Sex, Genes, and Traumatic Brain Injury (TBI): A Call for a Gender Inclusive Approach to the Study of TBI in the Lab

Traumatic Brain Injury (TBI) is a leading cause of morbidity and moribundity in the United States (Bruns and Hauser, 2003; Corrigan et al., 2010). A number of factors including sex influence TBI clinical outcome. Both clinical and lab studies show a clear influence of sex on TBI outcome. However, whether this is mediated by hormones, genes, or both is still under debate (Gupte et al., 2019; Ma et al., 2019; Mikolic et al., 2020). The majority of research focuses on factors of endogenous hormone signaling (release and reception) in natal males (Slewa-Younan et al., 2004; Dubal et al., 2006; Herson et al., 2009; Griesbach et al., 2015; Clevenger et al., 2018; Mollayeva et al., 2018; Spani et al., 2018; Ma et al., 2019). This excludes natal females and both males and females taking exogenous hormones for hormone replacement (HRT) or cross sex hormone therapy (CSHT) as part of a gender confirming therapy (Mollayeva et al., 2018; Spani et al., 2018; Ma et al., 2019; Giordano et al., 2020; Biegon, 2021). While transgender and gender non-conforming (TGNC) individuals make up 0.3–0.5% of the global population, they are affected by violence at higher rates compared to cisgender individuals (Jauk, 2013). Despite these higher rates of violence and increased risk of TBI, the TGNC population remains understudied in the TBI field (Safer et al., 2016). This bias extends to healthcare settings where many TGNC individuals face significant barriers to obtaining high-quality, compassionate medical care at primary care facilities, especially in emergency rooms, where most TBIs are diagnosed (Sanchez et al., 2009; Porter et al., 2016; Reisner et al., 2016; Safer et al., 2016; Dickey and Singh, 2017). Research regarding transgender health has dramatically increased, yet there is still significant room for improvement as TGNC individuals are at an increased risk for several health issues (Reisner et al., 2016; Ackerley et al., 2019; Neblett and Hipp, 2019; Yeung et al., 2019; Wiepjes et al., 2020). A gender inclusive approach in biomedical research is vital to our understanding and treatment of TBI. The aim of this paper is to call upon lab-based investigators to approach the study of TBI and also biomedical research in a gender inclusive manner.