First Evidence of Cardiopulmonary Adaptation to Physical Effort in Transgender Women After Long-Term Hormone Therapy: A Cross-Sectional Study
Authors: Alvares Leonardo A M , Santos Marcelo R , Souza Francis R , Santos Lívia M , Mendonca Berenice Bilharinho , Alves Maria-Janieire N Nunes , Costa Elaine Maria Frade , Domenice Sorahia 
Published: May 2021

Abstract
Introduction: Cisgender men (CM) and women (CM) present different acute cardiopulmonary (CP) adaptation to effort. The smallest arteriovenous difference in oxygen (O2) and cardiac output (CO) in CW determine a lower maximum VO2 (VO2max) than CM. CP capacity adaptation to effort of TW undergoing gender-affirming hormone therapy (GAHT) was not yet reported. Objective: To evaluate CP capacity of TW in long-term GAHT. Methods: A cross-sectional study was carried out with 8 TW (average age of 34.0 ±4.8 yo), 8 CM and 8 CW matched on age, body mass index and activity level. All TW were non-gonadectomized subjects and were in estrogen [transdermal estradiol (n=2), oral estradiol (n=3) and conjugated estrogen (n=3)], plus cyproterone acetate (n=8) therapy in an average time of 15.6 ±8.7 years. Body composition was assessed by InBody 720, and participants’ level of physical activity by IPAQ (International Physical Activity Questionnaire) short form. Total testosterone (ng/dL) levels of TW, CW and CM were 83,5 (12,0;637,0), 20,5 (12,0;41,0) and 480,5 (264,0;843,0), respectively. Hemoglobin levels of TW, CW and CM were 14,2 (13,5;14,9), 14,35 (12,8;14,7) and 15,35 (14,0;18,2), respectively. Everyone performed a CP exercise testing on a treadmill with an incremental effort. Results: Mean VO2max (L/min) in the group of TW was 2648±575.5, of CW 2128±394.0 and of CM 3235±554.0 (TWvsCW p=0.1311; TWvsCM p=0.0806; CWvsCM p=0.009). Free fat mass (FFM) of TW was 55.56±6.88 kg, CW 38.98±4,09 kg, and CM 64,98±6,29 kg (TWvsCW p&lt;0,0001; TWvsCM p=0,024; CWvsCM p&lt;0,0001). Analysis of VO2max/FFM (L/min/kg), TW′s rate was 46.6±6.2, CW′s was 54.6±8.4 and CM′s was 49.4±6.1 (TWvsCW p=0.0770;TWvsCM p=0.6942; CWvsCM p=0.3185). O2 pulse, VE/VO2 (ventilatory equivalents for O2) and VE/VCO2 (ventilatory equivalents for carbon dioxide) were similar in all groups. There was high correlation of O2pulse and free fat mass/height2 (FFM/Hgt2) of TW (r 0,925;p 0,008), not observed in CW (r 0.614;p0.105) or CM (r 0.737; p 0.037).% predicted Heart Rate (%HR) at effort was higher in TW (104) than in CW (95.8)(p=0.0221) and CM (100.3)(p=0.3334). Discussion: Aerobic capacity of TW was intermediate between CM and CW. Regards VO2 / FFM ratio, TW had a lower index than other groups. Since changes in pulmonary O2 diffusion, CO and blood circulation were ruled out as causing such data, it could be related to O2 uptake drops by the muscle. Increased sympathetic activity and %HR in TW and high correlation of O2pulse and FFM/Hgt2 make up compatible framework with exacerbation of ergoreflex. Conclusion: Our results support the finding of a VO2max similar between TW undergoing long-term GAHT and CW groups, despite the previous expose of TWs to testosterone during puberty. We hypothesized the presence of an increased ergoreflex sensitivity in TW individuals. These preliminary results should be confirmed by increasing the number of individuals studied.