Potential use of estrogen-like drugs for the prevention of Alzheimer's disease.

Prior epidemiological studies have shown decreased incidence of Alzheimer's disease among women who were long-term users of hormone replacement therapy. In vitro studies have shown that estrogens possess antioxidant activity, protect cells from the cytotoxic effect of beta-amyloid peptides, and decrease the amyloidogenic processing of the amyloid precursor protein. Animal studies have shown that estrogens promote neuronal plasticity and lead to decreased levels of cerebral beta-amyloid peptide accumulation via decreased amyloidogenic processing of the amyloid precursor protein. Recently, a randomized double-blind placebo-controlled study of the effects of estrogen plus progestin treatment in women over 65 years of age found that this treatment was associated with increased incidence of probable dementia. It is not known whether this combination of hormones or the late age at which the therapy was administered was responsible for the adverse outcome.