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March 5, 2003

Estrogen Replacement and Risk of Alzheimer DiseaseEstrogen Replacement and Risk of Alzheimer Disease

Author Affiliations

Letters Section Editor: Stephen J. Lurie, MD, PhD, Senior Editor.

JAMA. 2003;289(9):1100-1102. doi:10.1001/jama.289.9.1100-a

To the Editor: In their observational study, Dr Zandi and colleagues1 found an apparent reduction of about 40% in risk of AD among women who reported using HRT. In their accompanying Editorial, Drs Resnick and Henderson cite the fact that the reduction was greater for longer duration use as possible evidence that the reduction is not due to "healthy user" bias.2 Just as in the case of AD, observational studies have found large reductions in risk of coronary heart disease among users of ERT, and the reductions were greater for longer durations of use.3 However, the final standard for assessing the potential protective effect of ERT is a randomized controlled trial; randomization would eliminate healthy user bias. Results of 2 such trials, the Heart and Estrogen/Progestin Replacement Study4 and the Women's Health Initiative,5 have recently indicated that estrogen/progestin supplements do not prevent coronary heart disease and may even increase the risk of it. Healthy user bias can seriously confound the results of observational studies and underscores the need for caution in interpreting observational data as evidence of protection against diseases.

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