Serum testosterone levels and testosterone supplementation in cirrhosis: A systematic review

Nanfu Deng; Niharika Mallepally; Frederick B Peng; Aleem Kanji; Marco Marcelli; Ruben Hernaez

doi:10.1111/liv.14938

Serum testosterone levels and testosterone supplementation in cirrhosis: A systematic review

Liver Int. 2021 Oct;41(10):2358-2370. doi: 10.1111/liv.14938. Epub 2021 May 28.

Authors

Nanfu Deng¹, Niharika Mallepally¹, Frederick B Peng¹, Aleem Kanji^{1

2}, Marco Marcelli^{1

2}, Ruben Hernaez^{3

4

5}

Affiliations

¹ Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
² Section of Diabetes, Metabolism and Endocrinology, Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA.
³ Section of Gastroenterology, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA.
⁴ Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA.
⁵ Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.

PMID: 33966337
DOI: 10.1111/liv.14938

Abstract

Background & aims: Cirrhosis disrupts the hypothalamic-pituitary-gonadal axis causing low testosterone. Testosterone deficiency is associated with sarcopenia and osteopenia, leading to a state of frailty and worse clinical outcomes, morbidity and mortality. We aimed to conduct a systematic review on the relationship between serum testosterone and laboratory, anthropometric and clinical outcomes in observational and interventional studies in cirrhosis.

Methods: PubMed and EMBASE were searched from inception through 27 August 2020 and reviewed independently by two investigators; a third reviewer solved disagreement. A qualitative summary of relevant findings was done. Methodological quality was assessed using the Newcastle Ottawa Scale for non-interventional studies and the Cochrane Risk of Bias for interventional studies.

Results: Out of 3569 articles, 15 met inclusion criteria with six observational studies of 1267 patients and nine interventional studies of 580 patients. In observational studies, low serum testosterone level was associated with sarcopenia, shorter median time to hepatic decompensation, transplant requirement, higher model for end-stage liver disease (MELD) scores, and death in cirrhotic patients. Nine interventional studies (361 treated with testosterone vs 219 placebo, 1-36 months) showed that testosterone supplementation improved serum testosterone, appendicular mass and bone mineral density. However, no trial reported improvement in liver-related scores, complications, readmission rates or death.

Conclusions: Low serum testosterone is associated with increased morbidity and mortality in cirrhosis patients. Testosterone supplementation improved intermediate endpoints, but there was no conclusive data on clinical outcomes. Testosterone supplementation may be a promising strategy to improve frailty and decrease significant clinical complications in cirrhosis.

Keywords: cirrhosis; frailty; hypogonadism; osteoporosis; testosterone.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Systematic Review

MeSH terms

Dietary Supplements
End Stage Liver Disease*
Humans
Liver Cirrhosis / drug therapy
Severity of Illness Index
Testosterone*

Substances

Testosterone