What a long, strange trip it's been

An insider's take on the Women's Health Initiative

Misty Keasler


It’s been a 15-year roller coaster ride, but Marcia Stefanick isn’t ready to hop off just yet.

The largest-ever study of postmenopausal women’s health — the paradigm-smashing, controversy-generating Women’s Health Initiative — wraps up in February 2006. Stefanick, PhD, professor of medicine at the Stanford Prevention Research Center, served as chair of the WHI steering committee through most of the project — a post to which she has been continually re-elected by the 39 other principal investigators. 

Although the WHI had components that examined the health effects of a low-fat diet and of calcium supplements, most people associate it with one thing: hormone therapy. WHI studies published in 2002 and 2004 essentially blew up the conventional wisdom about hormone therapy and raised concerns among a few medical organizations that remain critical of the findings.

“It’s hard to keep going and have people attack you,” says Stefanick. “But I’m proud that the practice of prescribing hormones to postmenopausal women and to women with heart disease has been stopped because WHI gave us evidence it won’t benefit them.”

The what of WHI

The Women’s Health Initiative is a multimillion dollar, 15-year project sponsored by the National Heart, Lung and Blood Institute to assess strategies for preventing heart disease, breast and colorectal cancer, and osteoporosis among postmenopausal women ages 50-79. More than 161,000 women at 40 sites enrolled in the WHI study, which had two major arms: a randomized clinical trial and an observational study.

Hormones relieve hot flashes and other symptoms of menopause. But observational studies over the years had also suggested that hormones protected women against heart disease, weak bones and dementia. “Hormones were being prescribed to women who had very mild or even no menopausal symptoms as a way to prevent the diseases of aging, but this was being done without having the data to prove that it worked,” Stefanick says.

In 2000, four years of data from the WHI trial showed that the combination of estrogen and progestin increased the participants’ risk for heart attacks and strokes as well as blood clots. By the spring of 2002, increased risks for breast cancer were also noted. At that point, officials decided to halt the estrogen-progestin portion of the trial.

“We knew that once the women were informed, there were going to be all kinds of ‘What’s going on?’ questions and the scientific community had to have the data,” Stefanick says. And so she spent the next five weeks in a flurry of activity — collaborating on writing the scientific paper and drafting a letter to all WHI participants in addition to assisting in plans for informing the media.

The July 2002 announcement generated shock waves as anxious women inundated their doctors with questions as to whether they should continue taking their hormones — regardless of whether they were past menopause, as were the WHI participants. Stefanick acknowledges that “we didn’t do a good enough job of separating treatment of menopausal symptoms from the effects of menopausal hormones on diseases of aging.”

With hormone therapy being viewed in a harsher light, the decision in 2004 to halt the estrogen-only arm of the trial for similar reasons caused less of a stir. But many menopausal women remain confused about whether to take hormones. “Our understanding of menopause is much too primitive and largely wrong,” Stefanick says. Other questions remain for postmenopausal women as well, and that’s why Stefanick will continue as chair of the five-year extension study. “Some women have said, ‘Well, if I’ve been taking hormones and I already have a higher risk of heart attack, why don’t I just keep taking them,’ ” she says. “They want to know, and I think we owe it to them to learn more.”

Let the next ride begin.

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