Serum
testosterone is reduced in up to 90% of men with
cirrhosis, with levels falling as
liver disease advances.
Testosterone is an important anabolic
hormone, with effects on muscle, bone, and hematopoiesis. Many of the features of advanced
liver disease are similar to those seen in hypogonadal men, including
sarcopenia,
osteoporosis,
gynecomastia, and low libido. However, the relative contribution of
testosterone deficiency to the symptomatology of advanced
liver disease has not been well established. More recently, it has been demonstrated that low
testosterone in men with
cirrhosis is associated with increased mortality, independent of the classically recognized prognostic factors, such as the Model for
End-Stage Liver Disease score. Only several small clinical trials have examined the role of
testosterone therapy in men with
cirrhosis, none of which have resolved the issue of whether or not
testosterone is beneficial. However, in men with organic
hypogonadism due to structural hypothalamic-pituitary-testicular axis disease,
testosterone therapy has been shown to improve muscle mass and bone mineral density, increase
hemoglobin, and reduce
insulin resistance. Despite initial concerns linking
testosterone with
hepatocellular carcinoma, more recent data suggest that this risk has been overstated. There is, therefore, now a strong rationale to assess the efficacy and safety of
testosterone therapy in
cirrhosis in well-designed randomized controlled trials.