As reported by the New Haven Register, May 14, 2006.


By Abram Katz

Results of health studies leave women bewildered

Women chewed calcium to keep bones strong, swore off fat in their diets to keep colon cancer at bay and took hormones to help their hearts.

A week later, the world changed.

By mid-February, calcium seemed useless, fat didn't matter and hormones hurt hearts. Women were left confused and anxious by major studies suggesting that good health practices might really be bad.

The contrapuntal study was performed through the Women's Health Initiative (WHI), a program instituted by the National Institutes of Health. This research is intended to fill gaps in medical knowledge left by the historic exclusion of women from studies and trials and much more remains to be learned, experts said.

Since the WHI has other studies to go, many doctors and public health experts want to make sure that future results are presented in a clearer, less worrisome way.

But some believe that the very nature of the research is bound to culminate in complicated and conflicting results. Methodology requires tens of thousands of women of different ages and physical conditions, leading to results that must be peeled back like layers of an onion.

The media also get its share of criticism as a force that exaggerates, over-simplifies and sensationalizes findings.

"The Women's Health Initiative is a set of studies designed to study a number of interventions," said Dr. Carolyn Mazure, director of Women's Health Research at Yale, a post independent from the federal WHI.

The initiative's first task was to test the effects of postmenopausal hormone replacement therapy on heart health, followed by the effects of fat in diet on heart health, and then the effects of calcium and vitamin D supplements on fractures and cancer.

Based on prior studies, physicians believed that these measures were protective and many advised their women patients to follow the appropriate regimens.

But the study appeared to suggest the opposite.

Mazure said, "There's more to these studies than the one finding you read about in the paper," she said.

"By the mid-1990s hormone replacement therapy was being prescribed to millions of postmenopausal women. The question was whether all women should be taking it to protect the heart. The first study from the WHI showed that it was not cardioprotective for women who were post menopausal. Untargeted use is not necessary and not recommended," Mazure said the WHI study suggested.

A newer question is whether hormone replacement therapy benefits women if taken at the transition to menopause? "That is not yet known, and you don't throw the baby out with the bathwater," Mazure said.

Results of studies on women, particularly studies that overturn conventional wisdom, will be news, Mazure said.

"The research is understandable. It's the obligation of researchers and the media to explain what the findings really are. Very little in life is black and white," she said.

"We'll continue to see studies come out that are confusing and overblown by the media," said Dr. Peter Schulman, cardiologist and associate professor of medicine at the University of Connecticut Health Center.

Contradictory findings, confusion and additional studies are an inevitable byproduct of research, said Dr. Bruce Koeppen, dean for academic affairs at the University of Connecticut School of Medicine.

"The process of scientific understanding can be a long process. In medicine, you try to obtain the best evidence. As evidence changes, sometimes the conclusions change," he said.

"It's simply the nature of clinical research. It's often difficult to get a clear answer. Often there are confounding variables you didn't think of," Koeppen said.

"There was a complete flip-flop" in the WHI studies, said Dr. Hugh Taylor director of the Yale Menopause Program and associate professor at the Yale medical school.

Taylor said that the WHI study of hormone replacement therapy was flawed in several ways.

The WHI tracked about 161,000 women across the country for seven or more years to assess different ways of reducing the risk of heart disease, bone-depleting osteoporosis and breast and colorectal cancer.

"They found that a low-fat diet didn't decrease heart disease or breast cancer, that calcium and vitamin D didn't protect against osteoporosis. Now we're coming to the middle ground where the truth lies," he said.

Breast cancer has a latency period of five to 10 years, meaning that a shorter study would reveal cancers already present at the start of the study, Taylor said.

Hormone replacement therapy probably appeared to increase the risk of breast cancer by accelerating the growth of the preexisting tumors, he said.

Taylor is the principal investigator at Yale for the Kronos Early Estrogen Prevention Study, or KEEPS, which is recruiting subjects to see the effects of estrogen and progesterone on atherosclerosis in post-menopausal women.

Those interested in the study may call (203) 737-5465.

Women within three years of menopause would receive a reduced amount of estrogen and progestin. "These women should experience protection against heart disease," Taylor said.

"Some assumptions were turned over. As usual, the truth was somewhere in between. Studies need not swing from one end to the other, and they usually don't. It will be hard to minimize this 'pendulum' effect in studies in the future," he said.

A more generous release of information could lessen frightening pronouncements, Taylor said.

"Lately, these large studies of women get a lot of attention. Women become confused. This tends to raise concerns and casts doubt on the medical community," said Dr. Pamela Taxel, an endocrinologist and associate professor of medicine at the UConn Health Center.

"These are secondary analyses. We've had enough studies to show that if you don't get enough calcium and vitamin D, you get more broken bones," Taxel said.

Taxel said media coverage of studies, rather than the studies themselves, is what frightens women.

But some intermediary is necessary to translate medical journal language, she said.

Dr. Mary Pronovost of Bridgeport Hospital said more recent WHI studies suggest that hormone replacement therapy is useful in treating menopausal symptoms.

Patients confronted by clashing studies should talk to a thoughtful, informed doctor. There is no one "right" course of action, said Dr. Scott Wetstone, director of health affairs policy planning at the UConn medical school.