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Reproductive Endocrinology

ORF46-05 - Coagulation and Vascular Function in Transgender and Gender-Diverse Adults on Estrogen-Dominant Gender-Affirming Hormone Therapy

Monday, June 15, 2026
2:45 PM - 3:00 PM CT
Location: Room W179



Background: Transgender women and gender-diverse (TGD) individuals on estrogen-dominant gender-affirming hormone therapy (GAHT) have increased risk of venous thromboembolism (VTE) and myocardial infarction. Estrogen has prothrombotic effects and modulates endothelial function. However, data on the longitudinal effects of 17β-estradiol in combination with anti-androgen therapy (+/- progesterone), on coagulation and vascular function among TGD individuals remain limited. We prospectively evaluated changes in coagulation parameters and systemic markers of vascular function and inflammation among TGD individuals over 12 months following initiation of estrogen-dominant GAHT.

Methods: TGD adults recently initiated on or initiating GAHT with 17β-estradiol with anti-androgen therapy, were prospectively recruited. Laboratory assessments were obtained at baseline and at 12 months for the 26 participants who completed the study. Exclusions were: a history of atherosclerotic cardiovascular disease (ASCVD), prior orchiectomy, recent anti-platelet or anti-coagulant therapy, or >5 months of prior estrogen-dominant GAHT.

Results: Participants had a median age of 26 [20, 30] years. All were assigned male sex at birth, and most identified as transgender women (81%), with the remainder identifying as transgender women and non-binary (11%) or non-binary (8%). Participants were on oral/sublingual (61%), injectable (27%), or transdermal (12%) 17β-estradiol. Over the 12 months, prothrombotic changes were observed, including increases in Factor II, Factor VII, and Factor X activities, along with decreases in protein S activity and aPTT (all P< 0.05). No changes occurred in Factor V, Factor VIII, Factor IX, vWF activity or antigen levels, antithrombin III activity, fibrinogen, INR, or PT. In exploratory analyses, increases in Factor II and Factor VII were greater among progesterone users vs. non-users (12% vs. 1%, P=0.0466 and 19% vs. 5%, P=0.008, respectively), with a similar trend for Factor X. Changes in Factor X were positively associated with changes in BMI (β-estimate=2.36, P=0.02). In contrast, VCAM-1 decreased (620.7 [517.4, 722.2] to 523.5 [460.9, 592.9] ng/mL, P< 0.0001), while IL-6, ICAM-1, TNF-α, and adiponectin did not change. Significant changes in coagulation and inflammatory markers did not differ by estradiol route of administration, smoking status, GAHT duration, or changes in hormone levels.

Conclusions: Estrogen-dominant GAHT was associated with prothrombotic changes in multiple coagulation parameters and with reduced VCAM-1, a marker of endothelial activation. Progesterone use was associated with greater increases in select procoagulant factors, suggesting regimen-specific effects on thrombotic risk. Additional studies are needed to clarify the clinical implications of these mechanistic findings on VTE and ASCVD risk among TGD individuals.