that it increased the risks of developing certain diseases, including coronary heart disease, breast cancer, and stroke, it is natural to ask whether HT might have contributed to the divergence in life expectancy trends between U.S. women and women in many other high-income countries. The question can be broken down into two parts: Does HT increase mortality risk? and Was the use of HT significantly more common in the United States than in other high-income countries? Goldman (2010b) examines both of those questions in a paper prepared for the panel.

DOES HORMONE THERAPY INCREASE MORTALITY RISK?

The increased risk for coronary heart disease that the Women’s Health Initiative found among older women receiving HT was a surprise because earlier observational studies had found just the opposite (Goldman, 2010b). These earlier studies—which were based on observations of women given HT as part of normal medical practice rather than in randomized controlled trials—showed that women taking HT were generally from 35 to 50 percent less likely to develop heart disease than those not taking HT (Grodstein et al., 2000, 2006; Manson and Bassuk, 2007; Prentice and Anderson, 2008). For example, one meta-analysis of 32 previous observational studies calculated that women who had been treated with estrogen at some point had a 35 percent lower risk of developing coronary heart disease than women who had never been given estrogen (Grady et al., 1992).

By contrast, the Women’s Health Initiative and at least two other randomized controlled trials found an increased risk of coronary problems among women who were given HT. The results of the Women’s Health Initiative were particularly compelling as it involved 27,500 postmenopausal women and thus assembled a very large amount of data from which to draw conclusions about the effects of HT. The controlled trials reinforced some of the findings of the earlier observational studies—the benefits of HT in reducing the risk of colorectal cancers and hip fractures, for example, and an increased risk of breast cancer—but the new finding that HT increased the risk of coronary heart disease and stroke changed medical opinion on HT. Based on the judgment that the risks of HT appeared to outweigh the benefits, guidelines in the United States were modified to recommend against using HT for the prevention of cardiovascular disease in postmenopausal women. As a result, the use of HT has decreased dramatically since 2002 in the United States and other countries around the world (Barbaglia et al., 2009; Guay et al., 2007; Hersh et al., 2004).

Despite the evidence from the controlled trials, however, it appears unlikely that HT resulted in a significant increase in mortality among women in the United States. There are two reasons for this conclusion.

First, although the data indicate that HT—and the estrogen–progestin



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