By Leah Shafer
The "Problem of Women":
Clinical Trial Bias in Women's Health Care
No one would guess by looking at Marguerite Behn that she is
a medical pioneer of sorts. The trim 78-year-old grandmother lives
in a North Carolina retirement home, and she likes to swim three
times a week. Retired 14 years now, this schoolteacher takes her
husband for long walks every day; he has been confined to a wheelchair
since having two major strokes and developing Alzheimer's disease.
Come mealtime, she makes her way to the community dining hall,
takes a food tray to her table, and makes history.
Behn is participating in the Women's Health Initiative (WHI)
-- an expansive, $635-million, 15-year, multifaceted study of
postmenopausal women. It's the first of its kind. With every meal
she eats as part of her study, Behn is contributing to knowledge
about how diet and nutrition affect health. In fact, she is part
of a first wave of women participating in a nationwide medical
study specifically about women.
Ten years ago, a government study on women's health shocked Americans
and catapulted many people into action -- it was a sort of "shot
heard 'round the world." This study revealed that the very medical
research used to understand illnesses and develop remedies for
them was virtually ignoring women on all levels. The medical community
as a whole was not even considering women in clinical trials and
research. Landmark studies on estrogen and heart attacks; aspirin
and mortality; vitamins; cancer; and cholesterol were done on
men only. This male-only clinical trials bias made no sense, given
that both sexes are killed by many of the same diseases, especially
heart disease, cancer, and stroke.
Behn, through her daily participation in the WHI study, represents
the increasing participation of women in clinical trials of all
sorts. This is a step in the right direction, but there's still
a long way to go. After all, the point of all this is not just
to give women proportional representation, but also to analyze
the results of clinical trials for gender-specific differences.
Some researchers are simply not doing that, and until they do,
scientific understanding will remain precariously perched on a
point between two paradigms: women's health as solely the maternal
condition or women's health as a miniature version of men's. Neither
one will pave the way to a healthy future for women.
Very real differences
So what of this "problem of women," as Sigmund Freud put it?
Can women and men really be that different?
The answer is a resounding "yes," says Marianne Legato, M.D.,
professor of clinical medicine at Columbia University of Physicians
and Surgeons and a charter member of the Advisory Committee on
Research on Women's Health at the National Institutes of Health.
"Sex-based biological differences affect all the systems we've
looked at so far and the way they react to disease," Dr. Legato
says. "We are in a tremendous time warp; we are just beginning
to understand the differences between men and women."
These differences are often quite fundamental: Women's bodies
and men's bodies respond differently to both illness and remedy.
But this situation is couched in a certain irony; historically,
women's health has meant one thing only -- maternal health. To
the medical community, women were essentially considered "walking
wombs." So on the one hand, doctors wanted to make the ability
to bear children the most important part of being female. On the
other hand, however, they wanted to ignore all bodily implications
and reactions to the very hormones that make childbearing and
menstruating possible. Those hormone cycles make women systemically
different from men and affect everything from the prevalence of
certain diseases, such as osteoporosis, to the way drugs are absorbed
and metabolized by the body.
Changing this historical inequity has been a very slow process.
But the process sped up ten years ago in America and involved
the cooperation of America's powerhouse of federal medical research,
the National Institutes of Health (NIH).
A quick look in the rearview mirror
The NIH named its first female director in 1990, Bernadine Healy,
M.D., and she took up the issue with gusto. A tremendous amount
of action in the past decade has moved women's health research
from virtual obscurity to national prominence. Dr. Healy created
the Office for Research on Women's Health, which serves as a focal
point for women's health research at the NIH, and as a whole the
NIH has spent millions of dollars trying to bridge the knowledge
gap. Because the NIH funds more than 90 percent of basic biomedical
research done in the United States with its $11 billion annual
budget, this attention is critical. The NIH revitalization act
of 1993, created and passed by Congress, made it illegal to exclude
or ignore women in medical research.
But the NIH isn't the only government institution involved in
women's health research. The U.S. Food and Drug Administration
(FDA) has funded more than 100 scientific projects through its
Office of Women's Health; these projects include research into
women and HIV, breast implant safety, women and autoimmune disease,
and breast and ovarian cancers.
When we speak of major studies, we naturally return to the Women's
Health Initiative and Marguerite Behn. The WHI is so special because
it aims to answer questions about hormone replacement therapy
after menopause and about the effects of calcium and vitamin D
supplements and diet on heart disease, cancer, osteoporosis, and
other disease processes. It's the first major study to look at
socioeconomic, cultural, ethnic, and racial factors in relation
to the kinds of diseases women get and the way they respond to
treatments for those diseases.
The final results from the studies won't be available until 2005
or later, but several notable things have already come from the
WHI, including an April 2000 report showing that a small number
of women taking hormone replacement therapy have an increased
risk of heart attacks, strokes, or blood clots during the first
two years of use.
Behn is not in the hormone replacement therapy study, but is
instead in one looking at the effects of diet on disease and mortality.
This involves eating a structured diet that is rich in vegetables,
fruits, and grains and is limited to 24 grams of fat a day, about
the amount in a 4-ounce hamburger patty. She's been doing this
for five years and has no intention of stopping. "I'm motivated
because I feel that I'm doing something that's good for myself
and for other people because I've invested this much time already,"
she says. "Also, all my life I've made some sort of contribution."
Getting the numbers to count
Undoubtedly, we have the science and the funding to narrow the
significant knowledge gap on women's health issues. The United
States commits $25 billion to $30 billion of private and public
money to medical research annually, the largest amount in the
history of the world. But amidst this plentiful bounty, one of
the biggest barriers is getting women -- especially premenopausal
and minority women -- to participate in research studies and clinical
trials. Many women don't know much about medical research and
may be wary or wholly unaware of it.
"Since women have traditionally not been included in trials,
they need to be educated about them," said Phyllis Greenberger,
executive director of the Society for Women's Health Research.
"Women want and need different things than men in these trials
... for example, child care, hours of participation that are convenient,
and sometimes transportation."
A future system modeled on today's successes
Creating studies for women begs the question: Will women volunteer
their time and energy? They must, or the scientists working with
this first wave of women will find their efforts blocked by a
The medicine of the future is based on the wisdom of today and
the research of the past, so it will take longer than a single
decade of studies to change centuries of thinking about women's
health. We need to understand the mechanisms of disease in both
men and women so we can treat everyone, Dr. Legato says. Scientists
must continue to produce research that proves that women and men
are different creatures with unique medical needs and that women's
health means more than maternal health, so we don't subscribe
to the old physician's adage of the nineteenth century: "Almighty,
in creating the female sex, [has] taken the uterus and built up
a woman around it."
Another area to keep an eye on is the inclusion of minority groups,
specifically female minorities, in these same clinical studies.
As the medical community lifts its gaze from 18- to 65-year-old
white men as the standard subject for research studies and medical
treatment, it becomes easier to answer questions about our biology
as humans and create greater health care for everyone.
Outside link: Office
of Research on Women's Health at the National Institutes of Health
Outside link: Cancer
Trials, a service from the National Cancer Institute
Outside link: Women's