We Need More Female Cells, Animals, and Humans in Medical Research

Including both sexes in preclinical and clinical research doesn't only help women; it helps men, too.

Sep 26 2014, 5:10pm

Picture a heart attack and you'll probably imagine a person clutching their chest, a sudden and crushing pain radiating from their heart to their left arm.

That's what it tends to look like for a man. But a woman can present with rather different symptoms: a more subtle squeezing sensation that can extend out to their back or up to their chin, shortness of breath, or abdominal pain.

When it comes to medicine, men and women differ in many ways. They suffer diseases differently, they respond to drugs differently, and female cells can even behave differently than male cells. But we don't know the full extent of these distinctions yet, because medical research remains dominated by studies on the male sex.

"As a result of that, we have less information about women, and sex as a fundamental biological variable hasn't been considered as routinely as it should," Dr. Janine Clayton, the associate director for research on women's health at the National Institutes of Health, told me in a phone conversation.

She's spearheading a new initiative by the NIH to include both sexes in scientific research. This week, the organization announced $10.1 million in funding to encourage researchers to include both sexes in preclinical and clinical studies. In a comment piece in the journal Nature earlier this year, she explained that females are particularly underrepresented in cell and animal studies.

Considering female biology in research has very obvious advantages for women. By including sex as a variable, researchers have found some eye-opening differences in how women respond to diseases and treatments, and we're not just talking gynaecology. By identifying these differences, they're able to better tailor healthcare to women patients.

Recognising different cardiac symptoms is one example. "If you don't know about that difference, you may not follow up on those symptoms," Clayton said. As heart disease is the number one killer of women as well as men, awareness of the signs is critical.


But it's not just patients who miss sex-specific symptoms. A study published in the New England Journal of Medicine in 2000 found that women were much more likely to be misdiagnosed and sent home when they went to the emergency room with heart attack symptoms. Nonwhite patients were also more likely to be discharged. A study published earlier this year in the Canadian Medical Association Journal found that men presenting with cardiac symptoms also received crucial care significantly faster than women.

The lack of awareness around women's symptoms comes down to the fact that research has so strongly favoured males in the past—and continues to do so. "It's sort of a blind spot for some scientists, they just haven't thought about it," Clayton said. 

There's a need to point out the obvious: on a biological level, women are different to men. 

"A woman is not just a smaller man; all of her systems, although anatomically very similar, may work different," Marek Glezerman, the president of the International Society of Gender Medicine, told me. "This has profound implications on diagnosis and treatment." 

Glezerman thinks medicine is at the point with women as it was with children around 20 years ago, before which kids were generally presumed to be just like mini adults.

The sex difference has persisted because research has predominantly been conducted in male subjects without much thought. Ironically, the reason female animals are often excluded from preclinical research is the same reason they need to be included: because they're different.

Image: Rockefeller University Press

Clayton explained the decision to use males is an attempt to reduce variability. "The thinking was that the oestrous cycle, which is comparable to the menstrual cycle in women, would cause variability that would make it difficult for people to interpret their animal study results," she said.

It's now understood that these hormonal changes don't affect most results. In any case, given half the population is subject to menstruation for a large chunk of their adult life, I'd suggest any variability arising as a result might well be worth looking into.

This misplaced fear of the menstrual cycle and its variability is also one reason women have been absent from clinical trials in the past, though there are others. 

Glezerman pointed out that in 1977, the FDA effectively excluded all women of childbearing age from clinical trials in recommendations that followed a couple of high-profile catastrophes such as the birth defects crisis in the 1960s that resulted from women taking thalidomide for morning sickness.


Obviously additional safeguards must protect women who are pregnant, but ruling out all women from trials denied scientists the opportunity to discover sex differences—and that can also be dangerous. For example, many drugs are more likely to cause potentially fatal heart arrhythmia in women, so it's important to pick up these sex-specific risks before they're on the market. The FDA lifted the restriction on including women in clinical trials in 1993.

Not that many researchers were too fussed, according to Glezerman: It's generally easier to recruit men for studies as, despite growing gender equality, women are still more likely to be caring for children and suchlike. "This is something we have not overcome to this day," he said. Then there's the undeniable fact that science has just always been more interested in men. Look at the gender divide in animal genitalia research.

The landscape is changing as awareness is raised, and initiatives like the International Society of Gender Medicine and the NIH's commitment to using male and female cells and animals in research are helping to direct the change.

Because ultimately, including female specimens in preclinical trials and women in clinical trials doesn't just help women. It helps men too.

For instance, 2007 study found that female stem cells work better to regenerate muscle tissue in both male and female mice—something that would never have been recognised if the sex of the stem cells hadn't been introduced as a variable.

To take another example, Clayton said that women tend to recover from head trauma faster than men. "If we could understand what it is about the female brain that seems to have some kind of protective effect, we could maybe even design treatment that would help males," she explained.

And once we know more about how female biology differs from the male version we take as standard, perhaps we'll even be encouraged to make life-saving devices that fit women too.

xx is a column about occurrences in the world of tech, science, and the internet that have to do with women. It covers the good, the bad, and the otherwise interesting gender developments in the Motherboard world.