Journal
JOURNAL OF HEPATOLOGY
Volume 65, Issue 5, Pages 906-913Publisher
ELSEVIER
DOI: 10.1016/j.jhep.2016.06.007
Keywords
Cirrhosis; Sarcopenia; Liver disease; Muscle
Categories
Funding
- University of Melbourne
- Avant Mutual group
- NHMRC Career Development Fellowship [1024139]
- Bayer Pharma AG (Berlin, Germany)
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Background & Aims: Low testosterone and sarcopenia are common in men with cirrhosis and both are associated with increased mortality. Whether testosterone therapy in cirrhosis improves muscle mass and other outcomes is unknown. Methods: We conducted a 12-month, double-blinded, placebo controlled trial of intramuscular testosterone undecanoate in 101 men with established cirrhosis and low serum testosterone (total testosterone <12 nmol/L or free testosterone <230 pmol/L) in a single tertiary centre. Body composition was assessed using dual-energy X-ray absorptiometry at baseline, 6 and 12 months. Results: At study completion, appendicular lean mass was significant higher in testosterone-treated subjects, with a mean adjusted difference (MAD) of +1.69 kg, (CI +0.40; +2.97 kg, p = 0.021). Secondary outcomes included a substantially higher total lean mass in the active group (MAD +4.74 kg, CI +1.75; +7.74 kg, p = 0.008), matched by reduced fat mass (MAD -4.34 kg, CI -6.65; -2.04, p <0.001). Total bone mass increased (MAD +0.08 kg, CI +0.01; +0.15 kg, p = 0.009) as did bone mineral density at the femoral neck (MAD +0.287 points, CI +0.140; +0.434, p <0.001). Haemoglobin was higher with testosterone therapy (MAD +10.2 g/L, CI +1.50; +18.9 g/L, p = 0.041) and percentage glycosylated haemoglobin (HbAlc) lower (MAD -0.35%, CI -0.05; -0.54, p = 0.028). Mortality was non-significantly lower in testosterone-treated patients (16% vs. 25.5%, p = 0.352). There was no increase in adverse events in testosterone-treated subjects. Conclusion: Testosterone therapy in men with cirrhosis and low serum testosterone safely increases muscle mass, bone mass and haemoglobin, and reduces fat mass and HbA1c. This is the first evidence-based therapy for sarcopenia in cirrhosis and thus requires larger-scale investigation into its potential impact on mortality. Lay summary: Both low testosterone and muscle wasting are associated with increased risk of death in men with severe liver disease. Administering testosterone to men with liver disease who have low testosterone levels significantly increases their muscle mass. In addition, testosterone has non-muscle beneficial effects which may be able to increase survival in this population. (C) 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
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