Global coagulation assays in transgender women on oral and transdermal estradiol therapy

CONTEXT: The thrombotic effects of estradiol therapy in transgender women are unclear. Global coagulation assays (GCA) may be better measures of hemostatic function compared with standard coagulation tests. OBJECTIVE: To assess the GCA profiles of transgender women in comparison to cisgender controls and to compare how GCA differ between routes of estradiol therapy in transgender women. DESIGN: Cross-sectional case-control study. SETTING: General community. PARTICIPANTS: Transgender women, cisgender male and cisgender female controls. MAIN OUTCOME MEASURES: Citrated blood samples were analyzed for (i) whole blood thromboelastography (TEG®5000), (ii) platelet-poor plasma thrombin generation (calibrated automated thrombogram); and (iii) platelet-poor plasma fibrin generation (overall hemostatic potential assay). Mean difference (95% confidence intervals) between groups are presented. RESULTS: Twenty-six transgender women (16 oral estradiol, 10 transdermal estradiol) were compared with 98 cisgender women and 55 cisgender men. There were no differences in serum estradiol concentration (P = 0.929) and duration of therapy (P = 0.496) between formulations. Transgender women demonstrated hypercoagulable parameters on both thromboelastography (maximum amplitude + 6.94 mm (3.55, 10.33); P < 0.001) and thrombin generation (endogenous thrombin potential + 192.62 nM.min (38.33, 326.91); P = 0.009; peak thrombin + 38.10 nM (2.27, 73.94); P = 0.034) but had increased overall fibrinolytic potential (+4.89% (0.52, 9.25); P = 0.024) compared with cisgender men. No significant changes were observed relative to cisgender women. Route of estradiol delivery or duration of use did not influence the GCA parameters. CONCLUSION: Transgender women on estradiol therapy demonstrated hypercoagulable GCA parameters compared with cisgender men with a shift towards cisgender female parameters. Route of estradiol delivery did not influence the GCA parameters.