Author Affiliations: Department of Epidemiology and Biostatistics, University of California, San Francisco.
Over the past half-century, a growing belief among women and their physicians
held that "replacing" the estrogen lost at menopause would prevent many of
the manifestations of aging, including coronary heart disease (CHD), osteoporotic
fractures, and a decline in cognitive and sexual function. This attractive
and plausible view led to widespread use of hormone therapy after menopause
in the era before randomized trials with disease end points were required
for proving the effects of new drugs. Clinicians were drawn in by other accumulating
lines of evidence for CHD benefit that were consistently favorable: observational
studies showed less heart disease among women taking estrogen,1 pathophysiologic
mechanisms provided biological plausibility,2 and
clinical trials revealed improvements in blood lipid levels and other surrogate
Hulley SB, Grady D. The WHI Estrogen-Alone Trial—Do Things Look Any Better? JAMA. 2004;291(14):1769–1771. doi:10.1001/jama.291.14.1769
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