The present analysis provides an estimate of the average treatment effects of testosterone therapy in middle-aged men. Our findings are sufficiently strong to justify further interventional studies focused on alternative targets of androgenic treatment carrying more stringent clinical implications, in particular the cardiovascular, metabolic and neurological systems.

Overall, 656 subjects were evaluated: 284 were randomized to T, 284 to placebo (P) and 88 treated in cross-over. The median study length was 3 months (range 1-36 months). Our meta-analysis showed that in men with an average T level at baseline below 12 nmol/l, T treatment moderately improved the number of nocturnal erections, sexual thoughts and motivation, number of successful intercourses, scores of erectile function and overall sexual satisfaction, whereas T had no effect on erectile function in eugonadal men compared to placebo. Heterogeneity was explored by grouping studies according to the characteristics of the study population. A cut-off value of 10 nmol/l for the mean T of the study population failed to predict the effect of treatment, whereas the presence of risk factors for vasculogenic erectile dysfunction (ED), comorbidities and shorter evaluation periods were associated with greater treatment effects in the studies performed in hypogonadal, but not in eugonadal, men. Meta-regression analysis showed that the effects of T on erectile function, but not libido, were inversely related to the mean baseline T concentration. The meta-analysis of available studies indicates that T treatment might be useful for improving vasculogenic ED in selected subjects with low or low-normal T levels. The evidence for a beneficial effect of T treatment on erectile function should be tempered with the caveats that the effect tends to decline over time, is progressively smaller with increasing baseline T levels, and long-term safety data are not available. The present meta-analysis highlights the need, and pitfalls, for large-scale, long-term, randomized controlled trials to formally investigate the efficacy of T replacement in symptomatic middle-aged and elderly men with reduced T levels and ED.

).q RSNA, 2014 Purpose:To evaluate the diagnostic accuracy of unenhanced and quantitative contrast-enhanced ultrasonography (US) in the differential diagnosis of small nonpalpable testicular lesions. Materials andMethods:The local review board approved the protocol, and all patients provided written informed consent. One hundred fifteen patients (median age, 34 years; age range, 14-61 years) with nonpalpable testicular lesions were consecutively enrolled between 2006 and 2012 and underwent unenhanced scrotal US, contrast-enhanced US, surgical enucleation, and at least 18 months of follow-up. Clinical and histologic features were recorded, and qualitative and quantitative analysis of contrast-enhanced US time-intensity curves were performed. Logistic regression analysis was performed to explore features of malignancy. Receiver operating characteristic (ROC) curves were developed for cumulative unenhanced and contrast-enhanced US scores. Results:All lesions were 1.5 cm or smaller. Forty-four of the 115 patients (38%) had malignant tumors, 42 had benign tumors (37%), and 29 (25%) had nonneoplastic lesions. Conclusion:Benign testicular tumors are frequent incidental findings. Quantitative scrotal contrast-enhanced US is a noninvasive diagnostic tool that could improve the differential diagnosis and individualized management of small testicular lesions.q RSNA, 2014

Women and men, female and male animals and cells are biologically different, and acknowledgement of this fact is critical to advancing medicine. However, incorporating concepts of sex-specific analysis in basic research is largely neglected, introducing bias into translational findings, clinical concepts and drug development. Research funding agencies recently approached these issues but implementation of policy changes in the scientific community is still limited, probably due to deficits in concepts, knowledge and proper methodology. This expert review is based on the EUGenMed project (www.eugenmed.eu) developing a roadmap for implementing sex and gender in biomedical and health research. For sake of clarity and conciseness, examples are mainly taken from the cardiovascular field that may serve as a paradigm for others, since a significant amount of knowledge how sex and oestrogen determine the manifestation of many cardiovascular diseases (CVD) has been accumulated. As main concepts for implementation of sex in basic research, the study of primary cell and animals of both sexes, the study of the influence of genetic vs. hormonal factors and the analysis of sex chromosomes and sex specific statistics in genome wide association studies (GWAS) are discussed. The review also discusses methodological issues, and analyses strength, weaknesses, opportunities and threats in implementing sex-sensitive aspects into basic research.

Background-cGMP phosphodiesterase type 5 protein is upregulated in myocardial hypertrophy. However, it has never been ascertained whether phosphodiesterase type 5 inhibition exerts an antiremodeling effect in nonischemic heart disease in humans. We explored the cardioreparative properties of a selective phosphodiesterase type 5 inhibitor, sildenafil, in a model of diabetic cardiomyopathy. Methods and Results-Fifty-nine diabetic men (60.3Ϯ7.4 years) with cardiac magnetic resonance imaging consistent with nonischemic, nonfailing diabetic cardiomyopathy (reduced circumferential strain [], Ϫ12.6Ϯ3.1%; increased left ventricular [LV] torsion [], 18.4Ϯ4.6°; and increased ratio of LV mass to volume, 2.1Ϯ0.5 g/mL) were randomized to receive sildenafil or placebo (100 mg/d). At baseline, the metabolic indices were correlated with torsion, strain, N-terminal pro-B-type natriuretic peptide, vascular endothelial growth factor, monocyte chemotactic protein-1, and blood pressure. After 3 months, sildenafil produced a significant improvement compared with placebo in LV torsion (⌬: sildenafil, Ϫ3.89Ϯ3.11°versus placebo, 2.13Ϯ2.35°; PϽ0.001) and strain (⌬: sildenafil, Ϫ3.30Ϯ1.86% versus placebo, 1.22Ϯ1.84%; PϽ0.001). Sildenafil-induced improvement of LV contraction was accompanied by consistent changes in chamber geometry and performance, with a 6.5Ϯ11% improvement in mass-to-volume ratio over placebo (Pϭ0.021). Monocyte chemotactic protein-1 and transforming growth factor-␤ were the only markers affected by active treatment (⌬monocyte chemotactic protein-1: Ϫ75.30Ϯ159.28 pg/mL, Pϭ0.032; ⌬transforming growth factor-␤: 5.26Ϯ9.67 ng/mL, Pϭ0.009). No changes were found in endothelial function, afterload, or metabolism. Conclusions-The early features of diabetic cardiomyopathy are LV concentric hypertrophy associated with altered myocardial contraction dynamics. Chronic phosphodiesterase type 5 inhibition, at this stage, has an antiremodeling effect, resulting in improved cardiac kinetics and circulating markers. This effect is independent of any other vasodilatory or endothelial effects and is apparently exerted through a direct intramyocardial action. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00692237. (Circulation. 2012;125:2323-2333.) Key Words: cardiac magnetic resonance imaging Ⅲ diabetes mellitus type 2 Ⅲ diabetic diastolic heart failure Ⅲ fibrosis Ⅲ phosphodiesterase inhibitors heart failure I nhibition of phosphodiesterase type 5 (PDE5) exerts a relaxant effect on the smooth muscle cells of the trabecular structures of the corpora cavernosa, resulting in improved erections. More recently, PDE5 inhibitors have been claimed to offer cardioprotective effects. In vitro and in vivo studies in mice have shown that cGMP and its downstream protein kinase G are signals common to most pathways activated in cardiac hypertrophy. 1 Low levels of PDE5 protein and cGMP-mediated activation of protein kinase G have been found in unstimulated hearts. 2 However, in isolated mouse cardiomyocytes tr...