Cardiopulmonary Exercise Testing in Transgender and Gender-Diverse Patients: The Influence of Sex and Gender on Predicted Aerobic Capacity

Background: Sex assigned at birth is currently used to calculate predicted normative values for oxygen consumption 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 Question: What are the changes in functional aerobic capacity (FAC) and % predicted peak oxygen consumption (V˙O₂peak) when gender is used, instead of sex assigned at birth (SAB), to estimated normative predicted values among TGD patients aged > 14 years who are receiving GAHT? Study Design and Methods: We retrospectively analyzed 16 referred TGD patients (eight transgender men and eight transgender women) receiving GAHT at the time of the test. Data collected and analyzed included the following: 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. Results: In transgender women, the use of gender congruent normative predictive values, instead of SAB, significantly increased FAC (mean ± SE for SAB and gender, respectively, 69.70% ± 4.35% vs 87.82% ± 5.15%; P ≤ .0001) and % predicted VO₂peak (mean ± SE for SAB and gender, respectively, 66.53% ± 4.17% vs 89.69% ± 5.60%; P ≤ .0001). In transgender men, the use of gender congruent normative predictive values showed that both FAC and % predicted VO₂peak significantly decreased (approximately 20% and 25%, respectively). Deconditioning was the most frequent CPET finding among transgender men. Interpretation: Among TGD individuals receiving GAHT, the use of gender to calculate normative values affects % predicted peak exercise oxygen consumption 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.