Confusion Over Hormone TherapyHow perfect: Our hormones are all over the place — and so is the research on hormone therapy. In 2002, the Women’s Health Initiative (WHI) study seemed to prove that hormone therapy significantly raises our risk of getting breast cancer. This spring, data from two large studies showed that taking estrogen actually lowers the risk. But wait: Shortly after the good-news headlines appeared, further data from one of the studies revealed that women taking estrogen upped their odds of stroke — something we should have on our health radar, because cardiovascular disease is our number-one killer. Is it just us, or are the research findings and medical recommendations changing like hemlines? New Knowledge, More Nuance "What we’re seeing is an evolution of information," explains JoAnn Manson, MD, chief of preventive medicine at Harvard’s Brigham and Women’s Hospital and a coauthor of Hot Flashes, Hormones, and Your Health. "The reason the hormone pendulum kept swinging — good for you, bad for you — was the assumption that the original WHI results applied to all women. Now we have a more refined understanding that results may differ by age and time of menopause."The WHI study tracked more than 16,000 postmenopausal women between the ages of 50 and 79 who still had a uterus. The majority of participants — 67 percent — were over 60. Fewer than 2,000 women were between the ages of 50 and 54, the age when most of us suffer hot flashes and other symptoms that signal the onset of menopause. "The WHI study wasn’t about them, and that’s where it gets confusing," says Heidi D. Nelson, MD, a principal investigator at the Oregon Evidence-Based Practice Center in a study of managing menopausal symptoms. "You can’t apply WHI conclusions to younger women who are having symptoms."Recent research also points to the importance of how long you take hormones. The original WHI trial found that women taking estrogen plus progestin for nine years upped their risk of breast cancer by 26 percent. This finding was enough to halt the combined-hormone part of the study. But researchers continued another arm of the study, which followed more than 10,000 women who had had hysterectomies. These women took only estrogen (they didn’t need progestin, which protects the uterus).The results, released April 2004, showed that women who took estrogen alone for seven years had a slightly lower risk of breast cancer than those taking a placebo. Then, in May 2006, Harvard University’s Nurses’ Health Study of nearly 30,000 nurses found that women who took estrogen for 20 years or less did not increase their breast cancer risk. After 20 years, though, their risk jumped by 41 percent. What You Should Know About HormonesThe Estrogen ParadoxWhy does the protective estrogen effect appear to expire after 20 years? Richard Santen, MD, professor of medicine at the University of Virginia, in Charlottesville, calls it the estrogen paradox: "Short term, the research shows that estrogen reduces — and may even prevent — breast cancer. Long term, it causes cancer." His hunch is that two different processes may be at work. "Based on autopsy studies, five to 10 percent of women have breast tumors too small to be detected by a mammogram," he says. "In these women, estrogen alone may have gotten rid of breast cancer cells. Long-term estrogen use may cause genetic mutations, which may result in breast cancer."Don’t Forget the "Other" HormoneBefore you think this gives you an all clear to take estrogen without fear (as long as it’s for fewer than 20 years), there’s another fact to consider. Taken by itself, estrogen increases your risk for cancer of the endometrium, the lining of the uterus. Women with a uterus are advised to add the protective hormone progestin — but the danger of that combination of hormones is precisely what the WHI trial demonstrated.So now what? "Most cases of endometrial cancer from exposure to estrogen are mild and low-grade, and usually lead to hysterectomy — rarely more," notes Laura Esserman, MD, director of the Carol Franc Buck Breast Care Center at the University of California, San Francisco.