Transcending the Male-Female Binary in Biomedical Research: Constellations, Heterogeneity, and Mechanism When Considering Sex and Gender

Abstract

Accounting for the influences of sex- and gender-related factors on health is one of the most interesting and important challenges in contemporary health research. In biomedical research, models, experimental designs, and statistical analyses create particular challenges in attempting to incorporate the complex, dynamic, and context-dependent constructs of sex and gender. Here, we offer conceptual elaborations of the constructs of sex and gender and discuss their application in biomedical research, including a more mechanism-oriented and context-driven approach to experimental design integrating sex and gender. We highlight how practices of data visualization, statistical analysis, and rhetoric can be valuable tools in expanding the operationalization of sex and gender biomedical science and reducing reliance on a male-female binary approach.

Keywords: biomedical research; experimental design; gender; sex; sex and gender science.

Figure 1

Serum levels of a fictional protein, protometaglobulin, in male and female mice. Panels (A–D) all depict the same fictional data using different visualization approaches. (A) is a conventional bar graph showing mean ± 95% confidence interval; (B) is a bar graph also showing mean ± 95% CI overlaid with a scatter plot with a dot representing each individual animal; (C) dispenses with the bars and confidence intervals, showing the scatter plots with a horizontal bar indicating the mean; and (D) shows the scatter plots only, with the means written as text beside the legend. n = 24 for each group. Groups were compared using an unpaired t-test; ** indicates p < 0.01.