Postmenopausal Estrogen Therapy (ET) and Alzheimer's Disease (AD): Effect modificiation by smoking

Abstract

To investigate the association between ET and AD in postmenopausal women using a population-based case-control study design. Case patients were all postmenopausal women who developed AD from 1985–1989 in Rochester, MN (n = 277). One control subject from the same population and free of dementia was matched to each case patient by age (± 1 year; n = 277). Estrogen exposure was defined as any form of estrogen (oral, parenteral, topical, suppository) used for at least 6 months after the onset of menopause and before the year of onset of AD (or corresponding year in matched control subject). A history of ET, duration of use, and cumulative dose was ascertained by a detailed review of the complete medical records archived in the records linkage system of the Rochester Epidemiology Project. Among women with natural menopause, the frequency of ET use (≥6 months) was similar in AD cases (11.6%) and controls (14.3%; OR = 0.80; 95% CI = 0.45 to 1.41). However, among women treated with ET, cases had an earlier age at start of treatment (median = 50 versus 53 years; p = 0.05), and a shorter lag time between menopause and initiation of ET (median = 1 years versus 4 years; p = 0.11) than controls. Smoking (ever vs. never) was not associated with the risk of AD overall; however, we observed an interaction between smoking and ET. The OR for AD in ET users was 1.93 (95% CI = 0.65 to 5.74) among smokers, but was 0.54 (95% CI = 0.27 to 1.09) in non-smokers (p value for interaction = 0.06). For women who never smoked, the inverse association of ET with AD reached statistical significance for duration of ET longer than 3 years (OR = 0.33; 95% CI = 0.12 to 0.95). The possible interaction with smoking was also observed with cumulative dose of ET. Although we failed to show a significant overall association between ET and AD, our findings suggest that early ET use may predict AD in postmenopausal women. In addition, our findings suggest that ET may be protective for AD in women who have never been smokers.