Endocrine Abstracts

JOINT999

Aim: Cardiovascular safety of testosterone therapy has been a subject of controversies. A recent trial showed an increased risk of pulmonary embolism and atrial fibrillation in men with hypogonadism. The issue of cardiovascular safety of testosterone therapy also concerns female-to-male transgenders, for whom there are limited evidence. The aim was to assess in a real-life setting the safety profile and cardiovascular risk of testosterone therapy in these two different clinical settings: cisgender men with hypogonadism and transgender men.

Methods: We used TriNetx Research Collaborative network, a global federated health research network with access to electronic medical records from participating health care organizations, to identify and included participants. Diagnosis was done using the International Classification of Diseases, Ninth Revision and Tenth Revision, Clinical Modification (ICD-10-CM) codes, and medications. We used a 1:1 propensity-score matching for age and baseline characteristics to compare 117,908 cisgender men with hypogonadism treated with testosterone to 117,908 untreated cisgender men without a diagnosis of hypogonadism. Similarly, we compared matched 9,714 transgender men treated with testosterone to 9,714 untreated cisgender women treated with a contraceptive pill.

Results: After 5 years of follow-up, in cisgender men testosterone therapy was associated with a lower risk of myocardial infarction (HR: 0.94 95%CI [0.89-0.99], P=0.01) with no difference for stroke or total mortality. There was an increased risk of both atrial fibrillation (1.27 [1.22-1.32], P<0.0001) and acute pulmonary embolism/deep vein thrombosis (1.26 [1.18-1.34], P<0.0001). Transgender men treated with testosterone had a higher risk of acute myocardial infarction (2.82 [1.12-7.03], P=0.02) without significant difference for total mortality, stroke or atrial fibrillation compared to matched cis women treated with a contraceptive pill. Transgender men had a lower incidence of pulmonary embolism/deep vein thrombosis (0.46 [0.22-0.93], P=0.03) compared to matched cisgender women.

Conclusions: Testosterone treatment was associated in cisgender men with hypogonadism with a lower risk of myocardial infarction, but a higher risk of atrial fibrillation and venous thromboembolism as compared to men not treated with testosterone. Transgender men with testosterone therapy were at increased risk of myocardial infarction, without increased risk for atrial fibrillation or venous thromboembolism as compared to cisgender women.