Biochemical liver damage during gender affirming therapy in trans adults assigned female at birth: a meta-analysis

Purpose: To assess the effects of testosterone (T)-based gender affirming hormone therapy (GAHT) on liver blood tests (LBTs) in assigned female at birth adults, using a meta-analytic approach. Methods: Prospective and retrospective studies were selected that reported the prevalence of biochemical liver damage (BLD) and LBTs changes during T therapy. Data collected included pre-and-during therapy alanine-aminotransferase (ALT), aspartate-aminotransferase (AST), gamma-glutamyl-transferase (GGT), and alkaline phosphatase (ALP) mean concentration values. Results: The prevalence of BLD in 14 studies on 1698 subjects was 1% (95% CI 0.00–3.00; I2 = 14.1%; p = 0.82). In 17 studies on 2758 subjects, GAHT was associated with a statistically (but not clinically) significant increase in AST, GGT and ALP at 12 months and ALT at 3–7 (MD: 1.19 IU/l; 95% CI 0.31, 2.08; I2: 0%), at 12 (MD: 2.31 IU/l; 95% CI 1.41, 3.21; I2: 29%), but with no more significant increase at 24 months (MD: 1.71 IU/l; 95% CI −0.02, 3.44; I2: 0%). Conclusions: Analysis of aggregate estimates confirms a low risk of BLD and abnormalities in LBTs, transient in most cases, during T-based GAHT, thus suggesting a limited need for careful liver monitoring in AFAB people.