Sex

"Sex refers to a set of biological attributes in human and animals. It is primarily associated with physical and physiological features including chromosomes, gene expression, hormone levels and function, and reproductive/sexual anatomy. Sex is usually categorized as female or male but there is variation in the biological attributes that comprise sex and how these attributes are expressed."

Canadian Institutes of Health Research. (2023). "What is Gender? What is Sex? Retrieved from https://cihr-irsc.gc.ca/e/48642.html

Sex in health research design

Background

Healthcare access:

Important physiological, genetic1 and hormonal differences exist between male and female organisms. However, females have been historically underrepresented in medical studies1. This under representation has significant consequences when biological differences result in different causal mechanisms for health outcomes.


Healthcare outcomes:

Differences in physiology contribute to divergent outcomes in many (but not all) biological processes. 

Intersections

When sex is a significant factor, it remains important to consider how sex and gender intersect in understanding sexual difference in health status in human populations. 

Considerations to determine the applicability of sex in research

Consider whether or not there there documented sex differences in the subject of study's:

If sex differences in the object of study are previously documented, or expected, investigators should integrate sex as a biological variable into their research. 

If sex differences are not applicable (e.g. the research will use in vitro cells), a detailed explanation describing why sex is not relevant to the research should be included. 


What are reviewers looking for?

CIHR reviewers are instructed to evaluate submissions for clear description of whether or not: 

How can I incorporate sex into my health research?  

A successful consideration of sex will be integrated throughout the research design. CIHR provides practical suggestions for integrating sex and gender into the research design in a series of training modules that can be found here.  

Language

The use of precise, accurate terminology is fundamental to integrating sex and gender into research1. For a more comprehensive list of terminology used to describe sex, gender and sexual orientation please see Gender . It is also imperative to note that culturally sensitive language is always changing, and that the current usage may not be preferred in the future2.

Sex is a biological construct referring to a set attributes including chromosomes, genetic expression, hormones, and anatomy. 

Intersex describes a set of sexual attributes including chromosomes, hormones and anatomy that do not fit into exclusive binary categories of male or female.

Gender is a social construct referring to roles, behaviours, expressions and identities of girls, women, boys, men, and gender diverse people. 

Gender identity is a person's sense of themselves as being a 'man', 'woman', or other gender1.

Gender expressions are characteristics and behaviours of a person that are viewed as masculine or feminine within their culture.

Transgender refers to a state of being where a person's gender identity or gender expressions are not consistent with their assigned sex at birth1.

Cisgender refers to a state of being where a person's gender identity or gender expressions are consistent with their assigned sex at birth1.

Gender diverse refers to people who diverge from cultural gender norms in their gender expressions and/or gender identity1.

Beyond binary language 

There is increasing recognition that binary language (male/female, boy/girl, man/woman) perpetuates stigma and negative perceptions of sexually diverse, and gender diverse people.   

Best practices for incorporating sex into health research design

Use precise and accurate language. Do not rely on language that assumes concordance between sex and gender in your research. 

Confront implicit bias
Understand the distinction between sex and gender and describe the significance of the distinction in your research. The assumption of a concordance between sex and gender is an implicit bias that normalizes the experiences of cisgender people and contributes to the erasure and marginalization of transgender and gender diverse people. 

Do not centre male bodies and biological processes in your research. The implicit assumption that male bodies and biological processes are standard, and that female and intersex bodies and biological processes are particular and 'other' have historically suppressed research that centred female and intersex bodies and biological processes.     

Sample selection
Describe any exclusionary criteria and provide adequate rationale. For example, the inclusion criteria for a study of human development in utero should not refer to 'women' (a binary, gendered term) and thereby exclude transgender men and gender diverse individuals who experience pregnancy2. The exception would be if the research was confined to the experience of cisgender women, and this exclusionary focus would need to be empirically and theoretically justified.  

Measurement
Studies including both male and female cells, tissues or participants should record the sex of the observation. When studying human populations, gender identity should also be recorded. 

UBC suggests the following prompt to ascertain sex at birth when it is relevant to your study.[4]
"What sex were you assigned at birth?" [male; female; something else; prefer not to say]

Data analysis
Disaggregate analyses and results by sex whenever possible. If it is not possible, explain why not.

Analyze the data taking sex into account but do not centre male bodies and biological processes. When female and male subjects (or participants) are included together in a regression analysis, do not automatically centre male observations by assigning them to reference category.  

Whenever applicable, take gender (as distinct from sex) into account in your analyses. When possible, consider the intersection of sex and gender in your analyses by conducting subgroup analyses.

Reporting
Do not centre male bodies and biological processes in your reporting. Encourage inclusive research by using accurate and precise language to describe biological phenomena associated with sex, and distinguish sex from the social construction of gender.

Sex and Gender champions

Consider including a sex and gender champion on the research team to consider sex and gender throughout the process. The champion will integrate sex and gender concerns from proposal writing, community engagement, data collection, and data analysis, to dissemination of results.

https://cihr-irsc.gc.ca/e/50652.html


References
1 Madsen, T. E., Bourjeily, G., Hasnain, M., Jenkins, M., Morrison, M. F., Sandberg, K., Tong, I. L., Trott, J., Werbinski, J. L., & Mcgregor, A. J. (n.d.). Sex-and Gender-Based Medicine: The Need for Precise Terminology. https://doi.org/10.1089/gg.2017.0005

2 E. Coleman, A. E. Radix, W. P. Bouman, G. R. Brown, A. L. C. de Vries, M. B. Deutsch, R. Ettner, L. Fraser, M. Goodman, J. Green, A. B. Hancock, T. W. Johnson, D. H. Karasic, G. A. Knudson, S. F. Leibowitz, H. F. L. Meyer-Bahlburg, S. J. Monstrey, J. Motmans, L. Nahata, T. O. Nieder, S. L. Reisner, C. Richards, L. S. Schechter, V. Tangpricha, A. C. Tishelman, M. A. A. Van Trotsenburg, S. Winter, K. Ducheny, N. J. Adams, T. M. Adrián, L. R. Allen, D. Azul, H. Bagga, K. Başar, D. S. Bathory, J. J. Belinky, D. R. Berg, J. U. Berli, R. O. Bluebond-Langner, M.-B. Bouman, M. L. Bowers, P. J. Brassard, J. Byrne, L. Capitán, C. J. Cargill, J. M. Carswell, S. C. Chang, G. Chelvakumar, T. Corneil, K. B. Dalke, G. De Cuypere, E. de Vries, M. Den Heijer, A. H. Devor, C. Dhejne, A. D’Marco, E. K. Edmiston, L. Edwards-Leeper, R. Ehrbar, D. Ehrensaft, J. Eisfeld, E. Elaut, L. Erickson-Schroth, J. L. Feldman, A. D. Fisher, M. M. Garcia, L. Gijs, S. E. Green, B. P. Hall, T. L. D. Hardy, M. S. Irwig, L. A. Jacobs, A. C. Janssen, K. Johnson, D. T. Klink, B. P. C. Kreukels, L. E. Kuper, E. J. Kvach, M. A. Malouf, R. Massey, T. Mazur, C. McLachlan, S. D. Morrison, S. W. Mosser, P. M. Neira, U. Nygren, J. M. Oates, J. Obedin-Maliver, G. Pagkalos, J. Patton, N. Phanuphak, K. Rachlin, T. Reed, G. N. Rider, J. Ristori, S. Robbins-Cherry, S. A. Roberts, K. A. Rodriguez-Wallberg, S. M. Rosenthal, K. Sabir, J. D. Safer, A. I. Scheim, L. J. Seal, T. J. Sehoole, K. Spencer, C. St. Amand, T. D. Steensma, J. F. Strang, G. B. Taylor, K. Tilleman, G. G. T’Sjoen, L. N. Vala, N. M. Van Mello, J. F. Veale, J. A. Vencill, B. Vincent, L. M. Wesp, M. A. West & J. Arcelus (2022) Standards of Care for the Health of Transgender and Gender Diverse People, Version 8, International Journal of Transgender Health, 23:sup1, S1-S259, DOI: 10.1080/26895269.2022.2100644

3 Canadian Institutes of Health Research. (2023). "What is Gender? What is Sex? Retrieved from https://cihr-irsc.gc.ca/e/48642.html

4 Gender & Sex in Methods & Measurement. (n.d.). The University of British Columbia Centre for Gender & Sexual Health Equity.