Ventilatory Efficiency in Transgender Women: Implications of Gender-Affirming Hormone Therapy for Cardiorespiratory Responses.

Abstract

Ventilatory efficiency, a key parameter of cardiopulmonary function assessed through cardiopulmonary exercise testing (CPET), often demonstrates significant variability in transgender women because of the physiologic changes induced by gender-affirming hormone therapy. Understanding these differences is essential for optimizing clinical management and enhancing health outcomes within this population. How do ventilatory efficiency, particularly the CO₂ ventilatory equivalent (V˙e/V˙co₂), and other CPET variables differ between transgender women and matched cisgender control participants, offering insights into the physiologic impacts of gender-affirming hormone therapy? This case-control study included 51 participants, comprising 17 transgender women matched 1:1:1 by age, BMI, and physical activity levels with cisgender women and cisgender men. CPET assessments were conducted between August 2018 and September 2019, before the COVID-19 pandemic. Transgender women demonstrated significantly higher V˙e/V˙co₂ ratios at rest (31.4 ± 2.9), at the first ventilatory threshold (34.9 ± 3.9), and peak exercise (39.3 ± 5.3) compared with cisgender women (28.2 ± 2.5, 31.8 ± 3.2, and 35.4 ± 4.4, respectively) and cisgender men (27.4 ± 2.1, 30.8 ± 2.6, and 34.3 ± 3.5, respectively), with all comparisons reaching statistical significance (P < .001) and large effect sizes (η² = 0.30-0.34). The V˙e/V˙co₂ slope was also significantly elevated in transgender women (33.9 ± 4.2) compared with cisgender women (29.5 ± 5.0) and cisgender men (28.0 ± 3.5) (P < .001; η² = 0.29), indicating reduced ventilatory efficiency across the effort continuum. This study highlights substantial ventilatory inefficiencies in transgender women, likely associated with gender-affirming hormone therapy, underscoring the need for tailored clinical strategies to address these cardiopulmonary adaptations. These findings provide critical insights into the unique health needs of transgender individuals, contributing valuable data to support evidence-based care.