Tissue-specific alterations in ACE2 and TMPRSS2 expression following gender-affirming hormone therapy: a preliminary study.

PURPOSE: To investigate the effects of gender-affirming hormone therapy (GAHT) on ACE2 and TMPRSS2 expression in nasal and oral mucosa. METHODS: Transgender individuals initiating GAHT at the Endocrinology and Metabolism outpatient clinic were prospectively enrolled. Nasal and oral swabs were collected at baseline, 6 months, and 12 months. Age- and sex-matched healthy cisgender individuals served as controls. The impact of GAHT on ACE2 and TMPRSS2 expression in nasal and oral mucosa was evaluated using quantitative real-time PCR. RESULTS: The study included 35 individuals undergoing GAHT, including 19 assigned female at birth (AFAB) individuals undergoing masculinizing GAHT and 16 assigned male at birth (AMAB) individuals undergoing feminizing GAHT, with 31 completing follow-up. The control group comprised 15 cisgender males and 18 cisgender females. In AFAB individuals receiving testosterone therapy, nasal TMPRSS2 expression increased significantly from baseline at 12 months (p = 0.008), whereas oral TMPRSS2 expression remained stable (p = 0.810). Following one year of testosterone therapy, nasal TMPRSS2 expression in AFAB individuals was higher than in cisgender males, although the difference was not statistically significant (p = 0.290). Significant correlations between ACE2 and TMPRSS2 expression were observed exclusively in nasal mucosa after one year of GAHT in both AFAB and AMAB individuals (r = 0.699, p < 0.001 and r = 0.727, p = 0.007, respectively). CONCLUSION: Testosterone therapy was associated with increased nasal TMPRSS2 expression in AFAB individuals after 12 months, warranting further investigation of these tissue-specific transcriptional changes.