In the full report of a major study of hormone replacement therapy (HRT) and heart disease, researchers from Wake Forest University Baptist Medical Center write in this week''s New England Journal of Medicine that the treatment didn''t slow the progression of heart disease in older women, despite improvements in cholesterol levels.
The results of the study, the Estrogen Replacement and Atherosclerosis (ERA) trial, were first announced at the American College of Cardiology''s annual meeting in March.
"The evidence suggests that women with heart disease should not use estrogen replacement therapy as a treatment for heart disease," said David Herrington, M.D., M.H.S., lead investigator.
ERA used cardiac catheterization, a test that injects dye into the arteries, to measure narrowing in the heart''s arteries caused by a buildup of cholesterol. As vessel disease progresses, the arteries become smaller.
A total of 309 older women with heart disease were randomly assigned to take estrogen (Premarin®), estrogen combined with a progestin (Prempro®), or a dummy pill (placebo). Sophisticated computer techniques were used to measure subtle changes in their arteries over the 3.2-year study period.
"Overall, there were no differences between the groups in how quickly the disease progressed," said Herrington, associate professor of Cardiology.
No effect was seen despite improvements in cholesterol. For the women taking estrogen alone, low-density "bad" cholesterol decreased an average of 9.4 percent and high-density "good" cholesterol increased by 18.8 percent. For women taking estrogen plus progestin, the changes were 16.5 percent for bad cholesterol and 14.2 percent for good cholesterol.
"Improved cholesterol levels from conventional cholesterol-lowering medications typically result in slowing of disease progression and fewer heart attacks," said Herrington. "But in this study, improvements in cholesterol with estrogen had no effect on the progression of disease in the heart arteries."
Other studies have also confirmed HRT''s positive effects on cholesterol and other risk factors for heart attacks, including vessel elasticity.
"A possible explanation for HRT''s lack of effect on disease progression is that estrogen may also cause an adverse inflammatory response in the arteries that offsets the beneficial cholesterol effects," said Herrington. "Or perhaps HRT is better at preventing heart disease in younger, healthier women than at reversing disease in older women."
The mean age of the women in ERA was 65.8 years. Almost half (48 percent) of the
women were heart attack survivors.
ERA is the second major clinical study that calls into question the widely held belief that HRT is an effective treatment for heart disease. In 1998, HERS (the Heart and Estrogen/progestin Replacement Study) found that 2,763 women with heart disease who took estrogen and a progestin for four years had just as many heart attacks as women who didn''t take the treatment.
"ERA supports the findings of HERS. In both studies, there was no clear-cut evidence of benefit in women with established heart disease," said Herrington. He pointed out that the results don''t necessarily apply to younger, healthier women. Current studies, such as the Women''s Health Initiative, are designed to answer that question.
ERA study sites were at Wake Forest University Baptist Medical Center, Forsyth Medical Center in Winston-Salem, Moses Cone Hospital in Greensboro, Carolinas Medical Center in Charlotte, Hartford Hospital in Hartford, Conn., and the University of Alabama at Birmingham. The study was funded by the National Institutes of Health.
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Additional Sound bites from Dr. David Herrington