HRT Should Be Abandoned When It Comes to the Heart, Say Experts
Increases Short-Term Risk, Little Long-Term Benefit
By Aman Shah, MD
WebMD Medical News
Reviewed by Michael W. Smith, MD
July 5, 2001 -- Experts from the latest round of studies on the association between hormone replacement therapy and heart disease seem to agree -- the use of HRT should be abandoned for the prevention of heart disease, and its use should be limited in women altogether. The most recent series of studies on this controversial topic shows that HRT increases the risk of coronary disease in the short-term and does not appear to have any convincing long-term benefits either.
"This is one of the most dramatic divergences from observational epidemiologic studies and clinical trials," says JoAnn Manson, MD, chief of preventive medicine at Harvard's Brigham and Women's Hospital. Manson, author of a study in the July 3 issue of Annals of Internal Medicine as well as lead author of a review in the July 5 issue of The New England Journal of Medicine, tells WebMD that physicians counseling women about hormone replacement should "take coronary heart disease prevention out of the equation. It is not a factor."
L. Kristin Newby, MD, assistant professor of medicine at Duke University School of Medicine in Durham, N.C., and co-author of a study in the July issue of the Journal of the American College of Cardiology, says that the essential argument in favor of HRT was that since most heart disease in women occurs after menopause, estrogen replacement may be beneficial. This belief was reinforced when several epidemiologic studies reported that women on HRT have fewer cardiac events than women who don't take hormones.
In the JACC study, 1,857 postmenopausal women who had suffered from an acute MI were followed for 1 year. A little more than a quarter of these women had used HRT at some point following their MI. The incidence rate for cardiac events was 41% for new users compared to 28% for women who never used hormone replacement. The incidence rate for unstable angina was even more significant: 39% for HRT users vs. 20% for nonusers.
After adjusting for variables, HRT users had a 44% increased chance of suffering death, MI, or unstable angina compared to nonusers. Using progestin along with the estrogen appeared to decrease this risk.
Newby says her study supports the view that women who take hormone replacement are usually better educated, less likely to smoke, more likely to exercise, and eat a healthier diet. However, HRT itself increases the short-term risk of repeat coronary events.
The Annals study analyzes data collected in the Nurses' Health Study. Manson and colleagues found that in the 2,489 postmenopausal nurses with a previous MI or documented atherosclerosis, HRT increased the risk of a major coronary event in the short term by 25%.
However, in the longer term, this risk steadily improved, and longer-term HRT users had a 62% decrease in their major coronary event risk. Overall, the 2-year follow-up period produced a 35% decrease in second-event risk among HRT users.
Still, Manson says these findings suggest that it is time for women and their physicians to rethink hormone replacement therapy. In her clinical practice review in NEJM, Manson stresses that two major, recent, randomized trials showed no benefit in terms of secondary heart disease prevention from HRT. She writes that a recent "analysis of 22 mostly short-term trials that evaluated other effects of hormone replacement therapy showed an insufficient increase in the risk of cardiovascular events among women who were randomly assigned to receive hormone replacement therapy."
Overall, Manson says, "symptom relief remains an important indication for HRT for short term therapy -- 5 years or less. You can do that without having to worry. But with these new data, I think we have to say that fewer and fewer women would be good candidates for HRT."
"Long-term therapy, for 10 or 15 years, should be carefully weighed," she says. Manson points out that other studies have linked long-term use with increased risk for breast cancer, and "without an indication for heart disease prevention," it is difficult to make a case for long-term treatment. Manson says other osteoporosis treatments can protect a woman's bones without increasing the risk for MI or breast cancer.
University of California, San Francisco, researcher Deborah Grady, MD, MPH, tells WebMD that hormone replacement has been reduced to "two very important issues: One is this early increased risk that seems to occur, and second, perhaps more important, is the question of whether there is any effectiveness long term." Grady, who heads women's health research at UCSF, co-authored an editorial that accompanies Newby's study.
"There are no randomized trials that show long-term benefit," she tells WebMD.
Grady says she thinks the latest studies should "really change thinking about [hormone replacement therapy]." She adds, "In my own mind, I see no justification for long-term treatment."
Asked about the suggestion that there may be long-term benefit, Newby says, "That's tricky ... this suggestion of long-term benefit -- do we call that a benefit, or do we call this a null result?
"Ideally, if we could identify the women who could survive the initial risk, we might find women who could benefit from long-term HRT. But we don't have a way to identify these women at this time. At this point, as a clinician I see no reason to start a woman who has a history of coronary heart disease on HRT," she says.
Newby notes that these studies are secondary prevention studies, and proponents of hormone replacement say the real issue is primary prevention. Hormone replacement, the argument goes, will prevent heart disease if it is started before heart disease begins.
Newby doesn't buy this argument. "I know of no study in which a treatment that failed in secondary prevention was effective in primary prevention," she says.