Testosterone therapy increases muscle mass in men with cirrhosis and low testosterone: A randomised controlled trial

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• 作者：Marie Sinclair¹ ; ² ; ^{marie.sinclair@austin.org.au" class="auth_mail" title="E-mail the corresponding author} ; Mathis Grossmann¹ ; ³ ; Rudolf Hoermann¹ ; Peter W. Angus¹ ; ² ; ^&dagger ; ; Paul J. Gow¹ ; ² ; ^&dagger ;
• 关键词：MAD ; mean adjusted difference ; APLM ; appendicular lean mass ; HbA1c ; percentage glycosylated haemoglobin ; MELD ; model for end-stage liver disease ; DEXA ; dual-energy X-ray absorptiometry ; SHBG ; sex hormone binding globulin ; INR ; international normalised ratio ; LH ; luteinising hormone ; TUG ; timed-up-and-go ; SF36 ; short form 36 ; ADAM ; androgen deficiency of the ageing male ; IPAQ ; international physical activity questionnaire ; IQR ; interquartile range
• 刊名：Journal of Hepatology
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：65
• 期：5
• 页码：906-913
• 全文大小：834 K

文摘

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 (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.

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.

Clinical trial number

Australian New Zealand Clinical Trials Registry trial number ACTRN 12614000526673.