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15-Year Women's Health Study Comes to an End. Now What?

Posted on: Wednesday, 22 February 2006, 06:00 CST

PHILADELPHIA _ In the wake of the mixed results from the most ambitious, definitive study of postmenopausal women's health ever conducted, what's a woman to do?

That's the question now that the federally funded Women's Health Initiative has wrapped up. It took 15 years, $725 million, 40 medical centers, and the steadfast participation of 161,000 American women ages 50 to 79.

The WHI set out to test strategies touted as ways women could ward off cancer, heart disease, osteoporosis and Alzheimer's disease _ "the major causes of death, disability and frailty in older women of all races." Could hormone supplements fight these chronic diseases? Could a low-fat diet rich in fruits and vegetables? Could calcium and Vitamin D pills?

The WHI's hormone trials, which began reporting results in 2002, shattered conventional wisdom, reversed doctors' advice, and turned off the flow from cash-cow hormone products. The results of the diet and calcium/Vitamin D trials, published this month, are also surprising and controversial.

Still, translating the WHI into helpful advice is tough because the results are complex and reveal more about what doesn't work than what does. The bottom line:

Estrogen-progestin hormone therapy raised the risk of breast cancer, heart attack, stroke, dangerous blood clots, dementia, and incontinence, while cutting the risk of hip fracture and colon cancer.

Estrogen alone _ only for those who have had a hysterectomy _ had no significant effect on the risk of heart disease, colon cancer, dementia and breast cancer, but raised the risk of stroke and blood clots in leg veins. It cut hip-fracture risk.

A reduced-fat diet rich in fruits and vegetables had no significant effect on the risk of breast cancer or heart disease. It reduced the chance of developing polyps, a precursor of colon cancer, but did not reduce colon cancer.

Calcium/Vitamin D supplements had no effect on colon-cancer risk. It increased hip-bone density, but had no impact on hip fractures.

"The media like to boil down a complicated thing to a sound bite," says Marcia Stefanick, a Stanford University obstetrician-gynecologist and WHI researcher. Scientists "don't know how to do sound bites. It's been frustrating for us and confusing for women."

While the WHI results are sure to be dissected and debated for years, some lessons and recommendations are already clear, researchers and participants agree. Among the messages:

Don't rely on circumstantial evidence. Before the WHI, studies of women's health habits consistently found that those who took hormones had less heart disease and lived longer than women who opted not to.

These "observational" studies were bolstered by other circumstantial evidence. For example, unlike men, women rarely suffer heart attacks before age 50, when their estrogen plummets.

In 1990, Wyeth Pharmaceuticals in Collegeville, Pa., asked the Food and Drug Administration to add heart-disease prevention to the approved uses (hot flashes, vaginal dryness and bone protection) for its estrogen brand, Premarin, perennially among the most prescribed drugs in the United States. Although the FDA refused, hormones-help-the-heart became a mantra for drug companies, physicians, and women of a certain age.

The problem was, hormones weren't making women healthier _ rather, healthier women were taking hormones. They avoided such no-nos as smoking, drinking and getting fat.

In 1991, the government finally agreed to do what no one had done before: test the mantra with a "clinical trial." The WHI randomly assigned 27,300 healthy postmenopausal volunteers to take hormones or not, then followed them to see whether it helped their hearts, or other organs.

The rest is medical history.

"We had to fight to get this study," says Cynthia Pearson, executive director of the National Women's Health Network. "The lesson is: It's always worth doing the trial."

But Pearson isn't gloating. Although the hormone trial confirmed her views, the dietary findings defied her belief that a low-fat diet would reduce the chance of breast cancer.

Even clinical trials aren't perfect. In the wake of the WHI, the advice regarding hormones is clear: Use the drugs only for truly bothersome menopausal symptoms, and keep the dosage and duration to a minimum.

For a minority of women who suffer severe hot flashes, including those who plunge into menopause because of surgery or chemotherapy, hormones remain a no-brainer. Nothing douses the heat like estrogen.

For most women, however, hot flashes are an annoying discomfort that goes away after a year or so; the benefits of hormones aren't worth the risks.

As for diet and calcium/Vitamin D, the WHI does not have such clear advice because the results of these trials were "disappointing," as many WHI researchers put it.

That doesn't mean women should ignore current dietary and calcium recommendations. It's just that the benefits of avoiding fat and boosting calcium by 1,000 milligrams a day were so modest that they could be due to chance _ they were "not statistically significant."

Researchers say the results may have been weaker than expected because the women, being only human, didn't change their habits as much as everyone had hoped. On average after eight years, they had cut their fat intake to 29 percent, not the 20 percent goal. After seven years, only 59 percent of the calcium/D-takers were still swallowing the intended number of pills each day.

However, those who did take their pills had a 29 percent dip in hip fractures, and those who cut the most dietary fat lessened their breast-cancer risk.

Another thing that may have undercut the dietary results: The trial didn't distinguish between "good" and "bad" fats, as nutritionists now recommend.

The diet and calcium/D studies "essentially support the current recommendations," says Jacques Rossouw, the National Institutes of Health scientist who oversaw the WHI. "The trials weren't conclusive, but there were hints of a trend toward benefit. I think we will provide a firmer message in a few years."

That's why the WHI is asking all participants to fill out annual update forms through 2010.

Old theories die hard. Some physicians, even in the WHI, cling to the notion that hormones can protect women's hearts.

The WHI "used the wrong treatment on the wrong women and came to the wrong conclusions," contends John Studd, a professor of gynecology at Imperial College in London, on his Web site. "It was a study of staggering clinical incompetence."

This month, some WHI researchers published an analysis of estrogen-only trial data that showed a "suggestion" of lower heart-disease risk among women ages 50 to 59. This finding, not statistically significant, came on the heels of a new analysis from a long-running observational study of nurses that found hormones started early in menopause reduced their risk of heart disease.

In news releases issued this month by Wyeth, a physician who has received funding from the company said the findings supported the "emerging belief" that hormones could be beneficial if started around the time of menopause.

While women may be confused by the mixed messages, the battle against heart disease has moved on to better medicines, says Marian Limacher, a cardiologist at the University of Florida, Gainesville, and a WHI researcher.

"There are lots of other things we as cardiologists can advocate rather than going back to the old hormone story," she said.

___

(c) 2006, The Philadelphia Inquirer.

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Source: The Philadelphia Inquirer

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