Bicalutamide does not raise transaminases in comparison 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 has been 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 other methods of 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 data between 2015 and 2023. 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, BMI, baseline ALT or AST, and alcohol use, there was no difference in delta or maximum ALT or AST in bicalutamide and comparison groups. No individuals had an AST or ALT level > 3x ULN. Estradiol doses and Tanner stages were similar between groups in a subgroup analysis of individuals receiving pediatric care. Conclusion Bicalutamide was not associated with 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. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement CJH completed this work while supported by a career development award from the NICHD (K23HD096204). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Washington University Human Research Protection office gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.