Oral low-dose testosterone administration induces whole-body protein anabolism: a novel liver-targeted therapy — ASN Events

Oral low-dose testosterone administration induces whole-body protein anabolism: a novel liver-targeted therapy (#314)

Vita Birzniece 1 2 , Margot A Umpleby 3 , Anne Poljak 4 , David Handelsman 5 , Ken Ho 1 6
  1. Garvan Institute of Medical Research, Darlinghurst, NSW, Australia
  2. Blacktown Clinical School and Research Centre, UWS, Blacktown, NSW, Australia
  3. Diabetes and Metabolic Medicine, Faculty of Health and Medical Sciences, University of Surrey , Surrey, United Kingdom
  4. Bioanalytical Mass Spectrometry Facility, University of New South Wales, Sydney, NSW, Australia
  5. ANZAC Research Institute, Concord Hospital, University of Sydney, Sydney, NSW, Australia
  6. Centres for Health Research, Princess Alexandra Hospital, Brisbane, Qld, Australia

Objective: In hypopituitary men, oral delivery of unesterified testosterone (T) in doses that
result in a solely hepatic androgen effect, enhances protein anabolism during GH treatment (1).
We aimed to determine whether liver-targeted androgen supplementation induces protein
anabolism in GH-replete normal women.
Design: Eight healthy postmenopausal women received 2-weeks treatment with oral T 40
mg/day (crystalline testosterone USP). This dose increases portal T concentrations exerting
androgenic effects on the liver without spill-over into the systemic circulation (2).
Outcome Measures: Whole body leucine turnover, from which leucine rate of appearance
(LRa; an index of protein breakdown) and leucine oxidation (Lox; a measure of irreversible
protein loss) were estimated, together with energy expenditure and substrate utilization. We
measured liver transaminases, as well as testosterone, SHBG and IGF-I.
Results: T treatment significantly reduced LRa by 7.1 ± 2.5 % and Lox by 14.6 ± 4.5 %
(p<0.05). Liver transaminases did not change significantly, while serum SHBG fell within the
0>normal range by 16.8 ± 4.0 % and IGF-I increased by 18.4 ± 7.7 % (p<0.05). Peripheral T
0>increased from 0.4 ± 0.1 to 1.1 ± 0.2 nmol/l (p<0.05), with none exceeding the upper normal
0>limit. There was no change in energy expenditure, fat and carbohydrate utilization.
Conclusions: Hepatic exposure to unesterified T by oral delivery stimulates protein
anabolism by reducing protein breakdown and protein oxidation without inducing systemic
androgen excess in women. We conclude that a small oral dose of unesterified T holds
promise as a simple novel treatment of protein catabolism and muscle wasting.

1) Birzniece et al., J Clin Endocrinol Metab. 2011 Apr;96(4):1060-7.
2) Birzniece et al., Clin Endocrinol (Oxf). 2009 Nov;71(5):715-21.