The causal effect of bioavailable testosterone on primary biliary cholangitis in female patients: A Bidirectional Mendelian randomization analysis

Primary biliary cholangitis (PBC) primarily affects female in their 4th to 6th decade of life at which stage female's sex hormones change dramatically. Sex hormones have a wide range of effects on the liver and immune system. However, it remains unclear whether sex hormonal changes mediate the onset of PBC.This study investigated the causal effect between total testosterone (TT), bioavailable testosterone (BAT), sex hormone binding globulin (SHBG) in female and PBC using public GWAS summary data.Data on TT, BAT, SHBG in female were obtained from a previous study based on the UK Biobank. PBC GWAS summary data was obtained from a genome-wide meta-analysis. We used several methods to make the conclusion robust. Various sensitivity analyses had been conducted to assess the consistency of our findings.Our Mendelian randomization analysis revealed that the genetically predicted BAT in female was positively associated with PBC and SHBG in female was negatively associated with PBC. The results obtained from different methods are similar, which proves the reliability of the results.Our study supported a causal relationship of BAT and SHBG in female on PBC. To confirm the association between testosterone and PBC, more research should be conducted.