Association between sex hormones and erectile dysfunction in men without hypoandrogenism.

In addition to testosterone, various endocrine hormones, such as dehydroepiandrosterone sulfate (DHEA-S) and estradiol, may be involved in erectile function. However, the role of these sex hormones in the erectile function of men without hypoandrogenism remains unclear. This cross-sectional study included 398 community-dwelling men without hypoandrogenism. The participants were categorized into the non-ED and ED groups. Multivariable logistic regression analyses were performed to investigate the relationship between ED and serum sex hormone levels, including total testosterone, DHEA-S, estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin. Among the 398 men, 66 (17%) and 332 (83%) were categorized into the non-ED and ED groups, respectively. In the multivariable analyses, serum DHEA-S and estradiol levels were significantly associated with ED (odds ratio [OR]: 0.996, P = 0.030; OR: 1.082, P = 0.002; respectively), whereas serum total testosterone, LH, FSH, and prolactin levels did not demonstrate significant association. After adjusting for age, none of neutrophil-to-lymphocyte ratio, serum plasminogen activator inhibitor-1 levels, and skin advanced glycation end-products levels demonstrated significant correlation with serum DHEA-S and estradiol levels. In conclusion, lower testosterone levels did not affect ED in men with normal testosterone levels, whereas serum DHEA-S and estradiol levels were significantly associated with ED.

The association between uric acid and erectile dysfunction in US adults: NHANES 2001-2004.

BACKGROUND: -Recent evidence suggests that hyperuricemia may act as independent risk factors for erectile dysfunction (ED), in addition to the already established factors. The current evidence supporting this relationship remains insufficient. METHODS AND RESULTS: -A total of 3,810 participants from the NHANES pool between 2001 and 2004 were included in our study, comprising 1,093 individuals with ED and 2,717 individuals without ED. Univariable and multivariable logistic regression analyses were conducted to examine the relationship between uric acid (UA) and the prevalence of ED. In the fully adjusted model, no significant association was observed between UA and ED (OR = 1.02, 95% CI: 0.84-1.24), and no significant differences were noted among the various UA levels (p = 0.5). In our sensitivity analyses, employing a stricter definition for ED, no significant results were found in the fully adjusted model (OR = 0.85, 95% CI: 0.60-1.19). Furthermore, no significant differences were observed among the various UA levels (p = 0.083). CONCLUSIONS: -Our study did not establish a correlation between UA levels and ED. Nonetheless, further research with larger sample cohorts is required to verify these findings.

Concentrations of Bioelements (Zn, Cu, Fe, Cr, Mg, Mn) in Serum and Bone Tissue of Aging Men Undergoing Hip Arthroplasty: Implications for Erectile Dysfunction.

Background: Erectile dysfunction (ED) stands out as one of the most prevalent sexual disorders in men, with its incidence progressively escalating with age. As delineated by the International Consultation Committee for Sexual Medicine on Definitions/Epidemiology/Risk Factors for Sexual Dysfunction, the prevalence of ED among men under 40 years is estimated to be within the range of 1-10%. The aim of this study was to determine the relationship between the concentration of bioelements (Zn, Cu, Fe, Cr, Mg, and Mn) in the serum and bone tissue and the concentration of selected hormones in men with and without erectile dysfunction. Materials and methods: The retrospective cohort study included 152 men who underwent total hip arthroplasty for hip osteoarthritis at the Department of Orthopaedic Traumatology and Musculoskeletal Oncology at the Pomeranian Medical University in Szczecin. Certain exclusion criteria were applied to ensure the integrity of the study. These included individuals with diabetes, a history of cancer, alcohol abuse, liver or kidney failure, New York Heart Association (NYHA) class III or IV heart failure, and those taking medications that affect bone metabolism, such as mineral supplements, neuroleptics, chemotherapeutic agents, immunosuppressants, corticosteroids, or antidepressants. Patients with hypogonadism or infertility were excluded from the study. Results: The study showed an association between bioT concentrations and Cu concentrations in both patients with and without erectile dysfunction. A correlation between bioactive testosterone and Cr concentrations was also observed in both groups. Patients with erectile dysfunction showed a relationship between bioT concentration and Zn concentration, TT concentration and Mn concentration, FT concentration and Zn concentration, and E2 concentration and Cr concentration. An analysis of elemental concentrations in bone tissue showed an association between FT and Mg and Mn concentrations, but only in patients with erectile dysfunction. In patients without erectile dysfunction, a correlation was observed between FT and Cu concentrations. A correlation was also observed between bioT concentrations and Mg, Mn, and Zn concentrations, but only in patients with erectile dysfunction. In patients without erectile dysfunction, a correlation was observed between bioT and Cu concentrations. Conclusions: Studying the relationship between the concentration of bioelements (Zn, Cu, Fe, Cr, Mg, and Mn) in the serum and bone tissue and the concentration of selected hormones in men may be important in explaining the etiology of the problem. The study of the concentration of Zn and Cu in bone tissue and serum showed that these two elements, regardless of the place of accumulation, may be related to the concentration of androgens in men.

The association between lipid parameters and erectile dysfunction: a two-sample Mendelian randomization and case-control study.

PURPOSE: Lipid parameters have been shown to have significant predictive value for cardiovascular disease, but few studies have evaluated their correlation with erectile dysfunction (ED) in young men. METHODS: The case-control study encompassed 186 young ED patients (ages 20-40) and 186 healthy controls. Lipid parameters, including total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), TC/HDL ratio, TG/HDL ratio, and LDL-C/HDL-C ratio, were assessed in all participants. The International Index of Erectile Function (IIEF-5) scores were collected for all participants to evaluate erectile status. Multivariate logistic regression analysis was utilized to appraise the association of lipid-related parameters with ED. Single-nucleotide polymorphisms (SNPs) significantly correlated with lipid parameters (TC, TG, LDL-C, HDL-C) were selected from genome-wide association studies (GWAS) as instrumental variables (IV) (P < 5.0 × 10-8). Summary data for ED was gathered from a GWAS with a sample size of (n = 17,353 cases/28,210 controls). The inverse variance weighted (IVW) method was employed as the primary mendelian randomization (MR) analysis method to assess causal effects. Causal estimates were represented as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: Results from the case-control study revealed that, when compared with the control group, levels of LDL-C, TG, UA, LDL-C/HDL-C, TG/HDL-C, and TC/HDL-C in the ED group were significantly elevated (P < 0.01), while HDL-C was significantly decreased (P < 0.01) in the ED group. Multivariate logistic regression analysis indicated LDL-C/HDL-C as a risk factor for both the incidence and severity of ED (P < 0.001). Two-sample MR analysis demonstrated no significant causal correlation between lipid parameters-LDL-C (OR, 0.98, 95% CI, 0.88-1.08, P = 0.616), HDL-C (OR, 1.07, 95% CI: 0.96-1.19, P = 0.249), TC (OR, 1.07, 95% CI, 0.96-1.18, P = 0.208), TG (OR, 0.98, 95% CI, 0.80-1.13, P = 0.579) -and an increased risk of ED (all P > 0.05). CONCLUSIONS: The case-control analysis ascertained a significant association between LDL-C, HDL-C, LDL-C/HDL-C, and ED and its severity. However, results from the MR study do not support a causal role of lipid parameters in ED.

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.

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.

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.

[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%.

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.

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.

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.

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.

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.