The association of testosterone with sarcopenia and frailty in chronic liver disease

Abstract

BackgroundTestosterone is an important anabolic hormone responsible for maintaining body composition and muscle mass and circulates mostly albumin‐bound, or sex hormone binding globulin (SHBG)‐bound or free in the plasma. Of these fractions, the latter is bioactive and exerts the androgenic effects on male population. Liver cirrhosis, the advanced stage of any chronic liver disease characterized by permanent distortions to the hepatic architecture, disrupts the hypothalamic‐pituitary‐gonadal axis, leading to diminished levels of free testosterone and hypogonadism.MethodsWe retrieved the PubMed database to provide a synopsis of testosterone's physiology and action and summarize the effect of sarcopenia in pre‐cirrhotic and cirrhotic patients. Moreover, we scoped to provide insight into the relationship of testosterone levels with sarcopenia, frailty and survival in cirrhotic and non‐cirrhotic population as well as to discuss the efficacy of exogenous testosterone supplementation on the anthropometric parameters and survival of those patients.ResultsLow testosterone levels have been associated with sarcopenia, reduced body lean mass, decreased bone mineral density and frailty, thus leading to increased morbidity and mortality especially among cirrhotic patients. Furthermore, exogenous testosterone administration significantly ameliorated body composition on patients with chronic hepatic disease, without significant adverse effects. However, the current literature does not suggest any significant effect on survival of those patients. Moreover, the long‐term safety of testosterone use remains an open question.ConclusionLow serum testosterone is strongly correlated with sarcopenia, frailty, higher rate of hepatic decompensation and mortality. Nonetheless, exogenous supplementation of testosterone did not ameliorate the liver‐related outcomes and complications.

Serum zinc concentration as a potential predictor of presarcopenia in patients with chronic liver disease: a preliminary study

“…Age-related testosterone decline is associated with the development of sarcopenia ( 32 , 33 ) and, testosterone replacement therapy has been reported to increase muscle strength and lean body mass ( 34 , 35 ). In addition, randomized controlled trials in patients with liver cirrhosis have demonstrated the benefit of testosterone administration ( 36 ).…”

Glucagon-like Peptide 1, Glucose-Dependent Insulinotropic Polypeptide, and Glucagon Receptor Agonists in Metabolic Dysfunction-Associated Steatotic Liver Disease: Novel Medication in New Liver Disease Nomenclature

“…That effect could be mitigated by advising MASLD patients to increase their physical exercise in the form of both aerobic exercise and resistance training in order to minimize the potential harmful effect on skeletal muscle strength and the development of frailty, which is a rapidly recognized feature in patients with MASLD [116,117]. In this setting, specific pharmacological agents for preserving lean muscle mass have been proposed by the literature, and they include urocortin 2 and urocortin 3, testosterone, growth hormone, and activin type II receptor inhibitors [118,119]. Furthermore, MASLD as a multisystemic disease is strongly related to cardiovascular events, while the MASH fibrosis stage is an independent predictor of incident cardiovascular disease [120].…”

Positive association between serum bilirubin within the physiological range and serum testosterone levels

“…Besides aging, factors like obesity, dyslipidemia, metabolic syndrome, hypertension, diabetes mellitus, and chronic kidney disease have been linked to decreased TT levels and an elevated risk of developing TD [ 3 – 6 ]. TD can result in muscle atrophy, reduced strength, compromised cognitive function, poorer sleep quality, an increased risk of depression, and reduced life satisfaction in men [ 7 , 8 ]. Understanding the factors leading to this decline is essential for preventing TD and developing new treatments.…”