The findings come three years after a related WHI study found that a different type of hormone therapy - which combined estrogen and progestin - did result in a higher risk of breast cancer among postmenopausal women.
Marcia Stefanick, PhD, a Stanford University School of Medicine researcher who oversaw the latest WHI findings, said she hopes the results provide some clarity.
"The clinical trial results for estrogen-alone and for estrogen-progestin are very different - WHI is not flip-flopping," said Stefanick, professor of medicine at the Stanford Prevention Research Center and lead author of the study to be published in the April 12 issue of the Journal of the American Medical Association. "The use of estrogen-progestin clearly showed an increased risk for breast cancer; estrogen-only therapy shows no evidence of an increased risk."
The WHI is a 15-year, broad-based look at the causes and prevention of diseases affecting older women. In addition to hormone therapy, other WHI studies have examined heart disease, breast and colon cancer, and osteoporosis.
For the estrogen-alone arm of the study, which was stopped in 2004, researchers tracked nearly 11,000 women nationwide for about seven years. The women were between the ages of 50 and 79, and had previously undergone a hysterectomy. Half of the women were given a form of estrogen known as conjugated equine estrogens, while the other half were given a placebo.
In the latest analysis, researchers found no evidence that estrogen increased the risk of breast cancer. The women taking estrogen had fewer breast tumors (28 per 10,000 cases per year) than those in the placebo group (34 per 10,000 cases), but the difference of six fewer cases per 10,000 women per year was not deemed statistically significant, meaning that it could have occurred by chance.
Still, Stefanick added that other aspects of the WHI findings suggest women taking estrogen should have additional mammograms and breast biopsies to confirm that no breast cancer is present.
These results are markedly different from those arising from the estrogen-progestin arm of the study, in which a different group of postmenopausal women taking the combined hormone therapy were found to have a 26 percent increase in their risk for breast cancer.
Stefanick noted that it's important for women and physicians to distinguish between the two studies: the women in the combined estrogen-progestin trial still had their uteruses. Because estrogen-alone therapy increases the risk for endometrial cancer, women who haven't had a hysterectomy and who need relief from menopausal symptoms are also given progestin, which offsets the risk of that cancer.
The estrogen-progestin arm of the WHI study was called to an early halt in 2002 - three years ahead of schedule - when evidence from the trial showed that in addition to a higher risk of breast cancer, the women taking the combined hormone therapy also had a greater risk of stroke, blood clots and, in the first year of treatment, heart attack.
The estrogen-alone study was stopped in 2004, one year before its scheduled conclusion, because of concerns that estrogen increased the risk of stroke and blood clots. Stefanick and her colleagues pointed out that even though such risks increased with estrogen-alone therapy, the absolute risk for developing one of these conditions remained relatively low. She also said the initial data indicated that the risks of taking estrogen did not appear to outweigh the benefits, which included relief from menopausal symptoms, stronger bones and the suggestion of a decreased risk of breast cancer.
Stefanick said she understood why officials at the National Institutes of Health halted the estrogen-only trial, though she and other researchers would have liked to continue it to determine whether the findings held true beyond the first seven years of treatment. "The trial was originally supposed to last for eight years, and even at that length we felt like we weren't going to get all the answers that we wanted," she said. "That's my one regret - that we didn't take the trial to its planned end."
Since the end of both trials, Stefanick and the other WHI investigators have continued to analyze the data for a more detailed understanding of how hormone therapy affects women's health.
Both the estrogen-alone and estrogen-progestin studies turned the conventional wisdom about hormone therapy on its head. For many years, observational studies and other evidence indicated that in addition to relieving menopausal symptoms, hormone therapy helped protect women against heart disease and bolstered their overall health. However, neither trial showed any benefit in preventing heart disease, and both trials showed hormone therapy, while having some benefits, posed substantial health risks. Since the results of those trials were announced, the use of hormone therapy has dropped dramatically.
Now, a more nuanced picture is beginning to emerge, and the latest results may provide some reassurance to women seeking relief from menopausal symptoms. Indeed, among U.S. women using hormone therapy, the largest percentage use estrogen alone, so the findings have broad applications, Stefanick said.
She emphasized that hormone therapy should be used only to relieve the symptoms of menopause and not as a method of preventing disease. The Food and Drug Administration recommends that women use the lowest hormone dose needed to achieve treatment goals and limit the duration of the therapy.
Stanford University Medical Center integrates research, medical education and patient care at its three institutions - Stanford University School of Medicine, Stanford Hospital & Clinics and Lucile Packard Children's Hospital at Stanford. For more information, please visit the Web site of the medical center's Office of Communication & Public Affairs at http://mednews.