Testosterone Replacement Reduces Morbidity and Mortality for Most Patients With Cirrhosis.

Background & Aims: Many men with cirrhosis have low testosterone levels. This is associated with sarcopenia, anemia, and poor quality of life. Data are lacking, however, regarding the clinical impact of testosterone replacement.

Methods: We conducted an emulated clinical trial evaluating the impact of testosterone replacement among men who were diagnosed with hypogonadism at the same time as their diagnosis of cirrhosis (new user design). We used nationally representative Medicare data (2008-2020) to examine the risk of death, decompensation events, and fractures in patients who did or did not receive testosterone. We balanced treated and untreated with inverse probability of treatment weighting and evaluated outcomes using an intention-to-treat design.

Results: A total of 282 patients (7.4%) with testicular hypofunction and cirrhosis received testosterone replacement after diagnosis. Patients started on testosterone spent 28.6% of patient-days on therapy, and patients not started would spend 0.5% of patient-days on therapy (P < .0001). Testosterone use was associated with lower mortality (subdistribution hazard ratio [sHR], 0.92; 95% confidence interval [CI], 0.85-0.99). Testosterone also led to a lower risk of new decompensation events (sHR, 0.92; 95% CI, 0.86-0.99) and especially for ascites requiring paracentesis (sHR, 0.82; 95% CI, 0.76-0.89) and variceal hemorrhage (sHR, 0.67; 95% CI, 0.54-0.85) with less effect on hepatic encephalopathy requiring hospitalization (sHR, 0.92; 95% CI, 0.84-1.01) and fractures (sHR, 0.99; 95% CI, 0.91-1.08) and without increased risk of hepatocellular carcinoma (sHR, 1.09; 95% CI, 0.91-1.3). There was substantial heterogeneity of treatment effect across baseline subgroups.

Conclusion: In our target trial emulation of a nationally representative cohort of older patients with cirrhosis and hypogonadism, testosterone use improved clinical outcomes.