Marcia Stefanick was as surprised as anyone when the hormone-replacement trial she had directed since 1995 ended three years earlier than planned.
Stefanick, PhD ’82, chairs the steering committee of the nation’s first long-term, large-scale clinical trial of hormone replacement in healthy women. In July, the study was cut short because the results already showed that women taking the hormones faced increased risks of breast cancer and cardiovascular disease.
“I would never have predicted that we would know for sure at this point that the risks exceeded the benefits,” says Stefanick, a Stanford associate research professor of medicine. “We thought we would not have the answer until 2005.”
In the study, supported by the National Institutes of Health, 16,608 women between 50 and 79 who have intact uteruses were randomly assigned to take either a pill containing estrogen and progestin or a placebo each day. Stefanick and the other investigators hypothesized that the hormones would reduce bone fractures and heart disease.
As it turned out, they found that over 5.2 years, the women taking hormones had 29 percent more heart attacks, 41 percent more strokes, a 26 percent increase in invasive breast cancer and more than twice as many blood clots compared to those taking placebos. The benefits were a 34 percent reduction in hip fractures and 37 percent fewer incidents of colon cancer. (Postmenopausal women who have had hysterectomies are continuing in an estrogen-only study.)
“What we’ve provided now is very definitive information about how big the risks are and how small the benefits are,” Stefanick said in an interview in her office at the Stanford Center for Research in Disease Prevention. “With 6 million women on estrogen plus progestin in the country, we really needed to get that message out there in such a way that the medical community would recognize that this is not just a little controversy anymore. This is information that should, in fact, change their practicing habits if they’ve been prescribing these drugs for prevention.”
Stefanick acknowledges that the benefits of short-term hormone replacement in treating menopausal symptoms such as hot flashes “may justify the risks.” (A spokesperson for Wyeth-Ayerst, which makes the drug Prempro that was used in the study, says 90 percent of hormone-replacement prescriptions are for menopausal symptoms.) “As long as a woman understands that there are risks and is clear about what they are,” Stefanick says, “then she knows better than anybody whether she can tolerate the symptoms or not.”
Stefanick has been delivering talks called “Controversies in Hormone Replacement Therapy” for about four years—ever since a study of 2,000 women with histories of heart disease linked estrogen plus progestin with blood clots in lungs and legs. “It’s really quite interesting how often people have gotten quite angry with me for just presenting the data and making the argument that we needed evidence-based medicine.”
Now that the evidence is in, Stefanick says, “the medical community is in a bit of a tailspin because they’re being besieged by their patients.” She and the other investigators have been trying to “calm everybody down” in the aftermath of the initial press coverage. “The last four years have been a period of re-evaluation,” she said in July, “and the last three days have been a period of major reconsideration.”
