Effects of Testosterone Replacement Therapy on Cardio-Metabolic, Hormonal and Anthropometric Parameters in Obese Hypogonadal Men with Metabolic Syndrome

Abstract

Background and objectives: Metabolic syndrome (MS), characterized by central obesity, insulin resistance, dyslipidemia and hypertension is a well-known risk factor for the development of cardiovascular disorders. Globally, obese patients have a higher risk of morbidity and mortality, development of type 2 diabetes and cardiovascular disease. In addition, obesity leads to a decrease in serum testosterone and vice versa. We conducted randomized open-label trial, evaluating the effects of normalizing testosterone levels in obese hypogonadal men with metabolic syndrome. Methods: It was a prospective, open-label, randomized, and parallel group study. 60 patients (mean age 45,3 2,4 years ) with MS and total testosterone levels less than 12.0 nmol/L were enrolled and randomized 1:1 to receive testosterone undecanoate (TU) injections and metformin, or only metformin for 30 weeks. Lifestyle modification was recommended in both groups. The groups were well balanced at baseline. Primary endpoints were variations from baseline of cardiovascular (blood pressure (BP), arterial stiffness, endothelial function, carotid intima-media thickness) and body composition (body mass index (BMI), waist circumflex, percent of adipose tissue) parameters. Secondary endpoints were variations from baseline of hormonal (levels of total testosterone (TT), free testosterone (FT)) and metabolic (fasting glucose, lipids, uric acid) parameters. Results: In our study, a continuous decline of body weight, body mass index and waist circumference was observed in combination therapy group. Triglyceride, total and LDL cholesterol levels, uric acid and C-peptide level were decreased, and HDL cholesterol level was increased (P<0.05 for all) in testosterone with metformin group more than in metformin only group at 30 weeks. The positive impact on the cardiovascular parameters (arterial stiffness, endothelial function, carotid intima-media thickness) revealed during the study was more pronounced in the combination treatment group. No significant changes in safety parameters were detected in both groups. No serious adverse event with causal relationship was reported during the study. Conclusions: Study showed favorable effects of testosterone replacement in aging patients with low testosterone levels. TU effectively provides consistent TT concentrations within the normal range, improves cardio-metabolic and hormonal parameters, and has a positive impact on patient body weight, favorable safety profile and high level of patient tolerability.