A review of estrogen replacement therapy use in the prevention and treatment of Alzheimer disease

Abstract Retrospective studies have shown estrogen to be beneficial in preventing all-cause mortality. As women grow older, Alzheimer disease prevalence increases. Cognitive function preservation gains added importance in today's aging society. This article is a review of the available literature on estrogen replacement therapy's association with Alzheimer disease. The basic science data available on estrogen and the central nervous system show a positive effect on cerebral blood flow, brain-derived nerve growth factor synthesis in the hippocampus, and increased production of acetylcholine. Prevention trials show that the relative risk of developing Alzheimer disease in women undergoing estrogen replacement therapy is in the range of 0.4 to 1.9; however, four of the five studies discussed in this article have relative risks less than 1. Treatment trials are all very small, consisting of fewer than 20 patients. There is a consistent benefit seen when women with milder forms of Alzheimer disease undergo estrogen therapy for a few weeks. The benefit is ascertained via cognitive function tests and by subjective clinical assessment. Given the limited nature of the data available, it is impossible to draw any firm conclusions. Estrogen replacement therapy probably does exert a small positive effect on Alzheimer disease progression.