Gender bias in health research – a complex equation to solve?

Underrepresentation of women in study samples

In the research process, gender bias starts in the sample selection with women being underrepresented in clinical trials, particularly in the early phases of the studies in which safety, including safe dosage range and side effects of interventions, are determined (Ruiz-Cantero et al., 2007).

Their routine exclusion from clinical trials creates a lack of robust data on how to treat pregnant women, for several medical conditions. The evidence on how a disease will take hold or what will be the likely outcome is scarce, even though the World Health Organization warns that many diseases can have ‘particularly serious consequences for pregnant women or can harm the foetus’ (Criado Perez, 2019b). This lack of evidence from female patients may also result in delayed treatment; applying inappropriate, ineffective, or harmful treatments; or the withholding of effective treatments (Merone et al., 2022).

As a measure to ameliorate this situation, the National Institute for Health Revitalization Act of 1993 mandated the inclusion of women in studies of humans (Miller, 2014). Other positive developments include the German Society of Epidemiology which has, for more than a decade, required researchers to justify the fact that only one sex was included in studies where the results could potentially affect both sexes (Criado Perez, 2019b).

However, despite all these measures, the number of women included in drug and device trials still remains low. Even in studies of conditions with similar prevalence in women and men, women’s participation ranged from 25–45% (Melloni et al., 2010). Some studies inadvertently exclude women because of restrictive inclusion criteria based on sex differential parameters, such as size or normative blood parameters or the simple fact that women are not asked to participate (Miller, 2014).

There are several postulated reasons for preferring males in research, including concerns for decreasing fertility or harming pregnancy, researcher bias from predominantly male researchers, and perception of the male as representative of the human species and, therefore, the norm (Merone et al., 2022).

To reduce disparities in health outcomes between men and women, it is essential for scientists and clinicians to consider sex differences as one of the underlying physiological mechanisms of disease.

Being a (woman) researcher in a male-designed world

It is  known that male researchers receive more research funding than their female peers, but most of these studies have been observational. So, it is unclear whether imbalances stem from evaluations of female research investigators or their proposed research (Witteman et al., 2019). In 2014, the Canadian Institutes of Health Research created a natural experiment by dividing investigator-initiated funding applications into two new grant programmes: the project grant programme with no explicit review focus on the scientist and the foundation grant programme with an explicit review focus on the scientist. In this quasi-experimental study, it was found that sex-specific funding success was not significantly different in a new grant programme in which peer review focused on the proposed science, whereas another new grant programme focused on the scientist showed a significantly larger sex-related difference that disadvantaged women (the gap was 4·0 percentage points [6·7 lower–1·3 lower; 0·705, 0·519–0·960]).

Considering these numbers, granting agencies, such as the National Institute of Health, should take action to improve mechanisms so that researchers can address both sex and gender issues more completely in their grant applications. For example, the Canadian Institutes of Health Research requires grant applicants to respond to specific questions about sex and gender in research.

The progression of an academic career depends largely on the scientific curriculum of the researcher, for which largely counts how much is published in peer-reviewed journals and the citation rates of publications, however, there is still an imbalance in opportunities. A few studies (Budden et al., 2008; Roberts & Verhoef, 2016)  found that female-authored papers are accepted more often or rated higher under double-blind review (neither author nor reviewer is identifiable).

Citation is often a key metric of research impact, which in turn determines career progression. Several studies have reported that women are systematically cited less than men. In a cross-sectional study published by Chatterjee & Werner (2021), it was found that original research articles written by women as primary authors had fewer citations than those written by men. These differences were consistent over time. Moreover, women who co-authored with other women as senior authors had the fewest median citations, while men who co-authored with other men as senior authors had the most citations. While gender disparities in authorship have improved over time, this recent study confirms that women are still much less likely to be primary authors of articles published in high-impact medical journals.

The default male world in the way we write

The extent to which the male default rules the world becomes less surprising when we realise that it is also embedded in language. Numerous studies over the past forty years have consistently found that what is called the ‘generic masculine’ (using words like ‘he’ in a gender-neutral way) is not in fact read generically(Criado Perez, 2019a). The use of ‘generic masculine’ as the norm distorts scientific studies, creating a kind of meta-gender data gap: a paper by Vainapel et al. (2015) looking at self-report bias in psychological studies found that the use of the generic masculine in questionnaires affected women’s responses, potentially distorting “the meaning of test scores”. The authors concluded that its use ‘may portray unreal differences between women and men, which would not appear in the gender-neutral form or natural gender language versions of the same questionnaire’.

Sónia Cordeiro dos Santos, Sara Pedrosa Pimenta and Marlene da Costa Coimbra Lages are visiting the Department of Sport and Health Sciences/SHE Research Group from CiTechCare in Politecnico de Leiria.