PROJECT SUMMARY Gender-affirming hormone therapy (GAHT) is one of the most effective interventions for treating gender dys- phoria in transgender and gender nonconforming (hereafter transgender) youth, thereby reducing suicide risk. GAHT, particularly estrogen, may increase the risk of thrombosis. While hematologists often evaluate patients before GAHT start who are at risk of thrombosis due to personal/family risk factors, there are no guidelines or data to inform management. This lack of data leads to significant variation in clinical practice that may com- promise care. Because this knowledge gap hinders the ability of gender care clinicians and hematologists to provide optimal care to transgender youth, the objectives of this proposal are to prospectively examine biologic changes associated with thrombotic risk in a cohort of transgender youth receiving estrogen GAHT and to ex- amine the attitudes and practices of clinicians who make decisions about thromboprophylaxis for youth on GAHT. The proposed work is relevant to the priorities of understanding human biology (defining changes in thrombotic risk associated with estrogen GAHT) and reducing human disease (defining which transgender youth may benefit from thromboprophylaxis). The proposed research is innovative in the focus on transgender youth, comprehensive examination of changes in coagulation factors in youth using estrogen GAHT, and de- termination of factors influencing the treatment recommendations of hematologists for thromboprophylaxis among transgender youth with personal/family risk factors for thrombosis. The specific aims are to: 1) prospec- tively determine changes in coagulation that would predispose to thrombosis over the first 24 months of estro- gen GAHT in a population of transgender women (up to age 22 years at GAHT start); and 2) characterize the attitudes, practices, and intentions of hematologists caring for youth toward recommending thromboprophylaxis to TG youth with personal/family risk factors for thrombosis. In Aim 1, 75 transgender women up to 22 years of age who are starting estrogen GAHT will undergo thorough and systematic evaluation of hemostatic factors at baseline prior to GAHT start, and then at 3, 6, 12, 18, and 24 months, with interim telephone study visits. Hor- mone usage and adherence, coagulation parameters, thrombophilia polymorphisms, and platelet activation will be assessed. In Aim 2, well-established qualitative and survey research methods will be used. Up to 20 adult and pediatric hematologists will complete individual interviews. Data from these interviews will be used to gen- erate items for a new survey that will undergo survey development methods (cognitive interviews, pilot testing) before being fielded to a sample of U.S. and Canadian hematologists to understand their attitudes, behaviors, and intentions to recommend thromboprophylaxis to transgender youth at risk for thrombosis and factors asso- ciated with these intentions. The results of this work provide the foundation for 1) an intervention targeting phy- sicians to improve knowledge of thrombosis risk in the setting of GAHT and 2) development of clinical guid- ance to aid in referral, evaluation, and management of transgender youth at risk for thrombosis.

PROJECT NARRATIVE The proposed research is relevant to public health because understanding changes in coagulation factors that might increase the risk of a blood clot among transgender and gender nonconforming adolescents and young adults who are using estrogen for gender-affirming hormone therapy is important for physicians counseling transgender people about the risks of a blood clot, and for patients and their families to be able to make informed decisions about their health care. This research will also provide information about which youth with other risk factors for a blood clot should be evaluated and perhaps start anticoagulation before starting gender- affirming hormone therapy. Overall, the information that is learned from this work is important to the development of tools for both gender care clinicians and hematologists in order to standardize clinical practice, reduce health care inequalities, and improve the overall health of transgender and gender nonconforming adolescents and young adults.