The effect of testosterone on platelet activation and inflammation in transgender men.

Background and aims: Transgender men (female sex assigned at birth, male gender identity) who use testosterone have a higher cardiovascular risk compared to women and men from the general population, which cannot be fully attributed to traditional cardiovascular risk factors. Platelet activation and (endothelial) inflammation are interconnected mechanisms in the process of primary hemostasis, and thus the development of cardiovascular disease, but the impact of testosterone on these mechanisms is largely unexplored. Hence, we aimed to investigate the effect of testosterone on platelet activation and inflammation in vivo.

Methods: In this prospective cohort study 18 transgender men were included. Blood samples were taken at baseline and at 6, 12 and 52 weeks after testosterone initiation. We measured seven platelet activation markers (plasma thromboxane B2, Closure Time measured in two ways, CD63, CD62p, platelet-leukocyte complexes, immature platelet fraction), and twelve inflammation markers (high sensitivity CRP and 11 cytokines). Percentage changes relative to baseline were calculated at each time point using linear mixed model analyses.

Results: Platelet activation markers CD63, CD62p, and platelet-leukocyte complexes exhibited an initial tendency to increase at week 6, then slightly decreased at week 12, and again increased at week 52. Closure Time and immature platelet fraction remained stable throughout the study period. The collective of inflammation markers exhibited an overall tendency toward increase throughout the study period, which was most pronounced at week 52.

Conclusion: The results suggest that testosterone administration may increase platelet activation and inflammation. This may contribute to the higher cardiovascular risk in transgender men.

Study registration: EudraCT #2017-003072-31.