Abstract

Transgender females ( TGF ) are born biologically male, but identify as female. TGFs undergo Gender-Affirming Hormone Therapy ( GAHT ) to match their physical and sex characteristics with their perceived gender. Several studies indicate that GAHT is associated with increased cardiovascular ( CV ) risk. Previously, we reported that GAHT, 17β-Estradiol ( E2 ) supplementation with androgen suppression, in the normotensive male Sprague Dawley ( SD ) rat is associated with loss of lean mass and increased markers of CV risk. Yet, the effect of GAHT in the presence of preexisting hypertension and renal injury is unknown. Thus, this study tested the hypothesis that GAHT in the male spontaneous hypertensive rat ( SHR ) is associated with increased CV and renal risk. Methods: Male SHRs were randomly assigned to 2 groups: Control (n=4) and E2 [5 mg/day, pellet sc, replaced every 3 weeks, n=6]. E2 was initiated at 19 weeks of age at a dose to suppress endogenous testosterone coupled to elevated E2. Results: ( Table ) At 49 weeks of age (equivalent to a 40 year old man), body weight and total lean mass (EchoMRI) were significantly decreased in E2 SHR; as previously observed in E2 SD. Yet, total fat mass (EchoMRI) was significantly decreased in E2 SHR; moreover, 24 hour urinary proteinuria and cystatin C (ELISA) were also significantly decreased. Hypertension and renal injury are androgen-dependent in male SHR. Thus, despite the increase in E2 in the male SHR, androgen suppression induced by GAHT was renoprotective. Further studies will determine relevance of the SHR as a model of GAHT and explore long-term effects of E2.

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