The bone-preserving and cardiovascular benefits of estrogen replacement therapy in post-menopausal women are well documented. Recent evidence also suggests that estrogen therapy may exert a protective effect against Alzheimer's disease. Kawas and associates reviewed data from the Baltimore Longitudinal Study of Aging (BLSA) to determine whether estrogen replacement therapy confers a protective effect against the development of Alzheimer's disease.

The BLSA is a prospective, multidisciplinary study of aging conducted by the National Institute on Aging. It began in 1978. Data were gathered for 514 post- and perimenopausal women over a 16-year period. All of the study subjects underwent extensive testing every two years, including physical and neurologic examinations and neuropsychologic testing. Past and present use of estrogen therapy was assessed to determine the duration of estrogen use. The relative risk of development of Alzheimer's disease associated with estrogen use was calculated.

Forty-five percent of the 514 women eligible for the study reported estrogen use. A total of 34 cases of Alzheimer's disease occurred among 472 women in whom estrogen replacement status was known. Nine of these women had a history of estrogen replacement therapy. The relative risk for the development of Alzheimer's disease in estrogen users compared with nonusers was 0.46. Other variables, including age at menopause, age at menarche, years of natural cyclic estrogen exposure and duration of menopause, were not found to be significant factors. The protective effect did not increase with an increased duration of estrogen use.

The authors conclude that these results support previous case-control studies that have demonstrated a protective effect of estrogen replacement therapy against the development of Alzheimer's disease. An increased duration of use was not associated with an increase in the protective effect. Estrogen replacement therapy may become a tool in preventing or slowing the progression of Alzheimer's disease, but randomized clinical trials are necessary to confirm this association. A study of estrogen replacement in women with Alzheimer's disease is now in progress under the sponsorship of the Alzheimer's Disease Cooperative Study Unit, funded by the National Institute on Aging.