Testosterone Replacement Therapy in Relation With Cardiovascular Disease in Cisgender Women and Transgender People

AIMS: This study aimed to investigate the association of testosterone replacement therapy (TTh) with risk of cardiovascular disease (CVD), and CVD-specific outcomes, in cisgender women and transgender population, and to determine whether this association varies by menopausal status. METHODS: In 25 796 cisgender women and 1580 transgender people (≥30 years old) who were enrolled in the Optum's deidentified Clinformatics Data Mart Database (2007-2021), we identified 6288 pre- and postmenopausal cisgender women and 262 transgender people diagnosed with incident composite of CVD (coronary artery disease [CAD], congestive heart failure, stroke, and myocardial infarction). Prediagnostic prescription of TTh was ascertained for this analysis. Multivariable adjusted Cox proportional hazards models were used to examine the independent association of TTh with incident CVD. RESULTS: We found a 24% increased risk of CVD (hazard ratio [HR] = 1.24; 95% CI, 1.15-1.34), 26% risk of CAD (HR = 1.26; 95% CI, 1.14-1.39), and a 29% risk of stroke (HR = 1.29; 95% CI, 1.14-1.45) after comparing cisgender women who used TTh with nonusers. Stratification by age group showed similar effects of TTh on CVD, CAD, and stroke. Among transgender people, TTh did not increase the risk of composite CVD, including by age stratification. CONCLUSION: Use of TTh increased the risk of CVD, CAD, and stroke among cisgender women but not among transgender people. TTh is becoming more widely accepted in women, and it is the main medical treatment for transgender males. Therefore, use of TTh should be further investigated for the prevention of CVD.