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Rethinking HRT

Risks Small; Benefits Depend on Individual
By
WebMD Health News

Feb. 12, 2003 -- Nanette K. Wenger, MD, tells this story: A woman who'd just had bypass surgery came into her office in tears. Because it increases risk of heart disease, her doctor had taken her off hormone replacement therapy. "My life is not worth living," she said. "My menopausal symptoms are worse than my angina."

Wenger knows a lot about heart disease. She's chief of cardiology at Atlanta's Grady Memorial Hospital. She also knows a lot about hormone replacement therapy (HRT). An Emory University professor of medicine, she's been a part of most major HRT studies -- including the Women's Health Initiative (WHI).

It was the sudden closing of the WHI that started the current furor over HRT. The trial was stopped when it found that the small but serious risks from HRT outweighed its even smaller benefits. Risks and benefits, that is, for women who'd already passed through menopause without serious trouble.

"The women in these trials are not the women with the worst symptoms. Such women would never participate in a trial where they might get a placebo," Wenger tells WebMD. "Those trials do not apply to severely symptomatic women."

Wenger isn't the only expert who's seriously rethinking HRT. It's the topic of two papers in the Feb. 13 issue of The New England Journal of Medicine. Both agree that the WHI and other trials don't tell the whole story. And they note that many crucial questions remain open.

Francine Grodstein, ScD, and colleagues at Brigham and Women's Hospital look at why the WHI findings came as such a surprise. One reason, they suggest, is that women who volunteer for clinical trials are different from women who take HRT because they have symptoms -- exactly the point that Wenger makes.

"People don't like to hear this, but good studies often produce more questions than answers," Grodstein tells WebMD. "There are a lot more questions to ask than we used to think. We used to think we should give all women hormones. Now we know that isn't going to work. The thing a lot of people don't appreciate is how complex health is. No single study can tell us the answer. We just learn as we go along. We are now trying to learn what the right questions are."

The shocking thing about WHI wasn't its finding that women on HRT have an increased risk of breast cancer. The surprise was that HRT -- which earlier studies suggested would decrease risk of heart disease and stroke -- actually increased these risks. Moreover, there was a less-than-expected improvement in osteoporosis. It wasn't the size of these risks that stopped the trial, but the fact that the risks outweighed the benefit.

WHI was a clinical trial -- that is, women who entered the trial agreed to take the pills they were given, knowing that they had a 50-50 chance of getting HRT or placebo do-nothing pills. Earlier studies were observational -- they followed women already on HRT and looked at what happened.

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