Authors: Rebecca Rechlin, BSc Behavioural Neuroscience; Tallinn Splinter, BSc Biology, University of British Columbia | Editors: Negin Nia, Romina Garcia de leon (Blog Coordinators).
Published: August 26th, 2022.
Females have been overlooked in health research for decades, and despite 10 years of advancements and improvements in knowledge, this has still not changed significantly. Historically, there has been a long-standing bias of using males predominantly in scientific research instead of females, and as male and female health differ, this has led to health disparities for both males and females. Biological differences between females and males exist in diseases, such as in disease progression, symptomatology, and drug efficacy in many neurological and physiological diseases.
The study of these sex differences is essential for the understanding and advancement of disease treatment and precision medicine. For example women have double the risk for adverse drug reactions compared to men, which may in part be due to incorrect dosing (for instance despite both men and women being recommended the same dose for acetaminophen, an active ingredient in Tylenol, women break down the drug 60% slower than men). The biomedical and clinical research community is beginning to make corrections for these inequalities by issuing mandates for including females in clinical trials (such as by the NIH in 1993), and frameworks from funding agencies to address sex and gender in upcoming research (CIHR: Sex and Gender based Analysis (SGBA)) in 2010, and NIH: Sex As a Biological Variable (SABV) in 2016), however, there is still a long way to go to reach equality. Despite these mandates and increased approving attitudes towards these policies, the literature shows very little improvement in the analysis or examination of any potential sex differences.
Our study aimed to investigate whether and how possible sex differences were being investigated in neuroscience and psychiatry research. We looked at over 3,000 neuroscience and psychiatry studies in 2009 and in 2019 to see whether researchers were including both sexes in their studies. We found that only 53% of these studies actually included both males and females, and only 16.5% of these used an equal number of males and females throughout their study. Of the papers that used both sexes only 6% actually analyzed sex as a discovery variable. We found that the majority (60%) of the papers that used both sexes did not do any analysis by sex. This is concerning, as this means that we will lose out on important scientific discoveries if researchers are failing to embrace the power of studying potential sex differences.
Figure 1: An infographic depicting the change in percentages of total papers sampled reporting studies in 2009 and 2019 that used both sexes, a single sex, omitted sex, papers reporting studies that used an optimal design or analyses for the discovery of possible sex differences irrespective of discipline. Reprinted with permission from Rechlin et al. 2022
It is important to note that biology sex and gender are two different things, and neither one is binary. Sex refers to the biological and physiological attributes of females and males, whereas gender is a psychosocial construct that includes one’s gender identity, and the norms and expectations set out by society. In our analysis we focused on studies using males and females (or sex) in rodents, humans and in research using cell lines, but the study of gender differences is also important to study and examine in regards to disease and treatments.
However studying sex differences, while important is not the only path towards equitable findings and discoveries in both men and women’s health research. With that in mind we found that although 27% of all studies in 2019 were conducted in males, only 3% were in females only! That means there were 9x more studies in males than in females! This greater focus on male health likely contributes to the health disparity and contributes to the historical male bias in assuming females and males are the same. Single sex studies are still essential for the discovery of sex-specific diseases/conditions such as prostate cancer in males and cervical conditions in females. Females specific factors, such as pregnancy and menopause, contribute to health outcomes and disease risk. For example, depression has a higher prevalence in women than men, and the risk of depression is largely increased during perimenopause and during the postpartum period.
So what can we do to improve these disparities? For starters, researchers need to actually analyze their data by using sex as a factor (or discovery variable). This essentially means including sex as one of the independent variables of the study (and not just controlling for it), allowing for the discovery of potential sex differences. It is also important for researchers to use a balanced and consistent study design, meaning they need to use both males and females consistently and in relatively equal numbers throughout their study. And even if they don’t find any sex differences, then the paper should make that statement with supporting statistics and a table to show the means and variation of the dependent variables by sex. This information of no sex differences is just as important as the discovery of them.
For funding agencies, one solution is to have funding dedicated specifically for SABV and SGBA proposals and not as a supplement to regular funding. More training modules from funders or scholarly organizations with an SABV focus may help, however, enticing researchers to explore the influence of sex and gender in their data may be a more fruitful approach. If journals, especially those with higher visibility, adopt calls for papers using sex and gender-based analyses this may serve as a catalyst to ensure more researchers consider possible sex differences and further promote the notion that this research is important to publish. Since we published our paper - Nature journals have committed to ensuring sex and gender are considered in their study design, by requiring authors to state how and why sex/gender was considered, or to state why it was not. If implemented as intended, this is a good first step to increase the amount of studies considering sex and gender in their analysis, and may be a great leap towards fixing these health disparities.