Common Cause Of Erectile Dysfunction Research Articles

(065) Characterization of Cardiovascular Function, Metabolic Status and Erectile Function in Preclinical Model of Cardiometabolic Syndrome

Abstract Introduction Cardiometabolic syndrome is a widespread health issue and common cause of erectile dysfunction (ED). Cardiometabolic syndrome encompasses a group of indications including abdominal obesity, insulin-resistant glucose metabolism, dyslipidemia, and hypertension. To date, studies have looked at high fructose or high fat diets to induce cardiometabolic syndrome and ED in rodents, but these models do not closely model the clinical phenotype. Furthermore, the molecular basis of ED in cardiometabolic syndrome needs to be elucidated. Objective Our objective is to characterize the cardiovascular and erectile function, and metabolic status in the ZSF-1 obese rat. This hybrid rat is a cross between a Zucker diabetic fatty female and a spontaneously hypertensive heart failure male rat. We hypothesize that with age the ZSF-1 obese rats will demonstrate similar disease phenotype as seen clinically and develop ED. Methods We used male lean and obese ZSF-1 rats (n=8/group). We measured body weight weekly, and performed apomorphine erectile testing, MRI to assess body composition and glucose tolerance tests at 10, 20, 30 weeks. At 30 weeks, we assessed erectile function using ICP/MAP and vascular stiffness was measured via laser doppler pulse wave velocity (PWV). Additionally, acetylcholine (Ach)-mediated vasodilation, vasodilation to sodium nitroprusside (SNP), and contraction to phenylephrine (PE) was measured in thoracic and abdominal aortas. Aorta and penile segments were collected for histological analyses. Results On average, obese rats were 60% larger (230g) than controls, had greater percent body fat and had significantly impaired glucose tolerance at all time points (p<0.05). Over time, ZSF-1 obese rats developed ED as there was a significant decrease in apomorphine-induced erections by 30 weeks (p<0.05). ED was confirmed by significantly reduced ICP/MAP in ZSF-1 obese compared to lean rats (p<0.05). Obese rats were significantly more hypertensive compared to lean rats (MAP: 140.2 mmHg vs 99.6mmHg, p<0.05). Lean and obese rats had no difference in vascular stiffness indicated by PWV. In our tissue bath experiments, ACh-mediated vasodilation was significantly decreased in the thoracic aorta of obese rats (p<0.05) while the abdominal aorta was unchanged. SNP-mediated vasodilation was similar between groups in both thoracic and abdominal aortas. At high concentrations, PE-mediated vasoconstriction was significantly increased in the thoracic and decreased in the abdominal aortas of obese rats (p<0.05). Conclusions To our knowledge, this is the first report on the erectile function in the ZSF-1 rat model of cardiometabolic syndrome. The ZSF-1 obese rats had marked adiposity, hypertension, hyperglycemia and presented with aortic endothelial dysfunction and ED. We are currently assessing testosterone levels and penile fibrosis. We believe that the ZSF-1 rat is useful for studying ED as they gradually develop metabolic disease and ED over time like the human disease. Disclosure No.

Risk of unfavorable outcomes after penile prosthesis implantation - results from a national registry (INSIST-ED).

Like all surgeries, penile prosthesis implantation (PPI) has the potential for both postoperative complications and suboptimal patient satisfaction. In order to assess risk factors for poor satisfaction, we reviewed patients who had been prospectively recruited in a national multi-institutional registry of penile prostheses procedures (INSIST-ED) from 2014 to 20121. Patient baseline characteristics and postoperative complications were recorded. The primary endpoint of this study was unfavorable outcomes after inflatable PPI, defined as significant postoperative complications (Clavien-Dindo ≥2) and/or Sexuality with Quality of Life and Sexuality with Penile Prosthesis (QoLSPP) scores below the 10th percentile. A total of 256 patients were included in the study. The median age was 60 years (IQR 56-67). The most common cause of erectile dysfunction (ED) was organic (42.2%), followed by pelvic surgery/radiotherapy (39.8%) and Peyronie's disease (18.0%). Postoperative complications were recorded in 9.6%. High-grade complications (Clavien ≥2) occurred in 4.7%. At 1-year follow-up, the median QoLSPP total score was 71 (IQR 65-76). In all, 14.8% of patients were classified as having experienced unfavorable outcomes because of significant postoperative complications and/or QoLSPP scores below the 10th percentile. Logistic regression analysis demonstrated patient age to be non-linearly associated with the risk of experiencing unfavorable outcomes. A U-shaped correlation showed a lower risk for younger and older patients and a higher risk for middle-aged men. ED etiology and surgical volume were not associated with PPI outcomes. Physicians should, therefore, be aware that middle-aged men may be at higher risk of being unsatisfied following PPI compared to both younger and older patients.

In vitro high glucose increases apoptosis, decreases nerve outgrowth, and promotes survival of sympathetic pelvic neurons.

Diabetes mellitus (DM) is a common cause of erectile dysfunction (ED), yet the molecular basis of DM neurogenic ED remains unknown. In this study we examined the impact of high glucose on survival and growth of primary cultured pelvic neurons in a rat model and assessed whether coculturing with healthy Schwann cells (SCs) can rescue pelvic neuron growth in patients with DM. Major pelvic ganglia (MPGs) from adult male Sprague Dawley rats (n = 8) were dissociated and plated on coverslips. Neurons were exposed to high glucose (45mM) for 24 or 48hours and compared to time-matched controls (25mM). Neurons were stained for neuron-specific beta-tubulin, neuronal nitric oxide synthase, vesicular acetylcholine transferase, tyrosine hydroxylase, and TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling) assay. Schwann cells were dissociated from MPGs of healthy male Sprague Dawley rats (n = 4) and grown to confluence. Additional Sprague Dawley rats were made diabetic with streptozotocin (50mg/kg, n = 4), and 5weeks later MPGs were collected from these rats, dissociated, and cocultured on healthy SCs. Neurons and SCs were stained with beta-tubulin and S100. Length, branching, and survival of nitrergic, parasympathetic, and sympathetic neurons was assessed in neurons exposed to normal or high glucose concentrations, and neuron length was measured in neuron-SC coculture. The total number of neurons and the length and number of branches were significantly decreased after 24 and 48hours of high glucose (P < .05). The percentage of nitrergic neurons decreased 10% after 24 hours and 50% after 48 hours of high glucose (P < .05). After 24 hours of high glucose, cholinergic-positive neurons were unchanged; however, these neurons decreased 30% after 48 hours (P < .05). The proportion of sympathetic neurons increased 25% after 48 hours of high glucose (P < .05). At both timepoints, there was a 2-fold increase in the total apoptotic neurons with high glucose (P < .05). Neurite outgrowth recovered to control lengths after coculture of diabetic neurons with healthy SCs (P < .05). Glucose can be used as a tool to investigate the direct effects of DM on neuritogenesis. Our data suggest that an effective treatment for DM ED protects and repairs the penile neuronal supply. Exposing MPG neurons to high glucose offers a quick and, inexpensive proxy for DM-related conditions. A limitation of our study is that our model reflects type 1 DM, whereas clinically, most diabetic ED patients have type 2 DM. Culturing pelvic neurons in high glucose can be used as a tool to elucidate how to protect proerectile neurons from cell death and may lead to new therapeutic strategies for diabetic men suffering from ED.

Molecular Mechanism of Action of Low-Intensity Extracorporeal Shockwave Therapy for Regenerating Penile and Peripheral Nerves.

Sufficient functional repair of damaged peripheral nerves is a big clinical challenge in terms of long-lasting morbidity, disability, and economic costs. Nerve damage after radical prostatectomy is the most common cause of erectile dysfunction. In recent years, low-intensity extracorporeal shockwave therapy has been explored to improve the outcomes of peripheral nerve repair and regeneration. Research indicated that application of low-intensity extracorporeal shockwave therapy after nerve surgery promoted nerve regeneration and improved the functional outcomes, underlined the mechanisms related to increase of neurotrophic factors, Schwann cells activation, and cellular signaling activation for cell activation and mitosis induced by low-intensity extracorporeal shockwave therapy. We searched PubMed for articles related to research on these topics in both in vitro and in vivo animal models and found numerous studies suggesting that the application low-intensity extracorporeal shockwave therapy could be a novel treatment for erectile dysfunction induced by nerve injury and other disease related to nerve injury.

Эректильная дисфункция сосудистого генеза: комплексный подход к диагностике

Introduction. Erectile dysfunction (ED) combines many conditions leading to erectile dysfunction and disability to perform sexual intercourse. It was confirmed that the most common cause of ED is vascular disorders, primarily associated with atherosclerosis that leads to cardiovascular diseases. Objective. To analyze the available literature data about the methods for diagnosis vascular ED, including according to cardiovascular system status. Materials and methods. The results of the search in scientific databases Medline, EMBASE, Cochrane, Chinese BioMedical Literature Database, China National Knowledge Infrastructure, Elibrary.ru were analyzed. After a detailed verification of the reliability of sources, impact factors of journals and the sequence of presentation of the material, 63 most relevant scientific publications were selected directly for citation. Results. The first step of the vascular ED diagnosis is the monitoring of nocturnal penile tumescences. Next, the risk factors for cardiovascular diseases and ED are evaluated: anamnesis of elevated blood pressure, physical activity, smoking, body weight, measurement of blood pressure, blood analysis with the lipid and glycemic profiles. For the diagnosis of endothelial dysfunction (END), the determination of flow-dependent vasodilation of the brachial artery is used, with the possible determination of the rate of blood filling after decompression. After the END is confirmed in patients with ED, it is useful to determine the vascular age using the SCORE scale. For further management of the patient with ED and END, stratification of the associated with sexual activity cardiovascular complications risk is recommended. Conclusion. The proposed diagnostic algorithm will allow not only identify the vascular component of ED at an early stage, but also to avoid fatal cardiovascular complications by prescribing and recommending therapeutic and preventive measures to patients with asymptomatic cardiovascular diseases.

Molecular mechanism of action of low-intensity extracorporeal shockwave therapy for regenerating penile and peripheral nerves.

Sufficient functional repair of damaged peripheral nerves is a big clinical challenge in terms of long-lasting morbidity, disability, and economic costs. Nerve damage after radical prostatectomy is the most common cause of erectile dysfunction (ED). In recent years, low-intensity extracorporeal shockwave therapy (Li-ESWT) has been explored to improve the outcomes of peripheral nerve repair and regeneration. Research indicated that application of Li-ESWT after nerve surgery promoted nerve regeneration and improved the functional outcomes, underlined the mechanisms related to increase of neurotrophic factors, Schwann cells activation, and cellular signaling activation for cell activation and mitosis induced by Li-ESWT. We searched PubMed for articles related to research on these topics in both in vitro and in vivo animal models and found numerous studies suggesting that the application Li-ESWT could be a novel treatment for ED induced by nerve injury and other disease related to nerve injury.

The relationship between injury mechanism and sexual dysfunction in surgically treated pelvic fractures.

The aim of the study was to identify the incidence of new sexual dysfunction reported by the patient in surgical treatment of pelvic ring injuries, and to describe the relationship between new sexual dysfunction and type of fracture. Ninety-five patients who were operated for pelvic fracture were included in the study. Patients were evaluated according to age, gender, marital status, body mass index, trauma mechanism, fracture classification, genitourinary injury, accompanying injury, injury severity score, surgical technique, fixation material, duration of operation, functional outcomes, blood loss, complications, and sexual dysfunction. Functional outcomes were assessed with Female Sexual Functioning Index (FSFI), International Index of Erectile Function-5 (IIEF5), Arizona Sexual Experience Scale (ASEX), and Modified Majeed's pelvic outcomes grading scale (MPS). Genitourinary symptoms were erectile dysfunction (ED) in 13 men, ejaculatory dysfunction in 9 men, and dyspareunia in 23 women. Urethral stricture developed in 4 males and 1 female with the urethral injury. FSFI score, ASEX score, and MPS score showed the statistically significant difference between the fracture types (p = 0.021, p = 0.032 and p = 0.020, respectively). There were no significant difference between fracture types in terms of the IIEF5 score, and no significant relationship between fracture type and ED development (p = 0.141). Anteroposterior compression (APC) is the most common cause of sexual dysfunction in both sexes, independent of surgery. In addition, the most common cause of ED in men is vertical shear (VS). Especially patients with APC and VS injuries should be multidisciplinary evaluated with gynecology, urology, and psychiatry departments.

G protein-coupled receptor kinase 2 inhibition improves erectile function through amelioration of endothelial dysfunction and oxidative stress in a rat model of type 2 diabetes.

Type 2 diabetes mellitus (T2DM) is a common cause of erectile dysfunction (ED). It has been demonstrated that G protein-coupled receptor kinase 2 (GRK2) overexpression contributes to diabetic endothelial dysfunction and oxidative stress, which also underlies ED in T2DM. We hypothesized that GRK2 overexpressed and attenuated endothelial function of the cavernosal tissue in a rat model of T2DM. T2DM rats were established by feeding with a high-fat diet (HFD) for 2 weeks and then administering two intraperitoneal (IP) injections of a low dose of streptozotocin (STZ), followed by continuous feeding with a HFD for 6 weeks. GRK2 was inhibited by IP injection of paroxetine, a selective GRK2 inhibitor, after STZ injection. Insulin challenge tests, intracavernous pressure (ICP), GRK2 expression, the protein kinase B (Akt)/endothelial nitric oxide synthase (eNOS) pathway, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit gp91phox, nitric oxide (NO), reactive oxygen species (ROS) production, and apoptosis in cavernosal tissue were examined. Less response to insulin injection was observed in T2DM rats 2 weeks after HFD. Markedly increased GRK2 expression, along with impaired Akt/eNOS pathway, reduced NO production, increased gp91phox expression and ROS generation, increased apoptosis and impaired erectile function were found in T2DM rats. Inhibition of GRK2 with paroxetine ameliorated Akt/eNOS signaling, restored NO production, downregulated NADPH oxidase, subsequently inhibited ROS generation and apoptosis, and ultimately preserved erectile function. These results indicated that GRK2 upregulation may be an important mechanism underlying T2DM ED, and GRK2 inhibition may be a potential therapeutic strategy for T2DM ED.

Successful management of cavernosal artery pseudoaneurysm using microcoil embolization

Erectile dysfunction (ED) is a common condition among men and has several causes. Among men under the age of 40, pelvic or perineal trauma is the most common cause of ED. Pelvic or perineal trauma often results in arterial injury as the likely mechanism of ED. We present the case of a 14-year-old male diagnosed with a pseudoaneurysm causing arteriogenic ED secondary to blunt force trauma to the perineum. We successfully managed arteriogenic ED with superselective embolization using microcoils. We also conclude through a review of the literature that microcoil and Gelfoam yield similar outcomes. We believe that it is important for urologists to be familiar with the various treatment techniques used by interventional radiologists in order to properly manage post-traumatic arteriogenic ED.

Aging related erectile dysfunction-potential mechanism to halt or delay its onset.

Erectile dysfunction (ED) will visit every man at some time in his life. The age at when that knock on the door is heard is totally dependent on one’s genetics as well as other extrinsic factors. Unlike guests who come for a visit and then leave, once ED shows up it tends to hang around forever. To add insult to injury, the longer ED hangs around, the worse it will get. It is estimated that by the time a man is in his 40’s, he has about a 40% chance of having some form of ED and this prevalence increases about 10% per decade thereafter. This suggests that the aging related process that leads to ED begins early in life. It turns out that the most common cause of ED, regardless of the patient’s age, is due to a problem with the vascular system of the penis. However, this specific aging related vascular problem is not caused by arterial disease but due to a dysfunction and/or loss of the corporal smooth muscle cells (SMC), the main constituent of the corporal sinusoids. As one gets older, these SMC continue to degrade and disappear. When approximately 15% of these cells have been impacted, it results in an inability of the corporal tissue to retain and/or prevent the blood from “leaking” out of the corporal sinusoids into the systemic veins. However, the corporal SMC themselves begin to combat this aging process by expressing the inducible nitric oxide synthase (iNOS) enzyme to make nitric oxide (NO) in an attempt to quench the high intracellular oxidative stress responsible for the SMC apoptosis. When this iNOS pathway is then pharmacologically upregulated, reversal of these aging related changes in the corpora with correction of the venous leakage is observed. Since we believe that aging related ED is pathologically the same disorder as essential hypertension, the development of a therapeutic regimen that can halt, delay or possibly reverse the cellular processes that lead to aging related ED should also be applicable to those patients diagnosed with essential hypertension.

The Relationship between Systemic Hypertension and Erectile Dysfunction

Erectile dysfunction (ED) is well recognized as an aging-related disorder. Its prevalence and occurrence are similar to that seen in men with essential hypertension (EH). The most common cause of ED is vascular in origin, specifically corporal smooth muscle (CSM) dysfunction in which the CSM is unable to relax sufficiently enough to prevent the loss of blood from the corporal bodies. With EH, it is recognized that the arterial vessels of the systemic circulation become stiff and, like the vessels and sinusoids in the penis, are also unable to relax normally thereby resulting in an elevation of the systemic blood pressure. Since the smooth muscles both in the corporal sinusoids and in the media of the arterial vessels have a similar embryonic origin, it is logical to assume that the aging-related factors that affect the corporal tissue is the same that affect the smooth muscle and connective tissue within the media of the arterial system. This would explain the high prevalence of hypertension in men with ED and suggest that early prevention strategies for both ED and EH should be directed towards the smooth muscle and their supporting structures in each respective tissue.

Erectile dysfunction and cardiovascular disease

Erectile dysfunction (ED) is often a comorbid condition commonly associated with cardiovascular disease (CVD). It is important for physicians to understand that the relationship between ED and CVD is not a coincidence but rather a warning signal. The fact that the symptoms of ED normally arise before the symptoms of a cardiovascular event gives physicians the unique opportunity to see the possible future of their patients’ cardiovascular health. Vascular disease is the most common cause of ED. This article reviews the incidence of CVD and ED, the pathophysiology of ED, the risk factors associated with ED and CVD, and the evaluation and treatment options for men with ED, and discusses how ED may serve as an early warning for cardiovascular disease.

Brachial artery flow mediated assessment: A tool to predict the response to chronic PDE5 inhibition with tadalafil in patients with erectile dysfunction

Subjects, n 26 11 15 Age, years 60.9±9.6 59.4±10.7 62.0±8.9 BMI 26,5±3,5 26±3,5 26,9±3,5 HB1c 6,8±1,7 5,6±0,3 7,6±1,9 Smoking history 11/26 2/11 9/15 Comorbidities Diabetes, % 6/26 0/11 6/15 Hypertension, % 3/26 0/11 3/15 Diabetes+hypertension 6/26 0/11 6/15 ⁎ Corresponding author. Andrology, San Paolo Hospital, University of Milano, Via A. di Rudini, 8 20142 Milano, Italy. E-mail address: mancinis178@msn.com (M. Mancini). Impairment of cavernosal arteries responsiveness is the most common cause of erectile dysfunction (ED) whose pathogenesis primarily depends on vascular endothelial dysfunction [1]. Atherosclerotic risk factors increase the rate of ED and most male patients with angiographically documented coronary artery disease (CAD) exhibit ED [2]. Endothelial injury is a basic step in the development of artheriosclerosis and its in-vivo evaluation by brachial artery flow mediated dilatation (BAD) technique provides relevant clinical and prognostic information [3]. Phosphodiesterase 5 inhibition (PDE5i) is an effective strategy for ED improvement which improves BAD response in both ED and non-ED patients [4,5]. It is undefined whether different pretreatment endothelial BAD patterns may predict the ED response to chronic PDE5i therapy. 26 impotent patients with no previous cardiovascular events diagnosed by IIEF questionnaire (questions 1, 2, 3, 4, 5, and 15) were enrolled and grouped according to absence (group A; n=11) or coexistence of hypertension and diabetes comorbidities (group B; n=15, n=6 with diabetes n=3 with hypertension, n=6 with diabetes and hypertension). All underwent brachial artery flowmediated evaluation (high resolution ultrasound Philips 11 MHz linear-array transducer) with measures of BAD and hyperemic (HYP) response [6], penile Duplex Ultrasound (DS) cavernosal peak systolic velocity (PSV) measure [7], and IIEF questionnaire evaluation before and after PDE5i treatment with tadalafil 10 mg on alternate days for 30 days. Differenceswithin group A and between group A and Bwere tested by ANOVA analysis and paired and unpaired Student t-test when appropriate. Linear regression analysis with least square method was used to correlate delta PSV with delta BAD and HYP. Populations were similar in terms of age, BMI, HB1c, and smoking history (Table 1). In all patients, a trend but not statistically significant increase in PSV (p=0.08) after tadalafil was observed while IIEF increased significantly (pb0.01) (Table 2). Significant differences in the BAD response were observed between group A and group B before and after treatment, even though tadalafil did not cause significant BAD improvement in both populations. Conversely, group A exhibited a significantly greater HYP response both at preand post-tadalafil treatment (Table 3). Post-tadalafil HYP response was significantly increased just in group A. After disease distribution a significant correlation between delta PSV and delta HYP was found in group A unless group B (Fig. 1A and B, r=0.677; p=0.022 and r=0.24; p=NS). The major finding of our study is that BAD may be a helpful screening technique in the identification of impotent patients that very likely may or may not get a hemodynamic advantage from midterm PDE5i treatment with tadalafil at current doses. Our observation provides a rationale for systematically using PSV evaluation in combination with BAD in the management of ED patients. In populations with variable degrees of cardiovascular risk, brachial ultrasound assessment has emerged as a strong and independent predictor of cardiovascular morbidity and mortality [3]. In this regard, changes in arterial diameter are considered more reliable than changes in flow. This because variations in flow reflect those in forearm microcirculation and brachial artery occlusion may still induce some degree of responsiveness to post-ischemic reperfusion stimuli even when the lumen of brachial conduit artery does not change significantly. In the present study no correlation was observed between changes in BAD and PSV. Conversely, brachial artery HYP response correlated with changes in PSV, at least in ED patients without hypertension and/ or diabetes. Remarkably, this seems to reflect a behavior similar to that observed at penile microcirculatory level and support the idea that in the initial stages of a penile arterial disease, a reduced PSVmay arise from an impaired microcirculation reactivity rather than from a real atherosclerotic process. Major study limitations are the small number of patients investigated, especially when considering the subset with comorbid conditions such as diabetes or hypertension and the lack of a followup period with PDE5i drug withdrawal. In conclusion, a preserved reactivity at brachial artery level in the absence of comorbid conditions predicts a favorable response at penile microcirculatory level to standard doses of PDE5i treatment. This study was supported by funds provided by the Monzino Foundation, Milano-Italy. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [8].

Role and Management of Coagulopathies in Vascular Erectile Dysfunction

Erectile dysfunction (ED) is frequently a symptom of underlying vascular disease. Vascular risk factors are the most common cause of erectile dysfunction. Endothelium of the penile vasculature plays an important role in the physiology of penile erection. Most patients presenting with vascular erectile dysfunction have a combination of trivascular disease, that being diabetes, hypertension and dyslipidemia, which may result in endothelial dysfunction. Other co-morbidities for vascular erectile dysfunction include smoking, sedentary life style, obstructive sleep apnea syndrome and obesity. When common vascular risk factors are absent, the critical role of a hypercoagulable state as contributing risk factor should be suspected. The inherited hypercoagulable syndromes primarily have an effect on veins, and only occasionally result in arterial thrombosis. The acquired hypercoagulable states which may cause endothelial dependent erectile dysfunction include antiphospholipid antibody syndrome, protein s, protein c and antithrombin III deficiencies, factor V Leiden and prothrombin gene mutation, hyperhomocysteinemia, dysfibrogenenmia and plasminogen deficiency. This paper reviews common hypercoagulable states that may result in endothelial dysfunction, and be an unsuspected cause of ED.

Pathogenetic aspects of erectile dysfunction in patients with the metabolic syndrome

Background Although it is well known that the metabolic syndrome is a common cause of erectile dysfunction (ED) the pathogenesis of the latter in this group of patients is poorly understood. The present study aimed to improve our knowledge in this area. Methods The study included 385 men with ED (control group) who underwent a full evaluation, including laboratory and ultrasound assessment of endothelial function. Results The full complex evaluation showed that arteriogenic impairment in the cavernosal circulation was the primary pathogenic factor for ED in patients with the metabolic syndrome. The ultrasound-assisted measurement of postocclusive changes in the diameter of the cavernosal arteries, which reflects the local endothelial function, was the most valuable method in the diagnosis of this form of ED. In addition, a considerable number of patients with the metabolic syndrome demonstrated both hormonal and neurological disorders which also contribute to the pathogenesis of ED in this cohort of men. Conclusion The pathogenesis of ED in patients with the metabolic syndrome is multifactorial in nature: ED is primarily caused by arteriogenic disorders which are combined with neuropathic disorders in almost every second patient and with hormonal factors in every third one. In addition, psychomotor status has an impact on the development of ED in patients with metabolic syndrome.

Diabetes and the Impairment of Reproductive Function: Possible Role of Mitochondria and Reactive Oxygen Species

Diabetes Mellitus (DM), a state of chronic hyperglycemia, is a major cause of serious micro and macrovascular diseases, affecting, therefore, nearly every system in the body. Growing evidence indicates that oxidative stress is increased in diabetes due to overproduction of reactive oxygen species (ROS) and decreased efficiency of antioxidant defences, a process that starts very early and worsens over the course of the disease. During the development of diabetes, oxidation of lipids, proteins and DNA increase with time. Mitochondrial DNA mutations have also been reported in diabetic tissues, suggesting oxidative stress-related mitochondrial damage. Diabetes-related oxidative stress may also be the trigger for many alterations on sexual function, which can also include decreased testicular mitochondrial function. Although sexual disorders have been extensively studied in diabetic men, possible changes in the sexual function of diabetic women have only recently received attention. The prevalence of sexual dysfunction in diabetic men approaches 50%, whereas in diabetic women it seems to be slightly lower. Testicular dysfunction, impotence, decreased fertility potential and retrograde ejaculations are conditions that have been described in diabetic males. Diabetes is also the most common cause of erectile dysfunction in men. Poor semen quality has also been reported in diabetic men, including decreased sperm motility and concentration, abnormal morphology and increased seminal plasma abnormalities. In addition, diabetic men may have decreased serum testosterone due to impaired Leydig cell function. Among diabetic women neuropathy, vascular impairment and psychological complaints have been implicated in the pathogenesis of decreased libido, low arousability, decreased vaginal lubrication, orgasmic dysfunction, and dyspareunia. An association between the production of excess radical oxygen species and disturbed embryogenesis in diabetic pregnancies has also been suggested. In fact, maternal diabetes during pregnancy is associated with an increased risk of complications in the offspring, such as altered fetal growth, polyhydramnios, fetal loss and congenital malformations. In addition, hypocalemia and reduced bone mineral content are found in neonates of diabetic mothers. Abnormalities in gametogenesis and sexual function have also been documented in animal models for both types of Diabetes, which thus constitute an important research tool to both study the effects of the disease, and to test novel therapeutical interventions. Because sexuality and fertility are important aspects in the lives of individuals and couples, and considering that over 124 million individuals worldwide suffer from Diabetes, this review highlights the impact of Diabetes and associated oxidative stress on sexual function.

Erectile dysfunction: a sentinel marker for cardiovascular disease in primary care.

Erectile dysfunction (ED) is a common, age-related disorder that diminishes quality of life for affected men and their partners. While most ED is now recognized as organic in origin, both organic and psychogenic causes often conspire to reduce sexual function in men with ED. Vasculopathy has come to be recognized as the most common cause of ED, which has elevated ED's importance in the primary care setting as a sentinel to underlying cardiovascular disease. Identification of cardiovascular risk factors should be a routine part of the evaluation for ED and is as important as taking the patient's sexual, medication, and psychosocial histories. Involving the patient's partner in evaluation and management is often valuable. Treatment with phosphodiesterase type 5 inhibitors is effective in restoring sexual function for most men with ED, but patients and their partners should be encouraged to make an informed choice from among all available treatment options.

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.

The underlying pathophysiology and causes of erectile dysfunction

Physical organic causes are now thought to account for most cases of erectile dysfunction (ED), although there is often a psychogenic contribution to the condition. Atherosclerotic disease is estimated to account for 40% of ED in men over 50 years, and vascular disease, including diabetes, is a common cause of ED. ED may be considered an early marker for cardiovascular disease. Ageing is a strong risk factor, and both psychological conditions such as anxiety and depression and neurological conditions such as Parkinson's disease are also common risk factors. Pelvic surgery, with which there is a risk of nerve damage, may also result in ED. Other causes include endocrine disorders, and interactions from prescribed drugs such as antihypertensives, antidepressants, antipsychotics, hormone treatments, and histamine H2 antagonists such as cimetidine. Anatomical features and anatomical conditions such as Peyronie's disease are a less common cause of ED.

Increased estradiol levels in venous occlusive disorder: a possible functional mechanism of venous leakage

Venous insufficiency of the corpora cavernosa is the second most common cause of erectile dysfunction (ED). A functional insufficiency of the venous system has been hypothesised, but the cause is still unclear. To evaluate a possible endocrine mechanism, we have studied hormone profile in a group of nine patients with pure venous-leakage (VL) compared with a control group of 15 patients with ED of different origin. Prolactin, testosterone and gonadotropin levels did not differ among the two groups, while estradiol (E2) plasma concentration was significantly higher in VL patients compared to controls. Our data support the hypothesis that the steroid environment, in particular estradiol level, can influence venous vascular tone (via VEGF or NO), thus affecting venous leakage dysfunction. This point can explain a possible link between the high estradiol levels and a functional insufficiency of the venous system in ED.