It took neuroscientist Liisa Galea six rounds of grant competitions for a study on how pregnancy history could influence the development of Alzheimer’s to convince Canada’s largest health grant organization that the study did not have to include males.
For women’s health questions “we’re looking at something that’s very female specific,” said Galea, a professor of psychiatry at the University of Toronto.
“So it’s impossible to look at the male … for certain things, for example like examining the placenta during pregnancy — we cannot do that work in a male. We can’t physically do it.”
Canadian scientists say a requirement for health research to be inclusive has made it harder to receive grant funding for female-specific health studies. Ironically, this emphasis on inclusiveness is a response to a historical bias against female-specific studies that still persists today.
But research that is specific to females — or other identity groups — is actually necessary to develop the best medical treatments, they say.
“I think one of the challenges in our desire to overcome … mistakes of the past … is that we’re risking again — albeit perhaps well meaning — we’re risking losing some of those important physiological and social differences,” says Neeru Gupta, a social scientist at the University of New Brunswick.
‘Not just little men’
Historically, there has been a pervasive view in the scientific community that diseases do not manifest differently in males and females, says Galea, who is also the Treliving Family Chair in Women’s Mental Health at the Centre for Addiction and Mental Health in Toronto. This has led to medical diagnoses and treatments being developed largely on the basis of studies of males.
There is this idea that “women’s health is just what’s under our bikini. And I think that’s what a lot of people initially think of as women’s health, but it absolutely is not,” she says.
Samantha Cote, a neuroscientist and research manager at the Université de Sherbrooke, agrees. “Women are not just little men … [where] you can take a dose that you give to men and then just adjust it for women.”
“We’re seeing more and more evidence that hormones, reproductive status, reproductive history, has such a powerful effect on brain health,” said Cote, who studies how hormones affect the female brain.
“We know the hormones interact with so many systems across the body, and for so long, we’ve kind of ignored this, or assumed there’s not a huge difference between men and women,” she said. “By not studying them, we essentially would fail the women.”
On average, women are diagnosed about four years later than men in 770 diseases, researchers at the University of Copenhagen found in 2019.
“That delay in diagnosis costs lives,” says Galea, who has seen how women fall through the cracks in her own research of Alzheimer’s disease.
The diagnostic process for Alzheimer’s disease includes a verbal memory test, which women tend to perform better on than men. This can result in missed diagnoses for some women, says Galea, since the threshold for assessing whether a patient has Alzheimer’s is based on a lower male score.
Broader trend
In part to rectify a history of predominantly male-focused research, diversity and inclusiveness mandates today largely require researchers to study both sexes.
The Canadian Institutes of Health Research, a government investment agency that invests about $1 billion a year in health research, requires researchers to say how they plan to incorporate sex, gender, ethnicity and cultural factors into their research. The institute is the largest funder of health research in Canada, says Galea.
The goal of integrating a sex- and gender-based analysis into “CIHR-funded research [is] to ensure the science we fund is relevant and impactful for Canada’s diverse population,” the institute told Canadian Affairs in a written statement.
This analysis, which has been in place since 2018, followed a broader trend of increasing female representation in health research. In 1993, the U.S. Food and Drug Administration mandated women be included in all clinical trial studies sponsored by the National Institutes of Health, except where a disease only affects men.
But this approach of studying both sexes as equals has led to a medicine which is “nobody based,” says Gillian Einstein, a faculty member in the Department of Psychology at the University of Toronto.
Sex is taken out of the equation in many studies. “The final data won’t show which one was male or which one was female.”
“We do need people to look at sex and gender,” says Galea, who says the institute’s analysis actually makes it more difficult to get approval to conduct female-specific studies.
“I’ve been doing [this] for 28 years — like writing grants on this — and I’m actually finding it’s getting harder, rather than easier, to get funding in this area,” she said.
Natasha Rajah, a psychology professor at Toronto Metropolitan University who studies the neuroscience of aging and menopause, says research studies regularly include males as age comparisons for menopausal females.
She says this standard is outdated and works against studying female-specific health topics.
“First of all, it just doesn’t make sense. We have different biologies … It’s different, and different is not bad,” said Rajah, who also holds the Canada Research Chair in Sex, Gender, and Diversity in Brain Health, Memory, and Aging.
Galea is currently seeking funding for a study on perimenopause — a period during menopause when the ovaries gradually stop producing estrogen. She continues to be asked to add males to her research, she says.
“Why is understanding male biology going to explain … reproductive health in females?” she said.
Personalized medicine
Including all sexes and gender perspectives in medical studies ultimately leads to fewer
dedicated research studies specific to women, says Gupta, who is a professor in the department of sociology at the University of New Brunswick.
Currently, women’s health funding often includes funding for a diversity of other groups. For example, in 2022, Ottawa provided more than $20 million over five years for a National Women’s Health Research Initiative that was gender and LGBTQ+ inclusive.
“Trying to address all of intersectional identities in one big call, or one big grant [is] not fair to any of these groups,” says Rajah.
“It’s not fair to the Indigenous health. It’s not fair to LGBTQ+ health … and it’s not fair to women sex and gender research, because you’re actually giving very little support for each of them as a result.”
Tallinn Splinter, who co-authored a research paper with Galea, found that over a 10-year period only three per cent of studies funded by the Canadian Institutes of Health Research were female-specific. By contrast, 27 per cent were male-specific.
“When they were justifying why they only used males, a lot of the time, they would say that females were more hormonal … or they say that, previously, it’s been done in males, so therefore they’re only going to do their study in males. They wouldn’t even include females,” said Splinter.
Ensuring research is specific to distinct groups enables researchers to understand how diseases or conditions manifest differently — and to tailor their treatments accordingly.
In Alzheimer’s, for example, both males and females generally develop the disease by having more beta-amyloid protein in the brain, which results in sticky plaques that can cause brain cells to die. But females with a particular genetic makeup tend to have more neurofibrillary tangles, which tangle the communication tubes between brain cells, says Galea.
Last year, the U.S. Food and Drug Administration approved a new drug to combat sticky plaque production.
“When you look at the data, [the drug] does seem to be more beneficial to the men,” said Galea, who noted that nearly two-third of people with Alzheimer’s are women. “So if we can do something that targets the neurofibrillary tangles, could we benefit more women?”
Women’s health is at risk if sex differences are not considered, says Cote.
“[I]f we understood better when we need to intervene … we could do better personalized medicine that’s preventative,” she said. “We can reduce suffering, reduce the costs on the medical system and the burden, and really just give these individuals what they deserve.”
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