Reuters Health August 15, 2005 RISKS OF HORMONE REPLACEMENT NOT SURPRISING: REPORT QUOTABLE: "Among the recommendations Krieger and her colleagues make is that the 'precautionary principle' be applied to any drug being studied for preventive medicine. 'That is,' Krieger said, 'You don't prescribe healthy people potentially dangerous drugs.'" By Amy Norton NEW YORK (Reuters Health) -- The risks of hormone replacement therapy (HRT) have made headlines only in recent years, but there had long been warning signs that supplemental estrogen might be more hazardous than healthful, a new report contends. In 2002, a large US clinical trial called the Women's Health Initiative (WHI) was stopped when early findings showed that HRT after menopause slightly raised a woman's risk of breast cancer, heart attack, stroke and blood clots. Given the long-standing belief that HRT helped protect older women from cardiovascular disease, the findings were widely received with disappointment and surprise. But no one should have been caught off guard, a group of researchers and women's health advocates argues in a perspective piece published in the Journal of Epidemiology and Community Health. Not only had the potential cancer risks of estrogen replacement been known for decades, the presumed heart benefits were being questioned as early as the mid-1970s, according to the authors, led by Professor Nancy Krieger of the Harvard School of Public Health in Boston. "There were good grounds to have concerns before" the recent findings, Krieger told Reuters Health. The potential for estrogen replacement to promote cancer has been recognized since the 1930s, when synthetic estrogens first became available. Still, long-term HRT was for years prescribed as a way to battle the diseases of aging, including osteoporosis and cardiovascular disease. For many women, it was thought, the slightly increased risk of breast cancer might be offset by a lower risk of heart disease and stroke -- far bigger killers than breast cancer. But there was always uncertainty about the cardiovascular benefits of HRT, Krieger and her colleagues note. Krieger pointed to one study, started in the late 1960s, that found that giving men estrogen raised their risk of cardiovascular disease rather than lowering it, as expected. And when it came to women, the research evidence was often conflicting and indirect -- for example, coming from observational studies in which women on hormone replacement were found to have lower rates of heart disease. The problem with such evidence, as many researchers have noted, is that other differences between HRT users and non-users may have explained the lower heart risk; women on HRT, for example, tended to more affluent and in better overall health. But such cautions, as well as negative study findings, Krieger and her colleagues contend, "were dwarfed by the proliferation of studies favorable to HRT." In their view, an aggressive pharmaceutical industry, the regulatory framework and a general perception of menopause as a "disease" were all central to the issue. Once a drug is approved for a specific use, doctors are free to prescribe that medication for other conditions as well. This fact, coupled with industry influence, the report authors contend, were key to the growth of HRT. There was reason to believe HRT could have offered heart benefits, Krieger acknowledged, noting, for instance, that it was "biologically plausible" and had support from animal research. But, she argued, given the known cancer risks of estrogen, the evidence for HRT should not have been enough. Among the recommendations Krieger and her colleagues make is that the "precautionary principle" be applied to any drug being studied for preventive medicine. That is, Krieger said, "You don't prescribe healthy people potentially dangerous drugs." SOURCE: Journal of Epidemiology and Community Health, September 2005. Copyright Reuters 2005.