Endocrine Abstracts

Background: Sex based differences in the immune system are well-documented in the literature. The influence of sex on the immune system is primarily attributed via chromosomal and sex hormone mediation. Cis men generally exhibit a weaker immune response compared to cis women. This contrast extends to various immune-mediated diseases, where cis men show a higher incidence of cancer but fewer autoimmune diseases than cis women. Testosterone is part of gender affirming masculinizing hormone therapy. Transgender men often take testosterone to align with their gender identity. Despite the safety of testosterone use in this population, limited data exist regarding its effects on the immune system in transgender men. Questions persist about whether the immune modulation in transgender men on testosterone aligns with their assigned sex at birth or if a unique modulation occurs.

Methods: This study conducted between October 2022 and November 2023, as a prospective observational study involving 21 healthy transgender men with XX chromosomes. All participants were testosterone-naïve at baseline. Over a 6-month period, participants underwent routine clinical care, with testosterone levels targeted towards cis-men ranges. Immunological, hormonal, and biochemical parameters were assessed. TLR receptor expressions were measured on whole blood using real-time PCR at baseline and 6 month. β-actin and GAPDH served as housekeeping control genes.

Results: At the 6-month assessment, changes in TLR expressions were evaluated, revealing noteworthy alterations. TLR2, TLR3, TLR6, TLR10, CD14 and MD2 displayed varying degrees of modulation. Of particular interest, TLR8 exhibited a significant decrease expression from 3.5 [3.1, 4.3] to 2.6 [1.2, 3.3] (P= 0.0016), a similar decrease was also observed for TLR10 from 6.2 [5.3, 6.7] to 4.7 [3.5, 5.4] (P< 0.001).

Conclusion: This study sheds new light on the intricate dynamics of immune modulation in transgender men undergoing testosterone therapy, revealing specific alterations in TLR expressions. The statistically significant changes observed for TLR8 and TLR10 suggest a nuanced impact of testosterone on immune markers and once again demonstrates the immunosuppressive mechanism of testosterone. This study advances our understanding of hormone therapy’s immunological effects in transgender individuals. Furthermore, these findings can offer the potential to deepen comprehension of immune variations between genders, extending beyond the scope of transgender health.