Longitudinal Changes in Liver Enzyme Levels Among Transgender People Receiving Gender Affirming Hormone Therapy
Leila Hashemi, MD1,2, 3, Qi Zhang, MSPH4, Joseph Pisegna MD1,2, Michael Goodman MD, MPH
1VA Greater Los Angeles Healthcare System, Department of General Internal Medicine, Los Angeles, CA ; 2University of California Los Angeles, David Geffen School of Medicine, Los Angeles, CA; 3University of California Los Angeles, Department of Computational Medicine, Graduate Student in Master of Science in Medical Research, Los Angeles California; 4Rollins School of Public Health, Emory University, Atlanta GA; 5Emory University, School of Medicine, Atlanta, GA; 6The Atlanta VA Medical Center, Atlanta GA
Background: The effect of gender affirming hormone therapy (GAHT) on clinical laboratory parameters, including levels of liver enzymes alanine aminotransferase (ALT) and aspartate transaminase (AST), is an area of uncertainty in transgender health. GAHT is expected to affect levels of ALT and AST in transgender people because liver function is known to be regulated, at least in part, by circulating sex hormones. Estradiol may affect liver function through its action on estrogen receptor a, which acts as a coordinator of energy metabolism in the liver. Estrogen fluctuation affects synthesis of fatty acids and cholesterol, which in turn may be linked to liver enzyme production and regulation. In addition, low estrogen levels have been linked to increased risk of non-alcoholic fatty liver in both human and animal studies. The effect of testosterone on liver function is less understood although it is known that liver contains androgen receptors and testosterone is converted to estradiol by sequential actions of 5a-reductase and aromatase. Both lack of testosterone in men with hypogonadism and excess of testosterone in women diagnosed with polycystic ovary syndrome increase the risk of non-alcoholic fatty liver disease, and therefore may result in abnormal levels of liver enzymes. Methods: The data for this longitudinal study included 624 transfeminine (TF) and 438 transmasculine (TM) people and 4,090 cisgender males and 4,797 cisgender females enrolled in three integrated health systems. Time under observation in both groups was divided into two intervals: from the first blood test to the first filled GAHT prescription and from GAHT initiation to the most recent blood test result. As distributions of both liver enzyme concentrations were highly skewed, the ALT and AST values in all models were log-transformed. The linear regression coefficients from all models were exponentiated to obtain a ratio of mean liver enzyme values across categories of independent variables, and the final result was expressed as a relative difference (in %). Linear mixed models were used to compare changes in log-transformed ALT and AST values among transgender cohort members before and after GAHT initiation, and relative to the reference groups. The results were expressed as relative differences (in %) and the ratios of these differences (ratios-of ratios) along with the 95% confidence intervals (CIs) for pre to post GAHT changes and also compared to cis references. Results: Among TM study participants, the post GAHT ratios-of-ratios for AST were 1.61 (95% CI: 1.13, 2.31) and 1.57 (95% CI: 1.06, 2.31) relative to cisgender males and females respectively. For ALT, the corresponding comparisons yielded the ratios-of-ratios (95% CIs) of 2.06 (1.67, 2.54) and 1.90 (1.50, 2.40). No discernable changes were observed among TF participants. Other factors associated with higher enzyme levels included alcohol use/abuse and BMI ≥25 kg/m2. Conclusion: Feminizing GAHT is unlikely to influence ALT and AST levels. Clinical significance of the observed association between masculinizing GAHT and liver enzymes levels is not clear and requires further investigation
Acknowledgements: Funding sources for this work included Contract AD-12-11-4532 from the Patient Centered Outcome Research Institute and Grant R21HD076387 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development.
Breakout Room: Hashemi, Leila
View Poster: https://uclacns.org/symposium2021/11-Hashemi-Leila.pdf