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

Nasal TMPRSS2 expression increased significantly in AFAB individuals receiving testosterone therapy at 12 months compared to baseline.

• The increase in nasal TMPRSS2 expression was statistically significant (p = 0.008) at the 12-month timepoint.
• Oral TMPRSS2 expression in AFAB individuals remained stable over the same period (p = 0.810), indicating a tissue-specific effect.
• This finding highlights a divergence between nasal and oral mucosal responses to testosterone therapy.

After one year of testosterone therapy, nasal TMPRSS2 expression in AFAB individuals was higher than in cisgender males, though the difference did not reach statistical significance.

• The comparison between AFAB individuals at 12 months and cisgender male controls yielded p = 0.290.
• The cisgender male control group comprised 15 individuals.
• Despite the lack of statistical significance, the trend suggests testosterone may drive TMPRSS2 expression beyond typical male levels in nasal tissue.

Significant positive correlations between ACE2 and TMPRSS2 expression were observed in nasal mucosa after one year of GAHT in both AFAB and AMAB individuals.

• In AFAB individuals after 12 months of GAHT, the nasal ACE2-TMPRSS2 correlation was r = 0.699, p < 0.001.
• In AMAB individuals after 12 months of GAHT, the nasal ACE2-TMPRSS2 correlation was r = 0.727, p = 0.007.
• These significant correlations were observed exclusively in nasal mucosa and not in oral mucosa.
• No such significant correlations were reported at baseline, suggesting GAHT may coordinately regulate these genes in nasal tissue.

The study prospectively enrolled 35 transgender individuals initiating GAHT, with 31 completing the full 12-month follow-up.

• The GAHT group included 19 AFAB individuals undergoing masculinizing (testosterone) therapy and 16 AMAB individuals undergoing feminizing therapy.
• Nasal and oral swabs were collected at three timepoints: baseline, 6 months, and 12 months.
• The control group comprised 15 cisgender males and 18 cisgender females, matched by age and sex.
• Gene expression was quantified using quantitative real-time PCR.

The effects of GAHT on ACE2 and TMPRSS2 expression were tissue-specific, differing between nasal and oral mucosa.

• Testosterone therapy significantly altered TMPRSS2 expression in nasal but not oral mucosa in AFAB individuals.
• The co-regulation of ACE2 and TMPRSS2 after 12 months was observed only in nasal mucosa across both AFAB and AMAB groups.
• The authors describe these as 'tissue-specific transcriptional changes' warranting further investigation.