“With an average of 6.8 years of follow-up, we found no effect of CEE on coronary heart disease incidence rates, the primary motivation for this trial.”

Menopausal hormone therapy is of keen interest to physicians, researchers, and women in general, because of the large population that may be affected and the likelihood that hormones may have noteworthy effects throughout the body. Interest skyrocketed when our previous results on combined hormones ("Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results from the Women’s Health Initiative Randomized Trial." JAMA 2002: [288]321-333) showed that the risks of estrogen combined with progestin exceed benefits for chronic disease prevention. The combined hormone trial also gave evidence that previous observational studies had not provided reliable information on health effects of chronic diseases.

The recent article provides the first randomized trial evidence of the effects of conjugated equine estrogen (CEE) alone on the major clinical outcomes of coronary heart disease, stroke, cancer, and fractures; showing a profile of effects that is somewhat different from combined hormones and again differing from previous observational studies.

With an average of 6.8 years of follow-up, we found no effect of CEE on coronary heart disease incidence rates, the primary motivation for this trial. A significant (41%) increase in stroke incidence with CEE was detected, accounting for 12 additional women with strokes per 10,000 person-years, similar to the combined hormone findings. Deep vein thrombosis was also increased. Breast cancer rates were not significantly altered by CEE, though the data suggested a modest (23%) reduction, in contrast to the clear increase in breast cancer risk with combined hormones. No effect was seen on risk of colorectal cancer or total cancer. Fracture rates were significantly reduced by CEE (by 30%-40%), comparable to combined hormones.

First, I am an investigator and statistician with the Women’s Health Initiative Clinical Coordinating Center at the Fred Hutchinson Cancer Research Center. I’ve been involved with the WHI from its inception here in 1992. I was attracted to this work by the focus on women’s health, by the fact that these important public health questions were being addressed using the gold standard method of a randomized, double-blind, placebo-controlled trial, and by the high-caliber investigator team being assembled. From the beginning, it appeared to me that the results of these clinical trials, if completed as designed, would be of major public health importance, regardless of the results, and thus it would be worth a major investment of effort. Disease prevention research is challenging because of the size and duration needed in these studies to produce reliable results, but it holds tremendous potential for reducing morbidity and mortality. To date, there has not been sufficient demand for the same high-quality evidence for prevention as is required for treatment strategies. This is a substantial gap in our research agenda. Though the lack of benefit of hormones for heart disease was a surprise and a disappointment, these results serve as a useful reminder of the need for high-quality randomized trials of prevention strategies.