Gallbladder disease in transgender individuals: associations with gender-affirming hormone therapy

Transgender individuals frequently undergo gender-affirming hormone therapy (GAHT) during their gender transition which plays a vital role in gender identity affirmation. Cholelithiasis, a common condition affecting 10-15% of the US population, has been linked to estrogen therapy in cisgender women. Despite the fact that hormonal profiles achieved after GAHT are not always identical to cisgender individuals, the effects of GAHT on gallbladder disease (GBD) risk have not been evaluated in transgender populations. This research aims to address this gap utilizing a large nationwide database.

The study analyzed medical records data from the TrinetX database from 52,847 trans men and 38,114 trans women. Four cohorts were created: trans women and men either receiving either hormone therapy or no intervention. Descriptive statistics were calculated before matching to estimate disease burden. The groups were then propensity score matched on known risk factors (age, race, BMI, etc.) and rates of GBD were compared.

Before matching, trans women on hormone therapy (TWHT) had a significantly higher 10-year GBD probability than those naïve to therapy (TWNI) (4.69% vs 1.88%). For trans men, there was no significant difference in 10-year rates between those on therapy (TMHT) and those not (TMNI) (3.15% vs 3.87%). Cholecystectomy rates were significantly higher for TWHT than TWNI (1.10% vs. 0.57%), but similar between TMHT and TMNI (0.95% vs. 1.10%). After accounting for risk factors, TWHT had increased GBD risk (HR 1.832), while TMHT showed no significant change.

This study suggests a link between estrogen GAHT and increased GBD risk in transgender women. Notably, testosterone GAHT did not offer protection against GBD in transgender men, contrary to expectations. This study is, to our knowledge, the first to describe the burden of GBD in the transgender population and to investigate the effects of GAHT on GBD risk.