Feminizing and masculinizing gender-affirming hormone therapy affects fibrin clot characteristics in opposite...

The mechanisms behind the increased occurrence of thrombosis associated with gender-affirming hormone treatment (GAHT) are not clarified. We hypothesized that GAHT alters fibrin clot characteristics (formation, lysis, and structure) in a prothrombotic direction.

To investigate changes in ex vivo fibrin clot characteristics after 12 months of feminizing or masculinizing GAHT.

We included 251 transgender women and 320 transgender men aged >17 years in a prospective cohort study. Clot formation (velocity [V _max], maximum absorbance [MA], and overall hemostasis potential [OHP]), clot lysis, and structure (fiber density and diameter) were studied by turbidity 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).

In transgender women, feminizing GAHT increased V _max, MA, and OHP, while clot lysis decreased (total group, all P < .001). Oral estradiol was associated with the largest changes (Δ0-12 months: ΔOHP, 6.03 optical density × min; P = .02; Δclot lysis: -5.0%; P = .005). Fiber density and diameter remained unchanged. In transgender men, V _max, MA, OHP, and fiber diameter decreased following masculinizing GAHT, whereas clot lysis and fiber density increased (total group, all P < .001). We observed no between-group differences in clot characteristics at 12 months or for changes (Δ0-12 months).

Feminizing GAHT for 12 months had prothrombotic effects on the fibrin clot, whereas masculinizing GAHT had antithrombotic effects. The procoagulant effect was most evident with oral feminizing GAHT. This large cohort study provides important insights into the mechanisms linking GAHT to thrombotic risk.