KEY TAKEAWAYS

• Reporting guidelines recommend that researchers factor the role of sex into animal and clinical studies, but progress in adherence to these guidelines has been slow.
• Sex-based analyses have led to some key medical discoveries, and researchers are encouraged to examine data for sex differences to enhance study reproducibility and open up questions for scientific pursuit.

Medical research funders and publishers are increasingly calling for the role of sex to be considered in preclinical and clinical studies. In a recent Nature News Feature article, Dr Emily Willingham highlights the importance of reporting sex differences in medical research and examines why progress in this area has been slow.

Sex as a variable has important health implications. A recent example is COVID-19, which has higher mortality in men but affects more women in the form of long COVID. Accounting for sex can enhance the scientific rigour and reproducibility of a study, and even if there are no sex-based differences to report, negative findings are still informative.

Accounting for sex can enhance the scientific rigour and reproducibility of a study, and even if there are no sex-based differences to report, negative findings are still informative.

Yet, since the thalidomide tragedy in the late 1950s, women of childbearing age have been under-represented in clinical trials. Progress was made in the early 1990s, when the US National Institutes of Health (NIH) began requiring that women are included in clinical research. Both the NIH and EU now call for both sexes to be included in cell and animal studies.

In 2016, Dr Shirin Heidari led the publication of the Sex and Gender Equity in Research (SAGER) reporting guidelines, with the aim of encouraging authors to consider sex and gender differences in scientific publications. However, progress in adherence to these guidelines has been slow. An analysis of 720 papers published in 34 biology journals in 2009 and 2019 found that although the proportion of sex-inclusive studies had risen, the proportion incorporating sex-based analyses had decreased from 50% to 42%. Another study reported that even when sex is considered as a variable, treatment effects are often not compared properly between sexes, leading to misinterpretation of data.

The reasons for the relatively slow uptake of sex inclusion and reporting policies include:

• general resistance to change – some journals assert that the SAGER guidelines are not applicable to their fields
• cost – mice studies that include two sexes require more animals, which adds expense
• complexity of sex – some researchers argue that a binary definition based on specific anatomy or chromosome numbers is too limiting.

Encouragingly though, since sex inclusion guidelines were put in place, important medical discoveries have been made. One key finding is that risk of cardiovascular disease begins to rise at a lower blood pressure in women than in men – a revelation that came about from a call for studies looking specifically at sex differences in health outcomes. Considering the potential implications for medicine, we hope to see more researchers incorporate sex-specific analyses in their studies.

—————————————————–