Estrogen Replacement Therapy and Risk of Alzheimer Disease

TLDR

Alzheimer disease is a major public health problem, prompting the search for preventive factors. The study aimed to assess how estrogen replacement therapy, its dosage, duration, and formulation affect Alzheimer disease risk in postmenopausal women. A nested case‑control study within a 1981–1995 cohort of 8,877 postmenopausal women identified 248 Alzheimer cases and matched them to five controls each based on age and death year. Estrogen use lowered Alzheimer risk (OR 0.65), with greater reductions for oral versus nonoral routes, higher doses, and longer duration, especially in long‑term high‑dose users (OR 0.48).

Abstract

With Alzheimer disease emerging as a major public health problem, the identification of factors that might prevent this disease are important. Estrogen loss associated with menopause may contribute to the development of Alzheimer disease.To evaluate the effects of different estrogen preparations, varying dosages of estrogen, and duration of estrogen replacement therapy on the risk of Alzheimer disease in postmenopausal women.A case-control study nested within a prospective cohort study of residents of Leisure World Laguna Hills, a retirement community in Southern California. The cohort comprised 8877 women who were first mailed a health survey in 1981. Of the 3760 female cohort members who died between 1981 and 1995, 248 women with Alzheimer disease or other dementia diagnoses likely to represent Alzheimer disease (senile dementia, dementia, or senility) mentioned on the death certificate were identified. Five controls were individually matched to each case according to year of death and year of birth (+/- 1 year).The risk of Alzheimer disease and related dementia was significantly reduced in estrogen users compared with nonusers (odds ratio, 0.65; 95% confidence interval, 0.49-0.88). The risk was reduced for both oral and nonoral (i.e., 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 used 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% confidence interval, 0.19-1.17).This study suggests that estrogen replacement therapy may be useful for preventing or delaying the onset of Alzheimer disease in postmenopausal women.