Clinical Trials: Hormone Replacement Therapy
To be or not to be on hormone replacement therapy (HRT)the use of prescription drugs to "replace" the hormones estrogen and progesterone that the ovaries quit making at the time of menopauseis a major question many postmenopausal women are trying to answer. It's a difficult question because of some findings from the NIH's Women's Health Initiative (WHI) that were released last July. The NIH halted its trial of combination hormone replacement therapy (estrogen and progestin)citing long-term risk factors such as increased risks for heart attack, stroke and breast cancer. And for millions of women the news, as aptly put in a Time article, "struck like a hot flash."
The report concluded that for some women, the risks HRT outweigh the benefits (less osteoporosis and lower colon-cancer rates). And the HRT choice isn't made any easier by the fact that, right now, it's the only medical therapy available to provide relief from acute symptoms of menopause, such as hot flashes and night sweats.
To make matters worse, shoddy reporting has fueled public confusion. For example, a wire-service story that made the rounds last January cited the Food and Drug Administration as saying, "women should not take estrogen or combinations of estrogen and progesterone." The previous day's FDA news release, however, said no such thing. The release focused instead on new FDA guidance for manufacturers of estrogen and estrogen with progestin products regarding the language that should be used on the product label.
"Before the WHI results were announced, it was thought that HRT use would cut heart attack risks in half," says Ken Muse, associate professor of obstetrics and gynecology in the UK College of Medicine. "A major finding in the study was that with HRT, even though there's an improvement in cholesterol results, the risk of heart attack and stroke increases."
Thomas Kelly and Ken Muse are evaluating the effects of raloxifene, the first of the "designer estrogen" medicines, on behavior, memory and mood. The clinical trial is being conducted as part of the $8.3 million Center for Biomedical Research Excellence in Women's Health, funded by the NIH. This is the single largest grant ever awarded in the area of women's health at UK.
Muse says that because of these findings and the subsequent new and important questions about the benefits and risks of HRT, this is a particularly exciting time to be doing research in this area. "It's a tremendous clinical question right nowboth in the woman's mind and doctor's mind: How do you treat menopausal women? What's the best way to balance the benefits and risks?"
In September of 2000, Muse and a group of behavioral investigators at UK including Thomas Kelly, professor of behavioral science, initiated a clinical trial to evaluate the effects of raloxifene on behavior, memory and mood, a focus that has gotten scant attention, and was not part of the NIH study. Raloxifene is the first of the "designer estrogen" medicines, which have some of the effects of estrogen, but few, if any, of the drawbacks.
The trial is being conducted as part of the $8.3 million Center for Biomedical Research Excellence (COBRE) in Women's Health, funded by the NIH. This is the single largest grant ever awarded in the area of women's health at UK.
"The COBRE study is particularly crucial because most patients and most physicians are convinced that quality-of-life benefits that result from taking HRT, such as suppression of hot flashes and improved sleep, are important," Muse says. "There hasn't been much work done, though, on how HRT affects such things as mood, memory and clear-headedness, so we need to find out if there are benefits here as well."
In this study postmenopausal women who are not taking any form of HRT are evaluated for memory, object orientation and mood through a battery of tests, including brief computerized tasks and questionnaires as well as the evaluation of urine and blood samples. The women are then given estrogen, raloxifene (which targets only specific parts of the body), or a placebo.
Hormone effects will be determined by comparing behavioral measures before therapy began with those taken after one and six months of daily treatment. Kelly says the original plan was to do a one-year trial, but because of the recent NIH data on risks from long-term use, he and Muse cut the length of the study in half.
"Everybody agrees we need more research on HRT," says Vivian Pinn, head of the NIH's Office of Research on Women's Health, who was quoted in Newsweek. "It's taking time, but more answers are coming."
"Many central Kentucky women are taking an active role in helping solve these problems by participating in this research," Muse says. "We're happy to have this opportunity at UK to be leaders in advancing the science of women's health medicine."
For information on how to participate in this study, call 859/277-3799.
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