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

Birzniece, V, Umpleby, MA, Poljak, A, Handelsman, DJ and Ho, KK (2013) Oral low-dose testosterone administration induces whole-body protein anabolism in postmenopausal women: a novel liver-targeted therapy. Eur J Endocrinol, 169 (3). pp. 321-327.

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OBJECTIVE: In hypopituitary men, oral delivery of unesterified testosterone in doses that result in a solely hepatic androgen effect enhances protein anabolism during GH treatment. In this study, we aimed to determine whether liver-targeted androgen supplementation induces protein anabolism in GH-replete normal women. DESIGN: Eight healthy postmenopausal women received 2-week treatment with oral testosterone at a dose of 40 mg/day (crystalline testosterone USP). This dose increases portal concentrations of testosterone, exerting androgenic effects on the liver without a spillover into the systemic circulation. OUTCOME MEASURES: The outcome measures were 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, energy expenditure and substrate utilization. We measured the concentration of liver transaminases as well as of testosterone, SHBG and IGF1. RESULTS: Testosterone treatment significantly reduced LRa by 7.1 ± 2.5% and Lox by 14.6 ± 4.5% (P<0.05). The concentration of liver transaminases did not change significantly, while that of serum SHBG fell within the normal range by 16.8 ± 4.0% and that of IGF1 increased by 18.4 ± 7.7% (P<0.05). The concentration of peripheral testosterone increased from 0.4 ± 0.1 to 1.1 ± 0.2 nmol/l (P<0.05), without exceeding the upper normal limit. There was no change in energy expenditure and fat and carbohydrate utilization. CONCLUSIONS: Hepatic exposure to unesterified testosterone by oral delivery stimulates protein anabolism by reducing protein breakdown and oxidation without inducing systemic androgen excess in women. We conclude that a small oral dose of unesterified testosterone holds promise as a simple novel treatment of protein catabolism and muscle wasting.

Item Type: Article
Divisions : Surrey research (other units)
Authors :
Birzniece, V
Poljak, A
Handelsman, DJ
Ho, KK
Date : September 2013
DOI : 10.1530/EJE-13-0406
Uncontrolled Keywords : Administration, Oral, Aged, Anabolic Agents, Androgens, Energy Metabolism, Female, Humans, Insulin-Like Growth Factor I, Leucine, Liver, Middle Aged, Oxidation-Reduction, Postmenopause, Proteins, Proteolysis, Sarcopenia, Sex Hormone-Binding Globulin, Testosterone, Transaminases, Wasting Syndrome
Related URLs :
Depositing User : Symplectic Elements
Date Deposited : 17 May 2017 09:57
Last Modified : 24 Jan 2020 18:09

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