Week of August 19, 1998

Four-year study shows estrogen therapy didn't help lower heart disease in women with existing heart disease

CHICAGO (JAMA) "Women should not begin hormone therapy for the purpose of secondary prevention of heart disease, though it may be appropriate for women already receiving this treatment to continue, according to an article in the August 19 issue of The Journal of the American Medical Association (JAMA).

Stephen Hulley, M.D., from the University of California at San Francisco, and colleagues conducted a study (The Heart and Estrogen/progestin Replacement Study, [HERS]) to determine if estrogen plus progestin therapy alters the risk for coronary heart disease (CHD) events in postmenopausal women with established coronary disease.

The researchers found: "During an average follow-up of 4.1 years, treatment with oral conjugated equine estrogen [Premarin] plus medroxyprogesterone acetate [progestin] did not reduce the overall rate of CHD events in postmenopausal women with established coronary disease. The treatment did increase the rate of thromboembolic events [blood clots in the legs and lungs were three times more common] and gallbladder disease."

They continue: "Based on the finding of no overall cardiovascular benefit and a pattern of early increase in risk of CHD events, we do not recommend starting this treatment for the purpose of secondary prevention [i.e., women who already have coronary disease] of CHD. However, given the favorable pattern of CHD events after several years of therapy, it could be appropriate for women already receiving this treatment to continue."

The randomized, blinded study included 2,763 women from 20 U.S. clinical centers who had coronary disease, were younger than 80 years, and were postmenopausal with an intact uterus. The mean age of the participants was 66.7 years. Approximately one-half of the group went on hormone therapy, while the other half took a placebo.

The researchers did find that within the overall null effect, there was a statistically significant time trend, with more CHD events in the hormone group than in the placebo group in the first year and fewer in the fourth and fifth years. The authors add that this time trend should be interpreted with caution.

The results of this study differ from previous observational studies which have found lower rates of CHD in women who take hormone therapy. The authors believe the observational studies may be misleading because women who take postmenopausal hormones tend to have a better CHD risk profile and to obtain more preventive care than nonusers. The discrepancy between the findings of HERS and the observational studies may also reflect important differences between the study populations and treatments. "Only a randomized trial can establish the efficacy and safety of postmenopausal hormone therapy for preventing CHD."

The authors add that they did not evaluate the cardiovascular effect of treatment with unopposed estrogen, commonly used in women who have had a hysterectomy, or other estrogen plus progestin formulations. Another limitation of the study cited by the authors include not knowing whether their findings apply to healthy women. They did not study women without coronary disease.

The authors conclude: "Extended follow-up of the HERS cohort and additional randomized trials are needed to clarify the cardiovascular effects of postmenopausal hormone therapy." (JAMA. 1998;280:605-613)

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