Sex, hormones and Alzheimer's disease

Abstract

More women than men have Alzheimer's disease (AD). Longer duration of disease, less vascular dementia, and less testosterone in women than men may contribute to this disparity, but longer life span of women than men may be the largest factor. Retrospective studies suggested that hormone replacement therapy (HRT) might counteract this disparity by reducing the risk of developing dementia. However, a large, prospective study revealed the puzzling result that HRT increased dementia risk. Various mechanisms might produce this increase: greater risk of strokes, leading to dementia; use of medroxyprogesterone acetate and estrone, which might have somewhat different possible effects on neuronal and cerebrovascular function than may progesterone and estradiol; decrease of free testosterone which might protect against AD; a dose or delivery method perhaps producing drug levels that might lie outside a hypothetical beneficial range; and down-regulation of estrogen receptors on cholinergic neurons, possibly reducing cholinergic activity.