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

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 338-357-Steroid Hormone Actions
Basic/Translational
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-349
Vita Birzniece*1, Margot Umpleby2, Anne Poljak3, David J Handelsman4 and Ken Ho5
1Garvan Institute of Medical Research, Sydney NSW, Australia, 2Diabetes and Metabolic Medicine, Faculty of Health and Medical Sciences, University of Surrey, United Kingdom, 3Bioanalytical Mass Spectrometry Facility, University of New South Wales, Sydney, Australia, 4University of Sydney, Sydney NSW, Australia, 5Princess Alexandra Hospital, Woolloongabba QLD, Australia
Context: In hypopituitary men, oral delivery of unesterified testosterone (T) in doses that do not induce a pharmacological hepatic effect, enhances protein anabolism during GH treatment (1). This observation suggests that in the presence of GH, oral androgen therapy in low doses may enhance protein anabolism.

Objective: To determine whether liver-targeted androgen supplementation induces protein anabolism in GH-replete normal women.

Design: An open-label study.

Patients and intervention: 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).

Main 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. We measured liver transaminases, as well as testosterone, SHBG and IGF-I in peripheral blood, together with energy expenditure and substrate utilization.

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 normal range by 16.8 ± 4.0 % and IGF-I increased by 18.4 ± 7.7 % (p<0.05). Peripheral T rose from 0.4 ± 0.1 nmol/l at baseline to a mean level of 1.1 ± 0.2 nmol/l, with none exceeding the upper normal limit (3 nmol/l). There was no change in energy expenditure, fat and carbohydrate utilization.

Conclusions: Solely 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.

Nothing to Disclose: VB, MU, AP, DJH, KH

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm