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.     

Metabolic syndrome, testosterone deficiency and erectile dysfunction never come alone

Until a decade ago the ailments of elderly men, such as atherosclerosis, hypertension, diabetes mellitus, lower urinary tract symptoms and erectile dysfunction (ED), were regarded as distinct diagnostic/therapeutic entities but there is a growing awareness that these entities are not disparate and, to improve the health of the ageing male, require an integral approach. There is an inter-dependence between the metabolic syndrome, ED and patterns of testosterone in ageing men. The main features of the metabolic syndrome are abdominal obesity, insulin resistance, hypertension and dyslipidaemia, significant factors in the aetiology of erectile function. The metabolic syndrome is associated with lower-than-normal testosterone levels. A new concept of the role of testosterone in male physiology suggests that testosterone plays also a significant role in the development and maintenance of bone and muscle mass and is a determinant of glucose homeostasis and lipid metabolism. Testosterone is not only a factor in libido but exerts also essential effects on the anatomical and physiological substrate of penile erection. With these recent insights, the health problems of elderly men must be placed in a context that allows an integral approach. Treatment of testosterone deficiency is to become part and parcel of this approach.     

Screening for metabolic syndrome and testosterone deficiency in patients with erectile dysfunction: results from the first UK prospective study

Study Type – Diagnostic (exploratory cohort)
Level of Evidence 2b

OBJECTIVE

To screen patients with erectile dysfunction (ED) for the presence of metabolic syndrome (MetS), testosterone deficiency and cardiovascular (CV) risk factors, in a secondary referral centre in the UK, as men with ED have a high incidence of CV risk factors that might amount to MetS, with obesity, increased risk of coronary heart disease and type II diabetes; testosterone deficiency has also been associated with both ED and MetS.

PATIENTS AND METHODS

We assessed 124 men presenting with ED between March 2007 and August 2008. Data were collected prospectively for patient demographics, risk factors associated with MetS, and hypogonadism. MetS was assessed using the National Cholesterol Education Program Adult Treatment Panel III Criteria 2005 (based on three or more of five criteria: waist circumference, high triglycerides, low levels of high‐density lipoprotein cholesterol, hypertension and impaired glucose tolerance).

RESULTS

The mean (range) age of the men was 50 (16–76) years; 50 of 124 (40%) patients had MetS and 27% had hypogonadism. The latter was also associated with a low testicular volume and decreased libido. Ninety‐seven patients (82%) were either overweight or obese, and 64 (52%) were current or ex‐smokers.

CONCLUSIONS

Our audit confirms a high incidence of MetS and hypogonadism in patients with ED in the UK. We recommend routine screening for CV risk factors, MetS and testosterone deficiency in all patients in the UK with ED.     

Current approaches to erectile dysfunction and testosterone deficiency

Androgens are essential for the development of the penis and it is well known that testosterone play a critical role in the physiology of erectile function. From animal studies, testosterone insufficiency disrupts cellular-signaling pathways and induces pathologic alterations in penile tissues leading to erectile dysfunction. In human, the testosterone threshold for maintaining erection is low which explains the reason why some contracted men still have an erection due to the androgens produced by the adrenal gland. Testosterone alone can improve erectile function in hypogonadic patients. Associated with PDE5-I, testosterone supplementation is a treatment for the hypogonadic patients non responders to therapy. The article reviews the different aspects of the testosterone role in the pathophysiology of erection.     

Serum testosterone levels in diabetic men with and without erectile dysfunction

Diabetes mellitus is a common chronic disease, affecting 0.5–2% worldwide. The Massachusetts Male Aging Study reported that up to 75% of men with diabetes have a lifetime risk of developing ED. Type 2 diabetes is associated with low total serum testosterone (TT) identified in several cross‐sectional studies and systemic analyses. There is a lack of consensus regarding what constitutes the lowest level of testosterone within the boundaries of normality. In this retrospective study, we sought to evaluate the effect of associated co‐morbidities on serum total testosterone (TT) level in men with type 2 diabetes DM, either with or without erectile dysfunction (ED). Three hundred and ninety‐one patients were evaluated for erectile function using an abridged, five‐item version of the International Index of Erectile Function‐5. Measurements of TT, fasting lipid profile, blood sugar and glycated haemoglobin (HbA1c) were conducted. Penile hemodynamics was assessed using intracavernosal injection and penile duplex study. Hypogonadism was found in 126 cases (33.2%), and normal TT was observed in 254 (66.8%). ED was detected in 119 cases in the hypogonadal group (94.4%) as compared to 155/254 (61.0%) in eugonadal group, P = 0.0001. TT was lower in diabetic men with ED as compared to those with normal erectile function (EF), 392.4 ± 314.9 versus 524.3 ± 140.2 ng dl^?1, respectively, P < 0.0001. After exclusion of patients with hypertension and dyslipidaemia, 185 men were evaluated, and there was no difference in the mean TT level among men with ED 490.6 ± 498.2 ng dl^?1 versus normal EF 540.6 ± 133.4 ng dl^?1 although, HbA1c remained lower in men with normal erectile function. Receiver operating characteristic (ROC) curve of TT in men without associated co‐morbidities showed that EF was compromised at TT = 403.5 ng dl^?1 or less. Sensitivity of 63.3% and a specificity of 94.0% were detected. At this level, ED was found in 33/38 (86.8%) men with TT 403.5 ng dl^?1, whereas ED was observed in 57/147 (38.8%) men with TT ≥ 403.5 ng dl^?1 (P < 0.0001). We propose a cut‐off value of 403.5 ng dl^?1 of TT blood levels as an indicator for initiation of testosterone replacement therapy in diabetic men with ED. Further prospective controlled trials are recommended.     

The dark side of testosterone deficiency: I. Metabolic syndrome and erectile dysfunction

The metabolic syndrome (MetS) is considered the most important public health threat of the 21st century. This syndrome is characterized by a cluster of cardiovascular risk factors including increased central abdominal obesity, elevated triglycerides, reduced high-density lipoprotein, high blood pressure, increased fasting glucose, and hyperinsulinemia. These factors increase the risk of cardiovascular disease (CVD) and/or type 2 diabetes. Although the etiology of this syndrome is thought to stem from obesity and physical inactivity, the extent of interactions of the individual MetS components with one another remains poorly defined. Obesity, diabetes, hypogonadism, and specific hormone and metabolic profiles have been implicated in the pathophysiology of CVD. The evolving role of androgens in MetS and CVD is of paramount importance. Reduced androgen levels associated with hypogonadism or androgen deprivation therapy increase cardiovascular risk factors and produce marked adverse effects on cardiovascular function. MetS has been associated with hypogonadism and erectile dysfunction (ED), and MetS may be considered a risk factor for ED. It is suggested that MetS, diabetes, and CVD will increase in the upcoming decades. Thus, it is critically important to develop a better understanding of how obesity, diabetes and hypogonadism contribute to androgen deficiency and the various pathophysiologic states of vascular disease. In this review we discuss the current literature pertaining to androgen deficiency, MetS, and ED, because the relationship of these factors is of scientific and clinical importance. Specifically, we will focus on exploring the relationships between hypogonadism, obesity, MetS, and ED.     

Prevalence of erectile dysfunction in patients with metabolic syndrome

AIM: We wished to investigate the relationship between metabolic syndrome and erectile dysfunction (ED). MATERIALS AND METHODS: A total of 268 patients were included in this study. All of the patients were asked to fill in an International Index for Erectile Function (IIEF) questionnaire. The presence of metabolic syndrome was determined when any three or more of the five risk factors were present according to the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP)-III. The relationship between risk factor for metabolic syndrome and ED status was determined according to logistic regression analysis. RESULTS: Eighty-nine patients (33%) constituted the metabolic syndrome group. IIEF-EF domain scores of patients with and without metabolic syndrome were 17.7 +/- 7.9 and 21.7 +/- 7.5, respectively (P < 0.001). Seventy-four percent of patients with metabolic syndrome and 50% of patients without metabolic syndrome had ED (P < 0.001; odds ratio 2.9; 95% CI 1.7-5.0). Erectile function domain scores significantly decreased as the number of metabolic risk factors increased (P < 0.001). Patients with the risk factor of fasting blood glucose (FBG), waist circumference (WC), or hypertension (HT) had lower erectile function domain scores than the patients with other metabolic risk factors. Logistic regression analysis revealed that FBG and WC were the most important criteria for ED. CONCLUSIONS: Metabolic syndrome seems to be a potential risk factor for ED. We recommend patients with metabolic syndrome should be questioned about ED, and WC measurement might take part in the evaluation of ED.     

Relationship between metabolic syndrome and erectile dysfunction

AIM: To determine the relationship between metabolic syndrome (MS) and erectile dysfunction (ED) and to see which risk factors correlated the best with ED. METHODS: Seventy-nine cardiology clinic outpatients with coronary artery disease (CAD) and lipid metabolism disorder were recruited. They were categorized as having MS, hypertension (blood pressure greater than 130/85 mmHg) and dyslipidemia. ED was classified based on International Index of Erectile Function scores. Patients were grouped into quartiles based on body mass index (BMI). Chi-square, Pearson's correlation and regression tests were used for statistical analysis. RESULTS: The mean age of the patients was 56.6 years. ED was diagnosed in 59 (74.7 %) of the 79 patients. In the 38 patients with MS, all had ED. ED was not significantly correlated with cholesterol levels (P>0.05), but was found often in patients who had both hypercholesterolemia and HT (P<0.01). Nineteen (76 %) of the 25 patients who had dyslipidemia had ED. However, ED was not significantly correlated with dyslipidemia (P >0.05). Twenty-two of the 23 patients who had BMI greater than 30 had ED, which was significantly more prevalent than that in those who had normal BMI (P<0.01). ED was seen in 38 of 53 smoker patients. Although ED was more prevalent in cigarette smokers, it was not significantly different from non-smokers (P>0.5). Conclusion: ED is present in a high percentage of patients with MS. Among multiple risk factors for ED, MS correlates the most highly. The next most important risk group is the patients with hypertension +hypercholestrolemia and obesity (BMI 30).     

Erectile dysfunction, testosterone deficiency, metabolic syndrome and prostatic disease in Taiwan

The purpose of this article is to review the current status and associations between erectile dysfunction (ED), testosterone deficiency (hypogonadism), the metabolic syndrome (MS) and prostatic disease in Taiwan. The prevalence of ED among Taiwanese men older than 40 years was 17.7%, and self-reported ED was lower than International Index of Erectile Function (IIEF)-5 defined ED. Phosphodiesterase type 5 (PDE-5) inhibitors are the first line treatment, but intracavernosal injection and penile prosthesis still have their place. The serum total testosterone (TT) level showed a decline with age, and is one of the major factors that reduces quality of life (QoL). Testosterone deficiency and hypogonadism are associated with ED, which can be improved by testosterone replacement. The MS was reported to have a prevalence of 14–16% in Taiwanese men, and was associated with an increase in all-cause and cardiovascular disease (CVD) mortality. It was also reported to be associated with hypogonadism and ED. The incidence of prostate cancer (PCa) has been rapidly increasing, and its management has also been changing in Taiwan. In conclusion, we need to pay more attention to men's health in Taiwan.     

抗高血压药物对中老年男性高血压患者勃起功能的影响

目的 探讨不同抗高血压药物对于男性勃起功能的影响.方法 问卷调查2008年10月至2008年12月来我院就诊的已婚男性、原发性高血压患者244例,年龄40～70岁.记录服用的抗高血压药物并应用国际勃起功能指数-5(IIEF-5)评估其勃起功能.结果 244例高血压患者勃起功能正常者69例(28.28%),勃起功能障碍(ED)者175例(71.72%).其中轻度障碍者120例(49.1 8%),中度障碍者16例(6.56%),重度障碍者39例(15.98%).β受体滞剂组IIEF分值低于非β受体阻滞剂组,ED发生率高于非β受体阻滞剂组,其他药物组如血管紧张素转换酶抑制剂组、血管紧张素Ⅱ受体拮抗剂组、钙离子拮抗剂组、利尿剂组间差异均无统计学意义.结论 高血压患者中ED的发生率较高(175/244,71.72%), 服用β受体阻滞剂对患者勃起功能有不利影响,而其他药物对于勃起功能影响相似.     

Clinical practice experience with testosterone treatment in men with testosterone deficiency syndrome

OBJECTIVE

To report on a clinical practice series of testosterone‐replacement therapy (TRT) in men with testosterone deficiency syndrome (TDS), examining clinical efficacy, biochemical parameters and effects on prostate health over a 2‐year period.

PATIENTS AND METHODS

A retrospective review of 85 patients with symptoms of TDS and at least a 3‐month trial of TRT was performed in this single‐centre, clinical practice setting. Three domains of symptomatology were evaluated: libido, erectile function and energy levels. Symptoms were assessed by a combination of patient reporting, physician’s assessment and validated symptom assessment scores. Total testosterone (TT), calculated bio‐available testosterone (BT) and prostate‐specific antigen (PSA) levels were continuously measured and effects on prostate health were examined.

RESULTS

Only 38 (45%) patients in this cohort remained on TRT for >2 years. The most common reason for discontinuing treatment was lack of clinical response but those remaining on TRT had continued improvement in libido, erectile function and energy levels. During treatment, the average TT and calculated BT values significantly increased compared with the baseline values at most of the evaluated time points, with no significant change in average PSA values. In all, 15% of this cohort had some degree of progression of lower urinary tract symptoms. Seven patients had eight ‘for‐cause’ prostate biopsies either during supplementation or at any date after completion, with an only three positive for cancer.

CONCLUSIONS

Only 45% of men on TRT remained on treatment for >2 years in this clinical practice experience of men with TDS. Those remaining showed persistent improvement in their symptoms. The average TT and BT values increased significantly with no significant change in PSA levels.     

Testosterone deficiency and risk factors in the metabolic syndrome: implications for erectile dysfunction

The most common cause of erectile dysfunction (ED) is penile vascular insufficiency. This is usually part of a generalized endothelial dysfunction and is related to several conditions, including type 2 diabetes mellitus, hypertension, hyperlipidemia, and obesity. These conditions underlie the pathophysiology of metabolic syndrome (MetS). Hypogonadism, or testosterone deficiency (TD), is an integral component of the pathology underlying endothelial dysfunction and MetS, with insulin resistance (IR) at its core. Testosterone replacement therapy for TD has been shown to ameliorate some of the components of the MetS, improve IR, and may serve as treatment for decreasing cardiovascular and ED risk.     

Getting Urology involved in the treatment of men with erectile dysfunction,the metabolic syndrome and hypogonadism

Urologists play a significant role in the diagnosis and treatment of male erectile dysfunction (ED). But the context of diagnosing and treating ED has profoundly changed over the past decade, in that it is no longer viewed as an independent entity. Rather it is recognized that in many (but not all) patients, there is a close association with the so called “metabolic syndrome” and on occasions with hypogonadism. In order to treat men with ED appropriately in this context, it is important for the urologist to become familiar with the intricacies of the metabolic syndrome and also with the diagnosis and treatment of male hypogonadism.While understanding of the metabolic syndrome involves the urologist in the understanding the management of hypertension, dyslipidaemia and diabetes, (most of which will be have changed considerably since he first learnt about them at medical school), an understanding of testosterone metabolism is much closer to home. Urologists are trained to use testosterone withdrawal as a treatment for prostate cancer, and it is only a short intellectual step to believing that there is an association between testosterone replacement and the development of prostate cancer. However, while the evidence for the former is considerable, the evidence to support the latter relationship is lacking.There is increasing evidence that there is a role for the responsible treatment of elderly men who are hypogonadal with testosterone while at the same exercising due caution in relation to any potentially harmful effects of testosterone administration on the prostate and the hematopoietic system. To this end a number of sets of guidelines for diagnosing and treating elderly men with testosterone deficiency have been developed.     

154例中青年男性器质性勃起功能障碍患者与代谢综合征关联分析

目的:探讨中青年男性勃起功能障碍(erectile dysfunction,ED)与代谢综合征(metabolic syndrome,MS)及睾酮水平的相关性。方法:2012年2月至2014年1月,调查门诊154例20~59岁男性器质性ED患者与103例性生活正常男性的一般情况、腰围、血压、空腹血糖、总甘油三酯、高密度脂蛋白、血清总睾酮、国际勃起功能评分5项以及勃起功能指标,比较ED组与非ED组,以及ED患者中MS者与非MS者各项指标差别。结果:中青年ED组MS患病率显著高于非ED组MS患病率(P0.05),ED组与非ED组腹围、血压、腹围、空腹血糖、高密度脂蛋白及总睾酮均有有显著性差异(P0.05)。ED组中MS者与非MS者勃起功能各项指标及总睾酮有显著性差异(P0.05)。多元logistic回归分析MS各项指标及总睾酮与ED相关性分析,发现腰围与ED密切相关(P0.01)。结论:中青年ED患者并发MS患病率较正常人群明显增高,ED患者中并发MS者睾酮水平较低、勃起功能较差。中心性肥胖与中青年ED密切相关。     

Cardiovascular disease, metabolic syndrome and erectile dysfunction

PURPOSE OF REVIEW: Erectile dysfunction and cardiovascular disease share the same risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking, all of which are implicated in causing endothelial dysfunction. In this review, an overview is given on the role of endothelium in the pathophysiology of erectile dysfunction, cardiovascular disease, and the metabolic syndrome as well as the links between them. RECENT FINDINGS: Current literature offers strong evidence that endothelial dysfunction and erectile dysfunction are linked. Erectile dysfunction appears to be one of the earliest signs of systemic vascular disease and might be considered as an early marker for subclinical cardiovascular disease. Obesity is one of the many risk factors for cardiovascular disease and is also associated with hypertension, dyslipidemia, glucose intolerance, and insulin resistance, which together define the metabolic syndrome. Experimental, clinical, and epidemiologic studies support the association between metabolic syndrome and cardiovascular disease. SUMMARY: The above-mentioned risk factors are a potential threat to the penile endothelium and the smooth muscle tissue leading to functional and structural changes. These important pathophysiologic factors are the foundation for the strong link between erectile dysfunction and cardiovascular disease. Recent literature supports the link between metabolic syndrome and erectile dysfunction and highlights metabolic syndrome as a potential risk factor for the development of erectile dysfunction.