The increasing prevalence of obesity adds another dimension to the pathophysiology of testosterone deficiency (TD) and potentially impairs the therapeutic efficacy of classical testosterone replacement therapy (TRT).
We investigated the therapeutic effects of selective androgen receptor modulation with trenbolone in a model of TD with the metabolic syndrome (MetS). Male Wistar rats (n=50) were fed either a control standard rat chow (CTRL) or a high-fat/high-sucrose diet (HF/HS). Following 8 weeks of feeding, rats underwent sham surgery or an orchiectomy (ORX). Alzet mini-osmotic pumps containing either vehicle, 2 mg/kg/day testosterone (TEST) or 2 mg/kg/day trenbolone (TREN) were implanted in HF/HS+ORX rats. Body composition, fat distribution, lipid profile and insulin sensitivity were assessed. Infarct size was quantified to assess myocardial damage following in vivo ischaemia-reperfusion, before cardiac and prostate histology was performed. The HF/HS+ORX animals had increased subcutaneous and visceral adiposity; circulating triglycerides, cholesterol and insulin; and myocardial damage, with low circulating testosterone compared to CTRLs. Both TEST and TREN protected HF/HS+ORX animals against subcutaneous fat accumulation, hypercholesterolaemia and myocardial damage. However, only TREN protected against visceral fat accumulation, hypertriglyceridaemia and hyperinsulinaemia; and reduced myocardial damage relative to CTRLs. TEST caused widespread cardiac fibrosis and prostate hyperplasia, which were less pronounced with TREN. We propose that TRT may have contraindications for males with TD and obesity-related MetS. TREN treatment may be more effective in restoring androgen status and reducing cardiovascular risk in males with TD and MetS.
Endocrinology. 2015 Nov 19 [Epub ahead of print]
Daniel G Donner, Grace E Elliott, Belinda R Beck, Andrew C Bulmer, Alfred K Lam, John P Headrick, Eugene F Du Toit
Heart Foundation Research Centre, Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland, Australia. , Heart Foundation Research Centre, Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland, Australia. , School of Allied Health Science, Griffith University, Gold Coast, Queensland, Australia. , Heart Foundation Research Centre, Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland, Australia. , Cancer Molecular Pathology, Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland, Australia. , Heart Foundation Research Centre, Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland, Australia. , Heart Foundation Research Centre, Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland, Australia.