Venous Thrombo-Embolism Is Rare in Transgender and Gender Non-Binary Adolescents and Youth: A Multicenter Observational Study

Introduction An increasing number of adolescents and youth identify as transgender or gender non-binary (TNB). Gender-affirming hormone treatment (GAHT), including estrogen or testosterone therapy increase appearance congruence and psychological functioning, and decrease depression, anxiety and suicidal ideation. In adult TNB patients, estrogen therapy is associated with an increased risk of venous thromboembolism (VTE), while the thromboembolic risk of testosterone is less clear. A recent cross-sectional study conducted at Boston Children's Hospital (BCH) suggested that VTE is rare in TNB adolescents and youth and typically occurs in the setting of additional risk factors. Additionally, GAHT was not identified as a significant risk factor for thrombosis in this cohort. Herein, we sought to confirm our preliminary findings across 49 free-standing children's hospitals using an administrative database. Methods The study was deemed exempt by the Institutional Review Board at BCH. Administrative approval was obtained through the Children's Hospital Association. Data for this study were obtained from Pediatric Health Information System (PHIS), an administrative database that contains clinical and resource utilization data from inpatient, ambulatory surgery, emergency department, and observation encounters across 49 tertiary-care children's hospitals in the United States. Data quality and reliability are assured through a joint effort between CHA and participating institutions. International Classification of Disease, 9 th and 10 th Editions (ICD9/ICD10) codes were used to identify eligible subjects, defined as children (from birth to 21 years of age) hospitalized with VTE between 1/1/2012-12/31/2021 at one of 49-participating hospitals. ICD9/ICD10 codes for gender dysphoria were used to identify TNB adolescents and youth. Mean (SD) or median (range) were calculated for continuous data, and frequency with 95% confidence interval for categorical data. Results During the study period, 39,503 unique patients (birth-assigned females: 18,395 [47%]) were diagnosed with VTE. Mean age (SD) at VTE diagnosis was 7.7 (7.3) years. Only 23 (0.06%) patients had an ICD9/ICD10 diagnosis code for gender dysphoria. Of these 23 patients, six (26%) were birth-assigned males and 17 (74%) were birth-assigned females. Among these 23 patients, the median (range) age at VTE diagnosis was 16.2 (11.6, 20.5) years. VTE location for patients identified as TNB included: lower extremities (n=