scholarly journals The Effect of Testosterone on Cardiovascular Biomarkers in the Testosterone Trials

2017 ◽  
Vol 103 (2) ◽  
pp. 681-688 ◽  
Author(s):  
Emile R Mohler ◽  
Susan S Ellenberg ◽  
Cora E Lewis ◽  
Nanette K Wenger ◽  
Matthew J Budoff ◽  
...  

Abstract Context Studies of the possible cardiovascular risk of testosterone treatment are inconclusive. Objective To determine the effect of testosterone treatment on cardiovascular biomarkers in older men with low testosterone. Design Double-blind, placebo-controlled trial. Setting Twelve academic medical centers in the United States. Participants In all, 788 men ≥65 years old with an average of two serum testosterone levels <275 ng/dL who were enrolled in The Testosterone Trials. Intervention Testosterone gel, the dose adjusted to maintain the testosterone level in the normal range for young men, or placebo gel for 12 months. Main Outcome Measures Serum markers of cardiovascular risk, including lipids and markers of glucose metabolism, fibrinolysis, inflammation, and myocardial damage. Results Compared with placebo, testosterone treatment significantly decreased total cholesterol (adjusted mean difference, −6.1 mg/dL; P < 0.001), high-density lipoprotein cholesterol (adjusted mean difference, −2.0 mg/dL; P < 0.001), and low-density lipoprotein cholesterol (adjusted mean difference, −2.3 mg/dL; P = 0.051) from baseline to month 12. Testosterone also slightly but significantly decreased fasting insulin (adjusted mean difference, −1.7 µIU/mL; P = 0.02) and homeostatic model assessment‒insulin resistance (adjusted mean difference, −0.6; P = 0.03). Testosterone did not change triglycerides, d-dimer, C-reactive protein, interleukin 6, troponin, glucose, or hemoglobin A1c levels more than placebo. Conclusions and Relevance Testosterone treatment of 1 year in older men with low testosterone was associated with small reductions in cholesterol and insulin but not with other glucose markers, markers of inflammation or fibrinolysis, or troponin. The clinical importance of these findings is unclear and requires a larger trial of clinical outcomes.

Author(s):  
Daniel J Rader ◽  
Eleftheria Maratos-Flier ◽  
Amanda Nguyen ◽  
Doug Hom ◽  
Michael Ferriere ◽  
...  

Abstract Purpose To evaluate the safety and potential efficacy of LLF580, a genetically engineered variant of human fibroblast growth factor-21, for triglyceride lowering, weight loss, and hepatic fat reduction. Methods A multicenter, double-blind, parallel design trial in obese, mildly hypertriglyceridemic adults randomized (1:1) to LLF580 300 mg or placebo subcutaneously every 4 weeks for 3 doses. Results Of 64 randomized study participants, 61 (mean ± SD: age 45 ± 11 years, 49% male, 80/15/5% Caucasian/African American/other, body mass index 36.1 ± 3.8 kg/m2) received LLF580 (n = 30) or placebo (n = 31) at 7 research sites in the United States. LLF580 lowered serum triglycerides by 54% (least square mean placebo adjusted change from baseline), total cholesterol 7%, low-density lipoprotein cholesterol 12%, and increased high-density lipoprotein cholesterol 36% compared with placebo (all P < 0.001) over 12 weeks. Substantial reduction of liver fat of 52% over placebo (P < 0.001) was also demonstrated in the setting of improved liver function tests including alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase, the composite enhanced liver fibrosis score, and N-terminal type III collagen propeptide (all P < 0.05). Insulin and C-peptide levels and insulin resistance by homeostatic model assessment for insulin resistance were all lower, and adiponectin higher with LLF580 treatment compared with placebo, whereas fasting glucose and glycated hemoglobin were unchanged. Reductions in biomarkers of bone formation without differences in markers of bone resorption were observed. LLF580 was generally safe and well tolerated, except for higher incidence of generally mild to moderate gastrointestinal adverse effects. Conclusions In obese, mildly hypertriglyceridemic adults, LLF580 was generally safe and demonstrated beneficial effects on serum lipids, liver fat, and biomarkers of liver injury, suggesting it may be effective for treatment of select metabolic disorders including hypertriglyceridemia and nonalcoholic fatty liver disease. Assessments of longer term safety and efficacy are warranted. ClinicalTrials.gov Identifier NCT03466203


Author(s):  
Hsiao-Han Chao ◽  
Yi-Hung Liao ◽  
Chun-Chung Chou

Background: Aging and chronic degeneration are the primary threats to cardiometabolic health in elderly populations. Regular appropriate exercise would benefit the advanced aging population. Purpose: This study investigates whether the degree of weekly tennis participation exhibits differences in primary cardiometabolic parameters, including arterial stiffness, inflammation, and metabolic biomarkers in elderly tennis players. Methods: One hundred thirty-five long-term participants in elder tennis (>50 years old) were initially screened. Twenty-six eligible and voluntary subjects were divided into high tennis time group (HT) (14 ± 1.3 h/week) and low tennis time group (LT) (4.5 ± 0.7 h/week) by stratification analysis based on the amount of tennis playing activity time. The brachial-ankle pulse wave velocity (baPWV), blood pressure, ankle-brachial index (ABI), blood metabolic biomarkers, and insulin resistance were measured to compare the difference between HT and LT groups. Results: The baPWV was significantly lower in the HT group than that in the LT group (1283.92 ± 37.01 vs. 1403.69 ± 53.71 cm/s, p < 0.05). We also found that the HT insulin-resistant homeostasis model assessment (HOMA-IR) was significantly lower than that of LT (1.41 ± 0.11 vs. 2.27 ± 0.48 μIU/mL, p < 0.05). However, the blood lipid biomarkers (glucose, cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride) were not statistical different between HT and LT groups (p > 0.05). Conclusion: We demonstrated that under the condition of similar daily physical activity level, elderly with a higher time of tennis-playing (HT group) exhibited relatively lower arterial stiffness (lower PWV) and lower insulin resistance compared to those with lower time tennis-playing (LT).


2021 ◽  
Vol 10 (15) ◽  
pp. 3400
Author(s):  
Cathy Degroote ◽  
Roland von Känel ◽  
Livia Thomas ◽  
Claudia Zuccarella-Hackl ◽  
Jens C. Pruessner ◽  
...  

Hyperreactivity to stress may be one explanation for the increased risk of cardiovascular disease (CVD) in individuals with essential hypertension. We investigated blood lipid reactivity to the Montreal Imaging Stress Task (MIST), a psychosocial stressor, in hypertensive and normotensive men and tested for prospective associations with biological risk factors. Fifty-six otherwise healthy and medication-free hypertensive and normotensive men underwent the MIST. We repeatedly measured cortisol and blood lipid profiles (total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG)) immediately before and up to 1 h after stress. Lipid levels were corrected for stress hemoconcentration. Thirty-five participants completed follow-up assessment 2.9 ± 0.12 (SEM) years later. CVD risk was assessed by prospective changes in TC/HDL-C ratio, IL-6, D-dimer, and HbA1c from baseline to follow-up. The MIST induced significant changes in all parameters except TC (p-values ≤ 0.043). Compared with normotensives, hypertensives had higher TC/HDL-C-ratio and TG (p-values ≤ 0.049) stress responses. Blood lipid stress reactivity predicted future cardiovascular risk (p = 0.036) with increases in HbA1c (ß = 0.34, p = 0.046), IL-6 (ß = 0.31, p = 0.075), and D-dimer (ß = 0.33, p = 0.050). Our results suggest that the greater blood lipid reactivity to psychosocial stress in hypertensives, the greater their future biological CVD risk. This points to lipid stress reactivity as a potential mechanism through which stress might increase CVD risk in essential hypertension.


2020 ◽  
Vol 33 (7) ◽  
pp. 933-940 ◽  
Author(s):  
Pitchaya Satitpatanapan ◽  
Somchit Jaruratanasirikul ◽  
Hutcha Sriplung

AbstractBackgroundIn 2011, we described 64 girls diagnosed with central precocious puberty (CPP) during 1995–2009. In 2019, the former CPP patients were 16–30 years of age and had been followed-up for 6–20 years after cessation of gonadotropin-releasing hormone analog (GnRHa) treatment.ObjectivesTo determine the menstrual cycle, reproductive function, and long-term sequelae of the former GnRHa-treated and untreated CPP patients.MethodsSixty-seven former CPP women diagnosed during January 1995 to December 2010 were evaluated in 2019 for current menstrual cycle and pregnancy rate and for general health status, weight, height, blood pressure, and metabolic profiles of glucose, lipids, insulin, and testosterone.ResultsIn 2019, the former CPP women averaged 20.7 ± 2.7 years of age (range: 16.5–30). Eighty-three percent had a regular menstrual cycle. Of the 14 married women, six (43%) were fertile with 1–2 children. The untreated women had a significantly higher rate of obesity (BMI >25 kg/m2) than the GnRHa-treated women (72.1% vs. 36.6%, p < 0.01). Two women (3%) had polycystic ovary syndrome (PCOS). Fasting plasma glucose, serum high-density lipoprotein cholesterol (HDL-C), and testosterone levels were normal and similar between the GnRHa-treated and untreated participants. The serum insulin, cholesterol, triglyceride, low-density lipoprotein cholesterol (LDL-C), and homeostasis model assessment-insulin resistance (HOMA-IR) levels were higher in the untreated group than the GnRHa-treated group, but without significant differences.ConclusionsAt a 10–20-year follow-up, our former CPP patients had regular menstruation, normal reproductive function, and normal metabolic outcomes. The low prevalence of PCOS of 3% suggests that CPP is not a risk factor for PCOS, at least during early adulthood.


JAMA ◽  
2017 ◽  
Vol 317 (7) ◽  
pp. 717 ◽  
Author(s):  
Susan M. Resnick ◽  
Alvin M. Matsumoto ◽  
Alisa J. Stephens-Shields ◽  
Susan S. Ellenberg ◽  
Thomas M. Gill ◽  
...  

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Jacob Hartz ◽  
Ronald M. Krauss ◽  
Mikael Göttsater ◽  
Olle Melander ◽  
Peter Nilsson ◽  
...  

Background. Central arterial stiffness is a surrogate of cardiovascular risk and predicts cardiovascular mortality. Apolipoprotein B lipoproteins are also established cardiovascular risk factors. It is not known whether specific lipoprotein subclasses measured in the Malmö Diet and Cancer Study and previously shown to be associated with coronary heart disease also predict arterial stiffening after a mean period of 17 years. Methods. Lipoprotein particle analysis was performed on 2,505 men and women from Malmö, Sweden, from 1991 to 1994, and arterial stiffness was assessed by carotid-femoral pulse wave velocity (c-fPWV) on this same cohort from 2007 to 2012. Associations between c-fPWV and lipoprotein particles were determined with multiple linear regression, controlling for sex, presence of diabetes, waist-to-hip circumference, and smoking status at baseline, as well as heart rate (measured at the carotid artery), mean arterial pressure, antihypertensive and lipid-lowering medications, C-reactive protein (CRP), and age at the time of c-fPWV measurement. Results. The results confirm that triglycerides (TG) and high-density lipoprotein cholesterol (HDL-c) but not low-density lipoprotein cholesterol (LDL-c) predict c-fPWV. We identify a positive predictive association for very small, small, and medium (high risk), but not large LDL particles. There was a negative association for large HDL particles. The relationships between c-fPWV and high-risk LDL particles were unaffected by adjusting for LDL-c or CRP and were only mildly attenuated by adjusting for the homeostatic model for insulin resistance (HOMA-IR). Due to the collinearity of very small, small, and medium LDL particles and dyslipidemia (elevated TG and decreased HDL-c), the observed relationship between c-fPWV and high-risk LDL particles became insignificant after controlling for the concentration of HDL-c, large cholesterol-rich HDL particles, and TG. Conclusions. The development of central arterial stiffness previously associated with combined dyslipidemia may be mediated in part by LDL particles, particularly the very small-, small-, and medium-sized LDL particles.


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