Testosterone Replacement Therapy Improves Metabolic Parameters in Hypogonadal Men with Type 2 Diabetes but Not in Men with Coexisting Depression: The BLAST Study

Abstract

Introduction The association between testosterone deficiency and insulin resistance in men with type 2 diabetes is well established and current endocrine society guidelines recommend the measurement of testosterone levels in all men with type 2 diabetes or erectile dysfunction. Aim We report the first double-blind, placebo-controlled study conducted exclusively in a male type 2 diabetes population to assess metabolic changes with long-acting testosterone undecanoate (TU). Methods The type 2 diabetes registers of seven general practices identified 211 patients for a 30-week double-blind, placebo-controlled study of long-acting TU 1,000 mg followed by 52 weeks of open-label use. Because of the established impact of age, obesity, and depression on sexual function, these variables were also assessed for influence on metabolic parameters. Main Outcome Measure Changes in glycated hemoglobin (HbA1c) and the level of testosterone at which response are achieved. Results Treatment with TU produced a statistically significant reduction in HbA1c at 6 and 18 weeks and after a further 52 weeks of open-label medication most marked in poorly controlled patients with baseline HbA1c greater than 7.5 where the reduction was 0.41% within 6 weeks, and a further 0.46% after 52 weeks of open-label use. There was significant reduction in waist circumference, weight, and body mass index in men without depression, and improvements were related to achieving adequate serum levels of testosterone. There were no significant safety issues. Conclusions Testosterone replacement therapy significantly improved HbA1c, total cholesterol, and waist circumference in men with type 2 diabetes. Improvements were less marked in men with depression at baseline, and therapeutic responses were related to achieving adequate serum testosterone levels. Current advice on 3- to 6-month trials of therapy may be insufficient to achieve maximal response. Patients reported significant improvements in general health.

An update on the role of testosterone replacement therapy in the management of hypogonadism

“…The BLAST study showed improvements of 0.4% in glycated hemoglobin (HbA1c) at 6 months versus placebo and 0.87% after a further 12 months. The authors also showed reductions in total cholesterol (TC), LDL plus BMI, weight and waist circumference, along with improvements in sexual function and quality of life (Table 1) [Hackett et al 2014]. A 5-year registry of 255 men aged 36-69 [Traish et al 2014] treated with long-acting testosterone undecanoate (TU) has shown mean reductions in waist circumference of 8.5 cm, weight reduction of 15.5 kg, TC by 2.4 mmol/l, reduction in HDL, and triglycerides with HbA1c by 0.9% (7.06-6.16) [Traish et al 2014].…”

“…The ES stops short of recommending screening in high-risk groups such as T2DM [Bhasin et al 2010] but with ED rates of 78% and depression of 25% [Hackett et al 2014], most patients are highly symptomatic and merit screening according to guidelines on sexual dysfunction. Data from the Birmingham, Lichfield, Atherstone, Sutton and Tamworth (BLAST) study suggest that less than 5% of men with T2DM would be asymptomatic by questionnaire and have normal erectile function, meaning effectively that 95% of men with T2DM require testosterone measurement based on ES recommendations, assuming a thorough history has been taken.…”

Testosterone deprivation accelerates cardiac dysfunction in obese male rats

“…Furthermore, patients suffering from congestive heart failure (Jankowska et al 2006) and coronary artery disease (Li et al 2012) have been shown to have lower levels of testosterone compared with healthy men, and the severity of these conditions had a strong correlation with the degree of testosterone deficiency (Li et al 2012, Oskui et al 2013. Recent clinical studies demonstrated that testosterone replacement could improve insulin sensitivity, increase lean mass, and decrease subcutaneous fat (Dhindsa et al 2016) and also improve cardiometabolic parameters in type 2 diabetes men with testosterone deprivation (Hackett et al 2014) and in hypogonadal men with metabolic syndrome (Saad et al 2016).…”

Erectile dysfunction, diabetes and cardiovascular risk

“…31 In view of the association between hypogonadism and diabetes, researchers have postulated whether TRT can also improve metabolic parameters in diabetes. Studies have shown an association between TRT and reductions in HbA1c, 32 improvement in insulin resistance 33 and a reduction in body mass index. 34 A large Australian study (T4DM) is currently underway to assess whether …”