Harnessing the Power of Sex Differences: What a Difference Ten Years Did Not Make

Sex differences exist in a variety of neurological and psychiatric diseases in terms of prevalence, manifestation, and treatment but most past research has been conducted in males. Multiple mandates have been initiated across funding agencies (National Institute of Health, Horizon Europe, Canadian Institute for Health Research) and scientific publishers (Sex and Gender Equity in Research) for biomedical and clinical research to include both males and females in research and reporting. Although more studies are including males and females in their research there are issues in how studies are incorporating males and females in their experiments, as about a third of studies that use males and females do not report sample size and only half are conducting any analysis by sex. Furthermore, what has been lacking in the literature is a detailed assessment of not only how sex is reported in papers (e.g. sample sizes disclosed, balanced design, sex used consistently throughout the experiments) but also how the variable sex is included in any analyses (e.g. covariate). Here we investigated all papers in 2009 and 2019 in three high ranking journals for each of Neuroscience and Psychiatry. We found that there was a 30% increase in the percentage of papers that included both sexes from 2009 to 2019 such that 68% of studies in Neuroscience and Psychiatry used both males and females in 2019. Despite this increase, in 2019 only 19% of all studies used an optimal design for discovery of possible sex differences and only 5% analyzed with sex as a discovery variable. Of the studies that used males and females - 25% of studies do not disclose sample sizes, 36% of studies used an unbalanced design, and 15% of studies did not use both sexes consistently throughout the paper. The percentage of single sex papers remains unchanged across the ten years at 3% for female-only studies compared to 27% for male-only studies across both disciplines. Neuroscience had fewer papers that analyzed by sex at 20% compared to 61% of Psychiatry papers. We hope that these data will make it evident that more needs to be done to improve the inclusion of males and females in future studies to improve the health of men and women.