The thrombin generation potential increases after feminizing gender-affirming hormone treatment, decreases after masculinizing gender-affirming hormone treatment, and is determined by the hormone treatment regimen

Background: The effects of gender-affirming hormone therapy (GAHT) on the overall coagulation potential are not clarified. The global thrombin generation (TG) assay addresses the combined effect of coagulation factors and inhibitors. Objectives: We aimed to investigate changes in TG after initiation of feminizing or masculinizing GAHT. Methods: We included a cohort of 270 transgender women and 348 transgender men aged >17 years. The primary outcomes were TG variables (endogenous thrombin potential [ETP], peak TG, and TG lag time) measured at baseline and after 12 months of feminizing GAHT (3 groups of oral/transdermal estradiol and cyproterone acetate) or masculinizing GAHT (7 groups of intramuscular/transdermal testosterone). Results: In transgender women, ETP and peak TG increased after oral and transdermal estradiol (P < .001), and the largest increase was after oral estradiol (ΔETP: 113 nmol/L × min, P = .011; Δpeak TG: 28 nmol/L, P = .009). In transgender men, ETP or peak TG decreased after 6 testosterone modalities (P < .05) except transdermal testosterone. The largest 12 months effect was seen in transgender men receiving gestagen at baseline compared with intramuscular testosterone (ΔETP: −199 nmol/L × min, P < .001; Δpeak TG: −38 nmol/L, P = .008) and transdermal testosterone (ΔETP: −216 nmol/L × min, P < .001; Δpeak TG: −40 nmol/L, P = .007). Lag time was prolonged for 6 testosterone modalities (P < .05), except in the subgroup receiving baseline gestagen, with no between-group differences. Conclusion: Feminizing and masculinizing GAHT for 12 months affected coagulation in opposite directions. Feminizing GAHT was procoagulant, whereas masculinizing GAHT was anticoagulant. Of note, transdermal feminizing GAHT had the least pronounced procoagulant effect.