Quirks & Quarks

Women and science suffer when medical research doesn't study females

Medical science has a deadly historical bias problem: until very recently, most studies only included males

Medical science has a deadly historical bias problem: until very recently, most studies only included males

Medical research has a historical bias towards men, which includes medical models like Leonardo da Vinci's Vitruvian Man. It's time to meet, the Vitruvian Woman. (Ben Shannon / CBC)
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The issue of women not rising up through the STEM ranks goes beyond achieving gender parity for working scientists. When women aren't included in the scientific process at the highest levels, research isn't done that could save women's lives.

An illustration of this is what we're realizing is a deadly historical bias problem in medical science: until very recently, most studies only included male participants - and we now know this has serious implications for women's health.

"Male scientists typically included men because they saw the world through their lens and they naturally assume that whatever scientific findings they found in men they'd be able to extrapolate and apply to women. But what men of course don't appreciate is that women are not just small men,"  Dr. Cara Tannenbaum told Quirks & Quarks. Tannenbaum is the scientific director of the Institute of Gender and Health for the Canadian Institutes of Health Research.

Dr. Cara Tannenbaum, the scientific director of the Canadian Institute of Health Research's Institute of Gender and Health (CIHR)

This practice of excluding females — human and non-human — from most studies continued because there was a common belief that females were more complicated than males, said Tannenbaum. 

"Females certainly can get pregnant if you put them in animal studies, for instance. If you combine male and female animals together that would complicate the experiment. It was thought that females' hormone variations can be a confounder or interfere with the study results."

While this simplified the studies — it also made for bad science. Science that often didn't apply to women, because biologically, women are different from men.

Pretty much everywhere you look, when it comes to cardiovascular disease, you find a higher mortality in women- Dr. Thais Coutinho, University of Ottawa Heart Institute

Examples abound, said Tannenbaum. "When females are excluded from drug development research, the medications that are developed can result in side effects and even lethal toxicity that affects women and not men."

This isn't just about including female subjects into account. There are also important implications for who is doing the research. Analysis has shown that unless female researchers are directing scientific investigations, then the content of the research is less likely to take female biological sex into consideration.

The bias toward the male standard in biology — and the perception that women are too "complicated" to study — has meant that drugs, surgeries, and even public health interventions have been tested on men, male tissues and male lab animals. This has led to "standard" therapies and treatments that work for men - but less well or not at all on women, and this has implications for everything from cardiovascular health to pain control.

Factoring sex and gender differences into heart research

When it comes to heart attacks, women are more likely to die than men. More women than men die with heart failure. Even if they undergo heart bypass surgery, women die more often than men.

"So pretty much everywhere you look, when it comes to cardiovascular disease, you find a higher mortality in women," said Dr. Thais Coutinho, a cardiologist and clinician-scientist at the University of Ottawa Heart Institute.

Dr. Thais Coutinho, a cardiologist, associate professor of medicine, division chief at the University of Ottawa Heart Institute's Division of Cardiac Prevention and Rehabilitation, and the chair of the Canadian Women's Heart Health Centre. (Mark Totti )

Two thirds of the clinical cardiovascular research ever done either excluded women or if it included them, did not or could not analyze them separately. As a result there is no way to know if the findings of those studies apply as much to women as men.

And it's not just a matter of biological sex. Once you start studying men and women in more subtle ways, you learn new things. One of the interesting findings to come out of recent cardiovascular research is how gender — the roles we play in society — can affect recurrent heart attacks. 

"People that score more feminine on the gender role scale are more likely to have recurrent heart attacks after an initial heart attack and that can be a man and a woman," said Dr. Coutinho. "This is independently of the sex." 

Males and females process pain in different ways

"I've been finding sex differences for 20-25 years now in my laboratory. And sometimes we find them on purpose and other times we're working on something else entirely and there they are," said Jeff Mogil, a professor of pain studies at McGill University.

"I'm convinced now that sex differences are all over pain biology — at almost every level of analysis."

Dr. Jeff Mogil, E. P. Taylor professor of pain studies at McGill University (Craig Desson / CBC)

Mogil said he first realized there were differences as a student in graduate school. 

"I found that the drug that we were working on really, really worked in males and really, really didn't do anything at all in females."

But Mogil said he'd never forget the reaction he got when he reported his finding to the graduate student supervising the project.

"He said, 'Jeff, sex differences are to be enjoyed, not to be studied.'"

"He encouraged me to forget about the sex difference and go back to studying the drug. And of course, fortunately for my career, I ignored him completely and started studying sex differences on purpose from that point forward."

In 2015, Mogil showed how males and females use completely different cell types to process pain in the spinal cord.

This has major implications for drug development because if scientists develop a new pain analgesic by trying to manipulate one or another of those cells, then it might not work on half the population. 

Scientists used to exclude females from animal biomedical studies because scientists thought they'd get messier data because of their pesky fluctuating hormone levels. It turns out that male rodents give more variable data because they fight in their cages, which can affect results. (Craig Desson / CBC)

Policies now mandate the inclusion of females in studies

"Scientific funding organizations have taken the lead in producing policies that mandate the inclusion of women in studies," said Dr. Tannebaum. 

In 2010, the Canadian Institutes of Health Research adopted a policy of asking funding applicants how sex and gender are accounted for in their research. And more recently, the U.S. National Institute of Health adopted a similar policy.

If they continue to only use male animals in their studies, someone like me is just going to come along a few years later and publish a paper showing that they were half wrong.- Jeff Mogil, McGill University

"It's only been about three or four years in the United States where they've mandated inclusion, where in Canada, I feel like we are very much ahead of the game we've been doing this for a lot longer," added Dr. Tannenbaum. 

Mogil said he's seeing a difference already in his field of pain research. 

"As soon as four or five years ago where 80 per cent of papers that were published in the flagship journal in the field were using only male mice or male rats. And as of this year, 2019, so far that number is down to less than 50 per cent, so things are getting better," said Mogil.

And Mogil thinks that researchers should be strongly motivated to include females in their studies for one good reason - to protect their scientific reputations. 

"If they continue to only use male animals in their studies, someone like me is just going to come along a few years later and publish a paper showing that they were half wrong."

Leonardo da Vinci's Vitruvian man was meant to represent "perfect proportions in life and humanity," except — it only represents half of humanity's population. Behold the Vitruvian woman (Ben Shannon / CBC)

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