Allostatic Stress and Inflammatory Biomarkers in Transgender and Gender Expansive Youth: Protocol for a Pilot Cohort Study

Background: A growing number of adolescents are coming out as transgender and gender expansive (TGE). These teenagers have been shown to have significantly worse health outcomes than their cisgender peers. Hypotheses to explain this discrepancy are based on increased stress levels surrounding the societal acceptance of gender identity. In this context, elevated allostatic load (AL), which describes the wear and tear sustained by the body in response to repeated exposure to stress, has been associated with adverse long-term health outcomes. Objective: This protocol aims to measure AL among TGE adolescents compared with their cisgender peers and assess how AL varies depending on psychological stress and perceived societal acceptance. Methods: This is an observational proof-of-concept pilot study in which AL will be measured by assaying an array of inflammatory cytokines and cortisol in urine, saliva, and hair samples of TGE youth, and these parameters will be compared with those of age-matched control participants. A questionnaire will assess 4 aspects of psychosocial well-being: presence and management of depression and anxiety, gender identity support by family members, gender minority stress, and degree of perceived safety in the surrounding community Samples and surveys will be collected at 3 visits (baseline, 6 months, and 12 months). This study will incorporate TGE coinvestigators to inform all aspects of design, data collection, and analysis and ensure that practices are carried out in a respectful and sensitive manner. Results: As of May 2021, the start of data collection for this project has continued to be postponed as a result of the COVID-19 pandemic, which has both impacted the functioning of the clinic and funding requests. We hope to begin participant recruitment and interviews with coinvestigators soon. Conclusions: We hypothesize that AL will be primarily influenced by psychological well-being and perceived support and that it will be similar in TGE adolescents and in age-matched cisgender control participants when acceptance and perceived support are high. The results of this study have the potential to increase our understanding of the health challenges faced by TGE individuals during adolescence as well as to show that low levels of acceptance may have detrimental health outcomes secondary to elevated ALs; this may lead to the development of a biomarker profile to assess allostatic stress in TGE patients that can be used to guide management.