Estrogen replacement therapy for cognitive benefits: viable treatment or forgettable "senior moment"?

The perceived benefits of estrogen on cognitive function are one of the few remaining potential roles for estrogen replacement therapy. The justification for such a role has a strong biologic basis and is easily shown in animal models. Purported benefits for estrogen on cognitive function include neuroprotective, neurostimulating, and neurotrophic effects. The objective of this study was to review the literature and to evaluate the role of estrogen replacement therapy in improving cognition in Alzheimer disease, vascular dementia, premenopausal women, and postmenopausal women without dementia. Additionally, the authors separately looked at the neuroprotective effects of estrogen replacement therapy on the subsequent risk of dementia. The available data fail to show a therapeutic benefit of estrogen replacement therapy in Alzheimer disease. Surprisingly, limited data allow consideration of a possible role of estrogen in the management of vascular dementia. Additionally, younger females with low estrogen levels secondary to primary ovarian failure and Turner syndrome benefit from estrogen replacement therapy. Despite the limited role of estrogen replacement therapy in cognitive enhancement, neuroprotective properties are likely because several prospective studies indicate a reduced risk of Alzheimer disease. A critical window of opportunity seems to exist for this protective effect in Alzheimer disease because once established, the course of the disease is not affected by concomitant estrogen replacement therapy. The authors conclude that the use of estrogen replacement therapy is not substantiated for the treatment of patients with Alzheimer disease. Alternatively, because of the evidence for a possible neuroprotective effect, women at high risk for the development of Alzheimer disease may be appropriate candidates for estrogen replacement therapy. Such a decision should be made on a case-by-case basis, after careful consideration of the risks and benefits.