Sex contextualism in laboratory research: Enhancing rigor and precision in the study of sex-related variables

Madeleine Pape; Miriam Miyagi; Stacey A Ritz; Marion Boulicault; Sarah S Richardson; Donna L Maney

doi:10.1016/j.cell.2024.02.008

Sex contextualism in laboratory research: Enhancing rigor and precision in the study of sex-related variables

Cell. 2024 Mar 14;187(6):1316-1326. doi: 10.1016/j.cell.2024.02.008.

Authors

Madeleine Pape¹, Miriam Miyagi², Stacey A Ritz³, Marion Boulicault⁴, Sarah S Richardson⁵, Donna L Maney⁶

Affiliations

¹ Institute of Social Sciences, University of Lausanne, Lausanne, Switzerland. Electronic address: madeleine.pape@unil.ch.
² Center for Computational Molecular Biology, Brown University, Providence, RI, USA.
³ Department of Pathology & Molecular Medicine, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada.
⁴ Department of Philosophy, University of Edinburgh, Edinburgh, Scotland.
⁵ Department of the History of Science, Harvard University, Cambridge, MA, USA; Committee on Degrees in Studies of Women, Gender, and Sexuality, Harvard University, Cambridge, MA, USA.
⁶ Department of Psychology, Emory University, Atlanta, GA, USA; Harvard-Radcliffe Institute, Harvard University, Cambridge, MA, USA.

Abstract

Understanding sex-related variation in health and illness requires rigorous and precise approaches to revealing underlying mechanisms. A first step is to recognize that sex is not in and of itself a causal mechanism; rather, it is a classification system comprising a set of categories, usually assigned according to a range of varying traits. Moving beyond sex as a system of classification to working with concrete and measurable sex-related variables is necessary for precision. Whether and how these sex-related variables matter-and what patterns of difference they contribute to-will vary in context-specific ways. Second, when researchers incorporate these sex-related variables into research designs, rigorous analytical methods are needed to allow strongly supported conclusions. Third, the interpretation and reporting of sex-related variation require care to ensure that basic and preclinical research advance health equity for all.

Keywords: gender; health equity; precision medicine; research methods; rigor and reproducibility in science; sex as a biological variable; sex contextualism; sex differences.

Publication types

Review

MeSH terms

Biomedical Research*
Health Equity*
Humans
Sex*

Grants and funding

R01 GM152543/GM/NIGMS NIH HHS/United States