Bicalutamide does not raise transaminases clinically significantly compared to alternative anti-androgen regimens among transfeminine adolescents and young adults: a retrospective cohort study

Background: Bicalutamide is a potential anti-androgen for transgender individuals with feminizing embodiment goals, but use is limited because of hepatotoxicity in cisgender men with prostate cancer. This study compared transaminase changes in transfeminine adolescents and young adults (AYA) using low dose bicalutamide with individuals using another androgen blockade. Methods: A retrospective analysis was conducted using electronic health record data for patients starting gender affirming hormone therapy with at least 10 months of follow-up between 2015 and 2023. The primary outcome was change in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) from baseline. Linear mixed models compared change in ALT and AST from baseline and maximum ALT and AST values in bicalutamide and comparison groups. Secondary outcomes included % individuals with ALT and AST elevation more than 1, 2, or 3 times the upper limit of normal (ULN) (Fisher’s exact test), standardized mean estradiol dose by group (t test), and Tanner staging of breast tissue by group (Fisher’s exact test). Results: Eighty-four transfeminine AYA (median age 18) taking bicalutamide were compared to 69 transfeminine AYA (median age 19) taking GnRH agonists, spironolactone or no agent in addition to estradiol. In linear mixed models adjusted for baseline age, race, BMI, baseline ALT or AST, and alcohol use, there were no clinically significant differences in delta or maximum ALT or AST in bicalutamide and comparison groups. No individuals had AST or ALT levels > 3x ULN though % with AST > ULN was higher for bicalutamide (10.7 v 1.5%, p = 0.02). Estradiol doses and Tanner stages were similar between groups among individuals receiving pediatric care. Conclusion: Bicalutamide was not associated with a clinically significant change in transaminases as compared with other anti-androgen regimens over one year. Bicalutamide appears to be a safe anti-androgen for transfeminine individuals at low dose with close monitoring and deserves further study.