Sex and the human brain: Moving beyond the binary

Daphna Joel*

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review


There is a growing interest in sex and its relationship with different physiological systems (e.g., the cardiovascular, immune, and nervous systems). These are often studied within the sex binary framework, which a priori assumes that sex categories are important predictors of variability in the system under study. Here, I use the case of sex and the brain to demonstrate that the fact that sex-related variables affect another system or that there are group-level differences between females and males in the measures of that system do not necessarily imply that the affected system has a “female” and a “male” form or that sex category accounts for important and meaningful variability in that system. Such conclusions would be warranted only if explicitly tested and supported by converging evidence. In the case of sex and the brain, converging lines of evidence point to the opposite – even though sex-related genes and hormones affect many aspects of brain structure and function, sex categories are poor predictors of brain structure and function and the relationship between sex and the brain is better described under the “mosaic” hypothesis. This is because sex effects on the brain interact with other variables to create unique combinations (mosaics) of female-typical and male-typical brain measures within each brain. An empirical approach, which includes formulating and testing specific hypotheses, should replace the a priori sex binary framework also in other domains, in which there is evidence that sex-related factors play a role.

Original languageEnglish
Title of host publicationPrinciples of Gender-Specific Medicine
Subtitle of host publicationSex and Gender-Specific Biology in the Postgenomic Era
Number of pages8
ISBN (Electronic)9780323885348
StatePublished - 1 Jan 2023


  • Brain
  • Gender differences
  • MRI
  • Mosaic
  • Sex differences


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