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Postmenopausal Estrogen Replacement Therapy and the Risk of Alzheimer Disease
Sudha Seshadri, MD;
Gwen L. Zornberg, MD, ScD;
Laura E. Derby, DSc;
Marian W. Myers, MPH;
Hershel Jick, MD;
David A. Drachman, MD
Arch Neurol. 2001;58:435-440.
Background Previous studies have examined the relation between postmenopausal estrogen
replacement therapy (ERT) and the risk of Alzheimer disease (AD). The findings
have been inconsistent, since some studies have been interpreted as showing
a protective effect while others have reported no effect.
Objective To determine whether exposure to ERT is associated with a reduced risk
of AD.
Design Population-based nested case-control study.
Setting The United Kingdom–based General Practice Research Database.
Patients The base cohort consisted of women who were recipients of ERT (n = 112 481)
and a similar cohort of women who did not use estrogens (n = 108 925).
The 2 cohorts were restricted to women born on or before January 1, 1950.
From the 2 cohorts, we identified and verified 59 newly diagnosed cases of
AD and 221 matched control subjects.
Main Outcome Measure Prior and current use of ERT in cases compared with controls.
Results Among the 59 newly diagnosed cases of AD, 15 (25%) were current estrogen
users, while among the controls, 53 (24%) were current users. The adjusted
odds ratio comparing all current estrogen recipients with nonrecipients was
1.18 (95% confidence interval, 0.59-2.37). In estrogen users who took the
drug for 5 years or longer compared with nonusers, the odds ratio was 1.05
(95% confidence interval, 0.32-3.44). Odds ratios were similar for estrogen
recipients who received estrogens alone and recipients who received combined
estrogen-progestin treatment.
Conclusion The use of ERT in women after the onset of menopause was not associated
with a reduced risk of developing AD.
From the Framingham Heart Study and the Department of Neurology, Boston
University School of Medicine, Boston, Mass (Dr Seshadri); the Boston Collaborative
Drug Surveillance Program, Boston University School of Medicine, Lexington,
Mass (Drs Zornberg, Derby, and Jick and Ms Myers); and the Department of Neurology,
University of Massachusetts Medical Center, Worcester (Dr Drachman).
Corresponding author and reprints: David A. Drachman, MD, Department
of Neurology, University of Massachusetts Medical Center, 55 Lake Ave N, Worcester,
MA 01655 (e-mail: david.drachman{at}umassmed.edu).
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