Ruth A. Beckett is a wife and mother who last week committed herself to take a mystery pill every night for the next eight to 12 years. In this "double-blind" study, neither she nor the researchers giving her the pills knows whether they are estrogen or merely placebos.
"It's quite a commitment I'm making at the moment," she says uneasily as she completes the final paperwork at a Brookline office.
Like other post-menopausal women, Beckett had asked her doctor about hormone-replacement therapy. But she was faced with confusing responses.
"There was so little information," she says. "When women my age try to get information on whether to take estrogen, the information is not conclusive."
So Beckett enrolled in the Women's Health Initiative (WHI), the largest research study of women ever sponsored by the federal government. It is a 15-year, $628 million clinical trial sponsored by the National Institutes of Health (NIH).
At Brigham and Women's Hospital, a Harvard Medical School affiliate, WHI researchers are searching for explanations of the major causes of disease and death in post-menopausal women, including cardiovascular disease, cancer and osteoporosis.
They are examining the effects of hormone replacement therapy, low-fat diets and calcium and vitamin D supplements in women aged 50 to 79.
Dr. JoAnn E. Manson '75 is the principal investigator of the WHI at Brigham and Women's, one of the study's 16 nationwide vanguard centers responsible for program design and recruiting. She says she believes the study is desperately needed, since medical research has traditionally focused on men.
"Most previous clinical trials have been conducted in men only, and we now know that results from studies in men can't [always] be extrapolated to women," she says.
"[Men and women often] have different responses to diseases and treatment," Manson explains. "Certain diseases are more common or unique to women. In order to get answers, we need to study women directly."
Manson notes that ironically, the first randomized trial of a particular form of estrogen was performed solely on men, with the adverse affect of increasing the risk of coronary heart disease.
Health studies have usually been performed on all-male groups for economic reasons, doctors interviewed said. For example, since heart disease is more common in men than in women, researchers could follow smaller sample populations for a shorter period of time and find more data points if they limited their trials to men.
Manson also cites legitimate concerns of researchers that the menstrual cycle would alter data or that fetuses would be harmed if pregnant women were used in studies.
"But none of these reasons justify the exclusion of women from clinical trials, and I think that's being increasingly recognized," she says.
Although most of Manson's colleagues see the necessity of studies on women, some believe that strict quotas may hinder research.
Dr. Meir J. Stampfer, the co-investigator and lead author of a vitamin E study on women, says that some of the recent regulations Congress has imposed on the NIH go too far.
"I don't think we should slavishly follow a particular formula requiring certain percentages of population groups in all studies," he asserts.
But Stampfer acknowledges that the NIH policy to include different groups can be valuable.
"It's giving people an awareness that some subgroups differ in terms of their health risks and, therefore, the research should focus on that," Stampfer says.
At the WHI clinic in Brookline, the women who have volunteered to participate are grateful for the increased amount of research on women.
"I had not realized that as many [post-menopausal] women have heart attacks as men [in the same age group]," says Joan A. D'Alessandro, a participant in the dietary component of the WHI. "All we hear about is men. For myself personally, I wanted to hear those answers."
As part of her participation in the dietary trial, the slender D'Alessandro has attended regular private and group sessions with a nutritionist for the past year, discussing eating habits and sampling low-fat dishes.
The strongest motivation for the more than 160,000 women across the country who will participate in the WHI during its 15-year course is to find answers for posterity.
"I have a daughter [who] is 35. We are part of a study group that's going to show [what is] important to her diet," D'Alessandro says.
In a separate room, without overhearing the other woman, Beckett expresses the same sentiment. "I have three daughters, and I hope that when they get to be post-menopausal, they will have the answers."
A Pattern of Neglect
When Dr. Bernadine P. Healy became the director of the NIH in 1991, she led the formation of an agenda to find those answers.
Healy explains why there had been no randomized studies of estrogen in women until the WHI began recruiting participants in 1993, even though scientists had debated the benefits and side-effects of estrogen therapy for many years.
"For the longest time, there was the mindset that men are the normative standard," says Healy, a former member of Harvard's lesser governing board, the Board of Overseers. "As a result, it just somehow, curiously escaped people's minds."
She insists that sample populations in medical research must reflect the fact that women constitute 52 percent of the population. "The differences [in biology] between men and women are very distinct," she says.
Currently dean of the College of Medicine at Ohio State University, Healy notes that she is one of only three female medical school deans in the country, the same number as there were 25 years ago.
A bulldog for women's health issues, Healy recently wrote A New Prescription for Women's Health: Getting the Best Medical Care in a Man's World. In her book, she instructs women to be "assertive consumers" of their own medical care.
Healy says she perceives the gap between men and women's health research as a reflection of our "predominantly male-driven" society.
"There has been a long tradition of neglecting issues that are solely in the domain of women's health," she says.
The Debate Over Equality
Today, medical researches and the NIH appear to be moving towards ending that history of neglect.
The NIH no longer allows studies to exclude women without evidence that they are not affected by the disease under scrutiny.
"When we submit grants, it's actually an NIH requirement that we study women as well as men," says Dr. Eric B. Rimm, an assistant professor of epidemiology and nutrition at the Harvard School of Public Health.
Rimm was a scientific collaborator on two studies of vitamin E consumption and coronary disease published in 1993--one on men, one on women--which were performed at the Harvard Medical School, the Harvard School, of Public Health and Brigham and Women's Hospital.
"We're moving toward more equality in the funding of research," he says.
But some researchers believe the federal government would be applying a formulaic approach to science if it were to set quotas stipulating the number of ethnic minorities or women to be included in every new study.
Stampfer, the lead author of the vitamin E study on women, says it sometimes makes sense to oversample specific groups because they are predominantly affected by the disease in question. "[Allocations of funding] should be driven by science, not by politics," he says.
Stampfer says he disagrees with Healy's sentiment that the biologies of men and women are distinct enough to warrant separate research in every instance.
"We have to bear in mind that it's not different species here," he says. "For many instances, the biology is similar, if not the same, so we should not be forced to have the same number of men and women."
Rep. Louise M. Slaughter (D-N.Y.) says she can comprehend Stampfer's concern but disagrees with it.
"I can understand that as a microbiologist myself, but when one out of nine women in this country [is] getting breast cancer, it's an pidemic," Slaughter says.
She says she remembers when clinical trials focused disproportionately on men's health concerns in comparison to women's and is convinced Congress must continue working toward equality in research.
"[Before 1990] great strides were being made on prostate cancer, but the diagnosis of ovarian cancer was the diagnosis to die," Slaughter says.
"The Women's Health Office, a division of the NIH which opened in 1990, has made a great impact, but we've still got a long way to go," she says.
Slaughter says she fears what would happen if researchers and policy-makers were to return to the mindset that dominated research and excluded women before the Women's Health Office opened.
"I'm absolutely positive that should that office be done away with, they would do every study on white males," she says. "I'm dedicated as long as I'm here [to make sure] that doesn't happen."
Wanting Answers for the Future
Beckett, D'Alessandro and the thousands of other women who will commit themselves to the WHI also want to make sure that doesn't happen as well.
"Stress the need of this study to provide the doctors with more information," Beckett says. "At the end of it all, it's essentially a woman's decision with insufficient information."
Making her way through the long questionnaire required by the WHI to commit herself to the study, she wishes aloud that scientists will hold more answers in the future about women's health.
"Hopefully, in 10 years...." Beckett says, her voice trailing off. "Now we're guessing."