Serum folic acid: an effective indicator for arteriogenic erectile dysfunction.

Background: The present study is the first to explore the correlation between serum folic acid (FA) level and penile arterial peak systolic velocity (PSV) as measured via penile color Doppler ultrasonography (PDU), which directly reflects endothelial function in the penile artery. Materials and methods: A total of 244 consecutive erectile dysfunction (ED) patients and 72 healthy controls, recruited from the Andrology department and the Healthy Physical Examination Center of our hospital, respectively, from June 2020 to April 2022, were included in the study. Serum FA was measured in ED patients and healthy controls, and PDU examinations were conducted for all eligible ED patients. The Pearson method was used to evaluate the correlation between FA levels and PDU parameters in ED patients. A receiver operating characteristic (ROC) curve analysis was also performed to calculate the sensitivity and specificity of these parameters for prediction of arteriogenic ED. Results: After the PDU test, the average serum FA level among patients diagnosed with arteriogenic ED was 8.08 ± 2.64 ng/ml, lower than the average of 10.78 ± 2.87 ng/ml among healthy controls. There were no statistically significant inter-group differences on any basic parameters, including age, body mass index, fasting blood glucose, total cholesterol, and triglyceride. For further analysis, we divided the arteriogenic ED group into three subgroups by PSV range to compare serum FA levels among these subgroups. The mean FA levels in each of these groups were 5.97 ± 1.51ng/ml, and 8.21 ± 2.37ng/ml, and 10.55 ± 2.56ng/ml, while the corresponding PSV values were 15.75 ± 2.39cm/s, 23.53 ± 2.19cm/s, and 32.72 ± 1.64cm/s. Overall, a positive correlation between PSV and FA level was found among patients with arteriogenic ED (r=0.605, P<0.001). Furthermore, when FA level was used, with a cut-off value of 10.045 ng/ml, as a criterion to distinguish patients with arteriogenic ED from healthy controls, the area under the curve (AUC) was 0.772 (95% confidential interval: [0.696, 0.848]), for a sensitivity of 0.611 and specificity of 0.824. Conclusion: Serum FA level is positively correlated with PSV in ED patients, and has the ability to distinguish patients with arteriogenic ED from healthy controls. Taking these findings together, FA deficiency should be regarded as an independent risk factor for arteriogenic ED.

Low androgen status inhibits erectile function by increasing pyroptosis in rat corpus cavernosum.

BACKGROUND: The mechanism of erectile dysfunction (ED) caused by low androgen status is not fully understood. OBJECTIVES: To investigate whether low androgen status inhibits erectile function of rats by inducing pyroptosis in the corpus cavernosum (CC). MATERIALS AND METHODS: Thirty-six eight-weeks-old healthy male Sprague-Dawley rats were equally divided into six groups: sham-operated group (4w sham, 8w sham), castration group (4w cast, 8w cast), and castration + testosterone (T) group (4w cast + T, 8w cast + T). The rats in castration + T groups were injected with testosterone propionate subcutaneously every other day. After 4 and 8 weeks, the ratio of maximum intracavernous pressure (ICPmax)/mean arterial pressure (MAP), the level of serum T, the concentration of nitric oxide (NO) and interleukin-1ß (IL-1ß), the expression of NOD-like receptor pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC), Caspase-1 p20, gasdermin D-N (GSDMD-N), transforming growth factor ß1 (TGF-ß1), collagen-I, and collagen-III, the ratio of smooth muscle/collagen (SM/C), and the proportion of pyroptotic cells in the CC were analyzed. RESULTS: The ratio of ICPmax/MAP (3/5 V) and SM/C, the level of NO and serum T was significantly decreased in castration groups when compared to other groups (p < 0.01). NLRP3, ASC, Caspase-1, and GSDMD were mainly expressed in the cytoplasm of smooth muscle cells (SMCs) and endothelial cells (ECs) in the CC. The expression of NLRP3, ASC, Caspase-1p20, GSDMD-N, IL-1ß, TGF-ß1, collagen-I, and collagen-III was significantly increased in castration groups when compared with other groups (p < 0.01). The proportion of pyroptotic cells in the CC was increased significantly in castration groups when compared with other groups (p < 0.05). DISCUSSION AND CONCLUSION: Low androgen status inhibits erectile function of rats by promoting CC fibrosis and reducing NO synthesis through pyroptosis of SMCs and ECs in the CC.

A 6-month, double-blind, placebo-controlled, randomized trial to evaluate the effect of Eurycoma longifolia (Tongkat Ali) and concurrent training on erectile function and testosterone levels in androgen deficiency of aging males (ADAM).

BACKGROUND: Androgen deficiency of aging males (ADAM) largely manifests as sexual symptoms. Erectile dysfunction is one of the most common symptoms of ADAM. AIM: To ascertain the effect of concurrent training and supplementation with Eurycoma longifolia on erectile function and testosterone levels in men with ADAM, and the association of erectile function with levels of total testosterone. METHODS: 6-month, randomized, double-blind, placebo-controlled four-arm clinical. 45 men (47.38 ± 5.03 years) were randomized into 4 groups (G1: control + placebo; G2: control + Eurycoma longifolia; G3: concurrent training + placebo; G4: concurrent training + Eurycoma longifolia). 22 received a 200 mg supplement of Eurycoma longifolia and 23 underwent the intervention with concurrent training, 3 times a week for 60 min at progressive intensity. OUTCOMES: International Index of Erectile Function (IIEF-5), Aging Male Scale (AMS) and total testosterone. RESULTS: Erectile function demonstrated improvements in both interventions; however, the most significant results were obtained by men allocated to concurrent training + Eurycoma longifolia. CLINICAL IMPLICATIONS: A 200 mg supplement of Eurycoma longifolia and the practice of concurrent training for 6 months significantly improved the erectile function of men with ADAM. STRENGTHS & LIMITATIONS: The study's design stands out as a strength, in addition to the six-month intervention. The main limitation is the study not having groups that used only Eurycoma longifolia and only concurrent training. CONCLUSION: The combination of Eurycoma longifolia and concurrent training improved erectile function and increased total testosterone levels in men with ADAM.

Erectile Dysfunction, Testosterone Levels and Disease Activity in Ankylosing Spondylitis Patients.

OBJECTIVE: To study erectile function in male patients with Ankylosing Spondylitis (AS) trying to correlate it with sexual hormonal profile and disease activity. METHODS: We included 35 AS patients and 104 controls. Patients and controls answered the IIEF (International Index of Erectile Dysfunction) and had dosing of total testosterone, free testosterone (FT), bioavailable testosterone (BT), SHBG (serum hormone binding globulin), albumin and LH (luteinizing hormone). AS patients had epidemiological, clinical and treatment data obtained from the charts. AS disease activity was measured simultaneously with blood collection through Bath AS Disease Activity Index, ASDAS (AS Disease Activity Score) -ESR (using erythrocyte sedimentation rate) and ASDAS-CRP (using C reactive protein). RESULTS: The IIEF results were worse in AS patients than controls (P = .02). Total testosterone and SHBG were higher in AS (with P = .01 and P <.0001 respectively). Between the 2 groups, no differences in LH, FT, BT levels (all with P = ns) were found. In AS patients, the IIEF results did not correlate with total testosterone, SHBG, LH, FT, and BT but a negative association was found with Bath AS Disease Activity Index (P = .001) and ASDAS-CRP (P = .02). CONCLUSION: AS patients had worst sexual performance than controls that was linked to disease activity but not to male sexual hormonal profile.

Addressing male sexual and reproductive health in the wake of COVID-19 outbreak.

PURPOSE: The COVID-19 pandemic, caused by the SARS-CoV-2, represents an unprecedented challenge for healthcare. COVID-19 features a state of hyperinflammation resulting in a "cytokine storm", which leads to severe complications, such as the development of micro-thrombosis and disseminated intravascular coagulation (DIC). Despite isolation measures, the number of affected patients is growing daily: as of June 12th, over 7.5 million cases have been confirmed worldwide, with more than 420,000 global deaths. Over 3.5 million patients have recovered from COVID-19; although this number is increasing by the day, great attention should be directed towards the possible long-term outcomes of the disease. Despite being a trivial matter for patients in intensive care units (ICUs), erectile dysfunction (ED) is a likely consequence of COVID-19 for survivors, and considering the high transmissibility of the infection and the higher contagion rates among elderly men, a worrying phenomenon for a large part of affected patients. METHODS: A literature research on the possible mechanisms involved in the development of ED in COVID-19 survivors was performed. RESULTS: Endothelial dysfunction, subclinical hypogonadism, psychological distress and impaired pulmonary hemodynamics all contribute to the potential onset of ED. Additionally, COVID-19 might exacerbate cardiovascular conditions; therefore, further increasing the risk of ED. Testicular function in COVID-19 patients requires careful investigation for the unclear association with testosterone deficiency and the possible consequences for reproductive health. Treatment with phosphodiesterase-5 (PDE5) inhibitors might be beneficial for both COVID-19 and ED. CONCLUSION: COVID-19 survivors might develop sexual and reproductive health issues. Andrological assessment and tailored treatments should be considered in the follow-up.

Triglyceride-Glucose Index (TyG) is associated with erectile dysfunction: A cross-sectional study.

BACKGROUND: Erectile dysfunction (ED) is often associated with endocrine metabolic diseases such as metabolic syndrome (MetS) and diabetes mellitus (DM), in which insulin resistance (IR) plays a decisive role in pathology. Triglyceride-glucose index (TyG), a simple, inexpensive and easily accessible IR marker, is calculated by fasting serum glucose and triglyceride values. OBJECTIVES: We aimed to reveal the relationship between TyG index and ED. MATERIALS AND METHODS: Of 152 male patients, aged between 24-80 years, admitted to the urology outpatient clinic with complaining erectile insufficiency were evaluated. Liver function tests, complete blood count, fasting serum triglyceride, serum testosterone, fasting glucose, fasting insulin, and hemoglobinA1c (HbA1c) were analyzed. TyG index was calculated. All patients were requested to fill in the validated Turkish version of the 5-item International Index of Erectile Function (IIEF-5) survey. RESULTS: A total of 142 patients were included the study. ED was detected in 91 (64.1%) of the patients. BMI, fasting insulin level, fasting glucose level, IR, GGT, HDL, HbA1c, Triglyceride, TyG, DM, HT, and MetS status of the patients in ED group were statistically significantly higher compared to non-ED group (all P < .05). It was found that the cutoff value of TyG index for ED was 8.88 (AUC = 0.739, sensitivity 67%, specificity = 68.6%). In multivariate logistic regression analysis, age (OR = 1.07, 95% CI = 1026-1115, P = .002) and TyG index above 8.88 (OR = 3.865, 95% CI = 1686-8859, P = .001) were found as independent predictors of ED after accounting for BMI, serum total T and IR. CONCLUSION: TyG index might be useful in the diagnosis and follow-up of ED.

Comparison of hormone profile and systemic inflammation in patients presenting with sexual dysfunction: Which is important?

INTRODUCTION: Erectile dysfunction (ED) is the inability to achieve or maintain erection sufficient for satisfactory sexual performance. Although the definition is well known, there are controversial issues about the effects of hormones and inflammation on ED. OBJECTIVES: We aimed to compare the clinical value of the hormonal and inflammation parameters in sexual dysfunction. MATERIALS AND METHODS: A total of 152 patients diagnosed with erectile dysfunction between September 2018 and March 2019 and 101 healthy males were included in this prospective study as case group and control group, respectively. The 152 patients were divided into three groups based on their total International Index of Erectile Function (IIEF) scores: (I) severe ED, (II) mild-moderate ED and (III) mild ED. All groups were compared in terms of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and total testosterone (TT), estradiol, prolactin, testosterone-to-estradiol ratio and 25 (OH) vitamin D. RESULTS: Patient and control groups differed significantly in term of NLR, PLR, prolactin and vitamin D (p<0.001, p=0.004, p=0.002, p<0.001, p<0.001, respectively). NLR was more significant in determining the severity of ED (p<0.001). It was observed that libido score (the total score of IIEF items #11 and #12) was negatively associated with prolactin and NLR (p<0.001, p=0.023, respectively), was positively associated with vitamin D and TT (p<0.001, p=0.02, respectively), and was lower in severe ED patients. CONCLUSIONS: Although more clinical studies are needed, we think that our findings may be useful on these controversial issues of ED.

[Blood biochemical indexes in ED patients with kidney deficiency or non-kidney deficiency: A comparative analysis of 156 cases].

OBJECTIVE: To analyze the blood biochemical characteristics of the ED patients with different types of kidney deficiency or non-kidney deficiency. METHODS: We reviewed the clinical data on 156 ED patients treated in our Department of Andrology from May to July 2018 and, according to the traditional Chinese medicine (TCM) syndromes, divided them into four groups: kidney-yang deficiency (n = 48), kidney-yin deficiency (n = 34), kidney-yin+yang deficiency (n = 36) and non-kidney deficiency control (n = 38). We obtained and compared their blood biochemical indexes, including the levels of testosterone (T), estradiol (E2), cortisol (CORT), thyroid stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), nitric oxide (NO), total nitric oxide synthase (tNOS), and inducible nitric oxide synthase (iNOS). RESULTS: There were no statistically significant differences in the mean age, course of disease, IIEF-5 score and erection hardness score (EHS) among the four groups of patients. Pairwise comparison showed that, compared with the non-kidney deficiency controls, the patients in the kidney-yin deficiency group exhibited a dramatically higher level of CORT (ï¼»87.97 ± 45.59ï¼½ vs ï¼»121.78 ± 41.87ï¼½ µg/L, P = 0.002) and those in the kidney-yang deficiency group a remarkably lower level of FT3 (ï¼»5.44 ± 0.38ï¼½ vs ï¼»5.11 ± 0.54ï¼½ pmol/L, P = 0.008). The iNOS level was significantly higher in the kidney-yin deficiency group (14.42 ± 2.49 U/ml) than in either the control (12.71 ± 2.58 U/ml) (P = 0.039) or the kidney-yang deficiency group (13.05 ± 2.17 U/ml) (P =0.049). CONCLUSIONS: ED patients with different types of kidney deficiency syndromes have different blood biochemical indexes, which may help clarify the biological basis of the TCM syndromes of kidney deficiency in ED patients.

Sustained Glycemic Control Observed in Diabetic Men Who Improve Hemoglobin A1c Values to Allow for Elective Penile Prosthesis Placement.

OBJECTIVES: We hypothesize that men with diabetes mellitus whose inflatable penile prosthesis (IPP) implantation is delayed for unacceptably high hemoglobin A1c (HbA1c) will have durable improvements in their glycemic control after achieving acceptable HbA1c levels for surgery. METHODS: Per institutional protocol, an A1c <9% must be documented prior to IPP placement. After IRB approval, a single surgeon IPP database was retrospectively queried for data specific to diabetes mellitus management. Men without HbA1c values at ≥1-year follow-up were excluded. Univariate and multivariate statistical analyses were performed to assess associations with sustained HbA1c control. RESULTS: From January 2011 to March 2019, 138 diabetics undergoing IPP were identified. Thirty-seven were excluding for insufficient follow-up. Nineteen of the 101 analyzed men (18.8%) were delayed a median 4 months (range 2-17) for elevated HbA1c values (median 10.1, range 9.1-12.3). Following improvements, median preoperative HbA1c remained higher (8.2% vs 7.0%) in delayed men (P < .001). Among delayed recipients, 11 (58%) improved without medication changes while insulin was newly initiated (5) or dosage was increased (5) in 42%. At 32 months follow-up, a HbA1c <9% was similarly maintained in delayed and nondelayed men (74% vs 87%, P = .17). Delayed men more commonly required insulin therapy at follow-up (89.5% vs 54.9%, P = .008), but had a similar median change in BMI (+0.1 vs +0.1, P = .65). Device infection occurred in 1 nondelayed patient (0.7%). CONCLUSION: Men who improve HbA1c for IPP surgery are likely to demonstrate persistent improvement. IPP implantation appears to be safe in diabetic men with HbA1c <9%.

The Correlations of Clinical and Biochemical Indices of Vitamin D with Erectile Dysfunction.

Erectile dysfunction is a multifactorial disease; it has been demonstrated that endothelial dysfunction plays an essential role in the pathogenesis of this disease, and Vitamin D deficiency is considered to favor endothelial lesions. Our study, based on a group of 58 patients who have erectile dysfunction and a control group of 26 healthy subjects, tends to confirm that low levels of vitamin D could potentiate the severity of erectile dysfunction, promoting endothelial dysfunction. Statistical analysis using the Pearson's correlation criteria showed a robust and significant correlation between vitamin D levels and erectile dysfunction severity (ρ=0.752, p<0.000) according to the SHIM (Sexual Health Inventory For Men) questionnaire. Also, in patients with erectile dysfunction, there is a strong association between vitamin D and testosterone levels (ρ=0.728, p<0.000). At the same time, a negative correlation between vitamin D and BMI (ρ=-0.517, p<0.000); cholesterol (ρ=-0.560, p<0.001), and triglycerides(ρ=-0.529, p<0.005) was observed. Also, a moderate correlation between erectile dysfunction severity degree and testosterone levels (ρ=0.544) was also detected, and the same severity parameter of erectile dysfunction correlates negatively with cholesterol levels (ρ=-0.534). In its turn, the testosterone level correlates negatively with other biochemical indices: cholesterol (ρ=-0.694) and triglycerides (ρ=-0.670). Vitamin D level reduction, concomitantly with decreased testosterone and increased cholesterol, contributes to the development and maintenance of erectile dysfunction, more probably through endothelial mechanisms. The assessment of vitamin D values can be used as an independent marker in erectile dysfunction assessment. Thus, one of the diagnostic tests recommended for erectile dysfunction should be the determination of the vitamin D serum level.

Erythrocytes as markers of oxidative stress related pathologies.

Erythrocytes are deeply sensitive cells and important health indicators. During inflammatory response RBC, as a part of haematological system, are exposed to circulating inflammatory mediators and related oxidative stress. They present a highly specialized and organized cell membrane that interacts with inflammatory mediators and oxidative agents, leading to a variety of structural changes that promptly signal an abnormal situation. This review is aimed to provide an overview on erythrocyte involvement in physiological and pathological processes related to oxidative stress, such as aging, Down syndrome, neurodegenerative diseases, for instance Alzheimer Disease, erectile dysfunction and cardiovascular diseases. In particular this review will focus on the effects of oxidative stress on structural changes in the cell membrane and also on in the activity of erythrocyte enzymes such as membrane-bound, cytosolic glycohydrolases and RBC-eNOS. This review also underlines the potential clinical application of erythrocyte specific related parameters, which can be important tools not only for the study but also for the monitoring of several oxidative stress related diseases.

Different levels of estradiol are correlated with sexual dysfunction in adult men.

Ejaculatory dysfunction, including premature ejaculation (PE) and delayed ejaculation (DE), as well as erectile dysfunction (ED), constitute the majority of male sexual dysfunction. Despite a fair amount of data on the role of hormones and erection and ejaculation, it is inconclusive due to controversy in the current literature. To explore the correlation of male sexual dysfunction with hormonal profile, 1,076 men between the ages of 19-60 years (mean: 32.12 years) were included in this retrospective case-control study; 507 were categorized as ED, PE and DE groups. Five hundred and sixty-nine men without sexual dysfunction were enrolled in the control group. The background characteristics and clinical features of the four groups were collected and analyzed. The estradiol value was significantly elevated in the ED group than the control group (109.44 ± 47.14 pmol/L vs. 91.88 ± 27.68 pmol/L; P < 0.001). Conversely, the DE group had significantly lower level of estradiol than control did (70.76 ± 27.20 pmol/L vs. 91.88 ± 27.68 pmol/L; P < 0.001). The PE group had similar level of estradiol (91.73 ± 31.57 pmol/L vs. 91.88 ± 27.68 pmol/L; P = 0.960) but significantly higher level of testosterone (17.23 ± 5.72 nmol/L vs. 15.31 ± 4.31 nmol/L; P < 0.001) compared with the control group. In conclusion, elevated serum testosterone concentration was an independent risk factor for PE. Besides, there was a progressively increasing graded-distribution of estradiol values from DE to PE and ED groups.

Testosterone positively regulates functional responses and nitric oxide expression in the isolated human corpus cavernosum.

BACKGROUND: Testosterone (T) deficiency is associated with erectile dysfunction (ED). The relaxant response of T on the corporal smooth muscle through a non-genomic pathway has been reported; however, the in vitro modulating effects of T on human corpus cavernosum (HCC) have not been studied. OBJECTIVES: To compare the effects of various concentrations of T on nitric oxide (NO)-dependent and nitric oxide-independent relaxation in organ bath studies and elucidate its mode of action, specifically targeting the cavernous NO/cyclic guanosine monophosphate (cGMP) pathway. MATERIALS AND METHODS: Human corpus cavernosum (HCC) samples were obtained from men undergoing penile prosthesis implantation (n = 9). After phenylephrine (Phe) precontraction, the effects of various relaxant drugs of HCC strips were performed using organ bath at low (150 ng/dL), eugonadal (400 ng/dL), and hypergonadal (600 ng/dL) T concentrations. The penile tissue measurements of endothelial nitric oxide synthase (eNOS), neuronal (n)NOS, and phosphodiesterase type 5 (PDE5) were evaluated via immunostaining, Western blot, cGMP and nitrite/nitrate (NOx) assays. RESULTS: Relaxation responses to ACh and EFS in isolated HCC strips were significantly increased at all T levels compared with untreated tissues. The sildenafil-induced relaxant response was significantly increased at both eugonadal and hypergonadal T levels. Normal and high levels of T are accompanied by increased eNOS, nNOS, cGMP, and NOx levels, along with reduced PDE5 protein expression. CONCLUSION: This study reveals an important role of short-term and modulatory effects of different concentrations of T in HCC. T positively regulates functional activities, inhibition of PDE5 expression, and formation of cGMP and NOx in HCC. These results demonstrate that T indirectly contributes to HCC relaxation via downstream effects on nNOS, eNOS, and cGMP and by inhibiting PDE5. This action provides a rationale for normalizing T levels in hypogonadal men with ED, especially when PDE5 inhibitors are ineffective. T replacement therapy may improve erectile function by modulating endothelial function in hypogonadal men.

Serum vitamin D levels and type 2 diabetic erectile dysfunction: A protocol for systematic review and meta-analysis.

INTRODUCTION: Diabetic erectile dysfunction (DED) has gradually become a worldwide problem. Due to the mechanism of DED is not clear, it is impossible to treat it pertinently. Recently, some studies have shown that vitamin D is associated with DED, type 2 diabetes mellitus (T2DM) and erectile dysfunction (ED), but there is no systematic review and meta-analysis on the relationship between vitamin D and DED. METHODS AND ANALYSIS: The databases of English databases (PubMed, MEDLINE, EMBASE, Web of Science, Cochrane Library) and Chinese databases (China National Knowledge Infrastructure, China Biology Medicine Database, Wanfang Database, VIP Database) will be retrieved. The search strategy that will be run in the PubMed and tailored to the other database when necessary is presented in . RevMan 5.3 and Stata 11.0 will be used for Systematic Review and Meta-analysis. This protocol reported under the Preferred Reporting ltems for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) statement, and we will report the systematic review by following the PRISMA statement.(Table is included in full-text article.) RESULTS:: Through a systematic review, and meta-analysis when necessary, we can obtain the relationship between vitamin D and DED. We will share our findings in the third quarter of 2021. CONCLUSION: The association between serum vitamin D levels and type 2 diabetic erectile dysfunction will be assessed. Besides, the results of this review may provide some help for clinicians to make decisions. ETHICS AND DISSEMINATION: Ethical approval is not required as the review is a secondary study based on published literature. The results will be published in a public issue journal to provide evidence-based medical evidence for urologists and andrologists to make better clinical decisions. PROTOCOL REGISTRATION NUMBER: INPLASY202040164.

Naringin regulates erectile dysfunction by abolition of apoptosis and inflammation through NOS/cGMP/PKG signalling pathway on exposure to Bisphenol-A in hypertensive rat model.

This study investigated the effect of naringin (NRG) on extracellular metabolism of ATP through the NOS/cGMP/PKG signaling pathway induced by Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME) on exposure to Bisphenol-A (BPA) in penis. Fifty-six adult male albino rats were randomly distributed into eight (n = 7) groups. Group I: control animals, Group II was treated with 40 mg/kg L-NAME, Group III was treated with 50 mg/kg BPA, Group IV was treated with 40 mg/kg L-NAME +50 mg/kg BPA. Group V was administered with 40 mg/kg L-NAME +80 mg/kg NRG. Group VI was administered with 50 mg/kg BPA + 80 mg/kg NRG. Group VII was administered with 40 mg/kg L-NAME+50 mg/kg BPA + 80 mg/kg NRG. Lastly, group VIII was treated with 80 mg/kg NRG for 14 days. NRG prevented hypertension and erectile dysfunction by inhibiting the activities of angiotensin-converting enzymes, arginase, and phosphodiesterase-51 (PDE-51) with corresponding down-regulation of inflammatory markers including TNF-α and IL-B. Additionally, hypertensive erectile dysfunction was remarkably prevented by NRG as manifested by the declined activities of AChE, MAO-A and enzymes of ATP hydrolysis (ATPase, ADPase, AMPase and ADA) with resultant increase in NO level. Also, penile expression of antigen presenting cells, CD43 transcript, caspace-9 and tumor suppressor P53 proteins were repressed on treatment with NRG. This study validates the hypothesis that NRG may be a valuable remedy in abrogating penile inflammatory markers, apoptosis and enzymes of ATP-hydrolysis via NOS/cGMP/PKG signaling pathways in hypertensive rat model on exposure to environmental toxicant.

Is There an Association Between Vitamin D Deficiency and Erectile Dysfunction? A Systematic Review and Meta-Analysis.

Erectile dysfunction (ED) is found very frequently in the male population, in particular in its arteriogenic form, which also represents an important predictor of cardiovascular diseases (CVDs). Some evidence suggests that vitamin D could play a role in cardiovascular risk prevention thanks to its ability to reduce endothelial damage, oxidative stress, the production of inflammatory cytokines, and dyslipidemia. Since ED and CVDs have pathogenic mechanisms in common, numerous studies have evaluated a possible association between vitamin D deficiency (blood concentrations of 25-hydroxyvitamin D < 20 ng/ml) and ED, but with conflicting results. This meta-analysis was therefore performed to clarify the discrepancy of the data so far published. To achieve this, articles have been searched extensively in the Pubmed, MEDLINE, Cochrane, Academic One Files, Google Scholar, and Scopus databases from the first day they were created until January 2020. The search strategy included pertinent Medical Subjects Headings (MeSH) terms. Of the 431 items retrieved, only eight observational studies were included, resulting in a total sample size of 4055 patients. It was found that 25-hydroxyvitaminD (25(OH)D) levels did not show any significant difference between patients with and without ED. However, when patients with vitamin D deficiency only were taken into account, the international index of erectile function (IIEF) score for erectile dysfunction was significantly worse than in controls. This association remained significant even when eugonadal-only patients were considered. Finally, we found that eugonadal patients with severe ED have lower 25(OH)D3 levels than patients with mild ED. In conclusion, this meta-analysis suggests an association between vitamin D deficiency and the presence of severe forms of ED, independent of testicular function.

Controversial aspects of testosterone in the regulation of sexual function in late-onset hypogonadism.

BACKGROUND: Testosterone (T) plays a pivotal role in coordinating a series of psychological, cognitive and physical events that might (or might not) culminate in male sexual activity. In fact, T deficiency is associated, in a statistically significant way, with several sexual dysfunctions including erectile dysfunction (ED), reduction of spontaneous erection and hypoactive sexual desire (HSD). Although these associations are statistically significant, there is debate if they are also clinically meaningful. In addition, sexual dysfunctions are present also in several metabolic conditions - such as type 2 diabetes mellitus and obesity - that often associate with low T. In particular, this is the case of ED, but not of HSD, that, therefore, should be considered a more genuine correlate of T deficiency in adulthood and aging (late-onset hypogonadism, LOH). OBJECTIVES: The aim of this review is to scrutinize evidence from our and other studies on sexual effects of T replacement therapy (TRT) in LOH. MATERIALS AND METHODS: We will use preclinical and clinical data coming from our and other laboratories and meta-analyses. RESULTS: Intervention studies in clinical trials involving subjects with LOH, and their meta-analyses, indicate that TRT is able to ameliorate HSD, spontaneous erection and ED. However, the relative improvement of ED by TRT is marginal [2-3 points of International Index of Erectile Function-erectile function domain (IIEF-EFD)] and significantly smoothed in subjects with the aforementioned metabolic conditions. In LOH, positive effects of TRT on other domains of sexual activity, such as orgasm and sexual satisfaction, are also apparent in the different meta-analyses. DISCUSSION AND CONCLUSIONS: Hence, TRT is a reasonable treatment for restoring sexual drive in LOH, with some additional positive effects also on erection (spontaneous and sexual-related) and on orgasm. In contrast, preclinical and clinical studies indicate that T administration to eugonadal subjects does not improve male sexual activity.

Is milder psychological stress responsible for more severe erectile dysfunction?

China is a sexually conservative country compared with Western countries. To evaluate the psychological characteristics of Chinese erectile dysfunction (ED) patients, we conducted a cross-sectional study of 153 ED outpatients. Patients were interviewed with the Structured Interview on Erectile Dysfunction (SIEDY) for pathogenic quantification. ED was measured by International Index of Erectile Function (IIEF). Depression and anxiety were evaluated with 9-item Patient Health Questionnaire (PHQ-9) and 7-item Generalised Anxiety Disorder Scale (GAD-7) respectively. Most patients (74.5%) were <40 years old. IIEF-5 were significantly correlated with SIEDY scale 3 (r = .16, p = .040) and GAD-7 (p = .15, p = .033). The SIEDY scale 1 increased with age, but the IIEF-5, SIEDY scale 3, PHQ-9 and GAD-7 decreased with age. A negative correlation was observed between ED and psychological stress, which conflicts with many Western-country studies. Younger patients were characterised by milder ED but more psychological stress, while older patients were characterised by worse ED but less psychological stress. Which may be responsible for the conflicting result. Meanwhile, the much younger age distribution among Chinese ED outpatients may indicate that quite a few older ED patients (≥40 years) in China do not seek outpatient service which should merit more attention.

Does mean platelet volume (MPV) have a role in evaluation of erectile dysfunction and its severity? / ¿El volumen plaquetario medio desempeña un papel en la evaluación de la disfunción eréctil y su gravedad?

PURPOSE: The mean platelet volume (MPV) has important role in the pathophysiology of vascular diseases as a marker of the platelet activity. To investigate the association between mean platelet volume and erectile dysfunction (ED) and to search whether this marker can be used for diagnosis of ED. MATERIALS AND METHODS: Of the 312 patients with ED of various degrees, 122 patients without ED (IIEF-5>21) were included in this prospective study. Severity of ED was determined according to IIEF-5 questionnaire. MPV, fasting serum glucose, cholesterol, low density lipoprotein (LDL) and serum testosterone levels are also recorded. The mean platelet volume was calculated by the Coulter counter technique and sexual function was determined by International Index of Erectile Function erectile function domain (IIEF-5). RESULTS: The mean age of patients was 58.4 years. The mean MPV value of patients with ED was significantly higher compared to the non-ED patients (8.91 vs. 8.22, p = 0.0001). The severity of ED was shown to have a positive strong correlation with MPV values (r=0.719, p = 0.001). Mean serum triglyceride, glucose, total cholesterol and LDL cholesterol levels were noted higher in patients with ED. MPV values were found to be significantly higher in patients with ED. CONCLUSION: MPV level shows significant correlation with severity of ED. This cheap laboratory test can have potential to be a marker of ED. Further prospective larger studies with vascular wall thickness measurements should be conducted

OBJETIVO: El volumen plaquetario medio (VPM) desempeña un papel importante en la fisiopatología de las enfermedades vasculares como marcador de la actividad plaquetaria. El objetivo fue investigar la asociación entre el VPM y la disfunción eréctil (DE), y averiguar si este marcador puede utilizarse para el diagnóstico de la DE. MATERIALES Y MÉTODOS: De los 312 pacientes con disfunción eréctil de diversos grados, 122 pacientes sin disfunción eréctil (Índice Internacional de la Función Eréctil [IIEF-5]>21) se incluyeron en este estudio prospectivo. La gravedad de la DE se determinó según el cuestionario IIEF-5. También se analizaron el VPM, la glucosa sérica, el colesterol, la lipoproteína de baja densidad (LDL) y los niveles séricos de testosterona. El volumen plaquetario medio se calculó mediante la técnica de contador Coulter y la función sexual se estableció mediante el dominio de la función eréctil del IIEF-5. RESULTADOS: La media de edad de los pacientes fue de 58,4 años. El valor medio del VPM de los pacientes con DE fue considerablemente mayor en comparación con los pacientes sin DE (8,91 frente a 8,22; p = 0,0001). La gravedad de la DE mostró una fuerte correlación positiva con los valores de VPM (r=0,719; p = 0,001). Los niveles séricos de triglicéridos, glucosa, colesterol total y colesterol-LDL fueron más altos en pacientes con DE. Los valores del VPM se encontraron considerablemente mayores en pacientes con DE. CONCLUSIÓN: El nivel del VPM muestra una correlación importante con la gravedad de la DE. Esta prueba de laboratorio barata puede tener el potencial de ser un marcador de DE. Se deben realizar más estudios prospectivos más grandes con mediciones del espesor de la pared vascular

Losartan treatment significantly attenuates the fibrotic changes in the corpus cavernosum of castrated rats / El tratamiento con losartán atenúa de manera importante los cambios fibróticos en el cuerpo cavernoso de ratas castradas

INTRODUCTION AND OBJECTIVES: The aim of this study is to evaluate the effects of castration and subsequent losartan administration on the fibrosis-related parameters in the corpora cavernosa of castrated rats. MATERIAL AND METHODS: Twenty-four male rats were divided into four equal groups. Group 1:sham surgery plus vehicle (0.9% NaCl) (control:con), group 2:sham surgery plus losartan (con+los), group 3: castration plus vehicle (castration:cast) and group 4:castration plus losartan (cast+los). After four weeks of oral losartan treatment, corporal levels of transforming growth factor-beta (TGF-beta), thrombospondin-1 (TSP-1), alpha-actin, beta-actin and fibronectin were investigated by ELISA kits. Changes in the collagen and smooth muscle content were evaluated by histological analysis with Masson trichrome staining. RESULTS: Initial and post-treatment body weights of rats were similar among groups. Castration significantly increased the expression of TGF-beta, TSP-1 and fibronectin and resulted in a significant decrease in alpha-actin levels in the corpora cavernosa. Administration of losartan reduced the levels of TGF-beta, TSP-1 and fibronectin in castrated rats. Alpha actin levels also increased after losartan treatment. Beta-actin levels were not significantly different among 4 groups. The levels of all markers were similar in group 1 and 2. Rate of fibrosis was significantly higher in castrated rats and treatment with losartan reduced this rate. CONCLUSION: Castration increased the expression of fibrosis-related markers in the corpora cavernosa of rats. Administration of losartan significantly attenuated those changes and exerted an antifibrotic effect

INTRODUCCIÓN Y OBJETIVOS: El objetivo de este estudio es evaluar los efectos de la castración y la posterior administración de losartán en los parámetros relacionados con la fibrosis en los cuerpos cavernosos de ratas castradas. MATERIAL Y MÉTODOS: Veinticuatro ratas macho se dividieron en 4 grupos iguales. Grupo 1: cirugía simulada más vehículo (0,9% NaCl) (control:con); grupo 2: cirugía simulada más losartán (con+los); grupo 3: castración más vehículo (castración:cast) y grupo 4: castración más losartán (cast+los). Después de 4 semanas de tratamiento oral con losartán se analizaron los niveles de factor de crecimiento transformante beta (TGF-beta), trombospondina-1 (TSP-1), alfa-actina, beta-actina y fibronectina mediante kits de ELISA. Cambios en el colágeno y el contenido de músculo liso se evaluaron mediante análisis histológico con tinción con tricrómico de Masson. RESULTADOS: Los pesos corporales iniciales y posteriores al tratamiento de las ratas fueron similares entre los grupos. La castración aumentó considerablemente la expresión de TGF-beta, TSP-1 y fibronectina, y dio como resultado una disminución importante de los niveles de alfa-actina en los cuerpos cavernosos. La administración de losartán redujo los niveles de TGF-beta, TSP-1 y fibronectina en ratas castradas. Los niveles de alfa-actina también aumentaron después del tratamiento con losartán. Los niveles de beta-actina no fueron muy diferentes entre los 4 grupos. Los niveles de todos los marcadores fueron similares en los grupos 1 y 2. La tasa de fibrosis fue mucho mayor en las ratas castradas y el tratamiento con losartán redujo esta tasa. CONCLUSIÓN: La castración aumentó la expresión de marcadores relacionados con la fibrosis en los cuerpos cavernosos de las ratas. La administración de losartán atenuó considerablemente esos cambios y ejerció un efecto antifibrótico