MON-190 - Acute Cardiovascular Events after Estrogen Based Gender Affirming Hormone Therapy in Transfeminine Adults: Systematic Review and Exploratory Meta-Analysis

Background: Acute cardiovascular event risk following estrogen-based gender-affirming hormone therapy in transfeminine adults is a frequent clinical concern, but contemporary effect estimates compared to sex-specific reference groups remain limited.

Methods: PubMed was searched through December 2025 for longitudinal cohort studies of transfeminine adults with confirmed estrogen exposure, reporting incident myocardial infarction (MI), ischemic stroke, and venous thromboembolism (VTE) with both cisgender male (cis men) and cisgender female (cis women) comparison groups. Two reviewers independently screened studies and extracted adjusted effect estimates. Results were summarized by reference population. Exploratory random-effects meta-analysis combined log hazard ratios and adjusted standardized incidence ratios.

Results: Two cohorts met the inclusion criteria. In the US integrated health system cohort (n=2,842), incidence rates per 1,000 person-years were: myocardial infarction (MI) 2.9, stroke 4.8, and venous thromboembolism (VTE) 5.5. Compared to cisgender men, hazard ratios (HRs) were: MI, 0.9 (95% CI, 0.6–1.5); stroke, 1.2 (0.9–1.7); VTE, 1.9 (1.4–2.7). Compared to cisgender women, HRs were: MI 1.8 (1.1–2.9), stroke 1.9 (1.3–2.6), VTE 2.0 (1.4–2.8). In the estrogen initiation subgroup (n=853), VTE incidence was 4.3 per 1,000 person-years in the first 0–2 years (HR 1.5, 0.5–5.1) and 9.3 per 1,000 person-years after 2 years (HR 5.1, 2.1–12.6).

In the Dutch registry cohort (n=2,714; 23,907 person-years), incidence rates per 1,000 person-years were: MI 1.3, stroke 3.1, VTE 2.4. Socioeconomic status–adjusted standardized incidence ratios (SIR) compared to population men were: MI 0.50 (0.32–0.71), stroke 0.94 (0.72–1.19), VTE 1.81 (1.33–2.35); and compared to population women: MI 1.30 (0.84–1.85), stroke 1.20 (0.92–1.52), VTE 1.74 (1.28–2.26). Exploratory pooled relative risks (RR) versus cis men were: MI 0.66 (0.37–1.18), stroke 1.04 (0.82–1.32), VTE 1.85 (1.49–2.29, p< 0.001); versus cis women: MI 1.48 (1.08–2.03, p=0.014), VTE 1.84 (1.48–2.29, p< 0.001).

Conclusion: In transfeminine adults with confirmed estrogen exposure, risks of myocardial infarction (MI) and ischemic stroke were similar to those in cisgender men. However, the risk of venous thromboembolism (VTE) was elevated and may further increase after initiating therapy. These findings indicate that estrogen-based gender-affirming hormone therapy does not increase the risk of arterial events compared to cis men, but highlight the importance of targeted VTE risk reduction strategies and proactive cardiometabolic prevention.

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