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The HERS Trial Results: Paradigms Lost?

David M. Herrington, MD, MHS
[+] Article, Author, and Disclosure Information

From Wake Forest University School of Medicine, Winston-Salem, North Carolina.

Disclosure: Dr. Herrington is a member of the HERS Executive Committee and has received research support from Wyeth-Ayerst Research, sponsor of the HERS trial.

Requests for Reprints: David M. Herrington, MD, MHS, Department of Internal Medicine/Cardiology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1045; e-mail, dherring@wfubmc.edu.

Ann Intern Med. 1999;131(6):463-466. doi:10.7326/0003-4819-131-6-199909210-00012
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The Heart and Estrogen/progestin Replacement Study (HERS) found no overall effect of 4.1 years of therapy with estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. However, within the overall null effect, a 50% increase in cardiovascular events was seen in the first year, followed by fewer events after 2 years of treatment in the hormone therapy group than in the placebo group. Understanding the cause of this pattern of early increase and late reduction in risk is key to interpreting the HERS results and reconciling them with the large number of observational and other studies of the cardiovascular effects of estrogen. There are two possibilities. One is that the HERS regimen of estrogen plus progestin has no effect on risk for heart disease, and the pattern of changing risk over time is simply the result of chance or confounding. The other is that the pattern of early increase and late reduction in risk is due to real but opposing effects of this regimen. Several lines of evidence support each possibility. Attrition of a susceptible cohort of women uniquely at risk for a cardiovascular complication from hormone therapy coupled with a gradually progressive beneficial effect due to lipid lowering and other factors is a promising potential explanation. The HERS results remind us of the need for clinical trials to evaluate both the benefits and risks of new therapies. They also illustrate how much more we need to know about the cardiovascular effects of hormone replacement therapy.


Grahic Jump Location
Model of the possible impact of attrition of women with a susceptibility factor on the pattern of relative risk for myocardial infarction and death from coronary heart disease among women assigned to estrogen plus progestin or placebo over time in the Heart and Estrogen/progestin Study cohort. Left.Right.

White bars represent a projected pattern of relative risk, assuming attrition of a susceptible cohort and no beneficial effects of hormone replacement therapy. Striped bars represent a projected pattern of relative risk, assuming a monotonic reduction in risk beginning in year 2 and no harmful effects of the intervention in year 1. Results when these effects are combined.

Grahic Jump Location




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