Sexism In The Doctor's Office Starts Here

Even actual lab rats are subjected to science’s male bias.

11/09/2015 08:01 am ET | Updated Nov 10, 2015

When the Food and Drug Administration approved Addyi, a prescription drug for women with low libido, this summer, it did so with a major caveat: Absolutely no drinking while taking the drug, or risk serious side effects. There was only one problem with this recommendation: The researchers who analyzed Addyi's drug-interaction side effects tested the drug, which was designed for women, on men.

The drug-interaction study comprised 23 men and two women, far too small of a female sample size to assess women's risk of drinking while taking the drug. Since women are both more likely to have adverse drug reactions and to metabolize alcohol differently than men, the male results from the drug-interaction study were essentially worthless. So why didn't researchers make an effort to recruit female study participants?  

As it turns out, this summer's fiasco is just the tip of the iceberg. Women have been excluded or underrepresented in medical and scientific research for as long as those fields have been studied. 

One of the key ways women are left behind is by being excluded from or underrepresented in the clinical trials. Since clinical trial research advances our knowledge about everything from the efficacy of new drugs to which treatments work best for certain illnesses and certain groups of people, exclusion or underrepresentation in them means women are forced to accept second-class health care almost every time they receive health services. 

Clinical trials have a gender problem

Women make up 51 percent of the United States' population, but you wouldn't know it from looking at the demographics of a typical clinical trial. 

Forty-eight percent of cancer deaths are among women, but women only make up 40 percent of cancer treatment and prevention trials. And good luck getting appropriate representation in studies if you're a minority woman: 80 percent of participants in cancer treatment and prevention trials are white.

The disparity is especially stark in HIV research. Women make up a mere 11 percent of participants in trials for potential HIV cures, despite the fact that half of the world's HIV cases are in women. 

'One extreme to the other'

Historically, research and government policies were designed to protect women of childbearing age from experimental risk -- a legitimate, if paternalistic, concern.

In practice, however, these policies effectively eliminated all women from trials. "We moved from one extreme to the other," said Carolyn Mazure, director of Women's Health Research at Yale and the author of an article on the history of gender disparities in biomedical research that was published last month in BMC Women's Health.

The BMC article chronicles the United States' progress in including women in clinical trials over the past 20 years, starting with the landmark National Institutes of Health Revitalization Act in 1993, which required that women and minorities be included in federally funded studies. Though influential, the law did not require that women be equally included in trials, nor did it require that study results be analyzed by gender.

"These are large institutions with big histories," Mazure said. "Change comes slowly."

Indeed, science's rate of change in response to the gender-research gap has been downright glacial, and plagued by misinformation. Some researchers assumed -- wrongly -- that studies done on men would also apply to women, ignoring the differences between the sexes. Others believed that conditions traditionally thought to affect men, such as cardiovascular disease, didn't affect women to the same degree.

In reality, more women die of cardiovascular disease each year than men, a fact that fewer than 1 out of 5 physicians were aware of as recently as 2005, according to a study published in the journal Circulation. 

That knowledge gap can be deadly for women. A Circulation study published in 2009 analyzed 6,000 people who called 911 reporting cardiac symptoms, and found that women had a 50 percent greater chance of being delayed in an emergency medical services setting. They also arrived at the hospital an average of 2.3 minutes behind men who reported the identical symptoms.  

Even female animals are excluded from research

Sex-based bias isn't exclusive to human research. In animal research, female rodents are similarly excluded from study. That's important because animal studies are typically a precursor to testing in humans. If female animals (or female cells, for that matter) aren't researched from the get-go, scientists won’t take drugs or treatments that work especially well on female animals to human trial.

And gender disparities in animal research are significant. A 2011 study published in Neuroscience and Biobehavioral Reviews analyzed sex bias in animal research and found that male bias was evident in eight out of nine biological fields. It was especially pervasive in neuroscience, where among single-sex studies, exclusively male animals studies outnumbered exclusively female animal studies at a rate of 5.5 to 1. 

See the graph below for how female animals are excluded from research:

When researchers did include female animals, many didn't analyze the results by sex. Other scientists never reported the sex of the animals they were studying at all.

"We couldn’t even find out if they had used males or females, because some papers didn’t even bother to say," Annaliese Beery, an assistant professor at Smith College and lead author of the study, told The Huffington Post. "That, to me, is just unconscionable."  

Female mice have smellier urine. An actual justification used for an all-male study.

Part of the problem is an entrenched (and inaccurate) belief that women are more variable than men, and that female rodents are more variable than male rodents, Beery explained.

In other words, scientists assumed that women's menstrual and reproductive cycles and female animals' estrus cycles would make them more complicated to study. If researchers don't feel like tracking the estrus cycles of female mice, they just avoid studying them. 

But in 2014, researchers disproved this premise in a meta-analysis of nearly 300 studies that examined hundreds of traits and found that male and female mice were equivalently variable

"People will come up with weird explanations," said Beery, who said she has heard a variety of excuses -- from, "I just want to do things like everybody else does them," to "female mice have smellier urine" -- as to why researchers avoid studying female animals in their labs.

"If you go to publish a study just on females, you always get asked, 'Why didn’t you include males?'" she said. "If you go to publish a study on males, most people wouldn’t bat an eye."

The real-world effect of excluding women from health research

The average life expectancy for women in the United States is 80 years, and 76 years for men. Still, that gap has narrowed in recent years, from a seven-year gap in 1985 to a 4.6-year gap in 2010 -- the result of steady life-expectancy gains for men, compared to sluggish ones for women.

Among high school dropouts, the state of women's health is particularly dire. A 2012 study published in the journal Health Affairs found that despite advancements in modern medicine over the past few decades, in 2008, women who didn't finish high school died significantly earlier than female high school dropouts did in 1990 -- five years earlier, to be exact. 

While there's no proof that inclusion in health research would reverse these trends, women's stagnating longevity and premature deaths among female dropouts should at the very least indicate parts of the population whose health is worth studying.

Promising changes on the health research horizon

In the midst of all this gender inequity, there's a bit of good news from the NIH. Following calls to action by Beery and others in the field, the agency announced last May that it would require scientists to include both males and females in preclinical research.

"We now understand that sex matters in a significant way," Dr. Janine Clayton, the NIH's associate director for research on women's health, told the podcast Nature last year.  

The upgrade in research methods is encouraging -- but if history has taught us anything, the change will be slow.

"It’s still going to be a constant issue when males and females are used in studies," Beery said. "Are the results analyzed by sex? Are there enough females included that we really learn about the females?"

Mazure seems to agree. "We understand what the institutions are like," she said. "But we have to keep asking for more change, better results and for science to evolve."

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