Hormone replacement with estrogen plus progestin is often used to treat menopausal symptoms and to prevent osteoporosis and subsequent bone fractures. There has also been conflicting evidence that hormone replacement prevents heart disease. The association of hormone replacement with breast and uterine cancer has been well known, but usually these cancers present in early stages and do not affect survival. Estrogen and progestin are usually given together for women who have an intact uterus in order to prevent uterine cancer. Women who have had a hysterectomy usually are given estrogen alone. Researchers affiliated with the Women's Health Initiative have now reported that hormone replacement is not associated with prevention of heart disease, although overall survival was not affected one way or the other. Their results were published in the July 17 issue of the Journal of the American Medical Association.

In this study, 16,608 women ages 50-79 were randomly allocated to receive estrogen plus progestin or a placebo. The study was planned for 8.5 years but was terminated after 5.2 years. The primary endpoint of this study was coronary heart disease (CHD), which included nonfatal myocardial infarction and death from CHD. The other adverse endpoints were invasive breast cancer, stroke, pulmonary embolism (PE), endometrial cancer, colorectal cancer, hip fracture, and death due to other causes.

The study was stopped early because of the higher incidence of invasive breast cancer. The data indicate that there would be 8 excess cases of invasive breast cancer per 10,000 person- years for those taking hormone replacement. An additional 7 per 10,000 person-years will have a heart attack, 8 will have a stroke, and 18 will have blood clots. There were 6 fewer colorectal cancers and 5 fewer hip fractures per 10,000 person-years for those taking hormone replacement. Thus, there were 19 adverse events per 10,000 person-years for those taking hormone replacement. There was no effect of hormone replacement on survival with the 5.2 year follow-up of the study.

These researchers concluded that overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 5.2-year follow-up among healthy postmenopausal U.S. women. They suggested that hormone replacement should not be initiated or continued for primary prevention of CHD, even though the overall risks of taking hormone replacement therapy are small.

Comments: This study is of major interest and will change the way estrogen and progestin is prescribed for postmenopausal women. This study did not address the question of estrogen alone or estrogen alone in women who have had a hysterectomy. There is still an ongoing study of estrogen alone in 11,000 women being conducted by the Women's Health Initiative. That study is continuing because there is no evidence so far that the drug's risks exceed its benefits. That study is reputed to show no increased risk of breast cancer. Women should discuss the findings of this study with their physician before discontinuing their hormones.

Reference: Writing Group for the Women's Health Initiative Investigators, Risks and Benefits of Estrogen Plus Progestin in Healthy Postmenopausal Women; Principal Results From the Women's Health Initiative Randomized Controlled Trial. Journal of the American Medical Association. 2002;288:321-333.