Systemic vascular and organ functions in transgender women receiving feminizing hormone therapy

Although estrogen is known to confer cardioprotective benefits in cisgender women, transgender women on gender-affirming hormone therapy may experience unique cardiovascular risks. Emerging evidence suggests that feminizing hormone therapy may confer both beneficial and adverse effects on the cardiovascular, renal, and hepatic systems. In this cross-sectional study, transgender women receiving gender-affirming hormone therapy with orchiectomy (n = 15) or without orchiectomy (n = 15) were compared with age-matched cisgender men (n = 15) and cisgender women (n = 15). Transgender women had received hormone therapy for 11 ± 3 yr. Serum estradiol concentrations were significantly lower in cisgender men (33 ± 10 pg·mL^-1) than in transgender women with orchiectomy (141 ± 47 pg·mL^-1), transgender women without orchiectomy (116 ± 41 pg·mL^-1), and cisgender women (131 ± 38 pg·mL^-1), whereas serum testosterone concentrations were significantly higher in cisgender men (22.0 ± 6.1 nM) compared with the other groups (1.2 ± 1.1, 0.6 ± 0.3, and 1.0 ± 0.3 nM) (all P < 0.001). No statistically significant group differences were observed in brachial-ankle pulse wave velocity, brachial artery flow-mediated dilation, postocclusive skin reactive hyperemia, or blood nitric oxide concentrations (all P > 0.05). Blood urea nitrogen, creatinine, and liver enzyme concentrations were significantly higher in cisgender men than in the other groups (all P < 0.05). Collectively, these results indicate that no statistically significant differences were observed in macro- and microvascular function, as well as liver and renal function, between transgender women (with or without orchiectomy) and cisgender women.NEW & NOTEWORTHY The primary finding of the present study is that transgender women demonstrate similar macrovascular and microvascular function as well as renal and hepatic function to cisgender women. Regardless of marked differences in circulating sex hormone profiles, no evidence of vascular dysfunction or organ impairment was observed in transgender women. These findings suggest that prolonged exposure to an estrogen-dominant hormonal milieu is sufficient to induce a female-typical physiological phenotype across multiple organ systems.