Feminizing Hormone Therapy in the Hypertensive Male Rat Does Not Alter Baseline Cardiac Structure and Function

Recent studies indicate that the risk for cardiovascular (CV) disease is increased in transgender women who undergo gender-affirming hormone therapy (GAHT). Hypertension is a leading cause of cardiac impairment. The prevalence of hypertension increases with age and is greater than 30% in men in young adulthood. Yet, the effect of feminizing hormone therapy on cardiac function and structure in men who undergo GAHT in the presence of preexisting hypertension is unknown. The male spontaneously hypertensive rat (SHR) is used as a model to mimic essential hypertension. Thus, this study tested the hypothesis that feminizing hormone therapy in the male SHR is associated with impaired cardiac function and cardiac injury. Methods: Male SHRs were randomly assigned to Control (n=12) or E2 [5 mg/day, pellet sc, replaced every 3 weeks, n=11]. E2 was initiated at 19 weeks of age after the establishment of hypertension at a dose to suppress endogenous testosterone coupled with elevated E2. Cardiac function was measured via echocardiography (VEVO 3100); cardiomyocyte diameter and fibrosis via histology. Results: (Table) At 32 weeks of age (equivalent to a young adult man), heart rate, end-diastolic volume, stroke volume, and cardiac output were significantly decreased in E2-SHR versus Control-SHR, most likely due to the decrease in lean mass in E2-SHR. Yet, other indices of cardiac function were unaltered. Markers of cardiac injury, such as troponin (ELISA) and fibrosis, were unchanged, whereas pro-BNP (ELISA) was significantly decreased in E2-SHR. Cardiomyocyte diameter, an index of cardiac structure, was unchanged compared to control. Although low testosterone in men is associated with a higher incidence of CV disease, our data suggest that androgen suppression in chronic E2-treated male SHR is not associated with impaired cardiac function or an increase in markers of cardiac injury compared to control in young adulthood. Thus, our data suggest that GAHT in transgender women in young adulthood, despite the presence of androgen suppression, does not enhance CV risk. Whether CV risk is enhanced with continued exposure to GAHT across the lifespan requires further studies. [Table: see text] Funding sources: HL143459, P30GM149404, P20-GM-104357, P20-GM121334, T32-HL105324. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.