Women who received estrogen plus progestin as part of a major clinical trial on the benefits and risks of hormone therapy had a higher risk of breast cancer and other conditions three years after the study was discontinued as compared to women in the trial who received placebo, according to a follow-up study in the March 5 issue of the Journal of the American Medical Association (JAMA).

The Women's Health Initiative (WHI) trial of estrogen-plus-progestin involved more than 16,600 women ages 50 to 79 nationwide, including 1,100 Iowa women who participated at the University of Iowa and study sites in Des Moines and Davenport.

In July 2002, WHI researchers stopped the estrogen-plus-progestin study after five years of the planned eight-year trial. They reported that the estrogen-plus-progestin treatment did not prevent heart disease and that for women taking the medication, the risks—increased breast cancer, heart attacks, strokes and blood clots—outweighed the treatment benefits of fewer hip fractures and colorectal cancers.

Study co-author Robert Wallace, MD, professor of epidemiology in the UI College of Public Health, and his WHI colleagues analyzed the health risks and benefits experienced by 15,730 study participants who continued follow-up visits after they stopped taking the estrogen-plus-progestin therapy.

"In the three years after the trial medication was stopped, those women who were previously on the drug generally had a lowering of disease risks to levels similar to those who didn't take hormone therapy. For example, the differences in heart disease risk were no longer present," Wallace said.

However, Wallace noted, there was still an overall negative impact on the health of women who had taken estrogen plus progestin. "There was evidence of higher levels of breast cancer, lung cancer, stroke, blood clots and death among those who had taken this therapy earlier," he said.

Wallace added that while the risk of breast cancer remained higher for these women during the three-year follow-up period, the risk was less than that shown at the time the trial was stopped.

A summary of the trial's risks and benefits included outcomes for coronary heart disease, invasive breast cancer, stroke, pulmonary embolism, uterine cancer, colorectal cancer, hip fracture and death due to other causes. This analysis, called a global risk index, was found to be 12 percent higher for women in the estrogen-plus-progestin group as compared to the placebo group and did not change during the follow-up period, according to the study authors.

"The most important message to women who have stopped this hormone therapy is the need for a continued rigorous prevention and screening program through their physicians, for all important preventable conditions," Wallace said.

For more information:

Robert Wallace, MD