A potent liver-mediated mechanism for loss of muscle mass during androgen deprivation therapy

Teresa Lam*, Mark McLean, Amy Hayden, Anne Poljak, Birinder Cheema, Howard Gurney, Glenn Stone, Neha Bahl, Navneeta Reddy, Haleh Shahidipour, Vita Birzniece

*Corresponding author for this work

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Abstract

Context: Androgen deprivation therapy ADT in prostate cancer results in muscular atrophy, due to loss of the anabolic actions of testosterone. Recently, we discovered that testosterone acts on the hepatic urea cycle to reduce amino acid nitrogen elimination. We now hypothesize that ADT enhances protein oxidative losses by increasing hepatic urea production, resulting in muscle catabolism. We also investigated whether progressive resistance training PRT can offset ADT-induced changes in protein metabolism. Objective: To investigate the effect of ADT on whole-body protein metaboli sm and hepatic urea production with and without a home-based PRT program. Design: A randomized controlled trial. Patients and intervention: Twenty-four prostate cancer patients were studied before and after 6 weeks of ADT. Patients were randomized into either usua l care UC n = 11 or PRT n = 13 starting immediately after ADT. Main outcome measures: The rate of hepatic urea production was measured by the urea turnover technique using 15N2-urea. Whole-body leucine turnover was measured, and leucine rate of appearance LRa, an index of protein breakdown and leucine oxidation Lox, a measure of irreversible protein loss, was calculated. Results: ADT resulted in a significant mean increase in hepatic urea pro duction from 427.6 ± 18.8 to 486.5 ± 21.3; P < 0.01 regardless of the exercise intervention. Net protein loss, as measured by Lox/Lra, increased by 12.6 ± 4.9% P < 0.05. PRT preserved lean body mass without affecting hepatic urea production. Conclusion: As early as 6 weeks after initiation of ADT, the suppression o f testosterone increases protein loss through elevated hepatic urea production . Short-term PRT was unable to offset changes in protein metabolism during a state of profound testosterone deficiency.

Original languageEnglish
Pages (from-to)605-615
Number of pages11
JournalEndocrine Connections
Volume8
Issue number5
DOIs
Publication statusPublished - 1 May 2019
Externally publishedYes

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Copyright the Author(s) 2019. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

  • Hypogonadism
  • Prostate cancer
  • Sarcopenia
  • Testosterone
  • Urea production

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