Looking for a landmark

The year's big medical story was something that failed to work

By Daniel Q. Haney ~ The Associated Press

BOSTON -- Usually the biggest medical story of the year is a new pill or technique, a discovery that helps people live longer and better. But not in 2002.

Just the opposite. Many agree the most significant medical landmark of the year was the realization that a practice steadfastly accepted by a generation of doctors does more harm than good.

Millions of older women were told -- and believed -- that hormone replacement therapy would help them live longer and better by protecting their hearts and bones. It seemed obvious for a variety of scientific and common-sense reasons. Until last summer.

Then the Women's Health Initiative study showed that rather than slowing heart disease, the combination of estrogen and progestin actually increases the risk a bit. And, as previously suspected, it slightly ups the chance of breast cancer, too.

Although in hindsight earlier studies raised similar suspicions, this was inescapable evidence that for all those years, the doctors were wrong. The benefits of long-term hormone replacement therapy did not come close to outweighing its risks.

Rethinking assumptions

In the months since, these results have echoed through the medical world: Many women have stopped taking hormone pills or refused to start. Experts have tried to figure out why they were so mistaken about hormones' effects on the heart. And in many areas of medicine, doctors are rethinking their assumptions about how much evidence is needed to recommend any new treatment or habit intended to help healthy people stay that way.

"It's been the most dramatic sea change in clinical medicine that I have ever seen," said Dr. JoAnn Manson. "Hormone therapy has gone from being the norm to being shied away from."

Manson, chief of preventive medicine at Harvard's Brigham and Women's Hospital, was a director of the study, which assigned 16,600 women in their 60s to take either the combination hormone pills or dummy placebos. It found that besides the small increase in heart disease and cancer, women on hormones had slightly more strokes and blood clots and slightly less colon cancer and fractures.

Those in the study were well past menopause, and doctors say the message for them is clear: Do not go on hormones as a way to prevent the diseases of aging.

But what about somewhat younger women? Many start hormones in their 50s as temporary relief from hot flashes and night sweats. Even though the study was never intended to examine this use, doctors say the results have led menopausal women to opt against hormones anyway.

"Many women are reluctant to take the hormones even short-term for treatment of severe menopausal symptoms, and that can be unfortunate," said Manson. The pills work, and use for less than four or five years probably carry little risk, especially if women have no signs of heart disease.

However, the effect of this study on women's decisions about hormone replacement is just the start of its reverberation through medicine.

Story of the decade

"I think it's the medical story of the decade," said Dr. Lori Mosca, director of preventive cardiology at New York-Presbyterian Hospital. "It's had an enormous impact."

Many say it is shaping doctors' thinking about how solid the evidence should be before they recommend a variety of treatments intended to keep people from getting cancer, heart disease and Alzheimer's disease, among other things.

For instance, since the study came out, some doctors say they are reconsidering such things as vitamin therapy to prevent diseases in otherwise healthy people.

"Before we implement something widely and say it should be a standard of care," said Mosca, "we really need to understand the limits of the science we have."

The science behind the belief that hormones prevent heart disease was substantial. Experiments in animals support it. But the most persuasive underpinning was observational studies, the large, long-running reviews that follow people's health for decades, looking for links between their habits and the diseases that eventually befall them.

Repeatedly, those studies found that women who take hormone replacement have fewer heart attacks than those who don't. And, of course, it just made sense that estrogen is good for the heart.

"All science operates in a context. The context here was that many people were absolutely convinced that female hormones had to reduce the risk of heart attacks, because women get heart attacks at a much later age than men," said Dr. Lynn Rosenberg, associate director of Boston University's Sloan Epidemiology Unit.

Satisfying the skeptics

All that was missing to satisfy the skeptics was a so-called randomized, placebo-controlled, clinical trial, what the profession views as the gold standard of medical proof.

That was the Women's Health Initiative, an experiment designed to offer the absolute proof that estrogen wards off heart attacks, among its other health effects. Instead, it showed that the observational studies, which seemed so authoritative, had somehow led them astray.

What went wrong? Maybe women routinely prescribed hormone pills are simply healthier to begin with. Maybe those who stick with them have better living habits. Maybe the observational studies missed extra heart attacks that occurred soon after women started on hormones.

Whatever the reason, the lesson is obvious, says Dr. Elizabeth Barrett-Connor, a physician epidemiologist at the University of California, San Diego. "When we are talking about a medicine that healthy people take to prevent something they may never get, we really do need clinical trials."

The same kind of circumstantial evidence that made hormone replacement look so promising against heart disease is often cited as a reason for similar strategies against other ills. For instance, observational studies suggest that estrogen may prevent Alzheimer's disease and that vitamin E may slow Alzheimer's, cancer and heart disease.

But as a result of the Women's Health Initiative, many doctors say they are unwilling to take a chance on such strategies without a major experimental study to prove they truly work.

"We feel burned," said Dr. Samuel Gandy of Thomas Jefferson University, who studies estrogen's effects on Alzheimer's. That question is still being studied in the Women's Health Initiative, and "I'm just waiting for the data. I'm not saying any more about it."

ON THE NET

Women's Health Initiative: www.nhlbi.nih.gov/whi/