The Association of Free Testosterone Levels With Frailty Metrics in Advanced Chronic Liver Disease

Background: Frailty is common in advanced chronic liver disease (AdvCLD). Key assessment tools for frailty in this population include the liver frailty index (LFI), the 6-minute walk test (6MWT), and the gait speed test (GST). This study investigates the relationship between free testosterone (FT) levels and these frailty measures in men with AdvCLD. Methods: In this prospective cohort study of 197 male AdvCLD patients awaiting liver transplantation, frailty was assessed using the LFI, 6MWT, and GST. Participants were classified as having low or normal FT levels, and associations with frailty measures were analyzed using multivariable linear and logistic regression models. Results: Of the 197 patients, 41 (20.8%) had low FT levels. This group was more likely to have a higher Child-Turcotte-Pugh class, higher MELD-Na scores, and a history of hepatic encephalopathy compared with patients with normal FT levels ( P <0.05). Those with low FT also demonstrated greater frailty, with significantly poorer performance on the LFI and shorter distances on the 6MWT ( P <0.05); the GST difference did not reach statistical significance ( P =0.106). In multivariable regression analysis, including age, MELD-Na score, and Child-Turcotte-Pugh score, only low FT levels (OR: 2.4, P =0.043) were independently associated with frailty. Similarly, in multivariable linear regression, FT levels were independently associated with LFI scores and 6MWT ( P <0.05). Conclusion: Low FT is associated with increased frailty in male patients with AdvCLD. Additional research may help identify therapeutic approaches to improve frailty in this patient group.