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. OBJECTIVE: To investigate changes in TG after initiation of feminizing or masculinizing GAHT. PATIENTS/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, TG lag time) measured at baseline and after 12 months of feminizing GAHT (three groups of oral/transdermal estradiol and cyproterone acetate) or masculinizing GAHT (seven groups of intramuscular/transdermal testosterone). RESULTS: In transgender women, ETP and peak TG increased after oral and transdermal estradiol (p<
0.001), the largest increase was after oral estradiol (ΔETP: 113 nmol/l x min, p=0.011
Δpeak TG: 28 nmol/l, p=0.009). In transgender men, ETP or peak TG decreased after six testosterone modalities (p<
0.05) except transdermal testosterone (NS). The largest 12 months effect was seen in transgender men receiving gestagen at baseline compared with intramuscular testosterone (ΔETP: -199 nmol/l x min, p<
0.001
Δpeak TG: -38 nmol/l, p=0.008) and transdermal testosterone (ΔETP: -216 nmol/l x min, p<
0.001
Δpeak TG: -40 nmol/l, p=0.007). Lag time was prolonged for six testosterone modalities (p<
0.05), except in the subgroup receiving baseline gestagen, and with no between-group differences. CONCLUSIONS: 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.