The University of Melbourne, Australia; Gastroenterology and Hepatology, Austin Health, Melbourne, Australia.
The University of Melbourne, Australia; Endocrinology, Austin Health, Melbourne, Australia.
J Hepatol. 2016 Nov;65(5):906-913. doi: 10.1016/j.jhep.2016.06.007. Epub 2016 Jun 14.
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.
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 <12nmol/L or free testosterone <230pmol/L) in a single tertiary centre. Body composition was assessed using dual-energy X-ray absorptiometry at baseline, 6 and 12months.
At study completion, appendicular lean mass was significant higher in testosterone-treated subjects, with a mean adjusted difference (MAD) of +1.69kg, (CI +0.40; +2.97kg, p=0.021). Secondary outcomes included a substantially higher total lean mass in the active group (MAD +4.74kg, CI +1.75; +7.74kg, p=0.008), matched by reduced fat mass (MAD -4.34kg, CI -6.65; -2.04, p<0.001). Total bone mass increased (MAD +0.08kg, CI +0.01; +0.15kg, p=0.009) as did bone mineral density at the femoral neck (MAD +0.287points, CI +0.140; +0.434, p<0.001). Haemoglobin was higher with testosterone therapy (MAD +10.2g/L, CI +1.50; +18.9g/L, p=0.041) and percentage glycosylated haemoglobin (HbA1c) 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.
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.
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.
Australian New Zealand Clinical Trials Registry trial number ACTRN 12614000526673.
低睾酮和肌肉减少症在肝硬化男性中很常见，两者均与死亡率增加有关。睾丸激素治疗是否能改善肝硬化患者的肌肉质量和其他结局尚不清楚。
我们在一家三级中心对 101 名已确诊肝硬化且血清睾酮水平低（总睾酮 <12nmol/L 或游离睾酮 <230pmol/L）的男性进行了为期 12 个月的、双盲、安慰剂对照的肌内十一酸睾酮治疗试验。基线、6 个月和 12 个月时使用双能 X 射线吸收法评估身体成分。
研究结束时，接受睾丸激素治疗的受试者四肢瘦体重明显增加，平均调整差异（MAD）为+1.69kg（CI+0.40；+2.97kg，p=0.021）。次要结局包括活跃组的总瘦体重显著增加（MAD+4.74kg，CI+1.75；+7.74kg，p=0.008），同时脂肪量减少（MAD-4.34kg，CI-6.65；-2.04，p<0.001）。总骨量增加（MAD+0.08kg，CI+0.01；+0.15kg，p=0.009），股骨颈骨密度增加（MAD+0.287 点，CI+0.140；+0.434，p<0.001）。睾丸激素治疗后血红蛋白升高（MAD+10.2g/L，CI+1.50；+18.9g/L，p=0.041），糖化血红蛋白（HbA1c）百分比降低（MAD-0.35%，CI-0.05；-0.54，p=0.028）。接受睾丸激素治疗的患者死亡率无显著降低（16% vs. 25.5%，p=0.352）。接受睾丸激素治疗的受试者不良反应无增加。
对于血清睾酮水平低的肝硬化男性，睾丸激素治疗可安全地增加肌肉量、骨量和血红蛋白，减少脂肪量和 HbA1c。这是肝硬化肌肉减少症的首个循证治疗方法，因此需要更大规模的研究来评估其对死亡率的潜在影响。
澳大利亚和新西兰临床试验注册中心试验编号 ACTRN 12614000526673。
