Hormone replacement does not prevent heart attacks — or related problems — in older women with heart disease, researchers are reporting. In addition, the treatment increases the risks of blood clots and gallbladder disease, they say.
But they report no link between hormone treatment and any form of cancer.
The new findings, described today in The Journal of the American Medical Association, confirmed and extended the results of a study published in 1998, the Heart and Estrogen/progestin Replacement Study, or HERS.
"For women with heart disease, there were harms, and zero benefit," said Dr. Deborah Grady, who led the new study.
Dr. Grady is director of the University of California San Franciso/Mount Zion Women's Health Clinical Research Center.
The results mean that women with heart disease cannot expect hormone replacement to prevent heart attacks or strokes or stop the progression of artery disease, the researchers said.
Instead of undergoing hormone replacement therapy, such women should be treated with drugs that have been shown to prevent heart attacks, like aspirin, beta blockers, ACE (angiotensin-converting enzyme) inhibitors, other blood pressure drugs and medicines that lower cholesterol in the blood. The same approach was recommended a year ago by the American Heart Association.
Days before The Journal was published, groups that support some uses of hormone therapy issued statements citing limitations of the study's findings, saying they do not apply to most women approaching menopause, because the women in HERS had an average age of 67 and a diagnosis of heart disease.
A doctors' group, the American Society for Reproductive Medicine, issued a statement that said for women in early menopause, hormone replacement was the best way to relieve menopausal symptoms like hot flashes and prevent bone loss, "with minimal risk of side effects."
The group added, "The HERS study is not relevant for this younger patient population."
Wyeth, the company that makes Premarin, the most widely used form of estrogen replacement, issued a similar statement.
The American College of Obstetricians and Gynecologists said the HERS study did not determine whether hormone treatment could prevent heart disease in younger, healthier women. "Answers on this issue will have to come from other research studies," the group said.
Dr. Wolf Utian, executive director of the North American Menopause Society, said that if a woman had been using hormones for several years without problems, there was no reason to discontinue them, even if she had heart disease. The HERS study, Dr. Utian said, might frighten women "into walking away from therapy that for them as individuals might be beneficial."
Dr. Grady agreed that for younger postmenopausal women with severe symptoms like hot flashes and night sweats, hormone replacement was the most effective treatment.
But she said she was skeptical of the idea that hormones might eventually be proved to prevent heart disease in healthy women. Her reason, she said, was that medical treatments that prevented disease always helped treat it or slow it as well. Since hormone therapy does not help women who already have heart disease, there is little reason to think it can prevent the disease or to prescribe it for that purpose, she said.
The original HERS study included 2,763 women, who were studied for 4.1 years. The women were assigned at random to take either placebos or daily doses of estrogen (0.625 milligram) and a synthetic form of the hormone progesterone, a progestin (2.5 milligrams). The estrogen was Premarin.
The findings suggested that women who took hormones had a higher risk of heart attacks and other cardiovascular problems in the first year, and a decreased risk after the third year. Over all, there was no benefit to hormone treatment.
The results came as a surprise to many researchers. Earlier studies had suggested that hormone therapy could prevent heart disease, so some scientists thought it should also be able to slow the progression of pre-existing disease.
When the treatment did not help women who already had heart disease, some researchers said it was because those women were different from healthy ones, and it was simply too late for them.
But other researchers said the HERS findings cast doubt on the earlier studies that had suggested that hormones prevented heart disease. Those studies were observational, meaning that the women in them had decided on their own whether or not to take hormones, instead of being assigned at random to a treatment or placebo group.
Observational studies are generally not considered as reliable as research in which participants are picked at random to be treated or not, because people who take preventive medications may have underlying differences from those who do not, like healthier lifestyles.
A decline in the rate of heart attacks after the first year of hormone therapy suggested that eventually, the women on hormones might wind up with a lower rate of heart attacks than women not taking hormones.
To determine whether that occurred, the researchers kept studying the women. The study published today, HERS II, included 2,321 of the original women, and followed them for another 2.7 years.
The rates of heart attack and other heart problems evened out, so that there was no difference between the groups. There were 290 heart attacks or coronary deaths in the hormone group, and 293 in the placebo group.
But hormone users had a doubling of the risk of blood clots in the legs and lungs, mostly in the first few years of the study. Forty-nine women in the hormone group experienced such problems, compared with 24 in the placebo group. The rate of gallbladder disease needing surgery also increased, by about 45 percent, with 125 cases in the hormone group, and 86 in the placebo group.
Dr. Grady said the adverse effects on clotting and gallbladder disease probably applied to younger, healthier women as well.
"There is no reason in the world why the adverse effects won't generalize," she said.
In what may be the last nail in the coffin of the belief that hormone supplements are good for women with heart disease, a new study finds definitively that the treatment has no benefit, and some real drawbacks.
That disappointing result comes from a major study coordinated by UCSF that enrolled more than 2,300 postmenopausal women with heart disease, some who were assigned to take hormone replacement therapy, or HRT, and some who took a placebo.
After nearly seven years of follow-up, researchers found that the two groups had roughly the same rate of heart attacks -- and the HRT group had significantly more blood clots and gallbladder disease. Results of the study are being published today in the Journal of the American Medical Association.
The blood clot rate was twice as high in the hormone group over the entire study, with most of the risk occurring in the first few years. The rate of gallbladder disease requiring surgery was nearly 50 percent higher, bolstering evidence linking these conditions to hormone use.
"I think it proves definitively that there is absolutely no benefit among women who have heart disease from taking hormone replacement therapy, and there are some real harms," said Dr. Deborah Grady, head of the UCSF-Mount Zion Women's Health Clinical Research Center and author of the study.
FORMERLY A GENERAL TONIC
For decades, hormone supplements for women have been seen as a general tonic
capable of warding off diseases of old age, including bone loss and heart
disease. In the case of heart disease, it was thought that they mimic the
effects of natural estrogen, which helps keep cholesterol at healthy levels.
But evidence is mounting that HRT is mostly useful for treating menopausal symptoms like hot flashes and night sweats.
Recently, an international panel issued a report saying broader benefits from the therapy are unlikely, and the American Heart Association revised its recommendations last year, saying there was no longer evidence that it is helpful to women with a history of heart trouble.
Grady herself was once a proponent of wider use of HRT in older women because 58 out of 60 observational studies of women taking hormones found they had lower rates of heart disease. But it turns out that women who are chosen to receive HRT tend to be healthier overall, and the benefit could not be attributed to the supplements.
Still, many gynecologists swear by hormone replacement therapy and prescribe it routinely to patients once they enter menopause. Dr. Wulf Utian, executive director of the North American Menopause Society, is worried that the publicity over the latest study will cause women who are getting benefits from the therapy to stop taking it.
"I worry that they'll start saying, 'You can't trust the doctors or the pharmaceutical companies and, heck, I'm just going to go off everything,' " Utian said.
Another study under way
Still pending are results from another large study that is looking at whether HRT can prevent heart disease in women who don't already have signs. The findings aren't due until 2005, but Grady says early reports have created pessimism that a benefit will be found.
Dr. Diana B. Petitti, director of research for Kaiser Permanente in Southern California, said good alternative treatments were available to women with heart disease, such as beta-blockers, cholesterol-lowering drugs and even aspirin. Petitti has studied HRT for nearly 25 years and said there was clearly a change afoot in the way the medical community viewed the therapy.
"There was a period of great optimism and good reasons why people were promoting the use of HRT as a sort of all-purpose preventive agent, but my take is that there is now reason to be pessimistic about it for disease prevention," she said.
The jury is still out on whether HRT may help slow cognitive decline in older women, Petitti said. And the other major health benefit ascribed to HRT - - its ability to prevent bone loss -- has become less meaningful because there are now better drugs on the market that do the same thing and have fewer side effects.
The Associated Press contributed to this report.
|
If you have come to this page from an outside location click here to get back to mindfully.org |