Gender-affirming hormone therapy and liver diseases: a cohort study

Objective: The purpose of this study was to describe the incidence of liver-related outcomes, including liver disease and hepatic injury, in transgender and gender diverse (TGD) individuals receiving oestrogen-based or testosterone-based gender-affirming hormone therapy (GAHT). Design/methods: In this retrospective cohort study, we used a national electronic health record and claims database (Atropos Health) to describe the incidence of liver-related outcomes in TGD individuals receiving GAHT from 2015 to 2024. Adults with International Classification of Diseases (both versions 9 and 10) diagnosis codes for gender identity disorder/gender dysphoria who had received either oestrogen-based or testosterone-based therapies were included. Those with prior liver disease, alcohol use disorder or endocrine disorders were excluded. Liver enzymes, incident liver disease and metabolic outcomes were assessed at 1 year following initiation of GAHT. Results: Of the 16,379 individuals with available follow-up liver chemistries, 84.9% receiving oestrogen-based GAHT and 82.3% receiving testosterone-based GAHT had normal aspartate aminotransferase and alanine aminotransferase levels at 1 year. In both groups, approximately 2% of patients developed a new diagnosis of steatotic liver disease. New diagnoses of Budd-Chiari syndrome, cirrhosis or hepatocellular carcinoma occurred in less than 1% of all individuals. Metabolic and thrombotic complications, including venous thromboembolism, hyperlipidaemia and hypertension, were infrequent (1-3.4%) in both cohorts. Conclusion: This is a large real-world study assessing GAHT and liver-related outcomes. GAHT was associated with low rates of liver enzyme abnormalities, new liver disease and metabolic complications after 1 year.