BackgroundSex assigned at birth (SAB) is currently used to calculate predicted normative values for oxygen consumption (VO2) during cardiopulmonary exercise testing (CPET) in transgender and gender diverse (TGD) patients. It is unclear if this is physiologically valid once gender-affirming hormonal therapy (GAHT) has been instituted. Research QuestionWhat are the changes in functional aerobic capacity (FAC) and in percentage of predicted (%pred) peak VO2 when gender is used, instead of SAB, to estimated normative predicted values among TGD patients >14 years of age who are receiving GAHT? Study Design and MethodsWe retrospectively analyzed 16 referred TGD patients (8 transgender men, 8 transgender women) receiving GAHT therapy at the time of the test. Data collected and analyzed included: clinical indication for CPET, biometrics (age, height, and weight), CPET parameters (treadmill, Mayo Clinic protocol, without chest binder), chest imaging, echocardiographic results, and hemoglobin levels. ResultsIn transgender women, the use of gender congruent normative predictive values, instead of SAB, significantly increased FAC (69.70 ± 4.35 vs. 87.82 ± 5.15 [%]; mean ± SE; for SAB and gender, respectively; p= <0.0001) and %pred peak VO2 (66.53 ± 4.17 vs. 89.69 ± 5.60 [%]; mean ± SE; for SAB and gender, respectively; p= <0.0001). In transgender men, the use of gender congruent normative predictive values showed that both FAC and %pred peak VO2 significantly decreased (approximately 20% and 25%, respectively). Deconditioning was the most frequent CPET finding among transgender men. InterpretationAmong TGD individuals receiving GAHT, the use of gender to calculate normative values affects %pred peak exercise VO2 and FAC significantly. Body composition changes after GAHT require regular monitoring of muscle strength, lean body mass, and aerobic capacity. Cardiopulmonary symptoms among TGD patients should be assessed with these variables in mind –especially in the presence of chronic cardiac and pulmonary diseases.