International Journal of Impotence Research (2013) 26, 55–60 & 2013 Macmillan Publishers Limited All rights reserved 0955-9930/13 www.nature.com/ijir
ORIGINAL ARTICLE
Peripheral atherosclerosis in patients with arterial erectile dysfunction C Goksu1, M Deveer2, AK Sivrioglu3, P Goksu1, B Cucen2, S Parlak4, M Cetinkaya5 and L Altin4 Erectile dysfunction (ED)develops owing to pshycogenic, organic or/and both of these two factors. The aim of this study was to investigate the relationship between penile cavernosal arterial flow and peripheral athersosclerosis in men with ED. This study was conducted on 102 patients who had presented to Radiology Clinic with a prediagnosis of ED. Diabetes, hypertension (HT) and smoking were recorded. Blood were taken from all patients for analysis of fasting blood glucose, total cholesterol and high-density lipoprotein level. All the patients underwent high-resolution penile colour Doppler ultrasound (CDUS). The peak-systolic velocity and the end-diastolic velocity values in the bilateral cavernosal arteries were recorded. At the same session, all the patients underwent evaluation for bilateral common carotid artery and femoral artery intima media thickness and for the presence of atherosclerotic plaque. Patients were classified as ED of arterial origin and non-arterial origin according to penile CDUS findings. Of the total 102 patients, 43 (42.2%) had arterial ED and the remaining 59 (57.8%) were contained in non-arterial ED. There was a significant difference between groups for diabetes mellitus (DM), HT, atherosclerotic cardiovascular diseases (ACVD) and total cholesterol level (Po0.05). There was also a significant difference between groups for the presence of plaque in the carotid and the femoral artery (Po0.05). The relationship between smoking and arterial ED was not found to be statistically significant (P40.05). Non-diagnosed or silent DM, HT and ACVD can have roles in the etiology of arterial ED. Patients who are diagnosed as having arterial ED with Doppler Ultrasound should also be evaluated with B-mode ultrasonography for other peripheral vascular atheroschlerotic processes. In this way, subclinical cases can be detected and further possible complications can be avoided. International Journal of Impotence Research (2013) 26, 55–60; doi:10.1038/ijir.2013.35; published online 17 October 2013 Keywords: arterial erectile dysfunction; peripheral atherosclerosis
INTRODUCTION Erectile dysfunction (ED) is the failure of obtaining erection or maintaining erection sufficient for sexual performance, persisting constantly for at least along 6 months or recurrently. ED is a public health problem affecting more than half of the male population between the ages 40–70 years.1 ED develops because of psychogenic, organic or/and both of these two factors together; however, organic factors are more common. Diabetes mellitus (DM), hypertension (HT), hyperlipidemia and atherosclerotic cardiovascular diseases (ACVD) are the common risk factors.2,3 The level of damage in the penile vascular structures increases because of the severity of the risk factors and the longer duration of influence. Development of ED in severe coronary artery disease patients is also likely to be more severe. Similarly, the duration of DM and metabolic control affect the severity of ED.4–6 The basic mechanism having a role in the development of ED of organic origin developing secondary to the underlying risk factors is the development of atherosclerosis (AS), following endothelial dysfunction due to a decrease in nitric oxide synthesis and bioavailability. Because of the hemodynamic changes it creates in the penile vascular structures, AS damages the vascular flow needed for erection. These changes in the penile vascular structures can be imaged by penile colour Doppler ultrasound (CDUS), which is a minimally invasive examination.7 Penile CDUS allows measurement of the cavernosal artery blood flow velocity and objective evaluation of the venous structures and the integrity of the vascular structures needed for penile erection.
The aim of this study was to evaluate the other concurrent atherosclerotic changes in peripheric arterial structures, to explain the relationship with other diseases that exist in its etiology and to determine the place of penile CDUS in arterial ED, in patients with ED of arterial origin. MATERIALS AND METHODS This study was conducted on 102 patients who had presented to the Urology polyclinics of Ankara Numune Research and Training Hospital between January 2009 and May 2009, with the complaint of sexual dysfunction and who had been redirected to the Radiology Clinic with a prediagnosis of ED. Patients aged between 24 and 78 years with the complaints of ED for X6 months were included in the study. Patients having ejaculatory dysfunction but no ED according to the international index of erectile function questionnaire (over 25) were not included in the study. Detailed medical history was taken from all the patients, including drug intake and cigarette smoking. Patients with ACVD were diagnosed before they were referred to our clinic. Diabetes (fasting blood glucoseX110 mg dl 1), HT (blood pressureX130/85 mm Hg or treatment) were recorded. Blood were taken from all patients for analysis of fasting blood glucose, total cholesterol and high-density lipoprotein (HDL) level. All the patients underwent high-resolution penile CDUS (with the ultrasound brand Applio 500, Toshiba, Tokyo, Japan) using 7 and 12 mHz linear probes. Before the CDUS process, all the patients were informed about the aim of the test, the technique that would be used during the procedure and about the risks that could develop depending on this procedure. Written informed consents were obtained from all patients. To obtain the best quality from the procedure, the patients were taken into an isolated evaluation room while the tests were performed.
1 Department of Radiology, Fethiye Public Hospital, Mugla, Turkey; 2Department of Radiology, Mugla Sitki Kocman University Faculty of Medicine, Mugla, Turkey; 3Department of Radiology, Aksaz Military Hospital, Mug˘la, Turkey; 4Department of Radiology, Ankara Numune Education and Research Hospital, Ankara, Turkey and 5Mugla Sitki Koc¸man University Faculty of Medicine, Department of Urology, Mugla, Turkey. Correspondence: Dr C Goksu, Department of Radiology, Fethiye Public Hospital, Mugla, Turkey. E-mail: [email protected] Received 18 February 2013; revised 6 July 2013; accepted 28 August 2013; published online 17 October 2013
Peripheral AS in patients with ED C Goksu et al
56
Figure 1.
Color Doppler ultrasound (CDUS) of a patient with normal arterial blood velocity.
To all patients involved in the study, using a 25-G insulin injector, 2 cc (60 mg dose) of non-diluted papaverin was injected intracavernosally to any of the corpus cavernosum from a close localization to the penile root, perpendicular to the penis longitudinal axis.7 Following the injection, the peak-systolic velocity (PSV) and the end-diastolic velocity values in the bilateral cavernosus arteries (CAs) were recorded at the 5th, 10th and the 20th minutes. Values were expressed as average between left and right sides. After the process had been completed, taking the tumescence and the degree of erection into consideration, the erectile response was evaluated visually using the criteria of Broderick et al.8 The cases in which the PSV values were over 30 cm s 1 at the 5th minute and end-diastolic velocity values were below 5 cm s 1 at the 20th minute at the latest were considered as normal for ED of vascular origin (Figure 1). Patients with PSV values that were lower than 30 cm s 1 were considered as arterial dysfunction (Figure 2), and cases in which the enddiastolic velocity values did not decrease under 5 cm s 1 at the 20th minute were considered as venous (veno-oclusive) dysfunction.9 Patients were classified as ED of arterial origin and non-arterial origin according to penile CDUS findings. Of the total 102 patients, 43 (42.2%) had arterial ED and the remaining 59 (57.8%) were contained in non-arterial ED. At the same session, all the patients underwent evaluation for bilateral common carotid artery (CCA) intima media thickness (IMT) and for the presence of atherosclerotic plaque using a 7-mHz linear probe. The CCA IMT measurements were performed at the level of the CCA bulbus, 1 cm proximal from the bifurcation at the longitudinal axis according to Mannheim carotid IMT consensus IMT measurements lower than 0.9 mm were considered as normal, those between 0.9–1.3 mm were considered as a thickness increase and those with more than 1.3 mm were considered as plaque formation.10,11 The femoral arteries were evaluated for the presence of atherosclerotic plaque using a 7-mHz linear probe. The femoral artery measurements were performed at the level of the main femoral artery from the proximal of the bifurcation. The criteria for thickness used for carotid artery plaque evaluations were also used for the femoral arteries. All statistical analyses were performed using the SPSS 13.0 version software for Windows (Statistical package for Social Sciences Inc, Chicago, IL, USA). The w2 test was used in our study to evaluate the SPSS data. The statistical significance level was accepted as Po0.05. The study has been approved by the hospital ethics committee.
RESULTS One hundred and two patients between the ages of 24 and 78 (mean age: 51.98±11.88) were included in the study. ED of arterial origin was detected in 43 cases (42.2%) and ED of arterial origin was not detected in 59 cases (57.8%). Twenty-eight patients International Journal of Impotence Research (2014), 55 – 60
(27.5%) had DM, 19 patients had (18.6%) HT and 13 patients (12.7%) had ACVD. Whereas 49 cases (48%) were smokers, 53 cases (52%) were non-smokers. According to the w2-test, in all patients between the age, DM, HT, ACVD and PSV values and the arterial ED (Po0.05). However, the relationship between smoking and arterial ED was not found to be statistically significant (P40.05). The mean PSV of the CAs was 23.65 cm s 1 in 43 patients with arterial ED, 42.89 cm s 1 in 59 patients without arterial ED and the difference between the two groups was statistically significant (Po0.05; Table 1). Age distribution of patients with HT and DM between two groups are shown in Figure 3. The distribution of the total cholesterol, HDL and fasting blood glucose levels of the patients with and without arterial ED has been demonstrated in Table 2. According to this distribution, the relationship between total cholesterol and fasting blood glucose levels and the presence of arterial ED was found to be statistically significant (Po0.05), and there was no statistically significant difference between the serum HDL levels and presence of arterial ED (P40.05). The mean carotid IMT was measured as 1.236±0.6 mm in patients with arterial ED and as 0.825±0.2 mm in patients without arterial ED, and this difference was statistically significant (Po0.05; Table 3). The presence of plaque in the carotid artery and the femoral artery was found to be different between groups and this was statistically significant (Po0.05). According to these results, in patients with arterial ED there was an increased presence of plaque in the carotid and femoral arteries (Tables 4 and 5). On comparison of the visual evaluation of the five degrees of erectile quality and the presence of arterial ED, rather lower degrees were determined in patients with arterial ED. (1.95 vs 3.24). This was considered as statistically significant (Po0.05).
DISCUSSION ED is a condition the incidence of which increases with age.12 Although ED is not a life-threatening disease, it affects the quality of life of the patient and his partner in a negative way. In our study, we determined that diseases such as DM, HT and ACVD, which have high rates in the population accompany increased rates of arterial ED. For this reason, patients who are diagnosed as having arterial ED with penile CDUS should also be evaluated for other peripheral vascular atheroschlerotic processes. In this & 2013 Macmillan Publishers Limited
Peripheral AS in patients with ED C Goksu et al
57
Figure 2.
Table 1.
Colour Doppler ultrasound (CDUS) of a patient with arterial erectile dysfunction (ED).
Characteristics of patients between two groups Arterial ED Absent (n ¼ 59)
Present (n ¼ 43)
P-value
48.44±11.46
56.84±10.78
o0.05
DM N %
11 18.6%
17 39.5%
o0.05
HT N %
7 11.9%
12 27.9%
o0.05
Cigarette smoking N %
26 44.1%
23 53.5%
40.05
4 6.8% 42.89±6.97
9 20.9% 23.65±4.26
o0.05
Age (years) (Mean±s.d.)
ACVD N % CA PSV (cm s 1)
o0.05
Abbreviations: ACVD, atherosclerotic cardiovascular diseases; CA, cavernosus artery; DM, diabetes mellitus; ED, erectile dysfunction; HT, hypertension; PSV, peak-systolic velocity. Values are mean±s.d.
way, subclinical cases can be detected and further possible complications can be avoided. There are many factors having a role in the pathophysiology of ED. The major factors include neurogenic, hormonal, vascular, iatrogenic and psychogenic factors.13 In the present day, the major underlying factor in the etiology of ED of organic origin is widely accepted to be AS.13–15 In fact, ED and AS share the common risk factors (DM, HT, hyperlipidemia, smoking, obesity and sedentary life style).13 Diagnostic tests performed for the diagnosis of ED are recommended to patients who have received no benefit from oral medications, and/or to patients for whom surgery has been planned. Penile CDUS is one of the most important tests among these. Penile CDUS was performed for the first time by Lue et al.7 to evaluate the CA and function. In this imaging method, a careful & 2013 Macmillan Publishers Limited
evaluation after performing a functional penile erection by intracavernosal injection of vasoactive agents, reliable information is obtained about the penile arterial and venous systems. Following the procedure, the erectile response is evaluated visually by grading according to the criteria of Broderick et al.8 from phase 1 to phase 5, also taking the tumescence and erection angle into consideration. In our study, we evaluated the erectile quality visually after the penile CDUS procedure and a complete penile tumescence or a higher erectile quality formation was recorded in patients without detected arterial ED. In arterial ED-positive patients, lower phases were detected and as these results were assessed, a significant relationship was determined between arterial sufficiency or insufficiency and the visual erection phase. Similar to our results, Mulhall et al.16 determined a prominent correlation between the visual degree of penile erection and the degree of ED. As these data can direct the clinician for treatment selection, they can also be objective criteria for the radiologist during penile CDUS examination. Many studies have demonstrated that the severity of risk factors and the duration of influence have increased the severity of vascular lesions. In particular, the relationship between the duration of diabetes and the ED severity has been very clearly defined. In the study carried out by Kefi et al.,17 the vascular flow velocities obtained by penile CDUS in diabetic patients demonstrated the presence of ED. In the study conducted with 25 patients by Yaman et al.,18 the risk of arterial ED was reported to be threefold higher in diabetic men compared with nondiabetics, and in diabetic men, there was presence of arterial ED of a certain degree with a rate of 35–75%. In men with type 1 and type 2 DM, a higher risk of ED development has been clearly defined compared with nondiabetic men. In a large cohort study including more than 31 000 men between the ages 53 and 90 years, the age-dependent ED risk in men with DM was compared with men without DM, and the age-corrected relative risk was determined as 1.32.19 Different studies have reported the prevalence of ED in type 1 DM patients as 49%, and that in type 2 DM patients with moderate or severe ED as 34% and 24%, respectively.20,21 We, too, determined a significant relationship between DM and arterial ED in our study, in addition to a marked correlation between the fasting blood glucose levels and arterial ED. As HT causes AS and endothelial dysfunction in the pelvic and penile arteries in men between the ages of 40 and 70, HT is also a International Journal of Impotence Research (2014), 55 – 60
Peripheral AS in patients with ED C Goksu et al
58
Figure 3.
Table 2.
Age distribution of patients with hypertension (HT) and diabetes mellitus (DM) between two groups.
Table 3.
Biochemical differences between two groups
Carotid intima media thickness (IMT) among groups Arteial ED
Arterial ED
Total cholesterol Fasting glucose HDL
Absent (n ¼ 59)
Present (n ¼ 43)
P-value
179.71±37.43 105.54±51.05 38.54±6.24
207.42±42.53 116.40±53.1 37.53±7.99
o0.05 o0.05 o0.05
Abbreviations: ED, erectile dysfunction; HDL, high-density lipoprotein. Values are mean±s.d.
risk factor for ED. According to Doumas et al.,22 in middle aged males, the frequency of ED increases with the duration of HT. In one study conducted in Qatar with 642 patients between the ages of 25 and 75, of the 58.3% of HT patients, the presence of ED was determined in various phases.23 In our study, increased arterial ED rates were found in cases with HT and we determined a statistically significant relationship. Gades et al.24 obtained an evident correlation between the arterial ED and smoking. Further, they reported that although the effect of smoking on arterial ED was more evident in young patients, the conventional reasons stood out more clearly in elderly patients. In the same study, when the smokers, particularly those smoking more than 29 packs a year were compared with non-smokers, no significant relationship was found between them with regard to arterial ED. A relationship was determined between the number of cigarette packs smoked per year and arterial ED when former and current smoker men were compared. In our International Journal of Impotence Research (2014), 55 – 60
Carotid IMTp0.9 mm n % Carotid IMT40.9 mm n % Total n %
Absent (n ¼ 59)
Present (n ¼ 43)
48 81.4
5 11.6
11 18.6
38 88.4
59 100
43 100
Abbreviation: ED, erectile dysfunction. w2, 48.44; Po0.05.
study, we did not find any statistically significant relationship between smoking and arterial ED. We linked this to the more common conventional risk factors, which depend on the older mean age of our population. Besides, in our study, we only questioned the patients regarding the current smoking status and we did not obtain any information about former smoking, the amount of smoking per day and the duration of smoking. In a study performed by Kaiser et al.,25 36 male patients determined as having arterial ED with penile CDUS and those having no history of ACVD were compared with 27 normal healthy men with regard to biochemistry and peripheral vascular functions and, consequently, the brachial artery blood flow in & 2013 Macmillan Publishers Limited
Peripheral AS in patients with ED C Goksu et al
59 Table 4. The presence of plaque in the carotid artery in patients with and without arterial ED
Table 5. The presence of plaque in femoral artery in patients with and without arterial ED
Arterial ED Absent (n ¼ 59)
Arterial ED Present (n ¼ 43)
Plaque in the carotid artery Absent N 53 % 89.8 Present N 6 % 10.2 Total N 59 % 100
21 48.8 22 51.2 43 100
Abbreviation: ED, erectile dysfunction. w 2, 20.987; Po0.05.
Absent (n ¼ 59) Plaque in femoral artery Absent n % Present n % Total n %
Present (n ¼ 43)
51 86.4
14 32.6
8 13.6
29 67.4
59 100
43 100
Abbreviation: ED, erectile dysfunction. w 2, 31.23; Po0.05.
patients with arterial ED was found to be lower than that in normal individuals. The results of these studies support that ED is an early clinical sign of cardiovascular disease. In a study conducted by Tunc¸ et al.26 in 100 patients, an important part of patients who did not have a history of symptomatic cardiovascular diseases and who were presented due to ED, they demonstrated that ED was accompanied with ACVD and that this risk was higher, particularly in the older patient group. In our study, of the total 102 patients, 13 patients had a history of ACVD and 4 of these had been determined to have arterial ED (6.8% of the arterial ED patients); in 9 patients, there was detection of concurrent ACVD and arterial ED (20.9% of arterial ED cases). This gives the impression of a relationship between ACVD and arterial ED. Mulhall et al.27 followed up 3250 men with a mean age of 53 years for 22 months to determine the correlation between serum cholesterol levels, HDL levels and arterial ED, and they reported a direct correlation between ED and higher levels of cholesterol, and an inverse correlation between HDL levels and ED. In another study conducted in a total of 315 patients, 215 of whom had arterial ED and 100 of whom did not have arterial ED, the prevalence of hypercholesterolemia (total cholesterol 4200 mg dl 1 or 5.17 mmol l 1) was 70.6 in arterial ED-positive patients and 52% in arterial ED-negative patients.28 In a study conducted, although the serum low-density lipoprotein levels were found to be markedly higher in arterial ED patients, no relationship was determined for HDL and triglyceride levels. In the study conducted by Nikoobakht et al.,29 in 200 patients with mean age of 44 years, 100 of whom were healthy and 100 of whom had arterial ED, a relationship was determined between the total and low-density lipoprotein cholesterol levels and the arterial ED, and no relationship was found between HDL and triglyceride levels. We also found proportionality among the total cholesterol levels and arterial ED in our study, and found no statistical significance between arterial ED and HDL levels. There are also some studies in the literature reporting a relationship with HDL. For this reason, we consider that wider study groups are required, particularly with regard to HDL levels. Bocchio et al.30 evaluated the CCA IMT, the degree of vascular damage and the degree of ED in 270 men with concurrent ACVD risk factors and ED. In 50 men without the risk factors of ACVD compared with 220 men with risk factors, the IMT was found to be lower (Po0.05) and it correlated with the ED degree (P ¼ 0.0008). Although only 1 patient among the 50 men without ACVD risks had high-level IMT (40.9 mm), 17.7% (39/220) of the men with risk factors had high-level IMT, higher than 0.9 mm as an indicator of vascular changes. Moreover, more severe ED was found in patients with ACVD risk factors and high-level carotid IMT scores than in men without risk factors. According to the results of this & 2013 Macmillan Publishers Limited
study, a clinical correlation was found between the ED in men with ACVD risk factors and undiagnosed AS in common coronary arteries. Finally, based on the literature, the presence of vasculogenic ED should be considered as an early symptom of ACVD or as a risk factor for peripheral vascular disease.31 In our study, the mean carotid IMT measured from the 1-cm proximal of the CCA bulbus was determined as 1.236 mm in arterial ED patients and as 0.825 mm in patients without arterial ED. The difference among these IMTs was statistically significant. Of the total 43 patients with arterial ED, high-level carotid IMT patients constituted 88.4% of the population and the patients with lower than 0.9 mm carotid IMT with positive arterial ED constituted merely 11.6%. In another study conducted by Foresta et al.11 among 238 individuals, in arterial ED-positive patients, a peripheral arterial atherosclerotic process such as in the femoral artery was found to be higher when compared with the control group. Femoral artery plaque formation in arterial ED patients was found to be significantly higher in our study similar to other studies, and concurrence of femoral and carotid artery plaque formation was significantly higher. This information is worthwhile, indicating that high IMT levels and plaque formation in any peripheral vascular structure initiate the atherosclerotic process in other vascular structures. We consider that this condition and potential complications can be prevented with early treatment. Foresta et al.11 determined markedly decreased levels of CA PSV in patients with atherosclerotic lesions. At the same time, they reported a significant decrease in PSV levels in patients with both carotid and femoral artery plaque formation, compared with patients with isolated femoral or carotid artery plaque and high levels of IMT. In our study, the bilateral mean CA PSV levels were measured to be lower than normal levels in 77.6% of patients with high level (40.9 mm) carotid artery IMT, in 78.6% of patients with carotid artery plaques, in 78.4% of patients with femoral artery plaques, and in 82.6% of concurrent carotid and femoral artery plaque-formed patients. Owing to the fact that in the comparative study of Benson et al.32 conducted with selective arteriography, the lower limit of normal values for PSV had been recorded as 35 cm s 1, in other similar studies, the levels above 30–40 cm s 1 were accepted as normal.32,33 The mean bilateral CA PSV of the total 102 patients involved in our study was 23.65 cm s 1 in 43 cases with arterial ED and 42.89 m s 1 in 59 cases without arterial ED, and these results were significant statistically and consistent with the literature. There are some limitations in our study. First, with larger patient series, more accurate results can be obtained. Second, as we classified arterial ED patients as positive, we classified the venous International Journal of Impotence Research (2014), 55 – 60
Peripheral AS in patients with ED C Goksu et al
60 ED group as negative together with the normal patients. The effects of risk factors in venous ED patients may also have to be evaluated. Third, in patients with DM and HT, the relationship between the duration of the disease and the severity of arterial ED should be evaluated. As a consequence, an IMT increase in any vascular structure is informative about the beginning of an atherosclerotic process in the other vascular structures. Diseases such as non-diagnosed or silent DM, HT and ACVD can HAVE roles in the etiology of arterial ED and these diseases can be concurrent. For this reason, patients in whom arterial ED is determined following penile CDUS should undergo evaluation with B-mode ultrasound for the presence of atherosclerotic processes. In this way, subclinical vascular pathologies can be detected and further complications can be avoided. CONFLICT OF INTEREST The authors declare no conflict of interest.
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ORIGINAL ARTICLE
Peripheral atherosclerosis in patients with arterial erectile dysfunction C Goksu1, M Deveer2, AK Sivrioglu3, P Goksu1, B Cucen2, S Parlak4, M Cetinkaya5 and L Altin4 Erectile dysfunction (ED)develops owing to pshycogenic, organic or/and both of these two factors. The aim of this study was to investigate the relationship between penile cavernosal arterial flow and peripheral athersosclerosis in men with ED. This study was conducted on 102 patients who had presented to Radiology Clinic with a prediagnosis of ED. Diabetes, hypertension (HT) and smoking were recorded. Blood were taken from all patients for analysis of fasting blood glucose, total cholesterol and high-density lipoprotein level. All the patients underwent high-resolution penile colour Doppler ultrasound (CDUS). The peak-systolic velocity and the end-diastolic velocity values in the bilateral cavernosal arteries were recorded. At the same session, all the patients underwent evaluation for bilateral common carotid artery and femoral artery intima media thickness and for the presence of atherosclerotic plaque. Patients were classified as ED of arterial origin and non-arterial origin according to penile CDUS findings. Of the total 102 patients, 43 (42.2%) had arterial ED and the remaining 59 (57.8%) were contained in non-arterial ED. There was a significant difference between groups for diabetes mellitus (DM), HT, atherosclerotic cardiovascular diseases (ACVD) and total cholesterol level (Po0.05). There was also a significant difference between groups for the presence of plaque in the carotid and the femoral artery (Po0.05). The relationship between smoking and arterial ED was not found to be statistically significant (P40.05). Non-diagnosed or silent DM, HT and ACVD can have roles in the etiology of arterial ED. Patients who are diagnosed as having arterial ED with Doppler Ultrasound should also be evaluated with B-mode ultrasonography for other peripheral vascular atheroschlerotic processes. In this way, subclinical cases can be detected and further possible complications can be avoided. International Journal of Impotence Research (2013) 26, 55–60; doi:10.1038/ijir.2013.35; published online 17 October 2013 Keywords: arterial erectile dysfunction; peripheral atherosclerosis
INTRODUCTION Erectile dysfunction (ED) is the failure of obtaining erection or maintaining erection sufficient for sexual performance, persisting constantly for at least along 6 months or recurrently. ED is a public health problem affecting more than half of the male population between the ages 40–70 years.1 ED develops because of psychogenic, organic or/and both of these two factors together; however, organic factors are more common. Diabetes mellitus (DM), hypertension (HT), hyperlipidemia and atherosclerotic cardiovascular diseases (ACVD) are the common risk factors.2,3 The level of damage in the penile vascular structures increases because of the severity of the risk factors and the longer duration of influence. Development of ED in severe coronary artery disease patients is also likely to be more severe. Similarly, the duration of DM and metabolic control affect the severity of ED.4–6 The basic mechanism having a role in the development of ED of organic origin developing secondary to the underlying risk factors is the development of atherosclerosis (AS), following endothelial dysfunction due to a decrease in nitric oxide synthesis and bioavailability. Because of the hemodynamic changes it creates in the penile vascular structures, AS damages the vascular flow needed for erection. These changes in the penile vascular structures can be imaged by penile colour Doppler ultrasound (CDUS), which is a minimally invasive examination.7 Penile CDUS allows measurement of the cavernosal artery blood flow velocity and objective evaluation of the venous structures and the integrity of the vascular structures needed for penile erection.
The aim of this study was to evaluate the other concurrent atherosclerotic changes in peripheric arterial structures, to explain the relationship with other diseases that exist in its etiology and to determine the place of penile CDUS in arterial ED, in patients with ED of arterial origin. MATERIALS AND METHODS This study was conducted on 102 patients who had presented to the Urology polyclinics of Ankara Numune Research and Training Hospital between January 2009 and May 2009, with the complaint of sexual dysfunction and who had been redirected to the Radiology Clinic with a prediagnosis of ED. Patients aged between 24 and 78 years with the complaints of ED for X6 months were included in the study. Patients having ejaculatory dysfunction but no ED according to the international index of erectile function questionnaire (over 25) were not included in the study. Detailed medical history was taken from all the patients, including drug intake and cigarette smoking. Patients with ACVD were diagnosed before they were referred to our clinic. Diabetes (fasting blood glucoseX110 mg dl 1), HT (blood pressureX130/85 mm Hg or treatment) were recorded. Blood were taken from all patients for analysis of fasting blood glucose, total cholesterol and high-density lipoprotein (HDL) level. All the patients underwent high-resolution penile CDUS (with the ultrasound brand Applio 500, Toshiba, Tokyo, Japan) using 7 and 12 mHz linear probes. Before the CDUS process, all the patients were informed about the aim of the test, the technique that would be used during the procedure and about the risks that could develop depending on this procedure. Written informed consents were obtained from all patients. To obtain the best quality from the procedure, the patients were taken into an isolated evaluation room while the tests were performed.
1 Department of Radiology, Fethiye Public Hospital, Mugla, Turkey; 2Department of Radiology, Mugla Sitki Kocman University Faculty of Medicine, Mugla, Turkey; 3Department of Radiology, Aksaz Military Hospital, Mug˘la, Turkey; 4Department of Radiology, Ankara Numune Education and Research Hospital, Ankara, Turkey and 5Mugla Sitki Koc¸man University Faculty of Medicine, Department of Urology, Mugla, Turkey. Correspondence: Dr C Goksu, Department of Radiology, Fethiye Public Hospital, Mugla, Turkey. E-mail: [email protected] Received 18 February 2013; revised 6 July 2013; accepted 28 August 2013; published online 17 October 2013
Peripheral AS in patients with ED C Goksu et al
56
Figure 1.
Color Doppler ultrasound (CDUS) of a patient with normal arterial blood velocity.
To all patients involved in the study, using a 25-G insulin injector, 2 cc (60 mg dose) of non-diluted papaverin was injected intracavernosally to any of the corpus cavernosum from a close localization to the penile root, perpendicular to the penis longitudinal axis.7 Following the injection, the peak-systolic velocity (PSV) and the end-diastolic velocity values in the bilateral cavernosus arteries (CAs) were recorded at the 5th, 10th and the 20th minutes. Values were expressed as average between left and right sides. After the process had been completed, taking the tumescence and the degree of erection into consideration, the erectile response was evaluated visually using the criteria of Broderick et al.8 The cases in which the PSV values were over 30 cm s 1 at the 5th minute and end-diastolic velocity values were below 5 cm s 1 at the 20th minute at the latest were considered as normal for ED of vascular origin (Figure 1). Patients with PSV values that were lower than 30 cm s 1 were considered as arterial dysfunction (Figure 2), and cases in which the enddiastolic velocity values did not decrease under 5 cm s 1 at the 20th minute were considered as venous (veno-oclusive) dysfunction.9 Patients were classified as ED of arterial origin and non-arterial origin according to penile CDUS findings. Of the total 102 patients, 43 (42.2%) had arterial ED and the remaining 59 (57.8%) were contained in non-arterial ED. At the same session, all the patients underwent evaluation for bilateral common carotid artery (CCA) intima media thickness (IMT) and for the presence of atherosclerotic plaque using a 7-mHz linear probe. The CCA IMT measurements were performed at the level of the CCA bulbus, 1 cm proximal from the bifurcation at the longitudinal axis according to Mannheim carotid IMT consensus IMT measurements lower than 0.9 mm were considered as normal, those between 0.9–1.3 mm were considered as a thickness increase and those with more than 1.3 mm were considered as plaque formation.10,11 The femoral arteries were evaluated for the presence of atherosclerotic plaque using a 7-mHz linear probe. The femoral artery measurements were performed at the level of the main femoral artery from the proximal of the bifurcation. The criteria for thickness used for carotid artery plaque evaluations were also used for the femoral arteries. All statistical analyses were performed using the SPSS 13.0 version software for Windows (Statistical package for Social Sciences Inc, Chicago, IL, USA). The w2 test was used in our study to evaluate the SPSS data. The statistical significance level was accepted as Po0.05. The study has been approved by the hospital ethics committee.
RESULTS One hundred and two patients between the ages of 24 and 78 (mean age: 51.98±11.88) were included in the study. ED of arterial origin was detected in 43 cases (42.2%) and ED of arterial origin was not detected in 59 cases (57.8%). Twenty-eight patients International Journal of Impotence Research (2014), 55 – 60
(27.5%) had DM, 19 patients had (18.6%) HT and 13 patients (12.7%) had ACVD. Whereas 49 cases (48%) were smokers, 53 cases (52%) were non-smokers. According to the w2-test, in all patients between the age, DM, HT, ACVD and PSV values and the arterial ED (Po0.05). However, the relationship between smoking and arterial ED was not found to be statistically significant (P40.05). The mean PSV of the CAs was 23.65 cm s 1 in 43 patients with arterial ED, 42.89 cm s 1 in 59 patients without arterial ED and the difference between the two groups was statistically significant (Po0.05; Table 1). Age distribution of patients with HT and DM between two groups are shown in Figure 3. The distribution of the total cholesterol, HDL and fasting blood glucose levels of the patients with and without arterial ED has been demonstrated in Table 2. According to this distribution, the relationship between total cholesterol and fasting blood glucose levels and the presence of arterial ED was found to be statistically significant (Po0.05), and there was no statistically significant difference between the serum HDL levels and presence of arterial ED (P40.05). The mean carotid IMT was measured as 1.236±0.6 mm in patients with arterial ED and as 0.825±0.2 mm in patients without arterial ED, and this difference was statistically significant (Po0.05; Table 3). The presence of plaque in the carotid artery and the femoral artery was found to be different between groups and this was statistically significant (Po0.05). According to these results, in patients with arterial ED there was an increased presence of plaque in the carotid and femoral arteries (Tables 4 and 5). On comparison of the visual evaluation of the five degrees of erectile quality and the presence of arterial ED, rather lower degrees were determined in patients with arterial ED. (1.95 vs 3.24). This was considered as statistically significant (Po0.05).
DISCUSSION ED is a condition the incidence of which increases with age.12 Although ED is not a life-threatening disease, it affects the quality of life of the patient and his partner in a negative way. In our study, we determined that diseases such as DM, HT and ACVD, which have high rates in the population accompany increased rates of arterial ED. For this reason, patients who are diagnosed as having arterial ED with penile CDUS should also be evaluated for other peripheral vascular atheroschlerotic processes. In this & 2013 Macmillan Publishers Limited
Peripheral AS in patients with ED C Goksu et al
57
Figure 2.
Table 1.
Colour Doppler ultrasound (CDUS) of a patient with arterial erectile dysfunction (ED).
Characteristics of patients between two groups Arterial ED Absent (n ¼ 59)
Present (n ¼ 43)
P-value
48.44±11.46
56.84±10.78
o0.05
DM N %
11 18.6%
17 39.5%
o0.05
HT N %
7 11.9%
12 27.9%
o0.05
Cigarette smoking N %
26 44.1%
23 53.5%
40.05
4 6.8% 42.89±6.97
9 20.9% 23.65±4.26
o0.05
Age (years) (Mean±s.d.)
ACVD N % CA PSV (cm s 1)
o0.05
Abbreviations: ACVD, atherosclerotic cardiovascular diseases; CA, cavernosus artery; DM, diabetes mellitus; ED, erectile dysfunction; HT, hypertension; PSV, peak-systolic velocity. Values are mean±s.d.
way, subclinical cases can be detected and further possible complications can be avoided. There are many factors having a role in the pathophysiology of ED. The major factors include neurogenic, hormonal, vascular, iatrogenic and psychogenic factors.13 In the present day, the major underlying factor in the etiology of ED of organic origin is widely accepted to be AS.13–15 In fact, ED and AS share the common risk factors (DM, HT, hyperlipidemia, smoking, obesity and sedentary life style).13 Diagnostic tests performed for the diagnosis of ED are recommended to patients who have received no benefit from oral medications, and/or to patients for whom surgery has been planned. Penile CDUS is one of the most important tests among these. Penile CDUS was performed for the first time by Lue et al.7 to evaluate the CA and function. In this imaging method, a careful & 2013 Macmillan Publishers Limited
evaluation after performing a functional penile erection by intracavernosal injection of vasoactive agents, reliable information is obtained about the penile arterial and venous systems. Following the procedure, the erectile response is evaluated visually by grading according to the criteria of Broderick et al.8 from phase 1 to phase 5, also taking the tumescence and erection angle into consideration. In our study, we evaluated the erectile quality visually after the penile CDUS procedure and a complete penile tumescence or a higher erectile quality formation was recorded in patients without detected arterial ED. In arterial ED-positive patients, lower phases were detected and as these results were assessed, a significant relationship was determined between arterial sufficiency or insufficiency and the visual erection phase. Similar to our results, Mulhall et al.16 determined a prominent correlation between the visual degree of penile erection and the degree of ED. As these data can direct the clinician for treatment selection, they can also be objective criteria for the radiologist during penile CDUS examination. Many studies have demonstrated that the severity of risk factors and the duration of influence have increased the severity of vascular lesions. In particular, the relationship between the duration of diabetes and the ED severity has been very clearly defined. In the study carried out by Kefi et al.,17 the vascular flow velocities obtained by penile CDUS in diabetic patients demonstrated the presence of ED. In the study conducted with 25 patients by Yaman et al.,18 the risk of arterial ED was reported to be threefold higher in diabetic men compared with nondiabetics, and in diabetic men, there was presence of arterial ED of a certain degree with a rate of 35–75%. In men with type 1 and type 2 DM, a higher risk of ED development has been clearly defined compared with nondiabetic men. In a large cohort study including more than 31 000 men between the ages 53 and 90 years, the age-dependent ED risk in men with DM was compared with men without DM, and the age-corrected relative risk was determined as 1.32.19 Different studies have reported the prevalence of ED in type 1 DM patients as 49%, and that in type 2 DM patients with moderate or severe ED as 34% and 24%, respectively.20,21 We, too, determined a significant relationship between DM and arterial ED in our study, in addition to a marked correlation between the fasting blood glucose levels and arterial ED. As HT causes AS and endothelial dysfunction in the pelvic and penile arteries in men between the ages of 40 and 70, HT is also a International Journal of Impotence Research (2014), 55 – 60
Peripheral AS in patients with ED C Goksu et al
58
Figure 3.
Table 2.
Age distribution of patients with hypertension (HT) and diabetes mellitus (DM) between two groups.
Table 3.
Biochemical differences between two groups
Carotid intima media thickness (IMT) among groups Arteial ED
Arterial ED
Total cholesterol Fasting glucose HDL
Absent (n ¼ 59)
Present (n ¼ 43)
P-value
179.71±37.43 105.54±51.05 38.54±6.24
207.42±42.53 116.40±53.1 37.53±7.99
o0.05 o0.05 o0.05
Abbreviations: ED, erectile dysfunction; HDL, high-density lipoprotein. Values are mean±s.d.
risk factor for ED. According to Doumas et al.,22 in middle aged males, the frequency of ED increases with the duration of HT. In one study conducted in Qatar with 642 patients between the ages of 25 and 75, of the 58.3% of HT patients, the presence of ED was determined in various phases.23 In our study, increased arterial ED rates were found in cases with HT and we determined a statistically significant relationship. Gades et al.24 obtained an evident correlation between the arterial ED and smoking. Further, they reported that although the effect of smoking on arterial ED was more evident in young patients, the conventional reasons stood out more clearly in elderly patients. In the same study, when the smokers, particularly those smoking more than 29 packs a year were compared with non-smokers, no significant relationship was found between them with regard to arterial ED. A relationship was determined between the number of cigarette packs smoked per year and arterial ED when former and current smoker men were compared. In our International Journal of Impotence Research (2014), 55 – 60
Carotid IMTp0.9 mm n % Carotid IMT40.9 mm n % Total n %
Absent (n ¼ 59)
Present (n ¼ 43)
48 81.4
5 11.6
11 18.6
38 88.4
59 100
43 100
Abbreviation: ED, erectile dysfunction. w2, 48.44; Po0.05.
study, we did not find any statistically significant relationship between smoking and arterial ED. We linked this to the more common conventional risk factors, which depend on the older mean age of our population. Besides, in our study, we only questioned the patients regarding the current smoking status and we did not obtain any information about former smoking, the amount of smoking per day and the duration of smoking. In a study performed by Kaiser et al.,25 36 male patients determined as having arterial ED with penile CDUS and those having no history of ACVD were compared with 27 normal healthy men with regard to biochemistry and peripheral vascular functions and, consequently, the brachial artery blood flow in & 2013 Macmillan Publishers Limited
Peripheral AS in patients with ED C Goksu et al
59 Table 4. The presence of plaque in the carotid artery in patients with and without arterial ED
Table 5. The presence of plaque in femoral artery in patients with and without arterial ED
Arterial ED Absent (n ¼ 59)
Arterial ED Present (n ¼ 43)
Plaque in the carotid artery Absent N 53 % 89.8 Present N 6 % 10.2 Total N 59 % 100
21 48.8 22 51.2 43 100
Abbreviation: ED, erectile dysfunction. w 2, 20.987; Po0.05.
Absent (n ¼ 59) Plaque in femoral artery Absent n % Present n % Total n %
Present (n ¼ 43)
51 86.4
14 32.6
8 13.6
29 67.4
59 100
43 100
Abbreviation: ED, erectile dysfunction. w 2, 31.23; Po0.05.
patients with arterial ED was found to be lower than that in normal individuals. The results of these studies support that ED is an early clinical sign of cardiovascular disease. In a study conducted by Tunc¸ et al.26 in 100 patients, an important part of patients who did not have a history of symptomatic cardiovascular diseases and who were presented due to ED, they demonstrated that ED was accompanied with ACVD and that this risk was higher, particularly in the older patient group. In our study, of the total 102 patients, 13 patients had a history of ACVD and 4 of these had been determined to have arterial ED (6.8% of the arterial ED patients); in 9 patients, there was detection of concurrent ACVD and arterial ED (20.9% of arterial ED cases). This gives the impression of a relationship between ACVD and arterial ED. Mulhall et al.27 followed up 3250 men with a mean age of 53 years for 22 months to determine the correlation between serum cholesterol levels, HDL levels and arterial ED, and they reported a direct correlation between ED and higher levels of cholesterol, and an inverse correlation between HDL levels and ED. In another study conducted in a total of 315 patients, 215 of whom had arterial ED and 100 of whom did not have arterial ED, the prevalence of hypercholesterolemia (total cholesterol 4200 mg dl 1 or 5.17 mmol l 1) was 70.6 in arterial ED-positive patients and 52% in arterial ED-negative patients.28 In a study conducted, although the serum low-density lipoprotein levels were found to be markedly higher in arterial ED patients, no relationship was determined for HDL and triglyceride levels. In the study conducted by Nikoobakht et al.,29 in 200 patients with mean age of 44 years, 100 of whom were healthy and 100 of whom had arterial ED, a relationship was determined between the total and low-density lipoprotein cholesterol levels and the arterial ED, and no relationship was found between HDL and triglyceride levels. We also found proportionality among the total cholesterol levels and arterial ED in our study, and found no statistical significance between arterial ED and HDL levels. There are also some studies in the literature reporting a relationship with HDL. For this reason, we consider that wider study groups are required, particularly with regard to HDL levels. Bocchio et al.30 evaluated the CCA IMT, the degree of vascular damage and the degree of ED in 270 men with concurrent ACVD risk factors and ED. In 50 men without the risk factors of ACVD compared with 220 men with risk factors, the IMT was found to be lower (Po0.05) and it correlated with the ED degree (P ¼ 0.0008). Although only 1 patient among the 50 men without ACVD risks had high-level IMT (40.9 mm), 17.7% (39/220) of the men with risk factors had high-level IMT, higher than 0.9 mm as an indicator of vascular changes. Moreover, more severe ED was found in patients with ACVD risk factors and high-level carotid IMT scores than in men without risk factors. According to the results of this & 2013 Macmillan Publishers Limited
study, a clinical correlation was found between the ED in men with ACVD risk factors and undiagnosed AS in common coronary arteries. Finally, based on the literature, the presence of vasculogenic ED should be considered as an early symptom of ACVD or as a risk factor for peripheral vascular disease.31 In our study, the mean carotid IMT measured from the 1-cm proximal of the CCA bulbus was determined as 1.236 mm in arterial ED patients and as 0.825 mm in patients without arterial ED. The difference among these IMTs was statistically significant. Of the total 43 patients with arterial ED, high-level carotid IMT patients constituted 88.4% of the population and the patients with lower than 0.9 mm carotid IMT with positive arterial ED constituted merely 11.6%. In another study conducted by Foresta et al.11 among 238 individuals, in arterial ED-positive patients, a peripheral arterial atherosclerotic process such as in the femoral artery was found to be higher when compared with the control group. Femoral artery plaque formation in arterial ED patients was found to be significantly higher in our study similar to other studies, and concurrence of femoral and carotid artery plaque formation was significantly higher. This information is worthwhile, indicating that high IMT levels and plaque formation in any peripheral vascular structure initiate the atherosclerotic process in other vascular structures. We consider that this condition and potential complications can be prevented with early treatment. Foresta et al.11 determined markedly decreased levels of CA PSV in patients with atherosclerotic lesions. At the same time, they reported a significant decrease in PSV levels in patients with both carotid and femoral artery plaque formation, compared with patients with isolated femoral or carotid artery plaque and high levels of IMT. In our study, the bilateral mean CA PSV levels were measured to be lower than normal levels in 77.6% of patients with high level (40.9 mm) carotid artery IMT, in 78.6% of patients with carotid artery plaques, in 78.4% of patients with femoral artery plaques, and in 82.6% of concurrent carotid and femoral artery plaque-formed patients. Owing to the fact that in the comparative study of Benson et al.32 conducted with selective arteriography, the lower limit of normal values for PSV had been recorded as 35 cm s 1, in other similar studies, the levels above 30–40 cm s 1 were accepted as normal.32,33 The mean bilateral CA PSV of the total 102 patients involved in our study was 23.65 cm s 1 in 43 cases with arterial ED and 42.89 m s 1 in 59 cases without arterial ED, and these results were significant statistically and consistent with the literature. There are some limitations in our study. First, with larger patient series, more accurate results can be obtained. Second, as we classified arterial ED patients as positive, we classified the venous International Journal of Impotence Research (2014), 55 – 60
Peripheral AS in patients with ED C Goksu et al
60 ED group as negative together with the normal patients. The effects of risk factors in venous ED patients may also have to be evaluated. Third, in patients with DM and HT, the relationship between the duration of the disease and the severity of arterial ED should be evaluated. As a consequence, an IMT increase in any vascular structure is informative about the beginning of an atherosclerotic process in the other vascular structures. Diseases such as non-diagnosed or silent DM, HT and ACVD can HAVE roles in the etiology of arterial ED and these diseases can be concurrent. For this reason, patients in whom arterial ED is determined following penile CDUS should undergo evaluation with B-mode ultrasound for the presence of atherosclerotic processes. In this way, subclinical vascular pathologies can be detected and further complications can be avoided. CONFLICT OF INTEREST The authors declare no conflict of interest.
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Copyright of International Journal of Impotence Research is the property of Nature Publishing Group and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
