OBJECTIVE: This study evaluated the effects of testosterone replacement therapy (TRT) on insulin resistance, cardiovascular risk factors, and symptoms in hypogonadal men with type 2 diabetes and/or metabolic syndrome (MetS). RESEARCH DESIGN AND METHODS: The efficacy, safety, and tolerability of a novel transdermal 2% testosterone gel was evaluated over 12 months in 220 hypogonadal men with type 2 diabetes and/or MetS in a multicenter, prospective, randomized, double-blind, placebo-controlled study. The primary outcome was mean change from baseline in homeostasis model assessment of insulin resistance (HOMA-IR). Secondary outcomes were measures of body composition, glycemic control, lipids, and sexual function. Efficacy results focused primarily on months 0−6 (phase 1; no changes in medication allowed). Medication changes were allowed in phase 2 (months 6−12). RESULTS: TRT reduced HOMA-IR in the overall population by 15.2% at 6 months (P = 0.018) and 16.4% at 12 months (P = 0.006). In type 2 diabetic patients, glycemic control was significantly better in the TRT group than the placebo group at month 9 (HbA1c: treatment difference, −0.446%; P = 0.035). Improvements in total and LDL cholesterol, lipoprotein a (Lpa), body composition, libido, and sexual function occurred in selected patient groups. There were no significant differences between groups in the frequencies of adverse events (AEs) or serious AEs. The majority of AEs (>95%) were mild or moderate. CONCLUSIONS: Over a 6-month period, transdermal TRT was associated with beneficial effects on insulin resistance, total and LDL-cholesterol, Lpa, and sexual health in hypogonadal men with type 2 diabetes and/or MetS.

Objective: Serum testosterone levels are known to inversely correlate with insulin sensitivity and obesity in men. Furthermore, there is evidence to suggest that testosterone replacement therapy reduces insulin resistance and visceral adiposity in type 2 diabetic men. Adipocytokines are hormones secreted by adipose tissue and contribute to insulin resistance. We examined the effects of testosterone replacement treatment on various adipocytokines and C-reactive protein (CRP) in type 2 diabetic men. Design: Double-blinded placebo-controlled crossover study in 20 hypogonadal type 2 diabetic men. Patients were treated with testosterone (sustanon 200 mg) or placebo intramuscularly every 2 weeks for 3 months in random order followed by a washout period of 1 month before the alternate treatment phase. Methods: Leptin, adiponectin, resistin, tumour necrosis factor-α (TNF-α), interleukin (IL)-6 and CRP levels were measured before and after each treatment phase. Body mass index (BMI) and waist circumference were also recorded. Results: At baseline, leptin levels significantly correlated with BMI and waist circumference. There was a significant inverse correlation between baseline IL-6 and total testosterone (r=−0.68; P=0.002) and bioavailable testosterone levels (r=−0.73; P=0.007). CRP levels also correlated significantly with total testosterone levels (r=−0.59; P=0.01). Testosterone treatment reduced leptin (−7141.9 ± 1461.8 pg/ml; P=0.0001) and adiponectin levels (−2075.8 ± 852.3 ng/ml; P=0.02). There was a significant reduction in waist circumference. No significant effects of testosterone therapy on resistin, TNF-α, IL-6 or CRP levels were observed. Conclusion: Testosterone replacement treatment decreases leptin and adiponectin levels in type 2 diabetic men. Moreover, low levels of testosterone in men are associated with pro-inflammatory profile, though testosterone treatment over 3 months had no effect on inflammatory markers.

Dove Press is a member of the Open Access Initiative, specializing in peer reviewed Medical Journals. View articlesor submit your research for publishing

Metabolic syndrome and testosterone deficiency in men are closely linked. Epidemiological studies have shown that low testosterone levels are associated with obesity, insulin resistance and an adverse lipid profile in men. Conversely in men with metabolic syndrome and type 2 diabetes have a high prevalence of hypogonadism. Metabolic syndrome and low testosterone status are both independently associated with increased all-cause and cardiovascular mortality. Observational and experimental data suggest that physiological replacement of testosterone produces improvement in insulin resistance, obesity, dyslipidaemia and sexual dysfunction along with improved quality of life. However, there are no long-term interventional studies to assess the effect of testosterone replacement on mortality in men with low testosterone levels. This article reviews the observational and interventional clinical data in relation to testosterone and metabolic syndrome.

OBJECTIVE: There is a high prevalence of hypogonadism in men with type 2 diabetes. This will lead to an increase in assessments of hypogonadism. Statins could potentially decrease testosterone levels by reducing the availability of cholesterol for androgen synthesis. We compared testosterone levels and hypogonadal symptoms with statin use in a cross-sectional study of 355 men with type 2 diabetes. RESEARCH DESIGN AND METHODS: Total testosterone, sex hormone–binding globulin (SHBG), and estradiol were measured by an enzyme-linked immunosorbent assay. Bioavailable testosterone was measured by the modified ammonium sulfate precipitation method. Free testosterone was calculated using Vermeulen's formula. Symptoms of hypogonadism were assessed using the Androgen Deficiency in the Aging Male questionnaire. RESULTS: Statins were associated with lower total testosterone (11.9 vs. 13.4 nmol/l, P = 0.006) and a trend toward lower SHBG (29.4 vs. 35.3 nmol/l, P = 0.034) compared with no treatment. Bioavailable testosterone, free testosterone, estradiol, and hypogonadal symptoms were not affected. Subanalysis showed that atorvastatin was associated with reduced total testosterone (11.4 vs. 13.4 nmol/l, P = 0.006) and a trend toward reduced SHBG (27.6 vs. 35.3 nmol/l, P = 0.022) compared with no treatment, and there was an apparent dose-response effect with the lowest levels of total testosterone seen in men treated with ≥20 mg atorvastatin (9.6 nmol/l, P = 0.017). Simvastatin use was not associated with significant reductions in testosterone or SHBG levels. CONCLUSIONS: Assessing androgen status using total testosterone in men with type 2 diabetes treated with statins, particularly atorvastatin, may potentially lead to diagnostic error. Levels of bioavailable testosterone or free testosterone are recommended for the assessment of hypogonadism in this group if total testosterone levels are borderline.