Let's consider sex contextualism within sex-aware preclinical pharmacological research

It is now well established that consideration of sex and gender is essential to deliver effective healthcare and preventive strategies for all individuals, as well as to reduce health disparities. A sex-based perspective is indispensable in the context of drug research. This review focuses specifically on the concept of sex contextualism, which recognizes that sex encompasses a range of dynamic variables. It also reports some of the biological factors that must be considered in building sex contextualism. This approach provides a constructive framework for addressing sex-related biological differences, but its proper implementation requires the involvement of well-trained researchers with different expertise. To achieve truly sex-aware research it is necessary to adopt appropriate experimental designs, carefully select pre-analytical and analytical procedures, precisely define experimental variables, and rigorously report standards. Additionally, the gender of the investigators must be considered, since everyone is gendered, and numerous studies have demonstrated that the gender of the experimenter can influence research outcomes. In this review, we discuss strategies to incentivize sex-aware preclinical pharmacological research. Although this approach is more time-consuming and costly than those that ignore sex differences, it is essential for ensuring therapeutic appropriateness for all individuals.