Sex and gender disparities in biomedicine

Sex and gender disparities in biomedicine | Image Credit: © Flamingo Images - © Flamingo Images - stock.adobe.com.

According to a recent article published in Royal Society Open Science, gender has been given little attention in human biomedical research, despite the inclusion of sex in that field.

While sex and gender have been associated with significant impacts on infection and immunity, there is little consideration for them in clinical practice and public health. Pregnant individuals were not evaluated in early phase 3 clinical trials for the COVID-19 vaccine, and most COVID-19 policies worldwide did not consider sex and gender factors.

Higher rates of misdiagnoses and adverse drug events are observed in women compared to men, negatively impacting women’s health. Health disparities are worsened by lacking knowledge on health outcomes in transgender, non-binary, and intersex individuals.

In the recent article, authors stressed the importance of acknowledging sex- and gender-related questions in immunology. This includes improved efforts from funding agencies, researchers, scientific journals, and academic institutions.

Authors noted 6 bottlenecks for including sex and gender in immunity research. The first bottleneck is terminologyrelated, addressing how sex and gender are defined. As most studies evaluate cisgender individuals with a matching sex and biology, it may be difficult to determine which effects on health are sex-related vs gender-related.

Confusion may also exist because of the lack of consensus on quantitative measures of gender. As gender has significant social and cultural factors, health measures of gender may also be impacted by culture, class, and country. This indicates a need to determine differences in underlying mechanisms for sex and gender and present them in an understandable form for public health.

To elaborate on the mechanisms underlying sex and gender, incentives should be provided by academic institutions, funding agencies, and scientific journals. Data has indicated sex-related differences in influenza infection and vaccination, with socioeconomic factors contributing to influenza risk. This indicates a need for sex and gender to be integrated into the work of medical researchers.

The second bottleneck discussed is data related. There is little data on how shifts in sex hormone levels impact immunity and treatment outcomes. Data on health outcomes in transgender and non-binary individuals is also lacking. This includes data in electronic health records, disease registries, observational cohorts, and clinical trials.

Authors recommended improved guidelines from academic institutions, funding agencies, and scientific journals to improve data on sex and gender. Recommendations to include mandates for data disaggregation and checkpoints to evaluate the inclusion of a gender perspective were also discussed.

Along with sex at birth, authors believed human studies should include data on gender identity. To manage the complexity of sex and gender in immunity, authors recommended data be collected systematically.

The third bottleneck is translational. Animal studies are often performed on male animals only, causing issues when translating results of these studies to humans. These issues are worsened by the lack of female participants in human studies. Authors recommended animal research be combined with real-world evidence in humans to improve knowledge.

More diversity in clinical trials with the inclusion of gender minority groups may also lead to more accurate and detailed data. Methods for recruiting these individuals in clinical trials should be used in settings where recruitment may be difficult. Gender minorities included in clinical trials should be given respect and dignity. 

The fourth bottleneck is statistical. Sex and gender are often considered as cofounders in clinical trials, rather than variables. This could lead to inaccurate results on how sex and gender impact immune system responses. Authors suggested power analyses to measure appropriate sample sizes for sex and gender groups in human studies.

The fifth bottleneck was ethical. The lack of women and gender minority inclusion in clinical trials has led to harmful drug dosing or delayed diagnosis in these populations, creating an ethical problem. 

Pregnant people are also often excluded from trials, causing opportunities for drugs to be developed for these individuals to be lost. This has led researchers and organizations to advocate for pregnant people to be included in future research.

The final bottleneck is structural. Systemic discrimination and sexism continue to impact academic research, leading to a gap in clinical care. While women represent 78% of the population with autoimmune diseases, women-focused research received only 7% of the average annual NIH rheumatoid arthritis budget.

Authors emphasized recommendations for women and gender minorities to be included during each decision-making level from research to policy making. Researchers and organizations should also consider an intersectional approach for health outcomes.

The inclusion of sex has been seen in biomedical research, but gender is still not often considered. Authors urged researchers, academic institutions, pharmaceutical companies, policymakers, and scientific journals to address the 6 bottlenecks discussed in the article to increase equity in the field.

Reference

Pasin C, Consiglio CR, Huisman JS. Sex and gender in infection and immunity: addressing the bottlenecks from basic science to public health and clinical applications. R Soc Open Sci. 2023;10(7):221628. doi:10.1098/rsos.221628