Women's Health Initiative findings create confusion

Drawing any clear conclusions from the long-awaited trial results is not an easy task.

By Susan J. Landers — Posted March 13, 2006

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Washington -- Despite recent headlines trumpeting surprising findings from the Women's Health Initiative, the messages for postmenopausal women haven't changed, according to National Institutes of Health officials who ran the large study.

Physicians' advice should continue to be: Don't use hormone therapy to prevent heart disease; don't smoke; aim for a healthy weight; get moving; choose a diet low in saturated fat, trans fat and cholesterol; and keep a close eye on blood pressure, cholesterol and blood glucose levels.

This news should provide some comfort for physicians and patients who may have been buffeted by the recent interpretations of WHI findings.

Some of the results were unexpected and almost shocking. Low-fat diets apparently didn't provide the protection from heart disease and cancer that was promised in earlier studies, calcium and vitamin D didn't prevent as many fractures as was expected, and perhaps the use of estrogen alone was OK for some younger women.

Those results emerged from three randomized trials that were major components of the multimillion-dollar WHI. The trials began in 1991 to address cardiovascular disease, cancer and osteoporosis among postmenopausal women and included 161,000 women ages 50 to 79.

Despite its size, the WHI didn't find all the answers, and its findings were chock full of caveats.

"The data from my paper are not that clear-cut," said one investigator, Judith Hsia, MD, director of the lipid research center at George Washington University in Washington, D.C. She was the lead author of a study on conjugated equine estrogens and coronary heart disease that was published in the Feb. 13 Archives of Internal Medicine.

"The message that the study is trying to put out is that you can't just look at the heart disease risk with estrogen, you have to take the other things estrogen does, like cause stroke, blood clots, dementia and breast cancer as a whole effect."

Nonetheless, the results of Dr. Hsia's study do suggest that women ages 50 to 59 who have had hysterectomies could consider short-term use of conjugated equine estrogen because the benefit of eliminating severe hot flashes and vaginal dryness might outweigh the risk of cancer and heart disease for this group.

Dietary findings

Trial findings on the initiative's nutritional components also have caused much tumult. Three papers covering different low-fat diet outcomes were in the Feb. 8 Journal of the American Medical Association.

The results indicate that a diet low in fat but high in fruit, vegetables and grains does not significantly reduce the risk of breast cancer, colorectal cancer or cardiovascular disease in postmenopausal women.

Many researchers and clinicians didn't seem to believe it.

"Despite null findings from the WHI Dietary Modification Trial, dietary changes can have powerful, beneficial effects on [cardiovascular] risk factors and outcomes," wrote Cheryl A. M. Anderson, PhD, MPH and Lawrence Appel, MD, MPH, of Johns Hopkins University Bloomberg School of Public Health and School of Medicine in Baltimore, in an editorial accompanying the article. They also pointed to forthcoming papers that could clear up confusion.

The study authors themselves concluded that greater dietary change was probably necessary to have an impact on cardiovascular events. Plus, some fine-tuning has occurred about the types of fats that are beneficial since the WHI began.

"Just switching to low-fat foods is not likely to yield much health benefit in most women," noted Marcia Stefanick, PhD, professor of medicine at the Stanford Prevention Research Center in California and chair of the WHI steering committee. "Rather than trying to eat 'low-fat,' women should focus on reducing saturated fats and trans fats."

Findings from the third trial, reported in the Feb. 16 New England Journal of Medicine, found that calcium and vitamin D supplements demonstrated only a modest preservation of bone mass and prevention of hip fractures in older women, did not prevent other types of fractures or colorectal cancer and increased the risk of kidney stones.

The rate of hip fractures was about half of what was expected and thus decreased the study's power to show a significant finding, said lead investigator Rebecca D. Jackson, MD, an endocrinologist at Ohio State University in Columbus, Ohio.

"The low rates could be due to a number of factors, such as the high body mass index of participants, the inclusion of relatively few women over age 70 years and the fact that many participants were already using calcium and vitamin D supplements or were on hormone therapy," Dr. Jackson said.

Many researchers and clinicians questioned the finding. Some even maintained the position that they would urge their patients to stay the current course.

Negotiating through research on diet and nutrition is tricky. "There is so much contradictory information," said Edward Saltzman, MD, assistant professor of medicine at Tufts University School of Medicine in Boston. He compared recent findings to a revolving door. "First eat low fat and then high fat and so on."

The WHI hasn't helped matters with its seeming reversal of evidence that was thought be solid. At a meeting on public health and obesity, Dr. Saltzman joked to colleagues, "We might as well wait until the WHI comes out with their next paper that says obesity is actually good for us."

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Recent WHI trials

Low-fat dietary patterns: Objectives of the dietary modification trial were to evaluate the effect of a low-fat diet on cardiovascular disease, colorectal cancer and breast cancer. 40% of 48,835 menopausal women ages 50 to 79 were randomized to a group that was to reduce fat intake to 20% of daily calories and increase intake of vegetables and fruits to five servings per day and grains to six servings per day. Sixty percent were told to continue eating their normal diets. (Journal of the American Medical Association, Feb. 8)

Calcium and vitamin D: The calcium plus vitamin D supplementation trial had two objectives: to examine the effects of the supplements on fracture and on colorectal cancer risk. 36,282 postmenopausal women who were already enrolled in a WHI clinical trial were randomly assigned to receive 1,000 mg of elemental calcium as calcium carbonate with 400 IU of vitamin D daily or placebo. Fractures were ascertained for an average follow-up period of seven years and bone density was measured. (New England Journal of Medicine, Feb. 16)

Hormone therapy: The conjugated equine estrogens and coronary heart disease trial reported final results for the estrogen-alone arm of the hormone therapy trial. The trial had enrolled 10,739 women who had previously undergone hysterectomy. They were randomized to receive conjugated equine estrogens at 0.625 mg or placebo. (Archives of Internal Medicine, Feb. 13)

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External links

Women's Health Initiative (link)

"Low-fat dietary pattern and risk of invasive breast cancer," abstract, Journal of the American Medical Association, Feb. 8 (link)

"Low-fat dietary pattern and risk of colorectal cancer," abstract, Journal of the American Medical Association, Feb. 8 (link)

"Low-fat dietary pattern and risk of cardiovascular disease," abstract, Journal of the American Medical Association, Feb. 8 (link)

"Calcium plus vitamin D supplementation and the risk of fractures," abstract, New England Journal of Medicine, Feb. 16 (link)

"Calcium plus vitamin D supplementation and the risk of colorectal cancer risk," abstract, New England Journal of Medicine, Feb. 16 (link)

"Conjugated equine estrogens and coronary heart disease," abstract, Archives of Internal Medicine, Feb. 13 (link)

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