Diabetes and vascular impotence: does insulin dependence increase the relative severity?

AIM OF THE STUDY: Diabetes is a well documented risk factor for vascular erectile dysfunction (ED). We evaluated the relative roles of insulin dependence (IDDM) vs oral agent controlled diabetes (NIDDM) in predicting the etiologies and severity of ED: arterial insufficiency (AI), venous leakage (CVOD), and mixed vascular disease. The impact of additional risk factors were also analyzed: hypertension (HTN), coronary artery disease (CAD), and smoking (SM). METHODS: Retrospective data on 105 patients complaining of impotence who underwent pharmacotesting with PGE1 (Caverject) and color duplex Doppler was reviewed. Penile blood flow study (PBFS) data following a period of privacy and self-stimulation was compared. PBFS diagnostic criteria were: AI for peak systolic velocity (PSV) < 25 cm/s; CVOD for PSV > or = 35 cm/s and resistive index (RI) < 0.9; mixed vascular disease for PSV > or = 25 cm/s, PSV < 35 cm/s and RI > 0.9. Consistent dosing of PGE1 was used; 6 mcg for age < 60 y and 10 mcg for age > or = 60 y. Patients were NIDDM (79 out of 105) and IDDM (26 out of 105). Mean ages for NIDDM and IDDM were respectively 60, and 55 y. The relative significance of insulin dependence was assessed by Student's t-test. RESULTS: The most common etiology of ED was arterial insufficiency: mean PSV's did not significantly vary and were: 23.5 cm/s for NIDDM, and 21.6 cm/s for IDDM. PBFS parameters did not vary significantly for the risk factors of SM or HTN and diabetes. Mean peak systolic velocities were significantly different among diabetics with coronary artery disease: NIDDM/CAD, 22.9 cm/s compared to IDDM/CAD, 14.8 cm/s (P = 0.006). CONCLUSIONS: We found among the 105 diabetics the most common etiology of vascular ED based on Doppler criteria was arterial insufficiency, 64%. Statistical analysis of additional risk factors (SM, HTN, CAD) suggested that patients with IDDM and CAD have more severe cavernosal arterial insufficiency than patients with NIDDM and CAD. This data tends to support the theory that microangiopathy is the predominant factor in diabetic impotence, and that insulin dependent diabetes with 'large vessel' coronary heart disease have a similar pathology in the 'small vessels' regulating penile inflow which is unfortunately worse than their non-insulin dependent counterparts.     

Relationship of asymmetric dimethylarginine with penile Doppler ultrasound parameters in men with vasculogenic erectile dysfunction

Background

Asymmetric dimethylarginine (ADMA), a selective endogenous nitric oxide synthase inhibitor, is elevated in many conditions associated with erectile dysfunction (ED), such as hypertension, diabetes, hyperlipidemia, and renal failure; it is also increased in men with coronary artery disease and ED. The dynamic penile colour Doppler ultrasound is considered the gold standard for the evaluation of penile vascular damage.

Objective

We investigated whether the extent of ultrasonographically documented penile vascular disease is associated with higher ADMA levels.

Design, setting, and participants

One hundred four consecutive ED patients (mean age: 56 ± 9 yr) without manifest cardiovascular/atherosclerotic disease and 31 subjects with normal erectile function matched for age and traditional risk factors were studied.

Measurements

We evaluated penile dynamic colour Doppler parameters of arterial insufficiency (peak systolic velocity) and veno-occlusive dysfunction (end diastolic velocity) and measured systemic inflammatory markers/mediators.

Results and limitations

Compared to men without ED, ED patients had significantly higher ADMA levels (p < 0.001). ADMA was significantly increased in patients with severe arterial insufficiency (PSV < 25 cm/s) compared to subjects with borderline insufficiency and men with normal penile arterial function (p < 0.001, by analysis of variance). Multivariable analysis adjusting for age, mean pressure, other risk factors, high-sensitivity C-reactive protein, testosterone, and treatment showed independent inverse association between ADMA level and peak systolic velocity (p < 0.01). The combination of higher ADMA level with arterial insufficiency showed greater impact on 10-yr risk of a cardiovascular event compared to either parameter alone.

Conclusions

ADMA level is independently associated with ultrasonographically documented poor penile arterial inflow. This finding underlines the important role of ADMA as a marker of penile arterial damage and implies a contribution of this compound to the pathophysiology of generalised vascular disease associated with ED.     

Is sildenafil failure in men after radical retropubic prostatectomy (RRP) due to arterial disease? Penile duplex Doppler findings in 174 men after RRP

Sildenafil is frequently the first-line treatment for post-radical retropubic prostatectomy (RRP) erectile dysfunction (ED) with maximum treatment satisfaction rates of 43%-80%. The etiology of erectile dysfunction after RRP has been attributed to psychogenic, vascular, veno- occlusive or nerve injury causes. The purpose of this study was to gain insight into the penile duplex Doppler arterial parameters in men with ED after RRP who failed sildenafil. The purpose was to assess whether sildenafil failure after RRP is associated with underlying corporal arterial disease. A total of 174 consecutive men presenting with sildenafil refractory ED after nerve-sparing RRP underwent color duplex penile Doppler evaluation with vasoactive injection. Mean age was 59.6 y and mean time from surgery was 11.6 months. Some 81% (141/174) of the men had no pre-operative ED (PED). Significant differences in penile duplex Doppler parameters for arterial disease were seen between men with and without PED. In men without PED, 19% (27/141) manifested arterial insufficiency. However, in men with PED, 50% (16/33) demonstrated arterial disease. Nerve sparing status did not affect the presence of arterial disease. Sildenafil refractory erectile dysfunction after RRP in men without PED is not predominantly associated with penile Doppler parameters consistent with arterial insufficiency.     

Diabetes mellitus is associated with severe Peyronie's disease

OBJECTIVES: To evaluate the severity of penile deformity and penile blood flow variables in men with Peyronie's disease (PD) and diabetes mellitus (DM), and those with no risk factors. PATIENTS AND METHODS: Men with PD and DM (59 men, group 1) and those with no risk factors (109, group 2) were compared for penile blood flow variables, severity of penile deformity, patient's age, duration of PD, the presence of pain on erection, and the degree of erectile dysfunction (ED). The men were evaluated with penile duplex Doppler ultrasonography and were categorized into specific vascular groups, using established criteria. Penile curvature was objectively measured and stratified according to the Kelami classification. Results were compared using Student's t-test. RESULTS: Men with PD and DM (group 1) were significantly older than those in group 2. The duration of disease was significantly longer in group 1 than in group 2 (median 24 vs 12 months). The mean degree of penile deformity in group 1 was significantly higher than in group 2 (45.2 degrees vs 30.2 degrees). The rate of severe penile curvature (>60 degrees ) was more frequent in group 1 (27.1% vs 5.5%). Pain on erection was significantly higher in group 2 (39.7% vs 25.5%), whereas the rate of ED was more common in group 1 (81% vs 47%). Group 1 had poorer peak-systolic velocity values and significantly higher rates of arterial insufficiency and mixed vascular disease. Nonvascular causes were twice as common in group 2 than in group 1. CONCLUSIONS: This comparative clinical study suggests that the presence of DM as the only risk factor significantly increases the severity of PD. Furthermore, DM as a risk factor is associated with significantly worse vascular status, as shown by penile duplex Doppler ultrasonography, in men with PD.     

Penile vascular abnormalities observed long-term after surgical repair of penile fractures.

AIM: To assess the penile vascular system in men long-term after surgical treatment of penile fractures. PATIENTS AND METHODS: During a 15-year period, 36 cases of penile fracture underwent immediate surgical repair at the University of Istanbul, Turkey. At least 1 year after operation, all patients were invited for penile vascular evaluation. 15 patients accepted our call and were enrolled in our study. They were evaluated with detailed medical and sexual history, a serial of serum analyses, and penile color Doppler ultrasonography. RESULTS: By history, 6 of the 36 (16.6%) patients who had undergone surgical repair had erectile dysfunction (ED). The mean interval between surgical intervention for penile fracture and penile vascular evaluation was 3.6 +/- 1.9 (range 1.5-8) years. Evaluation of the penile vascular system of 15 men (mean age 35.7 +/- 17.3, range 21-63 years) revealed normal vascular system in seven (46.7%), while cavernosal insufficiency was observed in four (26.7%) and arterial insufficiency in three (20%) men. The remaining case (6.7%) was diagnosed to have mixed arterial and cavernous insufficiency. Erectile dysfunction in two cases was considered to be in psychogenic origin and vascular in the remaining four. CONCLUSION: Although immediate repair is reported to be the treatment of choice in penile fractures, ED of either a physiological or vascular origin can be encountered as a long-term sequel and deserves to be evaluated in detail.     

Risk factors of erectile dysfunction and penile vascular changes after surgical repair of penile fracture

This study was conducted to determine the preoperative and intraoperative risk factors of ED and the underlying penile vascular abnormalities among patients with penile fracture treated surgically. In all, 180 patients with penile fracture were treated surgically and followed up in one center. None of our patients had ED before the penile trauma and only two of them had risk factors for systemic vascular diseases, such as diabetes mellitus (one patient) and hypertension (one patient). After a mean follow-up of 106 months, 11 patients (6.6%) developed ED, 7 had mild ED and 4 had moderate ED. The main risk factors for subsequent ED were aging, >50 years, and bilateral corporal involvement. Among the 11 patients with ED, color Doppler ultrasonography (CDU) showed normal Doppler indices in 4 (36.4%), veno-occlusive dysfunction in 4 (36.4%) and arterial insufficiency in the remaining 3 (27.2%) patients. CDU assessments from the injured and intact sides were comparable. ED of either a psychological or vascular origin can be encountered as a long-term sequel of surgical treatment of penile fracture. Aging, >50 years, at presentation and bilateral corporal involvement is the main risk factors for subsequent development of ED.     

Penile Vascular Assessment Using Color Duplex Sonography in Men with Peyronie's Disease

Purpose

We assessed penile vasculature in men with Peyronie's disease using color duplex ultrasound.

Materials and Methods

A total of 99 consecutive men with Peyronie's disease underwent duplex ultrasound with 60 mg. intracavernous papaverine to gain an understanding of penile vasculature and its correlation to erectile rigidity. Patients were stratified into groups according to duplex ultrasound vascular parameters and the presence or absence of impotence (that is rigidity adequate for intromission).

Results

Of 97 men 31 (32 percent) complained of impotence, 8 of 99 (8 percent) had evidence of corporeal veno-occlusive dysfunction on duplex ultrasound (defined as end diastolic flow velocity greater than 4.5 cm. per second) and 43 percent had a history of vascular risk factors that may have contributed to erectile insufficiency. Impotent patients had decreased peak systolic flow velocity, increased end diastolic flow velocity and a higher percent of vascular risk factors (p = 0.0006, 0.027 and 0.0004, respectively) compared to potent patients.

Conclusions

Duplex ultrasound provides a dynamic noninvasive functional assessment of penile vasculature in Peyronie's disease. Although corporeal veno-occlusive dysfunction has been considered the primary vascular etiology of erectile dysfunction associated with Peyronie's disease, arterial insufficiency is a major contributor, which is best detected before definitive therapy.     

The risk of coronary heart disease in men with erectile dysfunction

OBJECTIVES: Erectile dysfunction (ED) is a common disorder of aging male and about 50% of the ED sufferers consult a physician in the Netherlands. As ED is strongly correlated with cardiovascular diseases, we explored how many patients with ED aged 40 to 69 years will develop cardiovascular disease in the Netherlands and, philosophize if and which preventive measures are available to reduce cardiovascular risks in this specific population. METHODS: 158 patients were included and were comprehensively evaluated. All patients underwent a penile-pharmaco duplex ultrasonography to evaluate the penile vascular status and a cut-off value for acceleration time of 100 ms was used to distinguish between patients with and without cavernous arterial insufficiency. Framingham risk functions were used to determine the 4 to 12 year coronary heart disease risk. The results were extrapolated to the Dutch ageing male population. RESULTS: In the age group 40 to 49 years and 60 to 69 years no significant difference was detected in coronary heart disease risk between patients with and without cavernous arterial insufficiency. In the age group 50 to 59 years patients with cavernous arterial insufficiency showed a significantly increased risk to develop coronary heart disease. It is estimated that in total, more than 25,000 ageing men with ED will develop coronary heart disease within 4 years and increases to almost 75,000 men within 12 years in the Netherlands. CONCLUSIONS: Screening on cardiovascular risk factors and taking preventive measures is recommended in men with ED. Men with cavernous arterial insufficiency aged 50 to 59 years are especially prone to develop coronary artery disease.     

Diagnostic value of nitric oxide, lipoprotein(a), and malondialdehyde levels in the peripheral venous and cavernous blood of diabetics with erectile dysfunction

Diabetes mellitus (DM) is the single most common cause of erectile dysfunction (ED) seen in clinical practice. Evaluation of penile arterial insufficiency in diabetic patients currently entails expensive and invasive testing. We assessed the diagnostic value of certain peripheral and cavernous blood markers as predictors of penile arterial insufficiency in diabetic men with ED. This study was conducted on a total of 51 subjects in three groups: 26 impotent diabetics, 15 psychogenic impotent men and 10 normal age matched control males. All subjects underwent standard ED evaluation including estimation of postprandial blood sugar and serum lipid profile. Peripheral venous levels of nitric oxide (NO), lipoprotein(a) (LP(a)), malondialdehyde (MDA) and glycosylated hemoglobin (HbA1c) were obtained in all subjects. Patients in the two impotent groups underwent additional measurement of NO, LP(a) and MDA levels in cavernous blood. They also underwent intracavernosal injection (ICI) of a trimix (papaverine, prostaglandin E1 and phentolamine mixture) and pharmaco-penile duplex ultrasonography (PPDU). Compared to patients in the psychogenic group, diabetic men had significantly lower erectile response to ICI (P<0.001), lower peak systolic velocity (PSV) (P<0.001), and smaller increase in cavernosal artery diameter (CAD) (P<0.001). Peripheral and cavernous levels of both LP(a) and MDA were higher in the diabetic group as compared to the psychogenic ED group (P<0.001), while the values of peripheral venous and cavernous NO were lower (P<0.001) in the diabetic men. Comparison of biochemical marker assays with the PPDU results showed a significant negative correlation between both venous and cavernous LP(a) and MDA levels on the one hand, and PSV, and the percentage of CAD increase on the other. At the same time, peripheral and cavernous NO levels had a significant positive correlation with the same parameters. Lipoprotein(a), MDA and NO levels were better predictors of low PSV than HbA1c, cholesterol or triglyceride levels. The finding of high levels of LP(a) and MDA with low levels of NO in the peripheral and cavernous venous blood of diabetic men with ED correlates strongly with severity of ED as measured by PPDU. This provides a rationale for further studies of biochemical markers as a surrogate for traditional invasive testing in the diagnosis of penile arterial insufficiency.     

Prevalence of asymptomatic coronary artery disease in men with vasculogenic erectile dysfunction: a prospective angiographic study

OBJECTIVES: Erectile dysfunction (ED) shares common risk factors with coronary artery disease (CAD). It has been suggested that ED may be considered a clinical manifestation of a generalized vascular disease affecting also the penile arteries. The aim of this prospective study was to evaluate angiographically the incidence of asymptomatic CAD in men with ED of vascular origin. METHODS: Fifty consecutive asymptomatic men, aged 41-74 years, with non-psychogenic and non-hormonal ED were comprehensively evaluated using medical history and examination, exercise treadmill test and stress echocardiography. Patients who had positive one or both of the two non-invasive procedures were referred for coronary arteriography in order to document CAD and evaluate the severity of the disease. RESULTS: The mean time interval between the onset of ED and cardiological assessment was 25 months (range 1-66). Smoking (32 patients/64%), hypertension (31 patients/62%) and hyperlipidemia (26 patients/52%) were the most common risk factors. Moreover, 35 men (70%) had two or more risk factors. Twelve patients (24%) with ED had positive one or both of the two non-invasive procedures and one patient presented with acute myocardial infarction before he completed the non-invasive investigation. Coronary arteriography performed in ten patients (in nine with positive one or both of the two non-invasive procedures [while the other three refused], and in the patient with acute myocardial infarction) demonstrated that one patient had three-vessel disease, two patients had two-vessel disease and six patients had single-vessel disease. CONCLUSIONS: A considerable proportion (9/47 or 19%) of patients with ED of vascular origin has angiographically documented silent CAD. These findings support the strategy that patients with ED should undergo further cardiovascular evaluation.     

Stratification of penile vascular pathologies in patients with Peyronie's disease and in men with erectile dysfunction according to age: a comparative study

PURPOSE: Erectile dysfunction (ED) occurs in 20% to 54% of men with Peyronie's disease (PD). We investigated the role of vascular status in the pathophysiology of ED in patients with PD. MATERIALS AND METHODS: A total of 509 consecutive men with PD (group 1--impotent 259, 1a, and potent 250, 1b, mean age +/- SD 54.6 +/- 4.4 years) and 507 consecutive men with ED only (group 2--mean age 49.4 +/- 12.4 years) underwent penile duplex ultrasonography (PDU). Detailed sexual and medical history, and focused physical examination were performed in all patients. Patients in the 2, groups were stratified according to age (18 to 80 years) and classified according to PDU results (normal vascular status, arterial insufficiency, veno-occlusive dysfunction [VOD] and mixed vascular pathology). RESULTS: VOD was observed in 23.1% and 42.8% of patients in groups 1 and 2, respectively (p <0.05). Although VOD was significantly more common in group 2 (ED alone) than in group 1a (PD plus ED) in the third decade (p <0.05), overall PDU results showed no statistical difference for VOD between these 2 groups (p >0.05). Of note, mixed vascular pathologies were significantly higher in group 1a than in group 2 in the third through fifth decades (p <0.05), while arterial insufficiency was more common in the seventh decade (p <0.05). CONCLUSIONS: While many groups have investigated the vascular causes of ED, the exact etiology of ED in men with PD remains controversial. A possible relationship between ED and VOD in patients with PD has been previously reported. The current PDU study demonstrates that for all ages except 30 to 39 years the prevalence of VOD in patients with PD plus ED is similar to that of patients with ED alone.     

Vascular risk factors and erectile dysfunction in a cohort of healthy men

To determine the impact of vascular risk factors in the genesis of erectile dysfunction (ED) in a cohort of healthy men. Participants of a health-screening project were carefully selected as men without known vascular disease. Erectile dysfunction was quantified via the IIEF5-questionnaire. All men underwent a detailed health examination including determination of blood pressure, blood lipid profile and fasting serum glucose. In total 1519 men (42.9+/-7.9 years) were analysed. Age (P < 0.01), elevated levels of total cholesterol (P = 0.04) and low-density lipoproteins (LDL) (P = 0.02) were associated with moderately to severely impaired erectile function (IIEF5: <12). Men with total cholesterol >240 mg/dl had a 2.7 (1.5-4.9)-fold increased risk for moderate to severe ED, the respective figure for LDL >160 mg/dl was 2.6 (1.4-4.9). In this well characterized, healthy population, elevated serum lipids are the most important risk factors for the development of ED.     

The application of digital pulse amplitude tonometry to the diagnostic investigation of endothelial dysfunction in men with erectile dysfunction

The application of digital pulse amplitude by fingertip peripheral arterial tonometry (PAT) device in patients with erectile dysfunction (ED) has never been performed. We investigated the diagnostic value of reactive hyperaemia (RH) and augmentation index (AI) as evaluated using PAT in men with ED of any origin. A total of 40 patients underwent diagnostic investigation for ED, including dynamic penile duplex ultrasound (PDU) and PAT device. Moreover, 30 patients without ED served as controls. According to PDU cutoff at 35 cm/sec, patients were divided into vascular (n = 30) and nonvascular (n = 10) ED aetiology. Moreover, controls with (n = 10) or without (n = 20) vascular risk factors (VRFs) were studied in a separate analysis. Average RH-PAT was not different in men with or without ED (P = 0.56) independently of VRFs. The AI was higher in men with ED compared with the controls (P < 0.0001) as well as when controlled for the presence or absence of VRFs (P < 0.0001). An inverse relationship between AI and PSV was also found (r2 = -0.72, P < 0.0001). In conclusion, an increased AI but not an impaired RH-PAT is present in men with vascular ED independently of VRFs and may represent an early detection of vascular impairment that may precede endothelial dysfunction in populations at low risk for developing vascular ED.     

Penile Doppler sonographic and clinical characteristics in Peyronie's disease and/or erectile dysfunction: an analysis of 1500 men with male sexual dysfunction

Study Type – Therapy (cohort) Level of Evidence 4 What's known on the subject? and What does the study add? Penile colour Doppler ultrasonography (CDU) can be an invaluable investigative tool to characterize penile abnormalities to complement clinical history and physical examination in the evaluation of men with Peyronie's disease (PD) and/or erectile dysfunction (ED). Although CDU findings between men with PD and those with ED were not markedly different, subtle differences were observed. The classic penile CDU findings in men with PD comprise tunical thickening, intracavernosal fibrosis, septal fibrosis and intracavernosal calcification, while, in men with ED, low peak systolic velocity and high end‐diastolic velocity are found on penile haemodynamics. Previously published studies have focused predominantly on either ED or PD exclusively, or examine the risk of progression to ED in the PD population. To our knowledge, this is the largest and most comprehensive analysis of penile CDU and clinical findings in men with PD and/or ED. The large sample size and multivariable analysis allow meaningful interpretation of the results. This study has found some substantial differences in the penile CDU findings of men with PD and/or ED that have not previously been reported. Although the risk factors of ED may be greater than those for PD, there is crossover in age, cardiovascular risk factors, trauma and penile CDU findings in men with PD and/or ED.

OBJECTIVE

• ? To explore the differences in penile colour Doppler ultrasonography (CDU) findings between men with Peyronie's disease (PD) and those with erectile dysfunction (ED).

MATERIALS AND METHODS

• ? Patients presenting with PD and/or ED who underwent penile CDU were recruited to the study.
• ? Patient demographics, comorbidities, International Index of Erectile Function‐5 scores, previous therapies and physical findings were documented.
• ? Penile curvature, presence of tunical thickening, septal fibrosis, intracavernosal fibrosis and calcification, and cavernosal vascular status were recorded.

RESULTS

• ? A total of 1500 men underwent penile CDU during the 10‐year period. Of these men, 891 men presented with PD and 609 men had ED only.
• ? Men with ED had higher rates of diabetes and coronary artery disease (P < 0.05).
• ? Isolated tunical thickening was more common in older men and in the PD cohort. The presence of intracavernosal fibrosis correlated strongly with difficulty maintaining erection (P < 0.05). Impaired cavernosal arterial flow was observed in men with decrease penile rigidity and penile pain, while higher end‐diastolic velocities were found in men with difficulty maintaining erection and tunical thickening on penile CDU.

CONCLUSIONS

• ? Men with PD and ED had many similarities and differences on penile CDU.
• ? Penile CDU continues to be an invaluable clinical tool in the management of men with male sexual dysfunction.

     

Serum 25-Hydroxyvitamin D Levels Are Not Associated with Subclinical Vascular Disease or C-Reactive Protein in the Old Order Amish

The relationship between vitamin D metabolites and subclinical vascular disease is controversial. Because low serum levels of 25-hydroxyvitamin D (25(OH)D) have been associated with many cardiovascular disease (CVD) risk factors, we hypothesized that serum 25(OH)D levels would be inversely associated with inflammation as measured by C-reactive protein (CRP) and with subclinical vascular disease as measured by carotid intimal medial thickness (cIMT) and coronary artery calcification (CAC). We measured 25(OH)D levels in 650 Amish participants. CAC was measured by computed tomography and cIMT by ultrasound. The associations of 25(OH)D levels with natural log(CAC + 1), cIMT, and natural log(CRP) levels were estimated after adjustment for age, sex, family structure, and season of examination. Additional analyses were carried out adjusting for body mass index (BMI) and other CVD risk factors. 25(OH)D deficiency (<20 ng/ml) and insufficiency (21–30 ng/ml) were common among the Amish (38.2% and 47.7%, respectively). 25(OH)D levels were associated with season, age, BMI, and parathyroid hormone levels. In neither the minimally or fully adjusted analyses were significant correlations observed between 25(OH)D levels and CAC, cIMT, or CRP (R ² < 0.01 for all). Contrary to our hypothesis, this study failed to detect a cross-sectional association between serum 25(OH)D levels and CAC, cIMT, or CRP. Either there is no causal relationship between 25(OH)D and CVD risk, or if there is, it may be mediated through mechanisms other than subclinical vascular disease severity.     

Original evaluation of endothelial dysfunction in men with erectile dysfunction and metabolic syndrome

We have recently demonstrated the diagnostic value of a new immunophenotype of blood endothelial progenitor cells (EPCs=CD45neg/CD34pos/CD144pos) and endothelial microparticles (EMPs=CD45neg/CD144pos/AnnexinVpos) in patients with arterial erectile dysfunction (ED) according to severity of cavernous arterial insufficiency evaluated through penile Doppler. The aim of this study was to evaluate both EPCs and EMPs in patients with arterial ED and metabolic syndrome (MetS), comparing these patients with another group of patients without MetS and ED and a third group with MetS but without ED. For this study 50 patients with arterial ED and MetS were selected (age: 55.0±3.0 years; range: 47-60). A group of age-matched (age: 54.0±2.0 years; range: 44-60) patients without arterial ED and MetS (n=30), and another group of age-matched (age: 57.0±4.0 years; range: 40-62) patients with MetS but without ED (n=20) represented the control groups. EPCs and EMPs were significantly higher in patients compared with other groups (P<0.01). Both EPCs and EMPs correlated positively with the age, body mass index, and score of international index of ED (version five items) and with the following cavernous artery indices: peak systolic velocity, acceleration time and intima-media thickness. Among control groups patients with MetS but without ED showed serum concentrations of EPCs and EMPs significantly higher (P<0.05) compared with patients without MetS and ED. Patients with arterial ED and MetS have higher EPCs and EMPs compared with patients with MetS but without ED and patients without MetS and ED.     

Erectile dysfunction as an early sign of cardiovascular disease

A body of evidence from basic science and clinical research is emerging to provide a compelling argument for endothelial dysfunction as a central etiologic factor in the development of atherosclerosis and vascular disease (ischemic heart disease, stroke, and claudication). Erectile dysfunction (ED) is another prevalent vascular disorder that is now thought to be caused by endothelial dysfunction. In fact, a burgeoning literature is now available that suggests that ED may be an early marker for atherosclerosis and cardiovascular disease (CVD). The emerging awareness of ED as a barometer for CVD represents a unique opportunity to enhance preventive vascular health in men. The diagnosis of ED could become a powerful clinical tool to improve early detection of atherosclerosis and initiate prompt aggressive medical management of associated cardiovascular risk factors.     

Elevation of asymmetrical dimethylarginine (ADMA) and coronary artery disease in men with erectile dysfunction

BACKGROUND: Coronary artery disease (CAD) and erectile dysfunction (ED) of vascular origin are closely related and share common risk factors. The endogenous NO synthase inhibitor asymmetrical dimethylarginine (ADMA) has recently been identified as an independent risk marker for cardiovascular disease and it was the purpose of the present study to investigate the role ADMA in ED with and without underlying CAD. METHODS AND RESULTS: We determined plasma ADMA levels in 132 men with ED. Patients were divided into a group of 56 men with underlying CAD (ED-CAD) and a group of 76 men without clinical evidence for underlying CAD (ED-No-CAD). Diagnosis of ED was based on the International Index of Erectile Function Score (IIEF-5). Plasma ADMA concentrations in the ED-CAD group were elevated as compared to the ED-No-CAD group, median (IQR): 0.76 (0.65-0.91) micromol/l ADMA vs. 0.49 (0.36-0.71) micromol/l, p < 0.001. In a multiple logistic regression analysis adjusting for hypertension, hypercholesterolemia, low HDL cholesterol and diabetes or fasting glucose > or =6.1 mmol/l, ADMA remained a strong and independent predictor for presence of CAD. Odds ratios for second and third tertiles as compared to lowest tertile of plasma ADMA were 3.3 (95%CI, 1.1-10.3; p = 0.041) and 8.7 (95%CI, 2.8-27.2; p < 0.001), respectively. CONCLUSION: As elevation of ADMA has been found to be associated with many risk factors for both CAD and ED, our data provide further strong evidence for the close interrelation of CAD and ED. Determination of ADMA may help to identify underlying cardiovascular disease in men with ED.     

Intima-media thickening of common carotid arteries is a risk factor for severe erectile dysfunction in men with vascular risk factors but no clinical evidence of atherosclerosis

PURPOSE: The association of erectile dysfunction (ED) with vascular damage in men without clinical atherosclerosis is unknown. By B-mode ultrasound we evaluated intima-media thickness (IMT) of common carotid arteries, a measure of vascular damage, in men reporting ED with or without vascular risk factors (VRFs) but no clinical atherosclerosis. MATERIALS AND METHODS: IMT of common carotid arteries was evaluated in 270 men with ED. A total of 50 men (mean age +/- SD 39.84 +/- 12.5 years) had no VRFs, 100 (mean age 47.92 +/- 10.94 years) were overweight and/or had hyperlipidemia, and 120 (mean age 53.95 +/- 9.73 years) were affected by type 2 diabetes and/or essential arterial hypertension. RESULTS: IMT was significantly lower in men with no VRFs compared to men with VRFs (p <0.05), and correlated with the severity of ED evaluated through the Sexual Health Inventory for Men (p = 0.0008). Of men with VRFs 17.7% (39 of 220) showed an IMT score indicative of vascular damage (1.00 mm or greater), while only 1 man with no VRFs had a high IMT. Men with VRFs and a high carotid IMT score demonstrated more severe ED, were older and had a higher serum level of C-reactive protein compared to men with VRFs and an IMT of less than 1.00 mm (p <0.05). A high IMT score but not an increased measure for each VRF, including aging, significantly increased the risk of severe ED (odds ratio 2.6, confidence interval 1.1 to 5.9) even after controlling for smoking and drugs associated with ED. CONCLUSIONS: ED in men with VRFs was the only clinical correlate of unrecognized atherosclerosis of common carotid arteries.     

Erectile dysfunction: anatomical parameters, etiology, diagnosis, and therapy

Functional anatomy of the human penis involves various parameters: cavernous tissue, covering integument, prepuce foreskin, corpora cavernosa, corpus spongiosum, glans, facia, arterial supply, venous drainage, lymph drainage, musculature, and nerve supply. Several factors affect the expression/degree of erectile dysfunction (ED) endocrine profile, aging/senescence, demyelinating diseases, and surgery. Risk factors of ED are: age, vascular factors, metabolic diseases (diabetes mellitus), neurologic diseases, and HIV/AIDS. Several drugs are associated with ED: antiandrogenic, anticholinergic, antidepressants, antihypertensive, major tranquilizers, anxiolytics, and certain medicines/metabolites. The International Index of Erectile Function (IIEF) is a multidimensional scale for assessment of erectile dysfunction. The main structures mediating erection are the corpora cavernosa or "erectile bodies," which are fused distally for approximately three-quarters of their length. They separate proximally to fuse with each ischial tuberosity of the pelvis. On their ventral surface lies the corpus spongiosum, which surrounds the urethra. Coital dysfunction is classified into "erectile dysfunction" (psychosexual and endocrine/neuro-endocrine) and "ejaculatory dysfunction" (psychosexual, and genitourinary surgery). Vasculogenic impotence was evaluated by high-resolution ultrasonography and pulsed Doppler spectrum analysis. Cavernosal, alpha-blockade is a technique used to evaluate and treat ED. Another diagnostic procedure for ED involves color floro and spectural Doppler imaging after papaverine-induced erection in impotent men. Color Doppler and duplex ultrasonography are used to evaluate Peyronie's disease. Sildenafil cilrate (Viagra) is an effective therapy of ED in men. Vardenavil is a highly selective phosphodiesterase 5 (PDE5) inhibitor which improved ED. Prostagland E1, vasoactive intestinal polypeptide (VIP), and phentolamine mesylate (administered by autoinjectors) have been applied to treat ED in patients resistant to other intracavernosal agents. Clinical trials were conducted on self-injection of vasoactive drugs, apomorphine SL, and tadalafil in diabetic men. Medical therapy of ED includes: medicated urethral system for erection (MUSE), intravenous pharmacotherapy, arterial revascularization, vacuum devices, two- and three-component inflatable penile prosthesis, semi-rigid penile prosthesis in situ, and inflatable one-piece penile prosthesis. Surgical therapy include procedures to correct Peyronie's penile deformity and penile deformity, procedures to avoid inevitable shortening accompanying Nesbit's disease, and for penile lengthening.