The study of estrogen and progestin replacement therapy known as HERS (the Heart and Estrogen/progestin Replacement Study) showed that daily dosages of estrogen and progestin (for 4.1 years of follow-up) were not associated with an increase in risk of coronary heart disease (CHD). However, a subsequent analysis of the data showed that there was a time trend, with more CHD events during the initial years of treatment and a decline in years 3 to 5. Once this pattern was recognized, women with CHD were advised to avoid beginning hormone replacement therapy (HRT) for preventing CHD events, but women who were already taking these medications were advised that they could continue. Grady and the other investigators in the HERS Research Group present results from the HERS II study, which consisted of women who elected to continue the regimen to which they had been randomized in the original study. HERS II sought to determine the cardiovascular implications of HRT after a total of 6.8 years of follow-up.

Postmenopausal women younger than 80 years were included if they had a history of cardiac disease (including myocardial infarction [MI], coronary-artery bypass graft, and percutaneous angioplasty of coronary-artery narrowing of more than 50 percent). Women who elected to participate in HERS II were followed to determine the occurrence of CHD events (CHD death, nonfatal MI, and congestive heart failure, among others). HERS II researchers had planned to follow participants for four years, but the study was discontinued at the second annual follow-up. Consequently, the average follow-up was 2.7 years.

HERS II enrolled 1,165 women in the placebo group and 1,156 women in the HRT group. There were no significant differences in CHD outcomes between the groups, with 62 deaths occurring in the HRT group and 63 occurring in the placebo group.

The authors conclude that there is no clear cardiovascular benefit from HRT, even though there initially appeared to be a slight benefit (i.e., in HERS) after several years of treatment. They support the recommendation that HRT not be used to reduce CHD events in post-menopausal women with CHD.

editor's note: This HERS follow-up study supports findings of other studies (such as the Postmenopausal Hormone Replacement Against Atherosclerosis trial and the Estrogen Replacement Atherosclerosis trial) showing that postmenopausal hormone replacement therapy did not slow atherosclerosis progression. Clinicians should use HRT only in women with a clear indication, not as a potential means of preventing various conditions.—g.b.h.