitive answers to questions about the long-term effects of ERT on cognitive aging and risk of developing AD should be provided by 3 ongoing clinical trials.