Reporting Sex, Gender, or Both in Clinical Research?

Virtually every clinical research report includes basic demographic characteristics about the study participants, such as age, and how many participants were male/men or female/women. Some research articles refer to this latter variable as sex, others refer to it as gender. As one of the first pieces of data reported, the importance of including sex appears undisputed. But what does the sex-gender category really entail, and how should it be reported?

With emerging evidence that both sex and gender have an effect, for instance, on how an individual selects, responds to, metabolizes, and adheres to a particular drug regimen,1 there is an ethical and scientific imperative to report to whom research results apply. This Viewpoint explains the contexts in which sex and gender are relevant and provides suggestions for improving reporting of this characteristic.

Terminology

Two common questions asked by clinical researchers are: (1) Should the sex or gender of the study participants be reported? and (2) What is the correct term for designating males and females or men and women? The answers depend on whether biological or psychosocial factors are under study. Sex and gender are not mutually exclusive. They are integrally related and influence health in different ways. According to the National Institutes of Health (NIH) and the Canadian Institutes of Health Research (CIHR), sex is considered a biological component, defined via the genetic complement of chromosomes, including cellular and molecular differences.4 Karyotype at birth is nearly equal for 46XX and 46XY. Sex is reflected physiologically by the gonads, sex hormones, external genitalia, and internal reproductive organs. The terms male and female should be used when describing the sex of human participants or other sex-related biological or physiological factors. Descriptions of differences between males and females should carefully refer to “sex differences” rather than “gender differences.”

Gender comprises the social, environmental, cultural, and behavioral factors and choices that influence a person’s self-identity and health. Gender includes gender identity (how individuals and groups perceive and present themselves), gender norms (unspoken rules in the family, workplace, institutional, or global culture that influence individual attitudes and behaviors), and gender relations (the power relations between individuals of different gender identities). At present, there are no agreed-upon, validated tools for assessing gender. A 2-step approach to questioning has been proposed, whereby participants are asked both their sex assigned at birth and their current gender identity.6 Authors should consider appropriate use of the words sex and gender to avoid confusing both terms.