Effect of testosterone on lipid metabolism and endothelium in men with type 2 diabetes mellitus and hypogonadism

Abstract

Background To date, knowledge about the effects of testosterone (T) on the cardiovascular system of men remains controversial and requires additional research. Especially the putative impact of T replacement therapy (TRT) on lipid metabolism and endothelial dysfunction as a starting mechanism for the development of cardiovascular pathology in men with type 2 diabetes mellitus (T2DM) presenting with T deficiency has to be elucidated. The aim of this work was to evaluate the effect of T replacement therapy on lipid metabolism and function of endothelium in men with T2DM and hypogonadism. Methods The study included 95 men (mean age 55,3±2,4 years) with T2DM and late onset hypogonadism, established according to EAU 2015 criteria. Parameters of carbohydrate and lipid metabolism, as well as ultrasound assessment of flow-mediated dilatation of the brachial artery (FMD-BA) and intima-media thickness (IMT) of brachial arteries were performed at baseline and after 9 months. Patients were randomized into 2 groups: 1 - 45 men receiving TRT, using 1% transdermal T-gel and 2 (control group) - 50 men, who were not assigned to TRT. Statistical analysis was carried out using the Wilcoxon - test for repeated measurements (STATISTICA 10 software package). Results During the treatment period no serious adverse events were registered. The study revealed a significant decrease in HbA1c (p<0.001), total cholesterol (p=0.009), triglycerides (p=0.004) and LDL (p=0.01) levels as well as an increase in HDL level (p=0.001) in the 1st group vs baseline and compared to the 2nd one. There was a decrease in IMT (from 1.0 [0.8; 1.1] to 0.7 [0.6; 0.9] mm, p=0.002) in the 1st group compared to the 2nd (p<0.001). The endothelium-dependent FMD-BA increased 1.5 - fold in men applying T-Gel vs baseline as well as compared to the control group at the time point of follow- up (p<0.001). At the same time TRT leaded to acceleration of the time until maximal vasodilation – it became twice faster (from 120 [90; 120] to 60 [60; 90] sec, p<0.001) compared to baseline and the 2nd group (p<0.001). Linear blood flow velocity increased markedly in the 1st group compared to the 2nd at the time point of follow-up (p=0.03). Conclusion TRT in men with T2DM and T deficiency leads to an improvement in carbohydrate and lipid metabolism together with a significant decrease in IMT and enhancement of endothelium vasomotor function, seems to facilitate a reduction in cardiovascular risk. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Russian Science Foundation

Association Between Sex Hormones Levels and Cancer Prevalence in Women, Especially Breast Cancer

“…As another important sex hormone in women, the effect of testosterone on lipid metabolism cannot be ignored. Studies have shown that the effects of testosterone on the cardiovascular system in men are realised through the regulation of lipid metabolism [49] . In an animal study on prenatal androgen exposure and ovarian lipid metabolism, it was found that cholesterol metabolism and steroidogenesis were speci cally altered in animals with prenatal hyperandrogenic sessions [50] .…”

Cardiovascular Health, Testosterone, and Oxandrolone: Leveraging the Myotrophic-Androgenic Ratio in Males with a Sarcopenic Obese Phenotype

“…This starts an inflammatory cascade of atherogenesis and is considered a cardiovascular risk factor as this atherosclerotic plaque may rupture or promote subsequent thrombus formation, all resulting in the possibility of MACE if such structures are unstable and find themselves dislodged to vessels of significance to the myocardium or other end-organs (i.e, the brain, causing cerebrovascular accidents) [18]. Nevertheless, there is conflicting evidence for this mechanism, as it has been replicated in supraphysiologic testosterone environments, and there are mixed results of testosterone and lipid distribution in the hypogonadal population, such as those with sarcopenic obesity [19][20][21][22][23][24].…”