Erectile dysfunction and lower urinary tract symptoms: a consensus on the importance of co-diagnosis.

Despite differences in design, many large epidemiological studies using well-powered multivariate analyses consistently provide overwhelming evidence of a link between erectile dysfunction (ED) and lower urinary tract symptoms (LUTS). Preclinical evidence suggests that several common pathophysiological mechanisms are involved in the development of both ED and LUTS. We recommend that patients seeking consultation for one condition should always be screened for the other condition. We propose that co-diagnosis would ensure that patient management accounts for all possible co-morbid and associated conditions. Medical, socio-demographic and lifestyle risk factors can help to inform diagnoses and should be taken into consideration during the initial consultation. Awareness of risk factors may alert physicians to patients at risk of ED or LUTS and so allow them to manage patients accordingly; early diagnosis of ED in patients with LUTS, for example, could help reduce the risk of subsequent cardiovascular disease. Prescribing physicians should be aware of the sexual adverse effects of many treatments currently recommended for LUTS; sexual function should be evaluated prior to commencement of treatment, and monitored throughout treatment to ensure that the choice of drug is appropriate.

Erectile dysfunction and coronary artery disease prediction: evidence-based guidance and consensus.

* A significant proportion of men with erectile dysfunction (ED) exhibit early signs of coronary artery disease (CAD), and this group may develop more severe CAD than men without ED (Level 1, Grade A). * The time interval among the onset of ED symptoms and the occurrence of CAD symptoms and cardiovascular events is estimated at 2-3 years and 3-5 years respectively; this interval allows for risk factor reduction (Level 2, Grade B). * ED is associated with increased all-cause mortality primarily due to increased cardiovascular mortality (Level 1, Grade A). * All men with ED should undergo a thorough medical assessment, including testosterone, fasting lipids, fasting glucose and blood pressure measurement. Following assessment, patients should be stratified according to the risk of future cardiovascular events. Those at high risk of cardiovascular disease should be evaluated by stress testing with selective use of computed tomography (CT) or coronary angiography (Level 1, Grade A). * Improvement in cardiovascular risk factors such as weight loss and increased physical activity has been reported to improve erectile function (Level 1, Grade A). * In men with ED, hypertension, diabetes and hyperlipidaemia should be treated aggressively, bearing in mind the potential side effects (Level 1, Grade A). * Management of ED is secondary to stabilising cardiovascular function, and controlling cardiovascular symptoms and exercise tolerance should be established prior to initiation of ED therapy (Level 1, Grade A). * Clinical evidence supports the use of phosphodiesterase 5 (PDE5) inhibitors as first-line therapy in men with CAD and comorbid ED and those with diabetes and ED (Level 1, Grade A). * Total testosterone and selectively free testosterone levels should be measured in all men with ED in accordance with contemporary guidelines and particularly in those who fail to respond to PDE5 inhibitors or have a chronic illness associated with low testosterone (Level 1, Grade A). * Testosterone replacement therapy may lead to symptomatic improvement (improved wellbeing) and enhance the effectiveness of PDE5 inhibitors (Level 1, Grade A). * Review of cardiovascular status and response to ED therapy should be performed at regular intervals (Level 1, Grade A).

Global experiences with vardenafil in men with erectile dysfunction and underlying conditions.

OBJECTIVE: Vardenafil has demonstrated efficacy for the pharmacological management of erectile dysfunction (ED). Accumulating evidence suggests that ED is frequently associated with underlying cardiovascular and metabolic conditions which are thought to be involved in the aetiology of ED. The present review aims to summarise and discuss the available evidence for the efficacy, safety and tolerability of vardenafil in patients with underlying conditions including diabetes, hypertension and dyslipidaemia. METHODS: Relevant articles were identified through a PubMed search of clinical trials and postmarketing surveillance studies of vardenafil in patients with ED including those with diabetes, hypertension and dyslipidaemia. RESULTS: Across all trials, vardenafil showed good efficacy for the treatment of ED in patients with diabetes, hypertension and dyslipidaemia. Vardenafil also showed a favourable safety and tolerability profile. The concomitant use of medication to treat hypertension or dyslipidaemia was not associated with an increase in adverse events following vardenafil treatment. CONCLUSIONS: The prevalence of both diagnosed and undiagnosed underlying conditions is high among men with ED. The evidence presented in this review suggests that vardenafil is efficacious and well tolerated in patients with ED and diabetes, hypertension and/or dyslipidaemia and can be recommended as first-line treatment for ED in patients with these conditions.

The triad of erectile dysfunction, hypogonadism and the metabolic syndrome.

AIM: To identify the relationship of erectile dysfunction, hypogonadism and the metabolic syndrome in the context of men's health. METHODS: An Expert Panel Meeting was held in December 2006 in Vienna, Austria. In addition a comprehensive literature search was conducted. RESULTS: Men have a higher incidence of cardiovascular events than women of similar ages which has led to the belief that testosterone is a risk factor for cardiovascular disease in men. The latter hypothesis is no longer tenable. On the contrary, low testosterone levels are associated with (visceral) obesity, the metabolic syndrome, diabetes mellitus, cardiovascular disease and erectile dysfunction (ED). Testosterone therapy does not lead to an increased incidence of cardiovascular disease or events such as myocardial infarction, stroke or angina. Until recently (visceral) obesity, the metabolic syndrome, diabetes mellitus, cardiovascular disease and ED were viewed as more or less independent entities affecting the ageing male. It was not recognised that hypogonadism is a common denominator. With a more integrative approach to the health situation of middle-aged and elderly men, these conditions appear closely interrelated in their manifestations, hypothetically in their aetiology, diagnostic strategy and also their treatment. CONCLUSION: Improving sexual health is a portal to identify health hazards and improving men's health. Appropriate diagnosis and medical work up of men presenting with sexual symptoms may have the benefit of the diagnosing and treating other important conditions, such as obesity, diabetes, hypertension and hyperlipidaemia.

Integrating partners into erectile dysfunction treatment: improving the sexual experience for the couple.

INTRODUCTION: Erectile dysfunction (ED) is a common condition estimated to affect more than 150 million men worldwide. ED should be regarded as a shared sexual problem which has significant detrimental effects both on the men who experience this condition and on their partners. EVIDENCE TO SUPPORT PARTNER INVOLVEMENT IN ED THERAPY: Evidence shows that the partner plays a key supportive role in the man's ED treatment and in successful long-term ED therapy. Including the partner in consultations may highlight discordant attitudes and communication problems between couple members which may indicate treatment acceptance or rejection, or realistic or unrealistic treatment expectations. OPTIONS FOR PARTNER INVOLVEMENT IN ED THERAPY: Most patients with ED consult their physician in the absence of their partner. Therefore, involving the partner in therapy can be challenging. Two options which physicians should consider are: encouraging the patient to bring the partner into the office and, often more realistically, seeking information about, and providing information to, the partner, via the patient. OBJECTIVES: The objective of these recommendations is to provide practical guidance on treating couples affected by ED, and suggest techniques that may be helpful in integrating the partner into the process of ED treatment.

The implementation of European Association of Urology guidelines in the management of acute epididymo-orchitis.

INTRODUCTION: Acute epididymo-orchitis is a common and increasing problem. This retrospective study reviewed whether the European Association of Urology guidelines for the management of acute epididymo-orchitis, which form the basis of this Trust's present inter-departmental guidelines, are being effectively implemented. PATIENTS AND METHODS: Case notes of 53 patients attending the emergency department with acute epididymo-orchitis over a 6-month period were reviewed retrospectively. The hospital results' database was used to confirm the diagnostic tests requested on patients at the time of their initial presentation. RESULTS: Of the study cohort, 26 patients were aged 35 years. The results demonstrated that a sexual history was documented in only 43.4% of cases. A mid-stream urine sample was sent for routine culture in 54.7% of cases whilst urine for the Chlamydia polymerase chain reaction (PCR) test was obtained in 17% and a urethral swab performed in 5.6%. Antibiotics were prescribed in 81% of cases. Of these patients, 46.5% received ciprofloxacin alone (mean age, 52 years; range, 18-87 years), 25.5% received doxycycline alone (mean age, 30 years; range, 18-45 years) and 21% received both ciprofloxacin and doxycycline (mean age, 33 years; range 18-49 years). In 26.4% of cases, verbal advice to attend a genito-urinary medicine clinic was given, whilst a formal telephone referral was made in only one case. Formal urological follow-up was arranged for only three out of 11 patients aged > 50 years. CONCLUSIONS: Although a joint emergency department/urology clinical protocol for the investigation and treatment of acute epididymo-orchitis already exists within the Trust, our current management conforms to this in only a minority of cases. Many different strategies can be employed in the implementation of clinical practice guidelines and all are associated with variable degrees of success. The regular movement of junior staff through each department necessitates that the distribution of management protocols and guidelines occurs at frequent intervals throughout the year and that their implementation is continuously monitored so that, if necessary, further implementation strategies can be employed.

The multinational Men's Attitudes to Life Events and Sexuality study: the influence of diabetes on self-reported erectile function, attitudes and treatment-seeking patterns in men with erectile dysfunction.

AIMS: To identify the prevalence of erectile dysfunction (ED) in men with diabetes, and to compare the perceptions of ED and the treatment-seeking behaviour of these men with men with ED without diabetes. METHODS: Phase I of this multinational study involved 27,839 men who were questioned about a number of men's health issues including ED, diabetes and cardiovascular conditions (i.e. hypertension, high cholesterol and angina). Epidemiological associations between these conditions were explored. Phase II involved 2912 men with self-reported ED, aged 20-75 years. Participants completed questionnaires concerning their ED, efforts to seek treatment for their ED, and potential influences that might affect treatment-seeking behaviour. Comparison of these responses was made between men with ED and diabetes and men with ED without diabetes. RESULTS: There was a clear association between self-reported ED and diabetes, hypertension, angina and high cholesterol. Men with diabetes were more likely to consider their ED to be severe and permanent and to speak to a physician or a nurse about their ED, compared with men without diabetes. Sildenafil use was similar in both groups, but men with diabetes were more likely to have discontinued use, mainly because of the lack of treatment efficacy. CONCLUSION: Men with diabetes were more likely to consider their ED to be severe and permanent, compared with men without diabetes. Furthermore, men with diabetes were more likely to discontinue sildenafil therapy, primarily because of poor efficacy. These findings suggest a need for alternative treatments for ED, especially in men with diabetes.

Patients at high risk for upper tract urothelial cancer: evaluation of hydronephrosis using high resolution magnetic resonance urography.

PURPOSE: We assessed the potential of magnetic resonance urography (MRU) in the evaluation of hydronephrosis not explained by standard investigation in patients at high risk for upper tract urothelial cancer. MATERIALS AND METHODS: A total of 23 consecutive patients in a specialist urological unit with unexplained hydronephrosis prospectively underwent MRU which comprised overview heavily T2-weighted MR urographic images followed by focused high resolution turbo spin echo T2-weighted sequences obtained in an axial and coronal oblique plane through the level of urinary obstruction. All were at high risk for urothelial cancer and had either contraindications to or problems with standard investigations including poor contrast excretion due to obstruction or renal failure, failed ureteral cannulation or contrast allergy. Clinical events and imaging followup, subsequent endoscopic/surgical findings and histopathology validated MR findings. RESULTS: In 23 patients with a high clinical suspicion of upper tract transitional cell tumors (TCC), 8 ureteral and 5 renal pelvic TCCs (2 bilateral) were diagnosed by MR, and confirmed histologically. In a further 5 patients benign causes for the hydronephrosis were found. No intrinsic or extrinsic pathology was demonstrable in 5 patients whose imaging findings were stable during 1 year of followup. CONCLUSIONS: MRU is a valuable noninvasive investigation for evaluating hydronephrosis in this group of patients with suspected urothelial cancer in which routine investigation had failed to provide clinically important information. Focused high resolution T2-weighted images were reliable in the diagnosis of ureteral and renal pelvic TCCs, and were valuable in excluding these and other mass lesions as the cause of hydronephrosis.

Buccal mucosal grafts for urethroplasty: surgical technique and morbidity.

We present an outline of the surgical technique for harvesting free buccal mucosal grafts for urethroplasty in 23 patients and an assessment of morbidity at the donor site. Any problems were recorded, particularly injury to the lingual and mental nerves, symptoms of obstruction of the parotid duct, and trismus. There were four early (less than 6 weeks) complaints of mild trismus and one late complaint. All the grafts were successful.

A biomimetic tissue from cultured normal human urothelial cells: analysis of physiological function.

The urinary bladder and associated tract is lined by the urothelium. Once considered as just an impermeable epithelium, it is becoming evident that the urothelium not only functions as a volume-accommodating urinary barrier but has additional roles, including sensory signaling. Lack of access to normal human urothelium has hampered physiological investigation, and although cell culture systems have been developed, there has been a failure to demonstrate that normal human urothelial (NHU) cells grown in vitro retain the capacity to form a functional differentiated urothelium. The aim of this study was to develop a biomimetic human urothelium from NHU cell cultures. Urothelial cells isolated from normal human urothelium and serially propagated as monolayers in serum-free culture were homogeneous and adopted a proliferative, nondifferentiated phenotype. In the presence of serum and physiological concentrations of calcium, these cells could be reproducibly induced to form stratified urothelia consisting of basal, intermediate, and superficial cells, with differential expression of cytokeratins and superficial tight junctions. Functionally, the neotissues showed characteristics of native urothelium, including high transepithelial electrical resistance of >3,000 Omega.cm(2), apical membrane-restricted amiloride-sensitive sodium ion channels, basal expression of Na(+)-K(+)-ATPase, and low diffusive permeability to urea, water, and dextran. This model represents major progress in developing a biomimetic human urothelial culture model to explore molecular and functional relationships in normal and dysfunctional bladder physiology.

Vardenafil: a new oral treatment for erectile dysfunction.

Vardenafil is a new phosphodiesterase type-5 inhibitor for the treatment of men with erectile dysfunction (ED). It was licensed in Europe in spring 2003 and in the USA in late 2003. It is a potent and selective inhibitor of the enzyme phosphodiesterase type 5, and in the presence of an erectile stimulus potentiates the intracellular actions of cyclic guanylate monophosphate. Several large, placebo-controlled trials have demonstrated efficacy both in the broad population of men with ED and in men with more difficult to treat ED. It is well tolerated with a side effect profile typical of this class of drugs. It has a rapid onset of action and has demonstrable efficacy for men using the medication for up to 2 years.

What is the relationship between male sexual function and lower urinary tract symptoms (LUTS)?

INTRODUCTION: There is considerable current interest in the relationship between LUTS and sexual function in men, and in particular whether there is a causative relationship between them. This observational study, performed in a single centre, seeks to explore this area further. METHODS: 1,420 patients attending a prostate assessment clinic were assessed by International Prostate Symptoms Score (IPSS), BPH impact index (BPH-II), Urinary flow rate (Q(max)), post-void residual volume (PVR) and the O'Leary sexual questionnaire (which assesses erectile, ejaculatory and sexual drive). The results were analyzed using univariate and multivariate techniques. RESULTS: Following exclusion of those with incomplete data, those who were not sexually active, those with PSA >20 ng/ml and those who refused to fill in the questionnaire, there were 696 evaluable patients. Using univariate techniques, age, IPSS, Quality of life (QOL), BPH-II, Q(max) and PVR all correlated with differing domains of sexual function including erectile and ejaculatory function. Multiple regression analysis demonstrated that age was overwhelmingly the most important predictor of sexual function, but that BPH-II and QOL were also predictive for some domains, while the IPSS score was not. CONCLUSION: This study confirms that a significant proportion of men with LUTS have sexual dysfunction. The relationship is complex and differs according to the type of sexual dysfunction.

An open-label, randomized, flexible-dose, crossover study to assess the comparative efficacy and safety of sildenafil citrate and apomorphine hydrochloride in men with erectile dysfunction.

OBJECTIVE: To compare the efficacy and safety of sildenafil and apomorphine in the treatment of men with erectile dysfunction (ED). PATIENTS AND METHODS: In all, 139 men with ED who were naïve to treatment were entered into an open-label crossover trial with two treatment periods, each of 8 weeks, separated by a 2-week washout period. Men were randomized to receive either sildenafil then apomorphine or apomorphine then sildenafil, and were allowed to titrate the dose on both drugs. The primary endpoint was the erectile function (EF) domain of the International Index of Erectile Function (IIEF), and other endpoints included diary data, the other domains of the IIEF, overall assessment questions and the Erectile Dysfunction Index of Treatment Satisfaction (EDITS) questionnaire. RESULTS: The EF domain score after treatment was 25.2 for sildenafil and 15.9 for apomorphine. The treatment difference of the adjusted means was 9.3 points (95% confidence interval 7.6-11.1; P < 0.001). After sildenafil the successful intercourse rate was 75%, vs 35% for apomorphine (P < 0.001), and the EDITS scores were 82.5 for sildenafil and 46.8 for apomorphine (P < 0.001). Of the men, 96% expressed a preference for sildenafil as a treatment for their ED. The side-effect profiles for both drugs were in keeping with published data. CONCLUSION: By all measurable endpoints sildenafil was superior to apomorphine in this open-label crossover study of men with ED who were naïve to therapy

The efficacy and safety of tadalafil: an update.

OBJECTIVE: To provide an update on the efficacy and safety of tadalafil, a phosphodiesterase-5 inhibitor, in the treatment of erectile dysfunction (ED). PATIENTS AND METHODS: In all, 2102 men (mean age 56 years) with mild-to-severe ED of various causes were randomized to placebo or tadalafil, taken as needed with no food restrictions, at fixed 'on-demand' doses of 10 or 20 mg in 11 randomized, double-blind, placebo-controlled trials lasting 12 weeks. The three co-primary outcomes were changes from baseline in the erectile function domain of the International Index of Erectile Function (IIEF) and the proportion of 'yes' responses to questions 2 and 3 of the Sexual Encounter Profile (SEP). Additional efficacy instruments included a Global Assessment Question (GAQ). RESULTS: Compared with placebo, tadalafil gave significantly better outcomes. Patients receiving either dose of tadalafil had a significant mean improvement of 6.5 and 8.6, respectively, in the IIEF erectile function domain score from baseline (P < 0.001 vs placebo). At both doses the mean success rate for intercourse attempts (SEP-Q3) was 58% and 68%, respectively, compared with 31% in the placebo group (P < 0.001), and 71% and 84% reported improved erections at the endpoint (GAQ), vs 33% on placebo (P < 0.001). Tadalafil was effective up to 36 h after dosing and was effective regardless of disease severity and causes, and in patients of all ages. The most frequent adverse events were headache, dyspepsia, back pain and myalgia. CONCLUSION: Tadalafil was an effective and well-tolerated treatment for ED.

The sexual habits of British men and women over 40 years old.

OBJECTIVE: To obtain a greater understanding of sexual behaviour and habits among men with and without erectile dysfunction (ED), and their female partners, to improve the management of ED in heterosexual men. SUBJECTS AND METHODS: A population-based study was conducted amongst men and women aged > 40 years. None of the subjects were partners in the same sexual relationship. Interviews were conducted on the Internet via a panel-based questionnaire. RESULTS: In all, 225 (32%) men had self-reported ED and 88 (26%) women reported that their partner had ED. For all men (with or without ED) the mean time from first thinking of intercourse to beginning intercourse was just under 1 h. During their most recent period of sexual activity, 87% of men with and 78% of men without ED had intercourse with ejaculation at most once within 24 h; 81% of men and 89% of women felt that it was neither very nor extremely important to have intercourse with ejaculation more than once in a 24-h period. CONCLUSIONS: This study reports for the first time the frequency of sexual activity in British men and women in heterosexual relationships, and describes the usual timings of sexual events. Few significant differences were identified between men with or with no ED.

Evaluation of painful hydronephrosis in pregnancy: magnetic resonance urographic patterns in physiological dilatation versus calculous obstruction.

PURPOSE: We evaluated magnetic resonance urography (MRU) appearances in symptomatic hydronephrosis in pregnancy and compared urographic patterns in physiological and calculous disease. MATERIALS AND METHODS: A total of 24 consecutive pregnant women with symptomatic hydronephrosis underwent MRU, comprising an overview fast T2-weighted examination of the abdomen and pelvis, and thick slab, heavily T2-weighted MRU images, followed by focused, high resolution T2-weighted sequences obtained in an axial and coronal oblique plane through the level of ureteral caliber change. RESULTS: Of these 24 pregnant women 15 were found to have physiological hydronephrosis, 7 had calculous disease and 2 had preexisting urinary anomalies. MRU findings in physiological hydronephrosis cases were extrinsic compression of the middle third of the ureter, no filling defect and a collapsed ureter below it. Obstruction by ureteral calculi was seen at points of ureteral narrowing in the ureter, that is at the vesicoureteral junction in 2 cases, in the compressed mid ureter in 3 and at the pelviureteral junction in 1. Nonobstructive renal calculi were seen in another patient. Calculi presented throughout pregnancy but physiological hydronephrosis presented only in the late second and third trimesters. With distal calculi the MRU appearance was the double kink sign with constriction at the pelvic brim and the vesicoureteral junction with a standing column of urine in the pelvic ureter. There was renal edema and perirenal extravasation. Small calculi were only identified using high resolution T2-weighted magnetic resonance imaging. CONCLUSIONS: MRU is a valuable and well tolerated investigation for evaluating painful hydronephrosis in pregnancy. There are characteristic and differing urographic appearances in physiological and calculous obstruction.

Bladder reconstruction--from cells to materials.

Surgical reconstruction of the urinary bladder is performed on patients of all ages for a diverse range of conditions, including congenital abnormalities, bladder dysfunction, trauma and cancer. The most common material utilized to augment or replace the bladder during these procedures is a segment of the patient's own intestine. However, this procedure ('enterocytoplasty') is associated with significant clinical complications that arise due to the exposure of the epithelial lining of the intestine to urine. A number of alternative approaches are being actively developed to find a practical and functional substitute for native bladder tissue. These range from 'composite enterocystoplasty', where the de-epithelialized intestine wall is lined with bladder epithelial cells that have been propagated in vitro, to augmenting the urinary system with natural or synthetic biomaterials that may incorporate in vitro-propagated cells. However, if tissue-engineered products are to have therapeutic application in bladder reconstruction, a number of issues remain to be addressed; these issues are discussed briefly below.

A systematic approach to erectile dysfunction in the cardiovascular patient: a Consensus Statement--update 2002.

Sexual activity is no more stressful to the heart when compared with a number of other natural daily activities, e.g. walking one mile on the level in 20 minutes. The cardiac risk of sexual activity in patients diagnosed with cardiovascular disease is minimal in properly assessed and advised patients. Erectile dysfunction (ED) is extremely common, affecting over half of men aged 40-70 years, and increases in frequency with age. ED and cardiovascular disease share many of the same risk factors and commonly coexist. ED in the otherwise asymptomatic man may be a marker for underlying coronary artery disease. ED in the diagnosed cardiovascular patient should be identified by routine questioning in general practice. Modern therapies can restore a sexual relationship in the majority of patients with ED and can lead to a substantial improvement in quality of life. The majority of patients assessed to be at low or intermediate cardiac risk, as defined later in this paper, can be effectively managed in primary care. Primary care treatment for ED in patients defined as high risk can be initiated following a specialist opinion and/or confirmation that the patient's cardiovascular condition is stabilised. There is no evidence that currently licensed treatments for ED add to the overall cardiovascular risk in patients with or without diagnosed cardiovascular disease. If one form of therapy is not effective, follow-up will identify the need for alternative approaches. The pro-active management of ED in the cardiovascular patient provides an ideal and effective opportunity to address other cardiovascular risk factors and improve treatment outcomes.