In 1898, German doctors fed fresh cow ovaries to a young woman suffering from severe hot flashes after having her ovaries removed. It was a milestone of sorts in women’s medicine, leading to crude hormone treatments and eventually commercially prepared drugs to relieve the symptoms of menopause.  It was also the beginning of a seemingly endless controversy about the safety and necessity of drug treatments for women at the end of their reproductive years.  By the 1960s, pharmaceutical companies and doctors were promoting hormones as a way for women to stay “feminine forever,” even as scientists and women’s health activists argued that more study was needed to assess the risks of the drugs, including cancer. They also warned that menopause should not be “medicalized” or treated like a disease.  All that debate was supposed to end in 1991, when Dr. Bernadine Healy, the first woman to run the National Institutes of Health, decided to embark on a major research effort focusing on women’s health issues at midlife.  The Women’s Health Initiative, a $625 million study, would examine the risks and benefits of menopause hormones, calcium and vitamin D supplements and low-fat diets. All told, the landmark study recruited more than 160,000 women, including 26,000 for the hormone research.  Scientists fully expected the results to be predictable, including that hormones could prevent chronic illness in women, including heart disease.  But the findings have consistently surprised, debunking conventional wisdom time and again — about hormones and health, calcium to protect bones and the importance of a low-fat diet. The results, while invaluable, have also had a negative effect, leaving some women feeling frustrated, betrayed and whipsawed by what often seem to be contradictory headlines. And they have fueled cynicism about the medical establishment’s treatment of women.  The Women’s Health Initiative first shocked the world in 2002, when it stopped its largest hormone study because it showed that a common combination of estrogen and progestin was harmful, increasing a woman’s risk for heart problems and breast cancer.  The news prompted women to abandon the treatment in droves. Later, other data suggested that the news wasn’t all bad, and that the risk of menopause hormones might vary depending on a woman’s age. Still more reports from the research initiative suggested that estrogen increased the risk for stroke, and that the cancers associated with a combination of estrogen and progestin drugs were the most deadly.  Then, last week, the study’s latest finding surprised again. The Journal of the American Medical Association reported that certain woman who used only estrogen during the study had markedly reduced risk for breast cancer and heart attacks.  “I have lost all confidence in the studies dealing with female hormone replacement,” wrote one reader on The New York Times’s Well blog.  Investigators with the research project, many of whom have been with it since it began, say that after years of bad news about hormones, the latest twist suggesting a benefit of estrogen for certain women just proves the value of scientific study.  “I think it’s the nature of doing large randomized trials,” said Andrea Z. LaCroix, the lead author on the Journal of the American Medical Association study and professor of epidemiology at the Fred Hutchinson Cancer Research Center in Seattle. “You may get answers you didn’t expect.”  There is no question that scientists now have a far greater understanding of women’s health at midlife than they did before the study. It is, without question, risky for an older woman long past menopause to start hormone treatment to prevent chronic disease. Doing so dramatically increases the risk for heart attack, stroke, breast cancer and other complications. While that may seem obvious today, back in the 1980s and early 1990s, doctors prescribed hormones to women of all ages.  “The W.H.I. has saved many lives,” said Dr. Susan Love, a longtime women’s health advocate and breast cancer researcher. “I think we should be celebrating the fact that we finally have research on women’s issues, an issue we fought hard for. The fact that the research results are not always clear is because our understanding of the biology and the science is not always clear. But the research is what gets us closer to the truth.”
Studies intended to be the last word on menopause revolutionized treatment, but they also led to confusion and debate.