These findings are the latest results to emerge from the WHI’s 15-year, multi-million dollar endeavor that is one of the largest prevention studies of its kind in the United States, said Cora E. Lewis, M.D., professor in the University of Alabama at Birmingham’s Division of Preventive Medicine, principal investigator for the WHI at UAB and co-author of the research paper. “Menopausal hormone therapy continues in clinical use, but questions remain regarding its risks and benefits for chronic disease prevention,” Lewis said. “Our data, which is a comprehensive, integrated overview of findings from the two WHI hormone therapy trials with extended post-intervention follow-up, continues to suggest that long-term hormone therapy is not the appropriate treatment. Small doses, used for a finite window, should be the appropriate practice for treatment of menopausal symptoms.”
The National Institutes of Health established the WHI in 1991 to address the most common causes of death, disability and impaired quality of life in postmenopausal women. The hormone study included 27,347 postmenopausal women, ages 50 through 79, who were enrolled at 40 U.S. centers beginning in 1993. Two randomized trials looked specifically at hormone therapy but were stopped in 2002 and 2004 because the health risks outweighed the benefits.
In one of the trials, women with an intact uterus received a combination therapy of estrogen plus progestin for an average of 5.6 years before the trial was stopped due to the greater number of women experiencing heart attacks, breast cancer, strokes, dementia and other issues on the active hormone pills, compared to women randomly assigned to placebo. Benefits reported from the trial included fewer hip fractures and cases of diabetes, as well as fewer vasomotor symptoms like hot flashes.
The other trial was for women with prior hysterectomy, and they received estrogen alone for an average of 7.2 years. The benefits and risks during the intervention in this trial were more balanced, with increased risks of stroke and venous thrombosis, reduced risk of hip and total fractures and a non-significant reduction in breast cancer. Neither regimen affected all-cause mortality. Both trials had additional follow-up through Sept 30, 2010.
“It was widely believed that hormone therapy was beneficial to women at the time we started these clinical trials in 1993, so much so that there were more than a few doctors around the country who thought the study was unethical because we would be randomizing people to a placebo and keeping some from the perceived benefits of hormone therapy,” Lewis said. “We’ve been following these women for 10 years now since the studies ended, and most of the increased risks seen in the women taking the estrogen-progestin combination dissipated. However, we still see some increased breast cancer risk in those who were on the estrogen-progestin combination.”
Patients in the clinical trial who took the estrogen alone did not have as many bad results during the trial. In fact, post-intervention saw a significant decrease in breast cancer.
“That wasn’t the case with the combination treatment,” Lewis said. “But with the estrogen taken by itself, that protection effect from breast cancer was pretty surprising. We didn’t expect to see that, but the fact is that breast cancer incidence rates went down in the United States after our first papers were published 10 years ago, and many women stopped taking hormones. There is no doubt that while these studies have been controversial, they were necessary and have had a tremendous impact.”
The National Heart, Lung and Blood Institute, NIH and the U.S. Department of Health and Human Services fund the Women’s Health Initiative.