By Amy D'Orazio

Sixteen thousand women participating in the Women’s Health Initiative (WHI) study were advised to stop taking the hormone replacement therapy (HRT) PremproTM in July after study organizers, who had been following women in the study for five years, noticed an increased risk of both breast cancer and heart disease in patients taking the drug. Prempro is a combined estrogen/progesterone replacement therapy, and an editorial accompanying the study results published in the July 17 issue of The Journal of the American Medical Association advises doctors to stop prescribing all estrogen/progestin HRT. Estrogen-only HRT was not a part of the study.

The WHI study started in 1993 and was designed to study the potential positive benefits of combined estrogen progesterone HRT on heart disease. HRT has been touted as the fountain of youth in some instances, a means for a woman past her childbearing years to retain the cardiovascular and bone health benefits of premenopausal women, while avoiding the unpleasant side effects of estrogen-deprivation, which include hot flashes, insomnia, and night sweats. Although HRT is used by an estimated six million women, until the WHI study, there had not been research that compared HRT to placebo in a large group of women. The trial was conducted across the country at 40 clinical centers with a planned followup of 8.5 years.

However, after a mean of 5.2 years on therapy, the study came to an abrupt halt when the lead investigators on the study realized that the risk of breast cancer was actually increasing. The investigators used a “global index” that weighs the risks and benefits of therapy. In this case it was hypothesized that a small increase in the risk of breast cancer might be justified if it were outweighed by a decreased risk of heart disease—the current No.1 killer of both men and women. However, in this case, the global index showed that not only did Prempro increase the risk of breast cancer by about 26%, but it also increased the risk of heart disease by 29%. What this means is that if there were 10,000 women taking HRT and 10,000 women taking a sugar pill, eight more women in the HRT group would get breast cancer, an additional seven would experience a heart attack, an additional eight a stroke, and an additional eight blood clots. HRT did appear to lower the risk of colon cancer by 37% and the risk of hip fractures by 34%, but these benefits did not outweigh the risks posed in terms of breast and heart health.

It is important to note that for women who are taking estrogen-only forms of HRT, such as Premarin®, these findings are not applicable. Estrogen-only HRT is usually given only to women who have undergone a hysterectomy. In women with an intact uterus, estrogen-only HRT can cause a small risk for the development of endometrial cancer. Women taking Premarin are being studied in a companion study involving 11,000 women. To date, there is no evidence that the risks outweigh the benefits, nor is there evidence that these patients will experience an increased risk of breast cancer.

To learn more about these studies and the recommendations of leading physicians, visit the website of the Women’s Health Initiative at www.nhlbi.nih.gov/whi/.