Testosterone therapy improves body composition, insulin resistance and markers of atherosclerosis in men with low testosterone and metabolic syndrome
Effects of testosterone undecanoate on cardiovascular risk factors and atherosclerosis in middle-aged men with late-onset hypogonadism and metabolic syndrome: results from a 24-month, randomized, double-blind, placebo-controlled study. Aversa A, Bruzziches R, Francomano D, et al. J Sex Med 2010;7(10):3495-3503.
The aim of this study was to evaluate whether long-term testosterone therapy could modify cardiovascular risk factors and atherosclerosis progression in a population of hypogonadal men with metabolic syndrome (MetS) and/or type 2 diabetes mellitus (T2DM). The randomized, double-blind, double-dummy, placebo-controlled, parallel group study enrolled 50 men (mean age 57 years) to receive intramuscular (IM) testosterone undecanoate (TU) 1000 mg every 12 weeks (n=40) or placebo transdermal gel (3-6 g daily; n=10) for 24 months. Hypogonadism was defined as total testosterone ≤11 nmol/L or free testosterone ≤250 pmol/L; MetS and T2DM were defined according to National Cholesterol Education Program-Third Adult Treatment Panel (NCEP-ATPIII) and International Diabetes Federation (IDF) criteria.1
What is known
Late-onset hypogonadism represents the progressive decline in serum testosterone associated with advancing age and characterized by a deficiency in serum testosterone levels below the young healthy adult male reference range of approximately 10–35 nmol/L (300–1000 ng/dL).2-4 Beyond the association of hypogonadism with erectile dysfunction,5 there is growing recognition that low testosterone is an independent risk factor for a range of cardiovascular and metabolic conditions, including MetS, obesity, T2DM, and cardiovascular disease (CVD) including atherosclerosis and myocardial infarction.6-12 MetS is characterised by a group of interrelated risk factors, including central abdominal obesity, elevated triglycerides, reduced high-density lipoprotein cholesterol (HDL-C), insulin resistance, impaired glucose tolerance, and hypertension.13 Therefore, ameliorating MetS may help to prevent cardiovascular events and delay the progression of CVD.
This is the first controlled study to investigate whether long-term testosterone therapy can counter cardiovascular risk factors and atherosclerosis progression in men with low testosterone and MetS.
What this study adds
Dr. Antonio Aversa, lead author of the study, commented that this controlled study demonstrated that prolonged testosterone therapy with TU improved body composition, insulin resistance and plasma surrogate markers of endothelial function and atherosclerosis, while markedly reducing the percentage of patients reporting three or more components of the MetS. Furthermore, although the sample size was not large, the striking results suggest that testosterone supplementation may have an important role in MetS patients to delay the progression of CVD. He noted that these findings are in contrast to a controversial study, which found an increased risk of cardiovascular adverse events in a population of older men with limitations in mobility and a high prevalence of chronic disease, despite similar plasma testosterone levels in the two studies.14 However, the present study “was more exhaustive in terms of investigation of plasma markers of atherosclerosis and thrombosis, and the intramuscular long-acting formulation was not associated with increased circulating estrogen levels.” In conclusion, TU should be considered as an adjunctive therapy for the treatment of those men affected by hypogonadism and MetS, in whom the correction of lifestyle factors alone may not be sufficient to decrease cardiovascular risk factors and the progression of artherosclerosis.
Figure 1: Change from baseline values of body composition and HOMA-IR after 12 and 24 months treatment with testosterone undecanoate (TU) or placebo. Note: from month 12, both the TU and placebo groups received TU 1000 mg every 12 weeks.