Background: The association between testosterone deficiency, metabolic syndrome (MetS) and type 2 diabetes (T2DM) is well established. Male hypogonadism is related to an increase in glycometabolic and cardiometabolic complications.
Objective: To evaluate magnitude of effects of testosterone replacement therapy (TRT) on testosterone normalization, parameters of the MetS and vascular function and morphology in obese hypogonadal male patients with T2DM.
Study design: SETH2 was a randomized, double blind, placebo-controlled clinical study of 55 obese diabetic males not treated with insulin, with confirmed late-onset hypogonadism. Two study groups were formed. Group T patients (n=28) were treated with testosterone undecanoate (1000 mg depot injection administered i.m. at first visit, with second injection following six weeks later and the remaining ones every 10 weeks following the previous) while group P patients (n=27) received placebo.
Methods: Ultrasound assessment of endothelial function flow mediated dilatation (FMD) of brachial artery and vascular morphology of carotid artery (intima media thickness - IMT), biochemical and hormonal blood sample analyses were performed at baseline and after one year. Effect size was assessed using Cohens d (with 95% confidence interval for Cohens d).
Results: TRT resulted in a statistically significant decrease of fasting plasma glucose (1.23±1.25 mmol/l, P<0.001; d=1.07, 95% CI: 0.51 1.64), HbA1c (0.94±0.88% points, P<0.001; d=1.03, 95% CI: 0.47 1.59), HOMA-IR (4.64±4.25, P<0.001; d=1.23, 95% CI: 0.66 1.81) and an increase in total (9.80±3.59 nmol/l, P<0.001; d=2.78, 95% CI: −3.62 −2.12), calculated bioavailable (5.76±2.16 nmol/l, P<0.001; d=2.79, 95% CI: −3.53 −2.05) and calculated free testosterone (248.29±99.45 pmol/l, P<0.001; d=2.61, 95% CI: −3.33 −1.89) and FMD (2.40±4.16% points, P=0.005; d=0.66, 95% CI: −1.20 −0.12). IMT has decreased in both groups; by 0.10±0.06 mm (P<0.001) in group T and by 0.05±0.09 mm (P=0.006) in group P; d=0.66, 95% CI: 0.11 1.20. No statistically significant effects were observed on other parameters of MetS.
Conclusion: TRT exerted very large effects on levels of testosterone (d ranging from 2.61 to 2.78) and on some parameters of MetS (d ranging from 1.03 to 1.25) with moderate effect on vascular function (d=0.65) and morphology (d=0.66).
18 - 21 May 2019
European Society of Endocrinology