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.

Feminizing GAHT increased thrombin generation potential in transgender women after both oral and transdermal estradiol administration.

• ETP and peak TG increased after oral and transdermal estradiol (P < .001)
• The largest increase was after oral estradiol (ΔETP: 113 nmol/L × min, P = .011; Δpeak TG: 28 nmol/L, P = .009)
• Cohort included 270 transgender women aged >17 years
• Measurements taken at baseline and after 12 months of GAHT
• Three groups of feminizing GAHT were studied: oral/transdermal estradiol combined with cyproterone acetate

Masculinizing GAHT decreased thrombin generation potential in transgender men across most testosterone modalities.

• ETP or peak TG decreased after 6 of 7 testosterone modalities (P < .05)
• Transdermal testosterone was the exception, showing no significant decrease in ETP or peak TG
• Cohort included 348 transgender men aged >17 years
• Seven groups of masculinizing GAHT were studied: intramuscular/transdermal testosterone formulations
• Measurements taken at baseline and after 12 months of GAHT

The largest decrease in thrombin generation in transgender men was observed in those who were receiving gestagen at baseline before switching to testosterone.

• Transgender men receiving gestagen at baseline and then intramuscular testosterone showed ΔETP: -199 nmol/L × min (P < .001) and Δpeak TG: -38 nmol/L (P = .008)
• Transgender men receiving gestagen at baseline and then transdermal testosterone showed ΔETP: -216 nmol/L × min (P < .001) and Δpeak TG: -40 nmol/L (P = .007)
• These were the largest 12-month effects observed among all testosterone treatment groups

Thrombin generation lag time was prolonged by masculinizing GAHT in most testosterone treatment groups.

• Lag time was prolonged for 6 of 7 testosterone modalities (P < .05)
• The subgroup receiving baseline gestagen was the exception, showing no significant prolongation of lag time
• No between-group differences in lag time were observed among the testosterone modalities

Transdermal feminizing GAHT had the least pronounced procoagulant effect compared to oral estradiol.

• Both oral and transdermal estradiol increased ETP and peak TG, but the largest increase was seen with oral estradiol
• Oral estradiol produced ΔETP of 113 nmol/L × min compared to smaller increases with transdermal estradiol
• This finding is noted as clinically relevant as transdermal administration may represent a safer option regarding thrombotic risk

The global thrombin generation assay was used to assess the combined effect of coagulation factors and inhibitors before and after GAHT.

• Primary outcomes were TG variables: endogenous thrombin potential (ETP), peak TG, and TG lag time
• A total of 270 transgender women and 348 transgender men were included
• Participants were aged >17 years
• Measurements were taken at baseline and after 12 months of feminizing or masculinizing GAHT
• Ten treatment subgroups were analyzed in total (3 feminizing, 7 masculinizing)