ESTROGEN REPLACEMENT THERAPY AND RISK OF ALZHEIMER-DISEASE

Background: With Alzheimer disease emerging as a major public health p roblem, the identification of factors that might prevent this disease are important. Estrogen loss associated with menopause may contribute to the development of Alzheimer disease. Objective: To evaluate the ef fects of different estrogen preparations, varying dosages of estrogen, and duration of estrogen replacement therapy on the risk of Alzheimer disease in postmenopausal women. Study Design and Methods: A case-con trol study nested within a prospective cohort study of residents of Le isure World Laguna Hills, a retirement community in Southern Californi a. The cohort comprised 8877 women who were first mailed a health surv ey in 1981. Of the 3760 female cohort members who died between 1981 an d 1995, 248 women with Alzheimer disease or other dementia diagnoses l ikely to represent Alzheimer disease (senile dementia, dementia, or se nility) mentioned on the death certificate were identified. Five contr ols were individually matched to each case according to year of death and year of birth (+/-1 year). Results: The risk of Alzheimer disease and related dementia was significantly reduced in estrogen users compa red with nonusers (odds ratio, 0.65; 95% confidence interval, 0.49-0.8 8). The risk was reduced for both oral and nonoral (ie, injections and /or creams) routes of administration. The risk decreased significantly with both increasing dosages (P=.01) and increasing duration (P=.01) of oral therapy with conjugated equine estrogen, the most commonly use d estrogen preparation. Within each dose category, the risk decreased with increasing duration of therapy, with the lowest observed risk in long-term users who received high doses (odds ratio, 0.48; 95% confide nce interval, 0.19-1.17). Conclusion: This study suggests that estroge n replacement therapy may be useful for preventing or delaying the ons et of Alzheimer disease in postmenopausal women.