Beneficial and adverse effects of testosterone on the cardiovascular system in men

Context: The widespread use of T therapy, particularly in aging males, necessitates knowledge of the relationship between T and the cardiovascular system. Evidence Acquisition: The review is based on a 1970 to 2013 PubMed search with terms related to androgens in combination with cardiovascular disease, including T, dihydrotestosterone, trial, mortality, cardiovascular disease, myocardial infarction, blood pressure, endothelial function, dyslipidemia, thrombosis, ventricular function, and arrhythmia. Original articles, systematic reviews and meta-analyses, and relevant citations were screened. Evidence Synthesis: Low T has been linked to increased blood pressure, dyslipidemia, atherosclerosis, arrhythmia, thrombosis, endothelial dysfunction, as well as to impaired left ventricular function. On the one hand, a modest association is suggested between low endogenous T and incident cardiovascular disease or cardiovascular mortality, implying unrecognized beneficial T effects, residual confounding, or a relationship with health status. On the other hand, treatments with T to restore "normal concentrations" have so far not been proven to be beneficial with respect to cardiovascular disease; neither have they definitely shown specific adverse cardiovascular effects. The cardiovascular risk-benefit profile of T therapy remains largely evasive in view of a lack of well-designed and adequately powered randomized clinical trials. Conclusions: The important knowledge gap as to the exact relationship between T and cardiovascular disease would support a cautious, restrained approach to T therapy in aging men, pending clarification of benefits and risks by adequately powered clinical trials of sufficient duration

Mediators of physical activity change in a behavioral modification program for type 2 diabetes patients

Background: Many studies have reported significant behavioral impact of physical activity interventions. However, few have examined changes in potential mediators of change preceding behavioral changes, resulting in a lack of information concerning how the intervention worked. Our purpose was to examine mediation effects of changes in psychosocial variables on changes in physical activity in type 2 diabetes patients.Methods: Ninety-two patients (62 ± 9 years, 30, 0 ± 2.5 kg/m, 69% males) participated in a randomized controlled trial. The 24-week intervention was based on social-cognitive constructs and consisted of a face-to-face session, telephone follow-ups, and the use of a pedometer. Social-cognitive variables and physical activity (device-based and self-reported) were collected at baseline, after the 24-week intervention and at one year post-baseline. PA was measured by pedometer, accelerometer and questionnaire.Results: Post-intervention physical activity changes were mediated by coping with relapse, changes in social norm, and social modeling from family members (p ≤ 0.05). One-year physical activity changes were mediated by coping with relapse, changes in social support from family and self-efficacy towards physical activity barriers (p ≤ 0.05). Conclusions: For patients with type 2 diabetes, initiatives to increase their physical activity could usefully focus on strategies for resuming regular patterns of activity, on engaging family social support and on building confidence about dealing with actual and perceived barriers to activity.Trial Registration: NCT00903500, ClinicalTrials.gov

Moxifloxacin dosing in post-bariatric surgery patients

Introduction Given the ever increasing number of obese patients and obesity related bypass surgery, dosing recommendations in the post-bypass population are needed. Using a population pharmacokinetic (PK) analysis and PK-pharmacodynamic (PD) simulations, we investigated whether adequate moxifloxacin concentrations are achieved in this population. Methods In this modelling and simulation study we used data from a trial on moxifloxacin PK. In this trial, volunteers who had previously undergone bariatric surgery (at least 6 months prior to inclusion), received two doses (intravenous and oral) of 400mg moxifloxacin administered on two occasions. Results In contrast to other papers, we found that moxifloxacin PK were best described by a three compartmental model using lean body mass (LBM) as a predictor for moxifloxacin clearance. Furthermore, we showed that the probability of target attainment for bacterial eradication against a hypothetical Streptococcus pneumoniae infection is compromised in patients with higher LBM, especially when targeting microorganisms with minimum inhibitory concentrations (MICs) of 0.5mgl-1 or higher (probability of target attainment (PTA) approaching zero). When considering the targets for suppression of bacterial resistance formation, even at MIC values as low as 0.25mgl-1, standard moxifloxacin dosing does not attain adequate levels in this population. Furthermore, for patients with a LBM of 78kg or higher, the probability of hitting this target approaches zero. Conclusions Throughout our PK-PD simulation study, it became apparent that, whenever optimal bacterial resistance suppression is deemed necessary, the standard moxifloxacin dosing will not be sufficient. Furthermore, our study emphasizes the need for a LBM based individualized dosing of moxifloxacin in this patient population

Incretin mimetics and enhancers for the treatment of type 2 diabetes mellitus

Recently, new therapeutic strategies based on the incretin system have been developed for the treatment of type 2 diabetes mellitus. The present mini-review aims to provide a short overview of the background of this incretin system and the therapeutic potential of incretin mimetics and enhancers (DPP-4 inhibitors). The function of the incretin system, which shows gradual failure in type 2 diabetes, can be restored by incretin mimetics or DPP-4 inhibitors, with subsequently an improve of glycaemic control without an increase of risk for hypoglycaemia, as long as not combined with glucose-lowering agents like sulfonylureas or insulin. Incretin mimetics have additional important weight-reducing properties, though associated with gastro-intestinal adverse events. DPP-4 inhibitors appear to be 'weight neutral' and show a safe profile in a Limited number of available clinical studies of short duration

Webgebaseerde diabeteseducatie, iets voor u?

Het internet heeft in een korte tijd een belangrijke invloed op ons leven gekregen. Eén van de mogelijkheden die het biedt is telemonitoring en meer specifiek: webgebaseerde diabeteseducati

Endogenous testosterone and cardiovascular disease in healthy men: a meta-analysis

Context The literature provides no clear answer as to whether low endogenous testosterone increases risk of cardiovascular disease (CVD) in healthy men. Objective Our purpose was to estimate the predictive value of testosterone for CVD and to identify study features explaining conflicting results. Data Sources Articles were identified by a Medline and Embase search and citation tracking. Study Selection Eligible were prospective population-based cohort and nested case-control studies of testosterone and atherosclerosis, stroke, myocardial infarction, ischaemic heart disease, death from coronary heart disease or mortality. Data extraction Two independent researchers re-expressed associations of testosterone and CVD in a uniform manner to be used in meta-regression analyses for identification of study features explaining conflicting results, and to estimate the predictive value of testosterone for CVD. Results and Conclusions 19 potentially eligible articles were identified. Overall, a weak independent association was found with an estimated summary RR of 0.89 for a change of one standard deviation in total testosterone level (95% CI 0.83 to 0.96). Age of study population and year of publication modified the relationship between testosterone and CVD. The estimated summary RR was 1.01 (0.95 to 1.08) for studies of men younger than 70 years of age, and 0.84 (0.76 to 0.92) for studies including men over 70 years of age. The latter studies showed a particular pronounced association if published after 1 January 2007. Results were largely confirmed by separate analyses of free-and bioavailable testosterone. The systematic review displayed no association between endogenous testosterone and risk for CVD in middle-aged men. In elderly men, testosterone may weakly protect against CVD. Alternatively, low testosterone may indicate a poor general health

Short-term changes in serum sex steroid levels and cardiac function in healthy young men

Introduction: Male obesity is associated with an increase in estradiol (E2) and a decrease in testosterone (T). And, although sex steroids are associated with cardiovascular disease, direct effects on cardiac structure and function are hardly investigated in humans. Methodology: Twenty healthy men aged 20–40 years were randomized into two groups. One group was given an aromatase inhibitor (letrozole) only, thus obtaining a high testosterone and low E2 (group T). The other group received an aromatase inhibitor plus an E2 patch (dermestril), reaching a low testosterone and high E2 (group E). Serum levels of both testosterone and E2 remained within the normal reference range. The men underwent an echocardiography by a single cardiologist before the start of the intervention and after 7 days. Results: Total and free E2 serum levels were positively associated with ejection fraction (r=0.7, P=0.002 and r=0.6, P=0.007 respectively) at baseline in the whole group. In group E global circumferential strain decreased significantly from −25.3%±3.9 to −19.6%±2.5 after 1 week as compared to baseline (P=0.01). No significant changes in systolic function were observed in group T. Cardiac structure remained unaltered. Conclusion: In young healthy men, an increase in E2 and decrease in testosterone levels significantly decreased circumferential strain. The finding justifies larger studies of longer duration to discover the exact nature of the impact of changed sex steroids on cardiac function and remodelling in obesity