Venous Thromboembolism in Transgender and Gender Diverse Individuals on Estrogen-Based Gender-Affirming Hormone Therapy.

Background: The use of estrogen-based gender-affirming hormone therapy (E-GAHT) has been associated with an increased risk of venous thromboembolism (VTE), but much of the evidence originates from data on cisgender women and from cohorts of transgender and gender diverse (TGD) individuals treated with older estrogen or estrogen/progesterone preparations, often at higher doses. Data on VTE risks associated with more modern E-GAHT regimens in TGD populations are scarce. Methods: A retrospective cohort study of adult TGD individuals who received E-GAHT within the Duke University Health System between January 1996 and June 2025 was conducted. The Duke Enterprise Data Unified Content Explorer (DEDUCE), a Duke electronic medical record search tool, was utilized to identify a cohort of TGD individuals who were prescribed E-GAHT. From this cohort, individuals who experienced a VTE during E-GAHT exposure were identified. Demographic characteristics and comorbidities were compared between the overall study cohort and those who experienced VTE using the SlicerDicer tool within Epic, supplemented by manual chart review. Results: Among 1173 adult TGD individuals prescribed E-GAHT, 16 (1.4%) experienced a VTE. Of these, 11 (68.8%) experienced a pulmonary embolism (PE with/without deep vein thrombosis [DVT]) and five (31.3%) experienced a DVT alone. Among the 16 patients with VTE, six (37.5%) had a transient surgical risk factor prior to VTE, three (18%) had significant non-surgical risk factors, and one (6%) had cancer. The remaining six (37.5%) patients experienced an unprovoked VTE. Patients with VTE were significantly older than the general population of TGD adults and were significantly more likely to experience hypertension, hyperlipidemia, and type 2 diabetes mellitus, compared to TGD patients without VTE. Conclusions: In this retrospective cohort, the proportion of TGD individuals on E-GAHT with VTE was lower than previously reported in the literature. Most events occurred in the presence of other established risk factors, suggesting that E-GAHT itself may confer a lower VTE risk than previously assumed. Larger prospective studies that evaluate both estrogen-specific and patient-specific risk factors are needed to clarify VTE risk in this population.

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Author Carly Elizabeth Kelley Medicine, Endocrinology, Metabolism, and Nutrition

Author Quinnette B. Jones Family Medicine and Community Health, Physician Assistant Pr ...