By Ben Sutherly The Columbus Dispatch, Ohio.
It has been credited with preventing thousands of cases of breast cancer. It has confounded medical experts on everything from diet to hormone therapy.
But the Women's Health Initiative also has cut through some of the clutter of smaller medical studies that offer contradictory conclusions about what's best for women's health.
In large part because of the federal government's initiative, "we know now that there are no shortcuts" to good health, said Dr. James Liu, chairman of the obstetrics and gynecology department at University Hospitals Case Medical Center in Cleveland.
"It has shifted the onus of medical care from disease incidence-based ... to prevention, which is probably the most cost-effective way of treatment."
The study also has narrowed a gender gap in the treatment of women, said Dr. Rebecca Jackson, associate dean for clinical research at Ohio State University's Wexner Medical Center, who has overseen some of the research.
"Health recommendations for women are now based upon the best science of how something works in women," Jackson said, not on data generated by studies of men.
More than 20 years after recruiting the first of more than 161,000 postmenopausal females -- nearly 3,800 of them in central Ohio -- the nation's largest study of older women isn't making a quiet exit from the medical scene.
The study is, and might always be, best known for its revelations that postmenopausal hormone therapy -- particularly estrogen-plus-progestin therapy -- increased the risk of heart attacks and breast cancer, particularly in women older than 60. (Such therapy, however, was found to lower the risk of fracture and menopausal symptoms.)
Though the study's massive clinical trials have ended, it continues to track 93,000 women.
About 8,000 women in their 60s through late 90s were chosen as part of a study to determine what contributes to successful aging, said Dr. Jacques Rossouw, the chief of the Women's Health Initiative since its inception.
An exome-sequencing program is revealing the genetic underpinnings of various conditions, particularly cardiovascular disease.
And while much of the past focus on heart failure has been on systolic heart failure, it's common for women to suffer from diastolic heart failure, which has not been as thoroughly studied.
"We see a potential for future findings that may be important to aging," Rossouw said.
And the initiative's large number of women, including a strong minority representation, continues to make it attractive to researchers, he said.
Brigham and Women's Hospital in Boston is recruiting women through the initiative for a trial that will examine the role of nutrients in the cocoa bean and multivitamins on the heart.
It will be the first large-scale randomized trial testing multivitamins in women. The study is funded by Mars Inc.
The Women's Health Initiative isn't the only long-running women's study that has relied on local residents.
Starting in 1976, about 122,000 nurses in 11 states -- including about 13,000 in Ohio -- have filled out questionnaires every two years for the Nurses' Health Study.
The study looked at married women 30 to 55 years old and documented the long-term consequences of the use of contraceptives, which at the time were far more potent than they are today.
Most of the risks were found to be low, said Dr. Frank Speizer of the Harvard School of Public Health, who headed the study for 25 years.
The study also shed light on the effects of estrogen on breast health and its role in coronary heart disease. Questions about diet were added in the 1980s.
Liu, who served as a primary investigator for the Women's Health Initiative at the University of Cincinnati, said its research into the effects of low-fat diets was inconclusive, in part because many women didn't trim enough fat from their diet to meet the study's parameters.
"It shows that nutrition is an evolving science," Liu said.
Nancy Henry, 78, of Columbus, enrolled in the Women's Health Initiative in 1995. She took part in the hormone-replacement trial -- she took a placebo -- as well as studies on low-fat diet and bone density.
Henry said the study inspired her to embrace fitness. "I can see the difference between myself and many women who were not privy to the information I learned from the study."