Thrombotic risk associated with gender-affirming hormone therapy

Transgender and gender-expansive (TG) people-those who identify with a gender other than their assigned sex at birth-frequently experience gender dysphoria, which is associated with negative health outcomes. One key strategy for improving gender dysphoria is the use of gender-affirming hormone therapy (GAHT): estrogen for feminization and testosterone for masculinization. Estrogen use in cisgender women is associated with well-established changes in hemostatic parameters, including increases in prothrombotic factors and decreases in inhibitors of coagulation. Cisgender women using estrogen have an increased risk of thrombosis. Studies of thrombosis risk associated with estrogen GAHT in TG people are less robust, with some studies limited by the use of hormones and hormone management strategies that are no longer recommended. However, TG women using estrogen appear to be at increased risk of both arterial and venous thrombosis, which may increase with longer time on estrogen. Testosterone use in both cisgender and transgender men is associated with increases in hemoglobin and hematocrit, which can lead to erythrocytosis and thus increased risk of thrombosis. The results of studies evaluating thrombosis risk in the setting of testosterone use are mixed. This review presents an overview of alterations in hemostatic parameters and thrombosis risk associated with use of exogenous estrogen and testosterone. Understanding what is known and unknown about thrombosis risk associated with use of these hormones is essential for hematologists who may be asked to evaluate TG people and provide guidance on management of those who may be at increased risk of thrombosis.