Testosterone Supplementation Improves Carbohydrate and Lipid Metabolism in Some Older Men with Abdominal Obesity (original) (raw)
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Testosterone therapy increased muscle mass and lipid oxidation in aging men
AGE, 2012
The indication for testosterone therapy in aging hypogonadal men without hypothalamic, pituitary, or testicular disease remains to be elucidated. The aim of this study was to investigate the effect of testosterone therapy on insulin sensitivity, substrate metabolism, body composition, and lipids in aging men with low normal bioavailable testosterone levels using a predefined cutoff level for bioavailable testosterone. A randomized, double-blinded, placebocontrolled study of testosterone treatment (gel) was done on 38 men, aged 60-78 years, with bioavailable testosterone <7.3 nmol/l and a waist circumference >94 cm. Insulin-stimulated glucose disposal (Rd) and substrate oxidation were assessed by euglycemic hyperinsulinemic clamps combined with indirect calorimetry. Lean body mass (LBM) and total fat mass (TFM) were measured by dual x-ray absorptiometry, and serum total testosterone was measured by tandem mass spectrometry. Bioavailable testosterone was calculated. Coefficients (b) represent the placebo-controlled mean effect of intervention. LBM (b=1.9 kg, p=0.003) increased while HDL-cholesterol (b=−0.12 mmol/l, p=0.043) and TFM decreased (b=−1.2 kg, p=0.038) in the testosterone group compared to placebo. Basal lipid oxidation (b=5.65 mg/min/m 2 , p=0.045) increased and basal glucose oxidation (b=−9.71 mg/min/m 2 , p = 0.046) decreased in response to testosterone therapy even when corrected for changes in LBM. No significant changes in insulin-stimulated Rd was observed (b=−0.01mg/min/m 2 , p=0.92). Testosterone therapy increased muscle mass and lipid oxidation in aging men with low normal bioavailable testosterone levels; however, our data did not support an effect of testosterone on whole-body insulin sensitivity using the euglycemic hyperinsulinemic clamp technique.
The Journal of clinical endocrinology and metabolism, 2018
Serum testosterone levels and insulin sensitivity both decrease with age. Severe testosterone deficiency is associated with the development of insulin resistance. However, the effects of long-term testosterone administration on insulin sensitivity in older men with low or low-normal testosterone levels remain unknown. The Testosterone Effects on Atherosclerosis in Aging Men Trial was a placebo-controlled, randomized, double-blind trial. The participants were 308 community-dwelling men, >60-years, with total testosterone 100-400ng/dL or free testosterone<50pg/mL. A subset of 134 non-diabetic men(mean age 66.7 ± 5.1 years) underwent an octreotide insulin suppression test at baseline and at 3 and 36-months after randomization to measure insulin sensitivity. Insulin sensitivity was estimated as the steady-state plasma glucose(SSPG) concentration at equilibrium during octreotide and insulin administration. Secondary outcomes included total lean mass(TLM) and total fat mass(TFM) by ...
Testosterone: a metabolic hormone in health and disease
Journal of Endocrinology, 2013
Testosterone is a hormone that plays a key role in carbohydrate, fat and protein metabolism. It has been known for some time that testosterone has a major influence on body fat composition and muscle mass in the male. Testosterone deficiency is associated with an increased fat mass (in particular central adiposity), reduced insulin sensitivity, impaired glucose tolerance, elevated triglycerides and cholesterol and low HDL-cholesterol. All these factors are found in the metabolic syndrome (MetS) and type 2 diabetes, contributing to cardiovascular risk. Clinical trials demonstrate that testosterone replacement therapy improves the insulin resistance found in these conditions as well as glycaemic control and also reduces body fat mass, in particular truncal adiposity, cholesterol and triglycerides. The mechanisms by which testosterone acts on pathways to control metabolism are not fully clear. There is, however, an increasing body of evidence from animal, cell and clinical studies that...
European Journal of Endocrinology, 2009
Objective: Insulin resistance is associated with metabolic syndrome and type 2 diabetes, representing a risk factor for cardiovascular disease. This relationship may be modulated to some extent by agerelated changes in sex hormone status. We examined whether lower testosterone or sex hormonebinding globulin (SHBG) levels in older men are associated with insulin resistance independently of measures of central obesity. Design: Cross-sectional analysis of 2470 community-dwelling non-diabetic men aged R70 years. Methods: Age, body mass index (BMI) and waist circumference were measured. Early morning sera were assayed for total testosterone, SHBG, LH and insulin levels. Free testosterone was calculated using mass action equations, and insulin resistance was assessed using a homeostatic model (HOMA2-IR). Results: Total testosterone, free testosterone and SHBG declined progressively across increasing quintiles of HOMA2-IR (all P!0.001) and correlated inversely with log HOMA2-IR (rZK0.27, K0.14 and K0.24 respectively, all P!0.001). After adjusting for age, BMI, waist circumference, highdensity lipoprotein and triglyceride levels, total testosterone was independently associated with log HOMA2-IR (bZ0.05, P!0.001), while SHBG was not. Serum total testosterone !8 nmol/l was associated with HOMA2-IR in the highest quintile (odds ratio (OR) 1.67, 95% confidence interval (CI) 1.02-2.73) as was total testosterone R8 and !15 nmol/l (OR 1.29, 95% CI 1.03-1.63). Conclusions: In older men, lower total testosterone is associated with insulin resistance independently of measures of central obesity. This association is seen with testosterone levels in the low to normal range. Further studies are needed to evaluate interventions that raise testosterone levels in men with reduced insulin sensitivity.
The Journal of Clinical Endocrinology & Metabolism, 2008
Background: Trials of testosterone therapy in aging men have demonstrated increases in fat-free mass (FFM) and skeletal muscle and decreases in fat mass (FM) but have not reported the impact of baseline body composition. Objective: The objective of the study was to determine the effect, in nonobese aging men with symptoms of androgen deficiency and low-normal serum testosterone levels, of testosterone therapy on total and regional body composition and hormonal and metabolic indices. Methods: Sixty healthy but symptomatic, nonobese men aged 55 yr or older with total testosterone (TT) levels less than 15 nM were randomized to transdermal testosterone patches or placebo for 52 wk. Body composition, by dual-energy x-ray absorptiometry (FM, FFM, skeletal muscle) and magnetic resonance imaging (abdominal sc and visceral adipose tissue, thigh skeletal muscle, and intermuscular fat) and hormonal and metabolic parameters were measured at wk 0 and 52. Results: Serum TT increased by 30% (P ϭ 0.01), and LH decreased by 50% (P Ͻ 0.001). Relative to placebo, total body FFM (P ϭ 0.03) and skeletal muscle (P ϭ 0.008) were increased and thigh skeletal muscle loss was prevented (P ϭ 0.045) with testosterone therapy and visceral fat accumulation decreased (P ϭ 0.001) without change in total body or abdominal sc FM; change in visceral fat was correlated with change in TT levels (r 2 ϭ 0.36; P ϭ 0.014). There was a trend to increasing total and low-density lipoprotein cholesterol with placebo. Conclusion: Testosterone therapy, relative to placebo, selectively lessened visceral fat accumulation without change in total body FM and increased total body FFM and total body and thigh skeletal muscle mass. Further studies are needed to determine the impact of these body compositional changes on markers of metabolic and cardiovascular risk.
Body composition, metabolic syndrome and testosterone in ageing men
International Journal of Impotence Research, 2007
The ageing process in men is marked by changes in body composition (loss of fat-free mass (FFM) and skeletal muscle, and gain in fat mass (FM)) and is associated with a decline in serum testosterone. Correlations between these aspects of ageing and the acknowledged role of exogenous testosterone in reversing the loss of FFM and gain in FM seen in adult men with congenital or acquired hypoandrogenism have led to the hypothesis that testosterone therapy in ageing men will result in favourable changes in body composition and may improve metabolic status and/or cardiovascular risk. Data from randomized controlled trials of testosterone therapy in ageing men addressing the endpoints of body composition and components of the metabolic syndrome and cardiovascular risk factors are reviewed, and the impact of the increasing prevalence of obesity on these relationships is considered.
European Journal of Endocrinology, 2006
Objective: Low levels of testosterone in men have been shown to be associated with type 2 diabetes, visceral adiposity, dyslipidaemia and metabolic syndrome. We investigated the effect of testosterone treatment on insulin resistance and glycaemic control in hypogonadal men with type 2 diabetes. Design: This was a double-blind placebo-controlled crossover study in 24 hypogonadal men (10 treated with insulin) over the age of 30 years with type 2 diabetes. Methods: Patients were treated with i.m. testosterone 200 mg every 2 weeks or placebo for 3 months in random order, followed by a washout period of 1 month before the alternate treatment phase. The primary outcomes were changes in fasting insulin sensitivity (as measured by homeostatic model index (HOMA) in those not on insulin), fasting blood glucose and glycated haemoglobin. The secondary outcomes were changes in body composition, fasting lipids and blood pressure. Statistical analysis was performed on the delta values, with the treatment effect of placebo compared against the treatment effect of testosterone. Results: Testosterone therapy reduced the HOMA index (K1.73G0.67, PZ0.02, nZ14), indicating an improved fasting insulin sensitivity. Glycated haemoglobin was also reduced (K0.37G0.17%, PZ0.03), as was the fasting blood glucose (K1.58G0.68 mmol/l, PZ0.03). Testosterone treatment resulted in a reduction in visceral adiposity as assessed by waist circumference (K1.63G0.71 cm, PZ0.03) and waist/hip ratio (K0.03G0.01, PZ0.01). Total cholesterol decreased with testosterone therapy (K0.4G0.17 mmol/l, PZ0.03) but no effect on blood pressure was observed. Conclusions: Testosterone replacement therapy reduces insulin resistance and improves glycaemic control in hypogonadal men with type 2 diabetes. Improvements in glycaemic control, insulin resistance, cholesterol and visceral adiposity together represent an overall reduction in cardiovascular risk.
AJP: Endocrinology and Metabolism, 2012
endocrine and metabolic systems on any level of organization. It is published 24 times a year (twice monthly) by the publishes results of original studies about Wang X, Smith GI, Patterson BW, Reeds DN, Kampelman J, Magkos F, Mittendorfer B. Testosterone increases the muscle protein synthesis rate but does not affect very-low-density lipoprotein metabolism in obese premenopausal women. Men and women with hyperandrogenemia have a more proatherogenic plasma lipid profile [e.g., greater triglyceride (TG) and total and low-density lipoprotein-cholesterol and lower high-density lipoprotein-cholesterol concentrations] than healthy premenopausal women. Furthermore, castration of male rats markedly reduces testosterone availability below normal and decreases plasma TG concentration, and testosterone replacement reverses this effect. Testosterone is, therefore, thought to be an important regulator of plasma lipid homeostasis. However, little is known about the effect of testosterone on plasma TG concentration and kinetics. Furthermore, testosterone is a potent skeletal muscle protein anabolic agent in men, but its effect on muscle protein turnover in women is unknown. We measured plasma lipid concentrations, hepatic very low density lipoprotein (VLDL)-TG and VLDLapolipoprotein B-100 secretion rates, and the muscle protein fractional synthesis rate in 10 obese women before and after trandermal testosterone (1.25 g of 1% AndroGel daily) treatment for 3 wk. Serum total and free testosterone concentrations increased (P Ͻ 0.05) by approximately sevenfold in response to testosterone treatment, reaching concentrations that are comparable to those in women with hyperandrogenemia, but lower than the normal range for eugonadal men. Except for a small (ϳ10%) decrease in plasma high-density lipoprotein particle and cholesterol concentrations (P Ͻ 0.04), testosterone therapy had no effect on plasma lipid concentrations, lipoprotein particle sizes, and hepatic VLDL-TG and VLDL-apolipoprotein B-100 secretion rates (all P Ͼ 0.05); the muscle protein fractional synthesis rate, however, increased by ϳ45% (P Ͻ 0.001). We conclude that testosterone is a potent skeletal muscle protein anabolic agent, but not an important regulator of plasma lipid homeostasis in obese women.