Histopathology of aortic media tunica and plasma oxidative stress assessment during testosterone deficiency in male rats

Sexual hormones are determinant players in cardiovascular diseases. The aim of this study was to investigate the effects of testosterone deficiency, induced by castration, on oxidative status and the histopathology of the aor-tic media tunica. The experiments were undertaken on a batch of 30 Wistar males’ rats randomised into 3 groups, 10 control (Con), 10 castrated (Cas) and 10 castrated then supplemented with testosterone (Cas-T). Our results showed that testosterone deficiency induced a significant decrease in myeloperoxidase activity (19,95 ± 1, 79 vs 34,86 ± 1,13, p˂0,0001) this was maintained even after testosterone replacement. Furthermore, testosterone deficiency decreased the antioxidant capacity by reducing GSH in plasma (0,118 ± 0,003 vs 0,15 ± 0,011, p˂0,05). Our results also indicate that testos-terone supplementation leads to a significant increase in ceruloplasmin lev-els (62,37 ± 15,89 vs 148,12 ± 27,77, p ˂0.05). The histomorphometric exami-nation of the aortic tunica media in castrated rats showed a significant de-crease of media thickness (274,7 ± 2,96 vs 317,6 ± 5,19, p ˂0.0001) and VSMC count (108,1 ± 6,47 vs 130 ± 6,147, p ˂ 0.05) associated with damaged and broken elastic lamina. Testosterone supplementation restores the media thickness and the count of VSMC. Our findings demonstrate that testos-terone deficiency leads to a decrease in the count of VSMC and a rupture of elastic lamina. Testosterone altered the plasma oxidative status through ac-tions on GSH, MPO and ceruloplasmin.

Advanced glycation end products, galectin-3, matrix metalloproteinase-9 activity in men with heart failure and concomitant benign prostatic hyperplasia with androgen deficiency

The aim was to evaluate serum levels of matrix metalloproteinases-9 activity, advanced glycation end products, galectin-3, C-reactive protein in men with heart failure and benign prostatic hyperplasiawith testosterone deficiency. The testosterone level was determined by immune-enzyme analysis. The content of advanced glycation end products in plasma were analysed by quantitative autofluorescence. The metalloproteinases-9 activity was estimated with fluorometry. The level of galectin-3, C-reactive protein was determined by immune-enzyme analysis. 1st group was made up by the men with heart failure and benign prostatic hyperplasia with testosterone deficiency; 2nd group – by the men without testosterone deficiency. The men with heart failure and benign prostatic hyperplasia with testosterone deficiency had a significantly higher level of advanced glycation end products, galectin-3, matrix metalloproteinases-9 activity in comparison with men with heart failure without testosterone deficiency (p<0.001). Correlation relations between serum advanced glycation end products in patients of the main group with age, ejection fraction, testosterone level were determined – r=0.48 (p<0.001), r=-0.62 (p<0.001), r= -0.66 (p<0.001) respectively. Receiver operating characteristic analysis for predictive role in heart failure with preserved ejection fraction have shown high degree of sensitivity and specificity for advanced glycation end products in serum (p<0.001). Middle-aged men with heart failure with preserved ejection fraction and benign prostatic hyperplasia with testosterone deficiency are characterised by increased serum advanced glycation end products, galectin-3, matrix metalloproteinases-9 activity, C-reactive protein. Serum advanced glycation end products are potential biomarkers of development of heart failure with phenotype of preserved ejection fraction in this cohort.

Low testosterone is associated with increased risk of major adverse cardiovascular events in smokers with erectile dysfunction

Purpose Tobacco cigarette smoking and decreased concentrations of testosterone are major risk factors of erectile dysfunction (ED) and independent predictors of cardiovascular disease (CVD). We investigated, whether testosterone deficiency has a complementary predictive value for CVD events in smokers with ED. Methods A cohort of 398 men with ED and without known atherosclerotic CVD (mean age: 55±10 years) were followed for the occurrence of major adverse cardiovascular events (MACE), (CVD death, coronary artery disease, stroke). Total testosterone (TT) levels were measured in all patients. Results Among the study population, 205 (52%) were smokers. During a mean follow-up of 6 years (range: 1–11 years), 30 (7.5%) patients demonstrated a MACE. Baseline TT levels were significantly lower and prevalence of smoking was higher in the CV-event group than the event-free survival group (P&lt;0.01 and P&lt;0.05, respectively). Kaplan–Meier analysis showed that patients with low TT (≤4.0 ng/mL) had a worse prognosis than patients with TT &gt;4.0 ng/mL (log rank: 6.52, P=0.011), and that smokers had a greater risk of adverse events than never smokers (log rank: 4.42, P=0.04). We then stratified all patients into four groups, on the basis of smoking status (current/never smokers) and low or high TT (≤ or &gt;4.0 ng/mL) and cardiac event-free survival curves were constructed by Kaplan–Meier analysis (figure). The event-free rate in smokers with low TT is significantly lower than that of smokers with low TT or never smokers with normal TT (log rank: 11.3, P=0.02). Smokers with low TT had an almost 4-fold higher risk of MACEs compared to never smokers with normal TT (adjusted hazard ratio: 3.91; P=0.030). Conclusion Cigarette smoking combined with low TT concentration is associated with a shorter event-free period compared with either smoking or testosterone deficiency alone. The measurement of testosterone concentration may be useful to further stratify the risk of ED smokers without known CVD. FUNDunding Acknowledgement Type of funding sources: None. Smoking testosterone deficiency and MACE

The Prostate Saturation Point after Testosterone Replacement Therapy in Testosterone Deficiency Patient

Background: The effect of testosterone on the prostate gland is an unresolved question. The prostate saturation model is a recent hypothesis explaining that the stimulation of prostate tissue by testosterone is limited to a certain level of testosterone due to the limited number of androgen receptors. However, data from the Thai patients related to this issue are still lacking and need to be explored. Objective: To investigate prostate changes after testosterone replacement therapy (TRT). Materials and Methods: A retrospective study including testosterone-deficient patients who had TRT between 2011 and 2017 at Ramathibodi Hospital was conducted. The change in prostate-specific antigen (PSA) levels before and after TRT, or after a 1-year observation, was measured and analyzed as the primary objective. As a secondary objective, the authors measured and evaluated normal PSA velocity (PSAV) in the patients after TRT. Results: One hundred eleven testosterone deficient patients were included for analysis. The mean age was 62 years old. The baseline testosterone level and PSA level at the beginning were 247 ng/dL and 1.16 ng/mL, respectively. After undergoing TRT for one year, the results showed that the testosterone and the PSA levels were 307 ng/dL and 1.46 ng/mL, respectively. In addition, the subgroup analysis illustrated that patients who had low baseline testosterone levels such as 247 ng/dL or less, had significant increase of PSA level after treatment. However, when the baseline testosterone level was more than 247 ng/dL, the PSA levels were steady after treatment. For the secondary-objective results, the PSAV of the testosterone deficiency patients after TRT was 0.3 ng/mL/year. Conclusion: The evidence clearly indicates that TRT significantly increased the serum testosterone level. However, it had a limited effect on PSA change. The present study results supported the hypothesis of the prostate saturation model. The authors believe that a testosterone level of 247 ng/dL can saturate all androgen receptors in the prostate gland and no longer increase prostate stimulation. Keywords: Prostate-specific antigen; Prostate cancer; Testosterone replacement Therapy; Prostate saturation

In-vivo skeletal muscle mitochondrial function in Klinefelter syndrome

Klinefelter syndrome (XXY) occurs in 1 in 600 males, resulting in testosterone deficiency and a high prevalence of insulin resistance. Testosterone deficiency in men is a known cause of insulin resistance, and mitochondrial dysfunction is hypothesized to mediate this relationship. The aim of this cross-sectional study was to evaluate muscle mitochondrial function in XXY compared with male controls. Twenty-seven boys with XXY (age 14.7±1.8 years) were compared with 87 controls (age 16.9±0.9). In-vivo calf muscle mitochondrial function was assessed via phosphorus magnetic resonance spectroscopy (31P-MRS) following 90 s of isometric 70% maximal exercise. Multiple linear regression was used to compare 31P-MRS outcomes (ADP and phosphocreatine (PCr) time constants, rate of oxidative phosphorylation (Oxphos), and Qmax or the maximal mitochondrial function relative to mitochondrial density) between groups after adjusting for age differences. There were no statistically significant differences in the mitochondrial outcomes of ADP, Oxphos, PCr, and Qmax between the groups. There were also no differences in a sensitivity analysis within the XXY group by testosterone treatment status. In this study, in-vivo postexercise skeletal muscle mitochondrial function does not appear to be impaired in adolescents with XXY compared with controls and is not significantly different by testosterone treatment status in XXY.