Everyone knows there are major differences between male and female bodies. However, it may come as a surprise that there’s been a longstanding aversion to include women in clinical studies. Despite efforts by major granting agencies including the Canadian Institutes of Health Research (CIHR) to correct for gaps, a recent study by Liisa Galea at the University of British Columbia showed that neuroscience and psychiatry studies are still not where they should be when it comes to gender parity in research subjects.
By analyzing 3,193 papers published in six leading academic journals (three in each discipline) between 2009 and 2019, Dr. Galea’s research group found that just over half of the papers included studies with both sexes – which is a 30 per cent increase over the previous decade. Yet, only 17 per cent used a balanced ratio of men and women, and only five per cent used best practices for discovering differences between the sexes. The analysis also found that male-only studies were eight times more common than female-only studies, which remained at a paltry three per cent over the 10-year period.
Why are women excluded?
The underrepresentation of women in clinical trials has a long history and is partly because of the assumption that ovarian hormone fluctuations lead to variations that cannot be experimentally controlled. While it is now acknowledged that the exclusion of women has hindered progress in understanding their response to medical treatment, this assumption is often cited by clinical researchers for why they are not included. A similar rationale was used in the papers analyzed by the UBC team, with the most frequent reasoning for female exclusion from clinical studies being to “reduce variability.”
Dr. Galea, a psychology professor, neuroscientist, and lead of the women’s health research cluster at UBC, said the notion that women are more hormonal than men is a myth that should not be a limiting factor in using females in research. “Women have monthly fluctuation in our hormones, but males have diurnal fluctuation – which means they have daily fluctuation in testosterone levels,” she said. Other research has shown that both men and women have daily fluctuations in the hormone cortisol and that factors such as diet and age can affect hormonal variation across both sexes.
It is also possible researchers believe that including any number of men and women is enough to satisfy grant requirements, and that they do not take it a step further to analyze results based on sex. Dr. Galea said this is a “red flag.”
“My worry is with five per cent actually looking at [sex differences], they are sort of checking boxes,” she said.
A third reason is that including women in studies may require more research subjects, thereby increasing costs. For Dr. Galea, more funding is needed so that researchers can understand how both sexes respond to disease. She has also argued that more women than men conduct proper sex-based analyses, but on average women have lower funding success rates.
The majority of studies looked at by the UBC research group did not analyze the data with sex as a factor, and those that did thought of it as a covariate or “nuisance” variable. By doing so, the studies were able to remove the effect of sex without looking at whether it made an impact. For example, a study may include 18 men and two women, with the women considered to be a covariate.
Dr. Galea said that it is possible researchers are not aware of best practices (e.g. Including an equal number of men and women in studies) for analyzing for sex differences because of a lack of consensus on how to do so. To create a more optimal design, she said researchers must begin by including an equal number of men and women and use sex as a “discovery variable” which would allow for exploration of possible sex differences, she said. Further guidelines from CIHR suggest that researchers clearly articulate whether the condition under study has or does not have prevalence based on sex, and that results should be disaggregated by sex when both are included.
While the rise in studies that included both sexes over the previous decade is positive, Dr. Galea said that researchers must go further to understand if sex impacted results. Doing so, she said, could have real consequences for the health of both genders.