The Joint Annual Scientific Meetings of the Endocrine Society of Australia and the Society for Reproductive Biology 2018

A liver mediated mechanism for loss of muscle mass during androgen deprivation therapy   (#68)

Teresa Lam 1 2 , Mark Mclean 1 , Amy Hayden 3 , Anne Poljak 4 , Birinder Cheema 5 , Howard Gurney 6 , Neha Bahl 2 , Navneeta Reddy 1 , Haleh Shahidipour 2 , Vita Birzniece 1 2 7
  1. Department of Diabetes and Endocrinology, Blacktown Hospital, Blacktown, NSW, Australia
  2. School of Medicine, Western Sydney University, Penrith, NSW, Australia
  3. Department of Radiation Oncology, Blacktown Hospital, Blacktown, NSW, Australia
  4. Bioanalytical Mass Spectometry Facility and School of Medical Sciences, University of New South Wales, Randwick, NSW, Australia
  5. School of Science and Health, Western Sydney University, Penrith, NSW, Australia
  6. Department of Medical Oncology, Westmead Hospital, Westmead, NSW, Australia
  7. Garvan Institute of Medical Research, Sydney, NSW, Australia


Introduction: Androgen deprivation therapy (ADT) is a common prostate cancer (PCa) treatment but results in muscular atrophy. Progressive resistance training (PRT) can mitigate changes in body composition. Testosterone regulates protein metabolism through inhibiting the hepatic urea cycle, limiting amino acid nitrogen elimination. We hypothesize that ADT enhances protein oxidative losses by increasing hepatic urea production, resulting in loss of muscle mass. The effect of ADT and PRT on hepatic urea production has not been studied.

Aim: To investigate the effect of ADT on whole body protein metabolism and hepatic urea production with and without a home-based PRT program.

Patients and Methods:  Hepatic urea production and whole-body protein metabolism were studied in 24 PCa patients before and after 6 weeks of ADT. Patients were randomised into either usual care (UC) (n = 11) or PRT (n = 13) starting immediately after their first ADT injection. The rate of hepatic urea production was measured by the urea turnover technique using 15N2-Urea as a stable tracer. Whole-body leucine turnover was measured, and leucine rate of appearance (LRa), and index of protein breakdown and leucine oxidation (Lox), a measure of irreversible protein loss, was calculated.

Results: ADT resulted in a significant increase in hepatic urea production (from 427.6±18.8 to 486.5±21.3; p < 0.01). Net protein loss, as measured by Lox/LRa increased by 12.6±4.9% (p=0.02). Lox/LRa significantly increased in the UC (p = 0.03), but not in the PRT group (p=0.23). There were no significant differences between the UC and PRT arms in terms of hepatic urea production or protein turnover.

Conclusion: The suppression of testosterone to castrate levels during ADT increases protein loss and hepatic urea production. Thus, the loss of muscle mass during ADT may be due to greater nitrogen losses through the urea cycle.