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April 10, 2001
HRT for Heart Disease ... A No-Brainer? Think Again Recent research indicates that hormone-replacement therapy may not help with heart disease

By Christine R. McLaughlin

illustration: can HRT fend off heart disease as well as previously thought?
Skipper Chong Warson

first letter it all sounds so simple. Women lose estrogen when they reach menopause; the loss of estrogen is known to contribute to heart disease. So it seems logical to replace the hormone with a synthetic substitute known as hormone-replacement therapy, or HRT. Indeed, for years doctors have prescribed such hormones to millions of women as a way to help prevent or alleviate heart disease, while simultaneously reducing menopausal symptoms such as hot flashes and memory loss.

Studies have shown, however, that long-term use of HRT increases a woman's risk of breast cancer. So it's been known that HRT is not for everyone.

But recently scientists have been questioning the wisdom of prescribing HRT to women for heart-disease prevention. And now there's one more consideration thrown into the mix: HRT may not provide any cardiovascular benefit to women who already have heart disease, according to study published recently in the New England Journal of Medicine.

HRT for heart health in question

In the study "Effects of Estrogen Replacement on the Progression of Coronary Artery Atherosclerosis," referred to as the ERA study, the researchers looked at 309 women whose average age was 65 -- all with documented coronary disease. Half were given HRT and the other half were given a placebo; they were followed for three years.

Despite improvements in cholesterol levels, the researchers could not prove that the health of the HRT subjects' hearts improved -- after examining the narrowing of their arteries and looking at the number of heart attacks the women experienced during the time of the study.

"In a sense they looked better on paper [because of cholesterol improvements], but weren't protected against [further] heart disease," said Girish Nair, M.D., a postdoctoral cardiology fellow who works with the lead researcher of the ERA study at the Wake Forest University School of Medicine, in Winston-Salem, North Carolina.


The profusion of HRT prescriptions was based mainly on the dozens of observational studies that showed improvements in heart-disease risk factors, such as cholesterol levels. But there were no controlled, clinical trials showing that hormones prevented heart disease or slowed its progress.


This was not the first time a clinical trial found that HRT didn't help women with established heart disease. In 1998, results of the Heart and Estrogen-Progestin Replacement Study, referred to as HERS, were published in the Journal of the American Medical Association.

In this landmark study, 2,700 women were followed for four years and randomly assigned to HRT or to a placebo. The findings showed that the use of estrogen plus progestin in postmenopausal women with heart disease did not prevent heart attacks or death from coronary heart disease.

"So [the ERA study] confirms the findings of HERS, that there is no cardiovascular benefit over the first three to four years of HRT in women with heart disease," clarifies Jacques Rossouw, M.D., acting director of the Women's Health Initiative of the National Heart, Lung and Blood Institute (NHLBI), in Bethesda, Maryland.

Preventing heart disease

Until the 1998 HERS study findings were published, HRT was commonly prescribed not only to treat existing heart disease in postmenopausal women, but also to prevent it altogether. In fact, in the early 1990s, the NHLBI did a survey of practicing physicians and found that more than half were prescribing it for preventing heart disease, says Dr. Rossouw.

The profusion of HRT prescriptions was based mainly on the dozens of observational studies that showed improvements in heart-disease risk factors, such as cholesterol levels. But there were no controlled, clinical trials showing that hormones prevented heart disease or slowed its progress.

And now doctors' recommendations are changing. For women without documented heart disease, the prevailing wisdom is now that HRT should not be prescribed for prevention until there are clinical trials proving its effectiveness, says Dr. Rossouw. (He and colleagues at the WHI are currently working on the most comprehensive primary-prevention study to date, involving 27,000 postmenopausal women. The study should be completed by 2005.)

"From what we know [based on the results of the ERA study and HERS], there really is no good reason to prescribe HRT to prevent a first heart attack or a second one -- that is, until we have more research data," says Dr. Rossouw.

Instead, there are many other strategies to ward of heart disease, such as not smoking, exercising, eating a healthy diet, and controlling one's weight. Early detection and treatment a of high blood pressure and high cholesterol can also help.

"We need to look beyond hormones to prevent heart disease," says Dr. Rossouw. "It's not the only game in town."

One size does not fit all

With the benefits in question and the risks still in place, HRT is sliding off the popularity scale. Does this mean it shouldn't be prescribed at all?

According to cardiologist and author of Heart Sense for Women (Lifeline Press, 2000), Stephen Sinatra, M.D., the decision about whether to use HRT should be based on several factors; it is helpful at alleviating hot flashes, vaginal dryness, memory problems, and osteoporosis.

"It's purely a quality-of-life issue, and if a woman cannot live in her body, then it could be useful [at helping with menopausal symptoms]," says Dr. Sinatra. "I tell my patients, 'Let's not make this decision in a five- to ten-minute office visit' and explain that this is a very confusing issue and needs to be revisited over and over again."

He advises women to take more responsibility for their health by reading as much as they can about HRT and heart disease and talking to other women about their experiences with it, rather than just relying on information from their doctors.

Dr. Nair adds that there are many proven treatments like aspirin use, beta blockers, and lipid-lowering therapies that are not being optimized in women who could really benefit from them. "We need to continue to maximize those proven therapies at this time until we have clearer evidence of any other method of prevention of heart disease."

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