Postmenopausal estrogen replacement therapy and the risk of Alzheimer disease.

Abstract

AN ESTIMATED 15% of older women will develop Alzheimer disease (AD) during their lifetimes,¹ and treatments that might reduce this risk are of great interest. A sharp decline in estrogen levels characterizes aging and menopause; the risks of developing osteoporosis and coronary artery disease—2 other conditions that affect women in their postmenopausal years—appear to be decreased by postmenopausal estrogen replacement therapy (ERT). Many basic neural mechanisms suggest that estrogen could beneficially affect the brain areas and processes involved in AD. Estrogen can enhance neuronal survival, inhibit apoptosis, and promote synaptogenesis and synaptic plasticity^2,3 alone and synergistically with nerve growth factor. It increases levels of acetylcholine in the basal forebrain and hippocampus, serves as an antioxidant protecting neurons from the toxic effects of β-amyloid and glutamate, enhances repair of neuronal injury via apolipoprotein E–dependent mechanisms, and improves cerebral blood flow.^4-6 However, biological plausibility alone does not establish a beneficial effect.