The first randomized primary pre-vention trial to study combined hormone replacement therapy (HRT) in healthy postmenopausal women was stopped early when researchers found an increased risk of breast cancer among women taking part in the study, according to an article published in the July 17 issue of JAMA (2002;288:321–333, 366–368).
The Women's Health Initiative (WHI) study found that women receiving the estrogen/progestin combination were also at higher risk for coronary heart disease, stroke, and pulmonary embolism, the report said. HRT did seem to lower the risk of colorectal cancer and bone fractures, but overall the risks outweighed the benefits, the researchers said.
More than 16,000 healthy post-menopausal women participated in the estrogen-plus-progestin component of the WHI study, a trial funded by the National Institutes of Health. All of the women were between the ages of 50 and 79, and all still had an intact uterus. The women began taking either a combination estrogen/progestin pill or a placebo each day, starting in the mid-1990s.
The women were supposed to be followed for an average of eight and one-half years, with the data safety and monitoring board looking at the results twice each year. The last scheduled review (May 2002) showed the results were significant enough that the trial was stopped after just over five years (mean follow-up).
The breast cancer incidence rate was 26 percent higher among those receiving HRT as opposed to those getting placebo. HRT increased the rates for heart disease (by 29 percent), stroke (by 41 percent), and pulmonary embolism (by 113 percent).
HRT did have some benefits, however. The incidence rates for colorectal cancer and hip fractures were 37 percent lower and 34 percent lower, respectively, in the HRT group. Endometrial cancer rates for the HRT and control groups were not significantly different.
In addition, the authors gave weight to each of these factors to come up with an overall “global index,” which indicated that the risks outweighed the possible benefits for these serious conditions by 15 percent. And HRT had no significant influence on the all-cause mortality rate.
In an editorial in the same issue, Suzanne Fletcher, MD, MSc, and Graham Colditz, MD, MPH, both of Harvard Medical School, said that 38 percent of postmenopausal American women currently use some form of HRT. But with this study publication, the wisdom of such use has now been called into serious question.
“Given these results, we recommend that clinicians stop prescribing this combination for long-term use. Primum non nocere applies especially to preventive health care,” the editorial authors wrote.