Association between folic acid,homocysteine, vitamin B12 and erectile dysfunction—A cross-sectional study

To evaluate the relationship between serum levels of folic acid (FA), homocysteine (HCY), vitamin B12 (B12) and erectile dysfunction (ED) and to explore their internal relationships. The study included 134 ED patients and 50 healthy controls. ED was assessed using IIEF-5 scores. ED group had lower median FA (6.08 versus 10.21; p < .001) and B12 (256.0 versus 337.5; p < .001) levels, and higher median HCY (11.4 versus 7.95; p < .001) levels, and these differences seemed to be more pronounced in the younger participants (age < 35 yr). FA decreased with the severity of ED (7.52 versus 6.15 versus 5.49 versus 3.97; p < .001), while HCY increased (10.35 versus 11.8 versus 12.9 versus 15; p < .001). Smoking and shift work were associated with lower FA levels. Multivariate analysis showed that serum FA and HCY revealed significant relation with ED. ROC analysis showed that FA ≤ 8.84 and HCY ≥ 10.35 were the best cut-off values for ED diagnosis. Both FA (r = −0.703, p < .001) and B12 (r = −0.576, p < .001) were negatively correlated with HCY. In conclusion, low FA levels and high HCY levels might be independent risk factors for ED. Low serum FA and B12 levels might co-cause high HCY levels and lead to ED.     

Novel predictive risk factor for Erectile Dysfunction: Serum folic acid

The purpose of this study was to compare the serum Folic Acid (FA) levels in patients with Erectile Dysfunction (ED) and healthy controls and whether levels vary with its severity. The study was carried out on 77 sexually active individuals, out of which 41 complained of ED and 36 were apparently normal. Patients were excluded if they had any diseases known to cause ED. The severity was further categorised based on IIEF-5 scores. Blood serum levels of testosterone, lipid profile, random blood sugar, liver function test, renal function test and FA levels were obtained in each patient. Independent-samples t test of significance was used when comparing between two means. Pearson's correlation coefficient (r) test was used for correlating data. All clinical and biochemical parameters except FA were comparable in both the groups. FA levels were significantly decreased in ED group (5.29 vs. 10.8; p value = .004). Smoking habits were comparable between the groups, and FA levels did not vary among smokers and nonsmokers (p value = .46). Serum FA levels significantly declined with increasing severity of ED (8.28 vs. 5.56 vs. 4.37 vs. 3.5; p value < .001). Thus, decreased FA might possibly be one of the novel risk factors for ED.     

Predisposing factors for erectile dysfunction and response to treatment in younger males: Are they different from those of older men? An observational-comparative study

We aimed to correlate the predisposing demographic and clinical factors for erectile dysfunction (ED) in young men and treatment response in these men with data from older men. The patients were divided into two groups: <40 years (group I, n = 58) and ≥40 years (group II, n = 73). ED was evaluated with the International Index of Erectile Function-5 (IIEF-5) questionnaire, and Beck's Depression Inventory (BDI) questionnaire was used to evaluate mood status. The number of patients with morning rigidity and normal libido was higher in group I (70.7% vs. 16.4%, p = .039 and 72% vs. 37%, p = .047). The increase in scores other than IIEF-Orgasmic Function and Sexual Desire domain scores after treatment was higher in the first group (p = .029, p = .035 and p < .001 respectively). In multivariate analysis, the factors predicting the low IIEF-Erectile Function domain score in young men were testosterone level and BDI score (p = .026 and p = .034). Although psychogenic factors contribute significantly to the aetiology of ED, hormone profile is more preserved in young men than in older men.     

Efficiency of intracavernosal alprostadil and oral clomiphene citrate combination treatment in penile vasculogenic erectile dysfunction patients accompanied by late-onset hypogonadism

In this study, the efficiency of intracavernosal alprostadil + oral clomiphene citrate (CC) treatment in late-onset hypogonadism (LOH) accompanied by penile vasculogenic erectile dysfunction (PVED) in patients irresponsive to phosphodiesterase type 5 inhibitor treatment was evaluated. A total of 31 patients with concurrent PVED and LOH were included in the study. The patients were given intracavernosal alprostadil (10–20 μg) and oral CC (50 mg) every day for 12 weeks. Before and after treatment, a 15-question International Index of Erectile Function (IIEF-15) questionnaire, Erection Hardness Score (EHS), Sexual Encounter Profile (SEP)2 and SEP3 levels were analysed, and follicle stimulating hormone (FSH), luteinising hormone (LH), total testosterone and prostate-specific antigen (PSA) levels were measured. In all, 41.9% of patients had pure arterial deficiency, 19.3% had pure venous deficiency, and 38.7% had arterial + venous (mixed) deficiency. A significant increase was detected in total testosterone, FSH, LH and PSA values after treatment when compared to values before treatment (p < .001, p < .001, p < .001 and p = .034 respectively). A significant recovery was observed in IIEF-15 subscores, EHS and SEP2-SEP3 results. In PVED patients accompanied by LOH, intracavernosal alprostadil and oral CC combination is an efficient, low cost, safely applicable and tolerable treatment.     

The impact of asexual trait and porn addiction in a young men healthy cohort

In the present study, we aimed to evaluate the association between asexual trait, erectile dysfunction (ED) and porn addiction in a community sample of young men. Between August 2019 and October 2019, a total of 559 young male adults were subjected to an online survey sponsored by social networks with the aim of assessing their sexual habits. The following questionnaires were administered: The International Index of Erectile Function (IIEF-5), Masturbation Erection index (MEI), Pornography Craving Questionnaire (PCQ) and Asexuality Identification Scale (AIS). The overall rate of ED according to IIEF-5 was 26.0% (165/478), the rate of ED according to MEI was 16.9% (81/478) and the rate ED in patients with AIS ≥23 indicating asexual trait was 10.0% (48/478). We found that IIEF-5 was positively associated with MEI (b = 0.32; p < .01) and negatively with AIS (b = −0.36; p < .01) and MEI was negatively associated with AIS (b = −0.36; p < .01). We found that MEI (odds ratio [OR]: 0.86; p < .01) and IIEF-5 (OR: 0.89; p < .01) were inversely associated with asexual trait. The presence of asexual trait can hide a greater risk of finding ED both in intercourse or masturbation. These results should be taken into consideration during the general assessment of the patient with sexual problems.     

Impact of antiangiogenic treatment on the erectile function in patients with advanced renal cell carcinoma

We longitudinally assessed erectile function as well as the willingness to use pro-erectile treatment in a cohort on AAT for advanced RCC. Thirty-seven patients with advanced RCC completed the five-item version of the International Index of Erectile Function (IIEF-5) and other interview items before (T0) and 12 weeks into therapy (T12) with AAT. Patients were further asked if they were willing to use and pay out-of-pocket for on-demand treatment with phosphodiesterase-5-inhibitors (PDE-5i). Statistical analysis was performed using nonparametric hypothesis testing. The IIEF-5 score at T12 was significantly decreased compared with T0 (p < .001). Subjective patient satisfaction regarding their sexual lives was associated with higher IIEF-5 scores at both time points (p = .006 and p = .03, respectively). At T12, subjective sexual contentment showed a nonsignificant trend towards decline (p = .074). Patients who opted for medical treatment of ED showed significantly better IIEF-5 scores at both time points compared with the rest of the cohort (p < .001 and p = .005, respectively). In summary, AAT seems to have a negative effect on erectile function in RCC patients, however, the role of psychosocial issues warrants further elucidation. Affected patients may benefit from a proactive approach promoting medical treatment of erectile dysfunction during AAT.     

Relationship between the G protein–coupled oestrogen receptor and spermatogenesis,and its correlation with male infertility

The aim of this study was to investigate the diagnostic value of serum G protein–coupled oestrogen receptor (GPER) levels and their correlation with semen parameters in men with infertility. The participants were divided into two groups as follows: 76 fertile control men (Group 1) and 77 infertile men (Group 2). Semen analysis, hormonal evaluation, serum GPER level and scrotal ultrasound of the participants were evaluated. Follicle-stimulating hormone and total testosterone levels were not significantly different between the groups (p = .413 and p = .535 respectively). The oestradiol level in Group 1 was significantly lower than that in Group 2 (p < .001). The serum GPER level was found to be significantly higher in Group 1 than that of Group 2 (p < .001). GPER levels were positively correlated with the total sperm count, sperm concentration, motility and morphology in Group 2 (r = 0.303, 0.345, 0.260 and 0.322, respectively, p < .001). In this study, GPER levels were positively correlated with sperm parameters, and it was hypothesised that the decrease in GPER expression might be associated with male infertility by adversely affecting spermatogenesis.     

Association of hypogonadism symptoms and serum hormones in aging males

The association between hypogonadism symptoms and the levels of serum hormones are still in debate. To investigate the relationship between hypogonadism symptoms and serum hormones in middle-aged and elderly Chinese men, this community-based cross-sectional study was conducted based on a total of 965 ageing men. The ageing males’ symptom (AMS) scale, International Index of Erectile Function-5 (IIEF-5), International Prostate Symptom Score (IPSS) questionnaires and related variables were assessed. Blood tests for total testosterone (TT), sex hormone-binding globulin (SHBG) and luteinising hormone (LH) were performed. Serum level of free testosterone (FT) and bioavailable testosterone (Bio-T) was calculated. The mean age was 56.34 ± 8.85 years. Total AMS score was significantly associated with all five serum hormones (LH: p < 0.001; SHBG: p < 0.001; TT: p =.043; FT: p = 0.007; Bio-T: p < 0.001). We identified sexual and somatic symptoms were obviously related to five serum hormones, while psychological symptoms seemed to have no association with serum hormones. After adjusting for age and BMI, multiple linear regression analysis indicated that LH had positive correlations with total AMS score, somatic and sexual symptom score (p < 0.05). In conclusion, LH and SHBG had the strongest correlation hypogonadism and might be used as early predictors for symptomatic hypogonadism in the near future.     

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.     

Effects of nonsteroidal anti-inflammatory drug (NSAID) use upon male gonadal function: A national,population-based study

Recent data have suggested that short-term NSAID use induces a state of compensated hypogonadism. Our aim was to investigate the association between chronic, regular NSAID use and compensated hypogonadism in a large, nationally representative cohort, the US National Health and Nutrition Examination Survey (NHANES) database. Men 20–80 years who answered the analgesic use questionnaire and underwent hormonal testing were included. Multivariable regression was utilised to determine the relationship between NSAID use and serum testosterone (T), anti-Mullerian hormone (AMH) and T:AMH ratio. Among 3,749 men, 505 (13.5%) reported regular NSAID use and 3,244 (86.5%) did not. Regular users had lower T (440.7 ± 27.0 vs. 557.0 ± 24.9 ng/dl, p = .005) and albumin (43.8 ± 0.2 vs. 45.1 ± 0.1, p < .001) compared to nonregular users. On multivariable analysis, only active smoking was significantly associated with T, AMH and T:AMH ratio (p < .001, p = .036 and p = .005 respectively). Regular NSAID use was not associated with T, AMH or T:AMH ratio (p = .523, p = .974, and p = .872 respectively). In this nationally representative sample of US men, regular and chronic NSAID use was not associated with alterations in T or compensated hypogonadism. These data should reassure patients and clinicians regarding the safety of NSAID use with respect to the risk of alteration in the hypothalamic–pituitary–gonadal axis.     

Evaluation of serum level of Osteocalcin hormone in male infertility

The suggested concept of “bone as an endocrine organ” had shed the light on the role of osteocalcin, an osteoblast secreted hormone, in regulation of testosterone production. This study aimed to assess the association between the active undercarboxylated form of osteocalcin (ucOC) and semen parameters and hormonal levels in infertile male patients. The study was carried on 34 infertile male patients and 20 fertile healthy control males. Semen analysis and serum level of testosterone, LH and FSH were performed in addition to serum level of ucOC in cases and controls. The results revealed significant differences between cases and controls in all measured semen and hormonal parameters. In addition, significant higher level of ucOC in cases than control group (p = .019). On the other hand, ucOC was not related significantly to any of the measured hormones or semen parameters. There was no significant correlation between ucOC and sperm concentration, total motility, morphology (p = .594, .640, .940 respectively) and similarly between ucOC and testosterone level or LH level (p = .275, .954 respectively). The significant higher level of ucOC in infertile cases cannot be used as a predictor of male reproductive parameters.     

Acute effect of microdissection testicular sperm extraction on blood total testosterone and luteinising hormone levels

Testicular sperm extraction is a common surgical procedure to retrieve spermatozoa from men with azoospermia which may affect the tissue and cause hypogonadism (Human Reproduction Update, 24 , 2018, 442). We aimed to evaluate the acute effect of micro-TESE on blood total testosterone (TT) and luteinising hormone (LH) levels. Between April 2018 and September 2019, 60 selected NOA (i.e. with normal TT and LH) patients were included in the study. After procedure, blood samples were collected to evaluate the levels of TT and LH at 1st and 24th hour and first week. Values were compared. In addition, patients were divided into two groups according to their body mass index. Mean age of patients was 27.37 ± 4.52 years, and mean of body mass index was 24.49 ± 3.78 kg/m². Mean TT levels at the 1st hour, 24th hour and the 1st week were 3.81, 3.50 and 3.05 ng/ml respectively. Mean LH levels at the 1st hour, 24th hour and the 1st week were 5.03, 5.15 and 5.46 IU/L respectively. Statistically significant differences between pre- and post-operative 24th hour and 1st week values were detected (p = .001, p < .001 respectively). No statistical differences were found between two BMI's groups. TT decreased in acute period after the procedure, whereas the increase of LH levels was observed after 24th hour.     

The interaction between inflammation,urinary symptoms and erectile dysfunction in early-stage prostate cancer treated with brachytherapy

Erectile function has been shown to decline as a function of increasing peripheral blood inflammatory markers, namely the neutrophil-to-lymphocyte ratio (NLR). We evaluated if the association between NLR and erectile dysfunction (ED) applies to patients with localised prostate cancer. We included 1,282 patients who underwent brachytherapy. ED was classified before treatment according to the Terminology Criteria for Adverse Event Scale version 3.0. ED was defined as the need for the use of oral pharmacologic or mechanical assistance to have satisfactory sexual function. We found that patients with ED were older (p < .001), more likely to have hypertension (p = .002), statin use (p = .002), diabetes (p < .001) or an IPSS ≥ 8 (p < .001). On univariable logistic regression analysis, an NLR of ≥3 was statistically significantly associated with ED (OR 1.32, p = .029). But on multivariable analysis, the association between elevated NLR and ED was not statistically significant (p = .17). Significant were age (OR 1.12, p < .001), IPSS ≥ 8 (OR 1.50, p = .008), the presence of hypertension, hyperlipidemia and diabetes (OR 2.27, p < .001), and prostate volume (OR 0.99, p = .041). The NLR does appear to be a surrogate marker of chronic inflammation that causes baseline ED in patients with localised prostate cancer.     

Sexual dysfunction in Indian men undergoing Double J ureteral stenting following ureteroscopy—A prospective analysis

This prospective study was aimed to evaluate the impact of an indwelling ureteral double-J stent on the sexual health of Indian men undergoing ureteroscopy. The first phase of the study included 30 men who were not counselled prior to stenting about possible sexual dysfunction, while in the next phase, 60 men were counselled about this. These 60 patients were assessed by a 6-point questionnaire: five questions from the International Index of Erectile Function-5 (IIEF-5) and an additional 6th question to assess pain during erection/ejaculation. Patients answered the questionnaire prior to ureteroscopy, at the time of stent removal and then 4 weeks after stent removal. A higher proportion of men in the second phase attempted sexual activity (68.3% vs. 26.7%; p < .001). Significant changes were noted in the total IIEF-5 score (mean 23.16 before vs. 15.65 after, p < .001) and individual IIEF-5 components: erection confidence (4.59 vs. 2.76, p = .017), maintenance ability (4.67 vs. 2.43, p = .006) and intercourse satisfaction (4.61 vs. 2.31, p < .001) and also the ‘pain’ question (2.83 post-stenting vs. 0.37 pre-stenting, p < .001). Most patients had a recovery of scores at 4 weeks after stent removal. Thus, ureteral DJ stenting leads to significant but temporary sexual dysfunction and patients need to be counselled regarding this.     

Smoking status and the baseline international index of erectile function score can predict satisfactory response to platelet-rich plasma in patients with erectile dysfunction: A prospective pilot study

Erectile dysfunction (ED) is a common condition with a significant impact on the quality of life. Regenerative medicine maladies are intended to repair or replace damaged tissues and organs through different therapeutic mechanisms. Our aim was to study the effect of intra-corporeal injection (ICI) of platelet-rich plasma (PRP) in ED patients. Thirty-four patients’ erectile function was evaluated by filling up an abridged form of the international index of erectile function (IIEF-5) before and after PRP therapy. ICI of PRP was done once per week for 2 months. All patients were prescribed PDE5Is for one month after PRP therapy. Penile haemodynamics was assessed using 20 µg of PGE1 before and 3 months after initiating PRP therapy. Interestingly, our study had shown that there was a statistically significant difference in the IIEF-5 score after ICI of PRP (−5.5, ±5.2, p=<0.001). Furthermore, in multiple logistic regression model for PRP responsiveness, smoking and IIEF score before PRP were the only significant independent variables (p = .040, p = .023 respectively). PRP injection for ED patients may be a promising modality as well as baseline IIEF-5, and smoking status can be used as predictors for a satisfactory response to PRP in such patients.     

Effect of low-intensity extracorporeal shockwave therapy on nocturnal penile tumescence and rigidity and penile haemodynamics

The study aims to evaluate the effect of low-intensity extracorporeal shockwave therapy (Li-ESWT) on nocturnal erection and penile haemodynamics. Patients with erectile dysfunction (ED) were enrolled from January 2018 to March 2019. Self-reported erectile symptoms, the International Index of Erectile Function-5 (IIEF-5) and Erection Hardness Scores (EHS), nocturnal penile tumescence and rigidity (NPTR) and cavernous duplex Doppler ultrasound (CDDU) were evaluated. NPTR and CDDU were evaluated by Rigiscan and vascular ultrasound system respectively. Comparisons of NPTR and CDDU parameters were performed before and after Li-ESWT (Renova, once a week, 4 weeks in total). A total of 35 cases (mean age 36.51 ± 11.47 years) were enrolled for analysis. The IIEF-5 (10.60 ± 5.99 vs. 15.13 ± 6.22, p = .003), EHS (p = .016) and self-reported erectile hardness (p = .014) were significantly improved after 1-month treatment. Nocturnal erection frequency (p = .010), duration of total erection (p = .017), duration of erectile rigidity ≥60% at penile tip and base (p = .014 and p = .002) and the best erectile rigidity at penile tip and base (p = .012 and p = .005) improved significantly after treatment. However, no CDDU parameters improved after Li-ESWT (all p > .05). Li-ESWT can effectively improve subjective erectile function and nocturnal erection in ED patients. Large sample and well-designed studies need to be developed for supporting the current findings.     

Comparison of the clinical efficacy of daily use of L-arginine,tadalafil and combined L-arginine with tadalafil in the treatment of elderly patients with erectile dysfunction

This study aimed to evaluate the efficacy of the daily oral administrations of L-arginine, tadalafil and combined L-arginine with tadalafil in treatments of elderly patients with erectile dysfunction (ED). It was designed as a single-blind placebo-controlled clinical trial. It was conducted on 120 male patients aged ≥60 years old with ED. Patients were randomised classified into four groups (n = 30 each). Oral daily use of L-arginine (5 g), tadalafil (5 mg), combined L-arginine (5 g) with tadalafil (5 mg) and placebo were taken for 6 weeks in each group of patients respectively. Patients were assessed before and after treatments using the Sexual Health Inventory for Men (SHIM) questionnaire and total serum testosterone. The means of Q1–5, total scores of SHIM and total testosterone, in L-arginine, tadalafil and combined L-arginine with tadalafil groups were significantly higher after treatments (p = .001). Combined L-arginine with tadalafil group had the highest SHIM scores and levels of total testosterone. This clinical trial deduced that the combined daily use of L-arginine with tadalafil therapy for elderly male patients with ED could significantly increase the SHIM scores and levels of total testosterone in comparison to L-arginine, or tadalafil alone.     

COVID-19 pneumonia causes lower testosterone levels

To evaluate the testicular damage caused by COVID-19, we prospectively evaluated 44 patients who applied to the COVID-19 outpatient clinic between March 2020 and July 2020. Patients' ages, COVID-19 PCR results, presence of pneumonia, total testosterone, luteinising hormone (LH) and follicle-stimulating hormone (FSH) values were recorded. It was evaluated whether there were significant differences between people who were positive for COVID-19 and those who were not. Any differences between those who had COVID-19 pneumonia and those who did not were also recorded. There was no difference between the FSH, LH and testosterone values of the COVID-19 PCR positive and negative patients (p = 0.80, vp = 0.62, p = 0.56 respectively). However when LH values were separated as low, normal and high, LH values were statistically significantly higher in the COVID-19 PCR positive group (p = 0.04). Thoracic computed tomography was performed in 42 patients. Testosterone levels were significantly lower in patients with COVID-19 pneumonia (p = 0.01). When FSH, LH and testosterone values were separated as low, normal and high, there was no difference in FSH and LH values (p = 1, p = 0.2). Testosterone levels were found significantly lower in patients with COVID-19 pneumonia (p < .001). Testosterone levels seem to decrease during acute COVID-19 infection, especially in the patient group with viral pneumonia.     

Dialysis modality and sexual dysfunction in male patients

Sexual dysfunction is an under-recognised problem in due to very limited number of studies in the literature. This study aims to evaluate the sexual dysfunction related effects of dialysis modality among male patients with chronic renal failure. All patients were asked to complete 2 questionnaires: Hospital Anxiety Depression Scale [HADS] and International Index of Erectile Function [IIEF-5]. A total of 51 patients who completed the questionnaires were included in the study. 31 of them were under haemodialysis (HD) treatment, and 20 were under peritoneal dialysis (PD) treatment. After adjustment for age and HADS score, there was no statistically significant difference between HD and PD groups in terms of the mean IIEF scores (55 vs. 40, p = .058), and the frequency of sexual dysfunction (12.9% vs. 30%, p = .163). Age (r = −0.553), blood pressure (r = −0.299/ −0.374), use of iron (r = −0.333), lipid levels (r = −0.281/ −0.276) and HADS-D score (r = −0.276) inversely associated with IIEF score (p < .05). To conclude, sexual dysfunction is more common in patients who receive PD therapy than those who receive HD therapy. Older age, higher blood pressure, iron treatment, higher lipid levels and the presence of depression were associated with higher prevalance of sexual dysfunction.     

Endocan is markedly overexpressed in severe erectile dysfunction

This study aimed to measure the serum endocan level of patients with erectile dysfunction (ED) and to investigate the possible association between this and vasculogenic severe ED. We performed a prospective analysis of 86 consecutive patients affected by ED. Patients were divided into severe ED (IIEF‐5 score < 7) and mild or moderate ED (IIEF‐5 score > 7). A strong negative correlation was found between serum endocan levels and peak systolic velocity (p < .001 and r = ?.665) in men with severe ED. Univariate logistic regression analysis demonstrated that tobacco consumption (p < .05), serum total 25‐hydroxyvitamin D (p < .01), serum endocan levels (p < .01), peak systolic velocity (p < .01), hypertension (p < .001), dyslipidaemia (p < .001), metabolic syndrome (p = .026) and a history of a cardiovascular event (p < .001) significantly increase the risk of severe ED. In the multivariate logistic regression model, we also found that age, hypertension, metabolic syndrome, cardiovascular events and higher serum endocan levels were independently associated with severe ED. Circulating endocan may be used in daily practice as a new marker that correlates with cardiovascular risks and the severity of ED disease.