The relationship of postmenopausal hormone therapy with all-cause dementia and Alzheimer's disease dementia has been controversial. Given continued interest in the role of hormone therapy in chronic disease prevention and the emergence of more prospective studies, we conducted a systematic review to identify all epidemiologic studies meeting prespecified criteria reporting on postmenopausal hormone therapy use and risk of Alzheimer's disease or dementia. A systematic search of Medline and Embase through December 31, 2012, returned 15 articles meeting our criteria. Our meta-analysis of any versus never use did not support the hypothesis that hormone therapy reduces risk of Alzheimer's disease (summary estimate = 0.88, 95% confidence interval: 0.66, 1.16). Exclusion of trial findings did not change this estimate. There were not enough all-cause dementia results for a separate meta-analysis, but when we combined all-cause dementia results (n = 3) with Alzheimer's disease results (n = 7), the summary estimate remained null (summary estimate = 0.94, 95% confidence interval: 0.71, 1.26). The limited explorations of timing of use-both duration and early initiation-did not yield consistent findings. Our findings support current recommendations that hormone therapy should not be used for dementia prevention. We discuss trends in hormone therapy research that could explain our novel findings and highlight areas where additional data are needed.
Keywords: Alzheimer disease; clinical trial; cognition; cohort studies; dementia; estrogen replacement therapy; hormone replacement therapy; systematic review.