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.

Testosterone has immune-modulating properties, and current in vitro evidence suggests that testosterone may suppress the expression of the proinflammatory cytokines TNFalpha, IL-1beta, and IL-6 and potentiate the expression of the antiinflammatory cytokine IL-10. We report a randomized, single-blind, placebo-controlled, crossover study of testosterone replacement (Sustanon 100) vs. placebo in 27 men (age, 62 +/- 9 yr) with symptomatic androgen deficiency (total testosterone, 4.4 +/- 1.2 nmol/liter; bioavailable testosterone, 2.4 +/- 1.1 nmol/liter). Compared with placebo, testosterone induced reductions in TNFalpha (-3.1 +/- 8.3 vs. 1.3 +/- 5.2 pg/ml; P = 0.01) and IL-1beta (-0.14 +/- 0.32 vs. 0.18 +/- 0.55 pg/ml; P = 0.08) and an increase in IL-10 (0.33 +/- 1.8 vs. -1.1 +/- 3.0 pg/ml; P = 0.01); the reductions of TNFalpha and IL-1beta were positively correlated (r(S) = 0.588; P = 0.003). In addition, a significant reduction in total cholesterol was recorded with testosterone therapy (-0.25 +/- 0.4 vs. -0.004 +/- 0.4 mmol/liter; P = 0.04). In conclusion, testosterone replacement shifts the cytokine balance to a state of reduced inflammation and lowers total cholesterol. Twenty of these men had established coronary disease, and because total cholesterol is a cardiovascular risk factor, and proinflammatory cytokines mediate the development and complications associated with atheromatous plaque, these properties may have particular relevance in men with overt vascular disease.

OBJECTIVE -The aim of our study was to assess the prevalence of clinical hypogonadism, based on both symptoms and biochemical available measures of testosterone deficiency, in men with type 2 diabetes.RESEARCH DESIGN AND METHODS -In a cross-sectional study of 355 type 2 diabetic men aged Ͼ30 years, total and bioavailable testosterone, sex hormone-binding globulin, BMI, and waist circumference were measured and free testosterone was calculated. Overt hypogonadism was defined as the presence of clinical symptoms of hypogonadism and low testosterone level (total testosterone Ͻ8 nmol/l and/or bioavailable testosterone Ͻ2.5 nmol/l). Borderline hypogonadism was defined as the presence of symptoms and total testosterone of 8 -12 nmol/l or bioavailable testosterone of 2.5-4 nmol/l. RESULTS -A low blood testosterone level was common in diabetic men, and a significant proportion of these men had symptoms of hypogonadism. Overt hypogonadism was seen in 17% of men with total testosterone Ͻ8 nmol/l and 14% with bioavailable testosterone Ͻ2.5 nmol/l. Borderline hypogonadism was found in 25% of men with total testosterone 8 -12 nmol/l and bioavailable testosterone between 2.5 and 4 nmol/l; 42% of the men had free testosterone Ͻ0.255 nmol/l. BMI and waist circumference were both significantly negatively correlated with testosterone levels in men, with the association being stronger for waist circumference.CONCLUSIONS -Testosterone levels are frequently low in men with type 2 diabetes, and the majority of these men have symptoms of hypogonadism. Obesity is associated with low testosterone levels in diabetic men. Diabetes Care 30:911-917, 2007

Low-dose supplemental testosterone treatment in men with chronic stable angina reduces exercise-induced myocardial ischemia.