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Cigarette smoking, hypertension and erectile dysfunction.

Smoking is associated with an increased risk of developing erectile dysfunction (ED). For example, in the Massachusetts Male Aging Study (MMAS), cigarette smoking amplified the risk of ED associated with other risk factors (e.g. hypertension, diabetes and dyslipidaemia) or with ageing. At the molecular level, several changes associated with smoking have been documented in man and experimental models. These changes could contribute to the pathogenesis of ED. Furthermore, studies performed in dogs demonstrated a smoking-related reduction in arterial flow and venous restriction. Similarly, impaired penile flow has been documented in men who smoke. Cigarette smoking also interferes with the effectiveness of intracavernous papaverine and PGEI. Quitting is the 'first-line' therapy of ED and one of the most important measures for the prevention of atherosclerosis.

Arteries↗

[Radiologic diagnosis of erectile dysfunction].

Possibilities of radiological cooperation in diagnostics and therapy of erectile dysfunction are demonstrated. Besides SKAT-testing and pharmaco-duplex-sonography, pharmaco-cavernosometry and cavernosography procure the decisive confirmation of venous leakage. The veins which are not compressable during erection can eventually be obliterated under radiological control with the help of mini-coils. Pelvic and penile arteriography are mandatory for the localization of arterial obliterations which can be treated either surgically or by angioplasty. The value of interventional radiological measures in the arterial region can be clearly substantiated in common iliac and internal iliac stenoses. However, the results obtained in the venous region by occluding interventional measures have yet to be evidenced by systematic examinations, as the surgical treatment has not shown much success up to now.

Angiography↗

Association between International Index of Erectile Function and axial penile rigidity in patients with erectile dysfunction.

We investigated the association between the International Index of Erectile Function (IIEF) and axial penile rigidity parameters in patients with erectile dysfunction (ED). A total of 516 male patients (491 patients with ED and 25 patients without ED) were assessed using IIEF. Patients were assessed for axial penile rigidity (APR) using a digital inflection rigidometer. Mean age+/-s.d. was 52.4+/-9.9 y. ED was mild in 11.4% of the patients, moderate in 40.1%, and severe in 48.5%. Regarding APR, the following was found: (1) no significant difference between patients who had a mild degree of ED and patients who had no ED (P>0.05); (2) a significant difference between patients with different degrees of ED (P<0.05 for each); (3) a significant association between overall presence of ED and low APR (P<0.05). IIEF score is associated with APR and can differentiate between patients with and without ED.

Adult↗

[Impase in the treatment of erectile dysfunction].

The authors review epidemiology, classification, etiology and pathogenesis of erectile dysfunction (ED), its diagnosis and treatment with a focus on mechanisms of action and efficacy of the drug impase. Impase is the drug of superlow doses of affinitively purified potentiated antibodies to human endothelial NO-synthase. The drug regulates NO synthesis in the cavernous bodies, enhances an NO relaxing action on their smooth muscles and blood flow in the penis under sexual stimulation. The drug demonstrated its high efficacy and safety in many clinical trials. Impase trial performed in the Research Institute of Urology in 2004 has found that impase is more effective in long-term administration, most of the examinees exhibited a clinical response only after one month of regular intake. The drug can be used both as the first-line monotherapy of ED and combined treatment of this disease. Clinical recommendations for practitioners on administration of impase are provided.

Adult↗

Pilot study of the transdermal application of testosterone gel to the penile skin for the treatment of hypogonadotropic men with erectile dysfunction.

Androgens influence important central and peripheral mechanisms of the erectile system. The relevance of a moderate decrease of serum testosterone level for erectile dysfunction (ED) has not been clarified so far. The aim of our study was to offer an easy transcutaneous method of androgen application. A previous study on the pharmacokinetic profile of the testosterone gel applied, showed marked elevation of the serum levels of testosterone. In our study, 46 hypogonadal patients with ED and total lack of vaginal penetration applied testosterone gel (4 mg/day; supplied by Azupharma, Germany) to the penile skin twice a day over 6-8 weeks, after a run-in period with placebo gel of 2 weeks. All patients showed decreased testosterone serum levels (<3 ng/ml) in at least two morning samples over a period of 3 weeks before treatment. Psychogenic etiology was excluded by a sexual psychologist. Patient age was 37-69 years (mean 53.5). Three patients (6.5%) responded to placebo in the run-in phase and were withdrawn from further treatment. Fifteen patients (32.6%) showed improved erection, allowing penetration and sexual intercourse. Twenty-eight patients (60.9%) did not respond to therapy. Local genital skin irritation was not observed. Elevation of peripheral testosterone was not correlated to a positive therapy response. A success-rate of 32.6% in this group of patients after exclusion of psychogenic patients and placebo-responders seems to justify further investigations. A medication period of 6-8 weeks is most probably too short to induce imaginable regenerative effects of testosterone on the erectile system. We therefore suggest that future double-blind and placebo-controlled studies should be designed for a minimum of 3 months. Testosterone gel may be a cost effective form of androgen administration.

Administration, Cutaneous↗

[Erectile dysfunction: a missed opportunity?].

The increasing of andrological valuation for erectile dysfunction (ED), happened in the last ten years, and induced chemical industries and sanitary system to supply correct answers from cultural, diagnostic and therapeutic views. All these events allowed the people to approach easily to uro-andrological valuations. This situation is perhaps a unique way to involve a great number of men in a wide uro-andrological screeening, that is useful, with a total patient and couple involvement, not only for a ED causes research, but also for incidental pathology screening (neoplastic or dismethabolic). Even if more expensive than a simplified diagnostic ED protocol (95% of the patients accept it, if there is a good counseling), this way of diagnostic valuation permit to hit the targets and to add permanently andrology to scientific specialty, as the science that studies the sexuality behaviour of the man and all its pathology.

Adult↗

Sildenafil citrate (Viagra) and erectile dysfunction following external beam radiotherapy for prostate cancer: a randomized, double-blind, placebo-controlled, cross-over study.

PURPOSE: To determine the efficacy of sildenafil citrate (Viagra) in patients with erectile dysfunction after three-dimensional conformal external beam radiotherapy (3D-CRT) for prostate cancer. METHODS AND MATERIALS: 406 patients with complaints of erectile dysfunction and who completed radiation at least 6 months before the study were approached by mail. 3D-CRT had been delivered (mean dose 68 Gy). Sixty patients were included and entered a double-blind, placebo-controlled, cross-over study lasting 12 weeks. They received during 2 weeks 50 mg of sildenafil or placebo; at Week 2 the dose was increased to 100 mg in case of unsatisfactory erectile response. At Week 6, patients crossed over to the alternative treatment. Data were collected using the International Index of Erectile Function (IIEF) questionnaire, and side effects were recorded. RESULTS: Mean age was 68 years. All patients completed the study. For most questions of the IIEF questionnaire there was a significant increase in mean scores from baseline with sildenafil, but not with placebo. Ninety percent of the patients needed a dose adjustment to 100 mg sildenafil. Side effects were mild or moderate. CONCLUSION: Sildenafil is well tolerated and effective in improving erectile function of patients with ED after 3D-CRT for prostate cancer.

Aged↗

Erectile dysfunction and cardiac disease: recommendations of the Second Princeton Conference.

Erectile dysfunction (ED) has been linked increasingly to cardiovascular risk factors and comorbidities. Considering the potential risk associated with sexual activity, guidelines were developed (Princeton I) for assessment and management of patients with varying degrees of cardiac risk. These guidelines were recently updated (Princeton II) based on new data concerning the link between ED and cardiovascular disease and the availability of additional phosphodiesterase type 5 inhibitors (vardenafil, tadalafil). Despite the need for careful risk assessment in all cases, sexual activity remains safe for the large majority of patients. However, all patients presenting with complaints of ED should be carefully assessed for the presence of cardiovascular risk factors (eg, obesity, hypertension, hyperlipidemia). Risk-factor modification, including lifestyle interventions (eg, exercise, weight loss) is strongly encouraged. Guidelines are presented for the management of acute coronary syndromes in patients taking phosphodiesterase type 5 inhibitors, including alternatives to the use of nitrates for these patients. Other drug interactions and the cardiovascular safety of testosterone replacement therapy are considered.

Cardiovascular Diseases↗

Intracavernous injection as an option for aging men with erectile dysfunction.

Sexuality remains a vital aspect of life in spite of aging. Advances in impotence research and increased knowledge of the pathophysiology of erection have completely changed the treatment of erectile dysfunction. Before oral therapy, intracavernous injection was considered as the first-line therapy for impotent patients. However, the new simple oral treatment raises the question as to whether intracavernous injection therapy is still a useful tool for treatment of aging men with erectile dysfunction. The efficacy and safety of oral therapy and intracavernous injection are reviewed.

Administration, Oral↗

A double blind, placebo controlled study of intracavernosal vasoactive intestinal polypeptide and phenotolamine mesylate in a novel auto-injector for the treatment of non-psychogenic erectile dysfunction.

Three hundred and four patients with non-psychogenic erectile dysfunction (ED) completed a dose assessment phase with intracavernosal injection utilizing 25 micrograms vasoactive intestinal polypeptide (VIP) combined with phentolamine mesylate 1.0 mg (VIP/P-1) or 2.0 mg (VIP/P-2) in an auto-injector for a response rate of 83.9%. In a sub-group of 183 patients who withdrew from one or more previous ED therapies, 82% responded with an erection suitable for intercourse. One hundred and ninety-five patients were subsequently treated in a placebo controlled phase. 75.1% responded to VIP/P-1, 12% to placebo (P < 0.001); 66.5% responded to VIP/P-2, 10.3% to placebo (P < 0.001), with the median duration of erection of 54 min. The principal adverse event was transient facial flushing in 2770 injections (33.9%). There was no pain post injection and two episodes of priapism (0.05%). Only nine patients withdrew because of adverse events. Over 85% and 95% of patients were satisfied with the drug and auto-injector, respectively. Over 81% of patients and 76% of partners reported an improved quality of life.

Adult↗

Computational models for detection of erectile dysfunction.

PURPOSE: Vascular comorbidities are well known to correlate with erectile dysfunction (ED) but a correlation with hypogonadism and depression is less clear. Using several linear and nonlinear mathematical models we investigated the correlation of age, hypogonadism and depression with ED using the Sexual Health Inventory for Men (SHIM) as a surrogate marker for ED. MATERIALS AND METHODS: A data set of 140 exemplars containing the input features age, total testosterone in ng/dl, Center for Epidemiologic Studies Depression scale score and output SHIM score (thresholded to 10 for moderate ED) was randomized into a modeling (training) set of 105 and a cross-validation (test) set of 35 with similar outcome frequencies preserved in each set. Using neUROn++, a set of C++ programs that we developed using the Cygwin (Red Hat, Raleigh, North Carolina) GNU C++ port for Windows (Microsoft, Redmond, Washington) distributed across Pentium (Intel, Santa Clara, California) platforms we modeled the data set using the linear methods, linear and quadratic discriminant function analysis, and logistic regression, and the nonlinear method of neural computation with several investigated architectures. RESULTS: A 4 hidden node network was found to have the highest accuracy compared to linear and quadratic discriminant function analyses, and logistic regression. ROC areas for the test set were 0.702, 0.645, 0.676 and 0.618, respectively. Analysis of the neural network demonstrated that moderate ED correlated with patient age and depression score. Forward and reverse regression of the neural network based on Wilk's generalized likelihood ratio test revealed that age was most significant (p <0.001), followed by Center for Epidemiologic Studies Depression Scale score (p <0.03), followed by testosterone (p >0.6). CONCLUSIONS: We investigated linear and nonlinear computational models of moderate ED. To our knowledge this is the first demonstration that SHIM correlates with age and a depression metric. Furthermore, moderate ED based on SHIM with a correlation with age may now provide a rationale and basis for future investigation into the understanding of age related erectile pathophysiology.

Adult↗

[Erectile dysfunction among Norwegian men over 40 years of age].

BACKGROUND: Erectile dysfunction (ED) is prevalent and often associated with chronic diseases and previous operations on the prostate. Our aims were to investigate the prevalence of ED among males seeking general practitioners and to register known risk factors. MATERIAL AND METHODS: During a short period in late 1998, 49 Norwegian general practitioners in the county of Østfold asked all their male patients over 40 years of age to anonymously fill in a questionnaire. RESULTS: 1,182 men completed the study. 20% stated that they had moderate ED, while 13% had complete ED. The prevalence of ED increased with age. Complete ED was found in 2% of those between 40 and 50, 5% between 50 and 60, 16% between 60 and 70, and in 37% of those above 70 years of age. The corresponding values for moderate ED was 6, 16, 32 and 28%. Moderate/complete ED was increased in the subgroups with hypertension, depression, diabetes, > one concomitant disease, and post prostate surgery. Physically "very active" individuals had less ED than the "non-active". No significant association was found with alcohol or tobacco. Most patients with ED wanted to discuss the problem with their general practitioners, but only 6% received treatment.

Adult↗

Transurethral alprostadil for the treatment of erectile dysfunction: results of a multicentre trial.

INTRODUCTION: The incidence of erectile dysfunction (ED) has been shown to increase significantly in Singaporean male population. Thus, this prospective study (no controls) assessed the clinical efficacy and safety of a medicated urethral system for erection (MUSE) in Singaporean male patients with a known history of ED. SUBJECTS AND METHOD: Eighty-six men with a mean age of 55.7 years with differential causes of ED were administered with MUSE in the clinic with a titration adjustment of 4 possible dose regimes (125, 250, 500 and 1000 mcg) till efficacy is achieved. Subsequently, patients were subjected to home treatment for a duration of 3 months. RESULTS: Sixty per cent of inclinic patients exhibited good responses and were given MUSE for home treatment. The efficacy rate for home treatment was 86%. Overall, the patients (n = 86) had a 51.2% success rate in achieving satisfactory sexual intercourse. Diabetic and psychogenic patients were noted to respond well to MUSE. No severe adverse events were found in this study. CONCLUSION: MUSE showed to be a safe, less invasive, well-tolerated and efficient alternative treatment for ED in Singaporean men.

Adult↗

Screening for erectile dysfunction as part of periodic examination programs--concept and implementation.

Erectile dysfunction (ED) can be an early and first sign of an underlying systemic disease. A screening program is offered by the Israeli Defense Force for career servicemen at the staff periodic examination center (SPEC), the aim of which was early detection of morbidity. We introduced the Sexual Human Inventory for Males (SHIM) questionnaire, in order to detect examinees with ED, and offer them suitable treatment options. The purpose of this study is to introduce the concept of an ED questionnaire as part of a screening program, and to describe the first months of its implementation. A computerized questionnaire is used to collect the medical history. The SHIM questionnaire was incorporated into the medical questionnaire. Relevant data including compliance to reply, SHIM scores, age and accompanying diseases of patients were collected from the computerized database of SPEC. A total of 2182 patients reported to SPEC from 1/5/01 to 1/11/01, 1980 of whom were males. Of the males, 881 (44.5%) chose to fill the SHIM questionnaire (mean age 34.5 +/- 6.7 y), and 244 of them (27.7%) had a score of 21 or less (20.7% had 17-21, 5.7% 11-16, 1.4% 0-10). The prevalence of ED and its severity increases with age. An inverted linear correlation was found between age and SHIM score (r = -0.22, P<0.0001). Prevalence of hypertension and diabetes mellitus is higher in patients with SHIM score < or =16 compared to those with a score > or =22. Only 15% of men with ED refer themselves for medical help. The concept of adding an ED questionnaire to a screening program may encourage more men to seek treatment, not only for their ED, but also for the underlying disease. The platform of a periodic examination offers maximum privacy to the examinees, resulting in better cooperation.

Adolescent↗

Improvement in erectile dysfunction after neurotrophic factor gene therapy in diabetic rats.

PURPOSE: Erectile dysfunction (ED) is a common but difficult to treat complication of diabetes mellitus (DM). We have previously reported herpes simplex virus (HSV) vector mediated delivery of nerve growth factor into the bladder to treat diabetic cystopathy and neurotrophin-3 (NT3) gene transfer for pyridoxine treatment. Nerve growth factor and NT3 are neurotrophic factors that may protect nerves from mechanical and metabolic damage. We investigated the effects of HSV mediated delivery of NT3 for the treatment of diabetic ED. MATERIALS AND METHODS: Male Sprague-Dawley rats weighing 300 to 400 gm were injected with 65 mg/kg streptozotocin to induce DM. After 4 weeks 20 microl containing 5 x 10 pfu replication defective HSV vector expressing lacZ (6 rats) or NT3 (6) were injected directly into the cavernous nerve sheath with a 30 gauge needle. Four weeks later the animals underwent measurement of intracavernous pressure under electrical stimulation (20 Hz, 0.5 millisecond and 10 V) of the cavernous nerve. Staining for lacZ and neuronal nitric oxide synthase in the major pelvic ganglia was also performed. RESULTS: beta-Galactosidase staining revealed lacZ positive neurons in the major pelvic ganglia. Maximal intracavernous pressure induced by electrical stimulation showed statistically significant mean values +/- SEM of 15.1 +/- 2.1 and 43.8 +/- 11.1 cm H2O in the lacZ and NT3 vector injected groups, respectively (p = 0.03). The mean number of neuronal nitric oxide synthase positive neurons per section in the NT3 group was significantly higher than that in the lacZ control group at 3.33 +/- 0.23 and 0.64 +/- 0.14 neurons per high power field, respectively (p < 0.001). CONCLUSIONS: We report that gene therapy for the treatment of diabetic ED is feasible with HSV vectors. NT3 gene therapy may be applicable for the treatment of ED induced by DM.

Animals↗

Clinical monograph for drug formulary review: erectile dysfunction agents.

BACKGROUND: Significant advances in the pharmacologic treatment of erectile dysfunction (ERD) have occurred in recent years, most notably the introduction of sildenafil, the first oral selective phosphodiesterase type 5 (PDE5) inhibitor, in 1998. Sildenafil quickly gained acceptance by the medical community and the public because of its broad efficacy for different types of ERD and its ease of use. Two PDE5 inhibitors, vardenafil and tadalafil, have since joined sildenafil to compete in the ERD market. A review was conducted by the Drug Information Service of a pharmacy benefits manager (PBM) to determine the relative merits and place in therapy of commonly used ERD drugs as part of drug formulary management process and decision making by the Pharmacy & Therapeutics (P&T) committee. OBJECTIVE: To provide readers with a comprehensive clinical monograph on ERD drugs written from a managed care perspective. METHODS: The PBM clinical monograph is designed to provide health plans with an evidence-based review of drugs, therapeutic classes, and disease states with a managed care focus. For each therapeutic class or disease review, an extensive and thorough literature search of MEDLINE is conducted for efficacy, safety, effectiveness, and humanistic and economic data. Drug/disease-state databases (UptoDate online, MICROMEDEX), U.S. Food and Drug Administration clinical reviews, key Internet sites, medical/pharmacy-related news sites, clinical guidelines, and AMCP dossiers are also reviewed. Formulary drug monographs prepared by the Drug Information Service of the PBM include a critical analysis and summary of disease-oriented and patient-oriented clinical outcomes, effectiveness, and humanistic data. Additional data considered and included in the formulary review process are clinical attributes, patent expirations/generic competition, off-label or pending indications, and pharmacoeconomic data. RESULTS: Despite the lack of head-to-head comparative studies, all 3 PDE5 inhibitors appear to have equivalent efficacy in the treatment of general ERD and ERD associated with diabetes and postprostatectomy. Sildenafil has additional efficacy data in the management of ERD associated with spinal cord injury and antidepressant medications. Tadalafil has the longest duration of action (up to 36 hours); this feature can be both beneficial (greater sexual spontaneity) or possibly detrimental (greater exposure to drug, delayed adverse events). All 3 PDE5 inhibitors appear to be generally well tolerated and have similar contraindications and warnings. However, vardenafil is the only PDE5 inhibitor with a cardiac conduction precaution. Alprostadil products are recommended in current ERD guidelines as second-line therapy for those who have not responded or cannot take the oral PDE5 inhibitors. Overall, higher clinical efficacy rates are achieved with intracavernous than with transurethral administration. CONCLUSION: A large amount of clinical efficacy and safety data has been published since the market launch of sildenafil in 1998. Sildenafil has the greatest body of efficacy and safety evidence. No comparative studies have been conducted with any of the PDE5 inhibitors. Differences in study populations, primary end points, and measurement tools make comparisons difficult. However, all PDE5 inhibitors appear to be roughly equivalent in efficacy, with minor differences in adverse event profiles. Until more comparative data are available, economic considerations will be a significant factor in choosing ERD products for formulary inclusion.

Carbolines↗

Prospective comparison of topical minoxidil to vacuum constriction device and intracorporeal papaverine injection in treatment of erectile dysfunction due to spinal cord injury.

OBJECTIVE: To compare the effectiveness of topically applied 2% minoxidil to that of intracorporeal injection therapy and vacuum constriction devices for the treatment of erectile dysfunction in the spinal cord injured (SCI) male. METHODS: Eighteen SCI men, aged nineteen to sixty-five years (median age, 29), and level of injury C7 to L3 (15 thoracic level) were prospectively evaluated. All patients were able to achieve only a poorly sustained reflex erection that was inadequate for satisfactory intercourse. No patient had suffered erectile dysfunction prior to his SCI. In each patient, 1 mL of a 2% minoxidil solution was applied as an aerosol spray to the glans penis. The erectile response was compared to that obtained with a vacuum constriction device (VCD) and intracorporeal papaverine injection. In each case, the subjective assessment by both the patient and the physician, as well as objective results of penile base rigidity as measured by the RigiScan DT Monitor Device, were recorded. RESULTS: Papaverine increased rigidity at the base of the penis by a median 77 percent (range, 30-100%). The VCD increased rigidity by a median 57 percent (range, 30-80%). Minoxidil induced no change in rigidity (range, 0-15%). No complications were observed for any method of inducing tumescence. CONCLUSIONS: Papaverine and VCD proved to be effective means of establishing penile erection in male SCI patients. Both subjective and objective erectile responses to minoxidil were poor. Nevertheless, the principle of topical therapy is an attractive alternative to existing modalities. Further investigation is warranted.

Administration, Topical↗

Community-based study of erectile dysfunction and sildenafil use: the Rancho Bernardo study.

OBJECTIVES: To evaluate erectile dysfunction (ED) using a validated self-administered 5-item questionnaire (5-item version of the International Index of Erectile Function [IIEF-5]) and the use of sildenafil in community-dwelling older men. METHODS: In October 1998, the IIEF-5 was mailed to all surviving members of an established community-based cohort of older men. The degree of ED was stratified by the erectile function domain score as complete (4 or less), severe (5 to 10), moderate (11 to 14), mild (15 to 18), or none (19 to 20). Men were also asked about sildenafil use and its effectiveness. RESULTS: A total of 976 men (64%) responded to the questionnaire. The internal consistency of the questionnaire construct was confirmed, with a Cronbach's alpha coefficient of 0.96 for all 5 questions. Eighty-nine percent of men younger than 50 years were sexually active compared with 37% of men older than age 80. Twenty-six percent of sexually active men reported complete (3%), severe (10.5%), or moderate (12.6%) ED. The prevalence of moderate or complete ED increased with age and was reported by 58% of men aged 75 to 79 years. Eleven percent of sexually active men had used sildenafil one or more times, with 63% reporting good or "terrific" effects and 11% reporting no benefit. The response to sildenafil deteriorated with age and increasing degree of ED. CONCLUSIONS: The results of this community-based study confirm the strong correlation between advancing age and the prevalence and degree of ED, with 33% of men aged 75 and older reporting at least moderate ED. Nevertheless, more than 33% of men older than 75 years remained sexually active. Of the 660 sexually active men, 81% reported satisfaction with sexual intercourse; only 11% had tried sildenafil.

Adult↗