Venous Thromboembolism Risk in Transgender Women on Feminizing Hormone Therapy: A Narrative Review of Formulation-Specific Risks, Management Strategies, and Evidence Gaps

The transgender population is growing, with more people seeking gender-affirming care. While estrogen-based gender-affirming hormone therapy (E-GAHT) is essential for transfeminine individuals, most evidence on associated venous thromboembolism (VTE) risks is outdated and no longer used in clinical practice. Routine primary anticoagulant prophylaxis is not recommended for low-risk individuals initiating E-GAHT. In selected patients with prior VTE, known thrombophilia, or multiple major thrombotic risk factors, prophylactic anticoagulation may be considered on an individualized basis after assessment of bleeding risk and shared decision-making, although this approach is not currently supported by high-quality prospective evidence. Contemporary 17β-estradiol regimens show substantially lower VTE rates, with transdermal formulations showing the most favorable safety profile. In the perioperative setting, continuation of E-GAHT or a reduced dose in high-risk groups with standard VTE prophylaxis, guided by Caprini scoring, is recommended, as no increase in postoperative VTE was observed in multiple retrospective cohorts and meta-analyses. In the transgender population, discontinuation of GAHT following a VTE event can cause significant emotional and psychological distress. Recent studies support continuing GAHT, preferably at a reduced dose, while initiating therapeutic anticoagulation, with extended or indefinite duration considered through shared decision-making.