Gender-affirming hormone therapy (GHT) in hypertensive rats: characterization of estrogen effects on cardiac hypertrophy

PIS DIEZ M; ESCUDERO DS; VERZOLETTO B; COLAREDA G; LOFEUDO, JM; MARTINEZ VR; VELEZ RUEDA, JO; PEREZ, NG; DIAZ, RG

Buenos Aires

Congreso; Congreso Anual SAFIS 2023; 2023

SOCIEDAD ARGENTINA DE FISIOLOGIA (SAFIS)

Introduction: GHT, aimed to align the characteristics of people with gender dysphoria with their identity, have been studied in terms of sexual hormone effects and main adverse effects. However, some concerns about its cardiovascular (CV) consequences remained unresolved, due to incongruence of the reported clinical evidence and the existing sex differences in CV functions. Transgender females (TGF) have major CV risk, but it is unclear if estrogen therapy (ET) per se or testosterone deprivation is related to the higher CV risk. In addition, it is even less clear whether preexistent hypertension in these populations can worsen CV condition.Aims: The aim of present work is to characterize the cardiac effect of ET in a model of TGF in spontaneously hypertensive rats (SHR). Methods: 3 month-old male SHR were assigned to 3 groups: GDX (gonadectomized for 3 months), TGF (GDX plus 1-month treatment with ET), SHAM. Dose and frequency of ET were selected according to replacement therapy, and simulating estrogen estrous peaks. Blood Pressure (BP) was monitored along the treatment, echocardiography was assessed previous to sacrifice. After sacrifice, collagen content, oxidative stress and protein expression were determined.Results: Testosterone deprivation prevented the increase in LV mass increase observed in SHAM, an effect that was canceled by ET (mg/mm: SHAM 27.7±1.4; GDX 21±4.2; TGF 27.1±0.8). No changes in BP or h/r ratio were found suggesting that the remodeling pattern remained unaltered. GDX presented a diminution in cardiac fibrosis that was partially reverted by ET (% of total collagen: SHAM 1.07±0.01; GDX 0.53±0.003; TGF 0.66±0.001). Both GDX and TGF hearts showed reduced reactive oxygen species (IF/ug protein: SHAM 15.3±12.2; GDX 9.2±4.6; TGF 3.2±0.5) together with an increased catalase expression (%: SHAM 100± 20; GDX 158±37; TGF 188±24), and an increased eNOS expression only in TGF (%: SHAM 100±35; GDX 106±33; TGF 157±26), that would indicate a lesser oxidative stress compared to SHAM. Body weight decreased in GDX, effect that was restored by ET (g: SHAM 358±10; GDX 339±9, TGF 344±7), while white adipose tissue index increased in GDX and increased more in TGF (WAT in g/g: SHAM 4.4±0.04; GDX 5.5±0.3; TGF 6.2±0.5). Conclusion: These preliminary results suggest that ET therapy in TGF comprises a complex scenario that deserves further investigation.