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Editorial |

The WHI Estrogen-Alone Trial—Do Things Look Any Better?

Stephen B. Hulley, MD, MPH; Deborah Grady, MD, MPH
JAMA. 2004;291(14):1769-1771. doi:10.1001/jama.291.14.1769.
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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 measures.3

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