Because of results of observational studies from the last 30 years, it has been thought that hormone replacement therapy (HRT) and supplementation with antioxidant vitamins (particularly vitamins E and C) might improve heart health in postmenopausal women. But since the much-publicized Women’s Health Initiative found in the summer of 2002 that HRT, in fact, might do more harm than good when it comes to cardiovascular health, the use of HRT for this purpose has been called into question. Data on the effectiveness of antioxidant vitamins for this purpose have been mixed.

Now, a study in the November 20, 2002 issue of the Journal of the American Medical Association (JAMA) corroborates existing evidence that HRT may not benefit heart health and also finds that supplementation with antioxidant vitamins may not, either. In fact, the results of this study indicate that both therapies may actually worsen cardiac health.

About the Study

Researchers from seven clinical centers in the United States and Canada studied 423 postmenopausal women who had existing heart disease, defined as at least one coronary artery that was narrowed by 15% to 75% (narrowed arteries inhibit blood flow to the heart and can lead to heart attack). The women were randomly assigned to receive either HRT pills (active group) or identical placebo, or antioxidant supplements of 400 IU vitamin E and 500 mg vitamin C (active group) or identical placebo. The trial was “double-blind,” meaning that neither the women nor the researchers knew which women were taking which treatments.

After an average of 2.8 years, the diameters of the women’s arteries were measured again, to detect if the narrowing improved, stayed the same, or worsened, and by how much. Women who died or had heart attacks during the course of the study were considered to have had the “worst” outcome and were classified as such for the purpose of statistical analysis.

The researchers did statistical analyses to determine the impact the two treatments (HRT and antioxidants) had on the narrowed arteries, compared with placebo.

The Findings

Researchers found that the average width of the coronary arteries narrowed in all subjects, and there was no statistically significant difference in the degree of that narrowing among the different treatments groups: HRT versus placebo HRT or antioxidants versus placebo antioxidants (although there was a trend toward worse narrowing in the HRT group). Likewise there was no statistically significant difference in mortality between women taking HRT and those taking HRT placebo (though there was a trend toward higher mortality in women taking HRT). However, 16 women who took antioxidants died compared with only six who took the antioxidant placebo, a statistically significant difference.

These results led the researchers to conclude that neither HRT nor antioxidant supplements provide cardiovascular benefit for postmenopausal women with heart disease, and, in fact, may potentially worsen cardiac health.

However, there are some limitations associated with this study:

  • The follow-up period was relatively short (average 2.8 years); because heart disease may be slower to progress in some people, the results could have been affected by the short follow-up period.
  • There may actually be an unfavorable association between worsening heart disease and the use of HRT and/or antioxidant supplementation in women, but the study was simply not larger enough to detect it.
  • Approximately 20% of the patients studied did not complete follow-up; of those who did complete follow-up, the women assigned to take HRT took only 67% of the prescribed medication, and the women assigned to take vitamins took 84% of the prescribed vitamins. These factors may limit the power of the study to detect an effect of either treatment (especially the HRT).

How Does This Affect You?

The results of this study add to a growing body of evidence that HRT and antioxidant vitamins likely do not have the benefits once thought for heart health in postmenopausal women with existing heart disease. However, the results are not necessarily applicable to women without existing heart disease. Women currently taking—or considering taking—either of these therapies should not change their regimens based on the results of this single study, without consulting their doctors first.

Keep in mind, too, that heart health is strongly influenced by additional lifestyle factors, including exercise, diet, and smoking.

It is also important to note that this study evaluated the use of antioxidant supplements , rather than antioxidants from foods. The results of this study do not mean that people should stop eating antioxidant-rich fruits and vegetables, which remain an important part of a healthful diet.