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Intracavernous alprostadil. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in erectile dysfunction.

Intracavernous alprostadil (synthetic prostaglandin E1) is a vasodilating agent which acts by relaxing the smooth muscles of the corpus cavernosum and by increasing the diameter of cavernous arteries; this leads to erection. Following intracavernous administration, alprostadil is either locally metabolised or rapidly cleared from the penis into the systemic circulation where it is extensively metabolised by the lungs. Studies suggest that long term use of intracavernous alprostadil may increase penile blood flow, although the clinical relevance of this is not currently known. In men with erectile dysfunction (ED), short term trials have shown that intracavernous alprostadil is superior or equal, in inducing erections, to other intracavernous agents such as papaverine, the combination of papaverine plus phentolamine, linsidomine and topical nitroglycerin (glyceryl trinitrate). Intracavernous alprostadil induced erections in around 70% of patients with ED of various origins in short term studies. 49 to 84% of patients accept the offer of joining self-injection programmes and 13 to 60% of these patients withdraw from such programmes for a variety of reasons. At therapeutic doses, intracavernous alprostadil is well tolerated. The most common adverse event of transient penile pain occurred in around one-third of patients and in 11% of injections, causing 3 to 5% of patients to withdraw from self-injection programmes. Potentially serious adverse events such as priapism and fibrosis occurred in 4 and 8% of patients. Overall, available data suggest that the efficacy of intracavernous alprostadil is superior or equal to that of other erectogenic agents which are in use. Furthermore, the drug is well tolerated especially with regard to serious adverse events. Thus, although further research is necessary to confirm its use in combination with other agents, alprostadil appears likely to become the intracavernous agent of choice for the management of erectile dysfunction.

Alprostadil↗

[Vardenafil for the treatment of men with erectile dysfunction after radical retropubic prostatectomy].

More than one-third of men may experience erectile dysfunction (ED) after nerve-sparing radical retropubic prostatectomy. A recent study has shown that vardenafil, a phosphodiesterase 5 inhibitor, could significantly improve the key indices of erectile function in men after unilateral or bilateral nerve-sparing radical retropubic prostatectomy. Few adverse events were observed in the study.

Double-Blind Method↗

Psychogenic erectile dysfunction: comparative study of three therapeutic approaches.

We administered the International Index of Erectile Function (IIEF; Rosen et al., 1997) questionnaire to 30 patients with psychogenic erectile dysfunction (ED) at baseline, immediately after treatment, and 3 months after treatment. We randomized patients into three groups: group I, who had weekly sessions of time-limited theme-based group psychotherapy for 6 months and 50 mg sildenafil citrate orally on demand; group II, who had an intake of 50 mg sildenafil citrate orally on demand for 6 months only; and group III, who had weekly sessions of time-limited theme-based group psychotherapy for 6 months. We analyzed data (15-item IIEF) for each group at three times during the study and compared by the data using analysis of variance (ANOVA), followed by the Bonferroni multiple comparison test. We used Cochran's Q-test for analysis between baseline and posttreatment stages of patients with remission of symptoms (EF equal to or higher than 26 points). Group III had a mean score higher than group II, with the difference being statistically significant (immediately after treatment, p = 0.033; at 3 months after treatment, p = 0.049; p < 0.05). All three therapeutic alternatives resulted in an improvement of erectile function domain score. However, significant differences from baseline were observed in groups I (p = 0.0009) and III (p = 0.0002) but not in group II (p = 0.135). The psychotherapy groups, I and III, had significantly higher scores compared with group II, in which patients were exclusively treated with sildenafil citrate. These findings suggest that time-limited theme-based group psychotherapy is an effective treatment for psychogenic ED.

Adult↗

Central nervous system agents in the treatment of erectile dysfunction.

In the last two decades, a better understanding of the mechanisms governing erectile function and the pathophysiologies underlying erectile dysfunction (ED) have led re-searchers to investigate novel treatment concepts. Selective type-5 phosphodiesterase inhibitors are recommended as first-line therapy because of their high efficacy, but 30% to 40% of patients who have ED do not respond adequately to these agents and require alternative methods. The central nervous system plays a fundamental role in sexual behavior. Animal models have advanced our understanding of the neuroanatomic and neuropharmacologic basis of centrally induced penile erections. Clinical research with apomorphine has demonstrated efficacy in men who have a range of ED. Recent interest has focused on other centrally acting agents for ED treatment, including the melanocortin receptor agonists.

Apomorphine↗

[Dissection of cavernous nerves in rat and model of neurological erectile dysfunction].

OBJECTIVES: To identify rat cavernous nerve and establish a rat model of erectile dysfunction caused by injury of cavernous nerve. METHODS: Ten rats were undergone dissections. 30 experimental rats were randomized into 2 groups, cavernous nerve were identified by electrical stimulation. One month after surgery, rat models were evaluated by electrical stimulation. RESULTS: The anatomic structure of cavernous nerve in rats are highly similar to human beings, the erection can be evoked by stimulating cavernous nerves, and after cavernous nerve injury it can not be evoked (P < 0.05). CONCLUSION: Because of the highly similarity of cavernous nerve between rats and human beings, so as the suitable price, rat should be used as the ideal ED experimental animal. The model of ED caused by cavernous nerve injury is reliable.

Animals↗

Development and validation of a risk score for somatic erectile dysfunction: combined results from three cross-sectional surveys.

OBJECTIVES: Some men with erectile dysfunction (ED) have difficulties discussing their condition with their physicians. Existing screening and diagnostic tools for ED often require the administration of personal questions regarding the condition. We present a simple risk score to estimate the individual likelihood of somatic ED, based on age and existing health conditions. METHODS: Data from the Cologne Male Survey (n = 4396) were used to develop a multivariable logistic regression model for the individual ED likelihood. The regression equation was both internally and externally validated using data from a national study (Berlin study) and a multinational cross-sectional study (MALES study). RESULTS: A final regression equation including age, pelvic surgery, diabetes mellitus, arterial circulatory disorder, heart disease, smoking, and hypertension reached an area under the receiver operating characteristic curve of 0.84 (0.5 means random and 1.0 perfect discrimination). Internal validation did not indicate any relevant overfit and the external validation results (national data: AUC = 0.75; multinational data: AUC = 0.67) are similar to those of other popular risk scores. CONCLUSIONS: The validated ED risk score developed from the regression equation can be used as a screening tool to identify patients who are at a high risk of somatic ED. This tool can facilitate entering into discussions between physicians and patients regarding erectile function.

Adult↗

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.

Age Factors↗

[Consensus on the clinical approach to erectile dysfunction in patients with cardiovascular disease].

The most common physical risk factors for erectile dysfunction (ED) are atherosclerosis, heart disease, hypertension and diabetes. Since accessibility to easy and efficacy drug for ED therapy, GPs are increasingly at the front line in the management of ED and are often best-placed to discuss this problem with cardiovascular male patients. This consensus aims to provide practical advice on the management of ED in patients with diagnosed cardiovascular disease and also addresses the assessment of the cardiovascular risk in restoring sexual activity in these patients. A risk assessment algorithm has been drawn up to aid clinicians in deciding the level of cardiovascular risk that would be associated with a return of sexual activity as well as criteria for referral to specialists for further cardiac evaluation. Treatment options are briefly reviewed and follow-up process identified.

Adult↗

[Discussion of correlative factors and risk in patients with diabetic erectile dysfunction].

OBJECTIVES: To probe into the pathogenesis, prevention and treatment way of diabetic erectile dysfunction (DED). METHODS: The age, course, blood pressure, history of drink and smoke, relationship with DED were investigated in 126 DED patients of 320 diabetes mellitus. RESULTS: The prevalence of DED in male diabetic patients was 39.4% (126/320). It was found by the analysis of Logistic regression that the values of OR rise to 1.8467, 1.2614, 1.4508, 1.3212, 1.2065, 5.3464 (P < 0.01), along with adding of 5 years in course, 10 years in ages, 2% in HbA1C, 4 kPa in systolic blood pressure, positive history of smoking and drinking respectively. CONCLUSIONS: Drinking is the most dangerous factor among all risk factors for occurrence of DED. It is very important to control blood pressure well, and to give up tobacco and drink in preventing occurrence of DED.

Adult↗

[Electrophysiologic diagnosis in erectile dysfunction].

So far, electrophysiological examinations have rarely been used in the diagnosis of erectile dysfunction (ED) mainly because the methods available only allow somatic neuron pathways to be examined whose relevance for the mainly autonomically controlled crection is evaluated differently. At present, impaired penile nerve supply as the possible cause of ED can only be evaluated through neurophysiological screening of the somatic and autonomic pathways of the pelvic floor, and not just by one simple method. Diagnosing ED should include testing of motoric efferences through electroneurography of the pudendal nerve and electromyography of the external anal sphincter and the urethral sphincter. Sensitive afference is tested with somatosensory evoked potentials of the pudendal nerve. New methods that are available for the examination of autonomic pathways are the penile sympathetic skin response and the EMG of the corpus cavernosum. Together with the other electrophysiological examinations, they allow neurogenic causes to be determined and differentiate not only between central and peripheric lesions, but also between acute and chronic changes. Prognosis can also be estimated. A crucial diagnostic deficit is the fact that it is still not possible to test the parasympathetic system directly.

Autonomic Nervous System↗

Prevalence of undiagnosed prostate cancer in men with erectile dysfunction.

OBJECTIVE: To explore the prevalence of prostate cancer in men presenting with erectile dysfunction (ED). PATIENTS AND METHODS: In a prospective study, 127 men with ED of at least 6 months duration underwent screening for prostate cancer using prostate specific antigen (PSA) and a digital rectal examination (DRE). Men with a high PSA level (> 4 ng/mL) had sextant biopsies taken under sedoanalgesia. The serum testosterone level was measured in all the men. RESULTS: Twenty-six men were aged < 50 years and all had a normal PSA level; of 101 men aged > 50 years, 20 had an abnormal PSA. The detection rate for prostate cancer using PSA and DRE was 5%, which was not significantly higher than in the general population. All the detected cancers were clinically significant (> T2a, Gleason grade > 4). Two of the five men diagnosed with prostate cancer were Afro-Caribbean. Of the 127 men, 31% had a low serum testosterone level, but there was no association between testosterone and PSA levels. CONCLUSIONS: Prostate cancer is no more common in men with ED than in the normal male population. Therefore, routine screening for prostate cancer in men with ED is not indicated.

Adult↗

[Vascular surgery, implant surgery and vacuum erectile aids. Review-overview-prospects of 3 therapy options in erectile dysfunction].

Vascular surgery or penile prosthesis implantation are the main surgical options for erectile dysfunction. In this category, penile revascularization is the only causal therapy for selected patients: males younger than 50 years of age at time of surgery, maximum of two risk factors, exclusion of diabetes mellitus. Long-term success decreased to 53% to 55% in comparison to first encouraging reports of 80% success. Venous surgery resulted in an even more distinct decline of success the longer the elapse of time after surgery. Long-term success dropped under 40%, leaving only a few indications for penile venous ligation. In contrast, penile prosthesis implantation results in high satisfaction rates. Despite this, it is not generally recommended as first choice surgical management as it is linked to irreversible damage of the cavernosal bodies. Among numerous types of penile implants, preference is nowadays mostly given to the three-piece hydraulic models. However, such complications as defective or perforated cylinders in up to 35% after 5 years have arisen, depending on the type of implant. In a selected patient group, vacuum constriction devices with a mean patient acceptance of 75% (50% to 90%) seldom result in complications and are thus considered to be a well-established therapeutical option.

Arteriovenous Shunt, Surgical↗

Group treatment of secondary erectile dysfunction.

The effects of three group treatment formats on 20 men with secondary erectile dysfunction and their partners were contrasted. After a comprehensive medical and psychological screening, each couple was assigned to one of three treatment groups (Communication Technique Training, Sexual Technique Training, Combination Treatment) or to one of two control groups (Attention-Placebo, No-Treatment). Couples in the three treatment groups and the attention-placebo group participated in their respective formats in twice-weekly sessions for a total of 20 hours. The no-treatment control group received sex education and treatment after a 5-week waiting list period. All three treatment groups fostered substantial gains so that between-format differences were not statistically significant. Subject variables which predicted success/experience ratio gains included age of the male partner, perceived level of relationship adjustment, and the male partner's success/experience ratio prior to treatment. Eighty-one percent of the treated men reached the criterion of 80% or greater success/experience ratio (successful penetration and subsequent ejaculation) at the 6-month follow-up. Good nocturnal tumescence prior to treatment was correlated with a better treatment outcome than poor tumescence.

Adult↗

Erectile dysfunction is a marker for cardiovascular disease: results of the minority health institute expert advisory panel.

INTRODUCTION: Cardiovascular disease and its related comorbidities are associated with significant morbidity and mortality and affect a disproportionately large number of African Americans and Hispanics. The prevalence of cardiovascular disease is increasing worldwide, which underscores the urgency to improve methods of prevention and early detection. AIM: To develop a risk assessment and management algorithm for primary care patients with erectile dysfunction (ED) that facilitates diagnosis, early intervention, and prevention of cardiovascular disease. METHODS: The Minority Health Institute (MHI) convened an Expert Advisory Panel of cardiologists and urologists to design a new practice model algorithm that uses ED as a clinical tool for early identification of men with systemic vascular disease. A draft of the algorithm was presented at a national symposium and comments from symposium participants were considered in the development of the final algorithm. MAIN OUTCOME MEASURES AND RESULTS: Erectile dysfunction is common and has long been considered a secondary complication of cardiovascular disease, diabetes, hypertension, and dyslipidemia. However, a growing body of evidence challenges this view, suggesting instead that ED is an early manifestation of atherosclerosis and a precursor to systemic vascular disease. Endothelial dysfunction is the etiologic factor linking ED and cardiovascular disease. CONCLUSIONS: The recognition of ED as an early sign of systemic cardiovascular disease offers an opportunity for prevention, particularly in high-risk and underserved minority populations. The MHI algorithm stipulates that all men 25 years old and older regardless of sexual dysfunction complaints should be asked about ED. The presence of ED should prompt an aggressive assessment for cardiovascular risk and occult systemic vascular disease.

Algorithms↗

Prevalence of Peyronie's disease among patients with erectile dysfunction.

PURPOSE: To assess the prevalence of Peyronie's disease (PD) among patients with erectile dysfunction (ED). MATERIALS AND METHODS: A total of 1,440 male patients with ED were enrolled in this study. Patients were interviewed for ED using the International Index of Erectile Function (IIEF). All patients were also screened for socio-demographic data and risk factors for ED that included age, smoking, diabetes, hypertension, dyslipidemia, Ischemic Heart Disease (IHD), and psychological disorders. The diagnosis of PD was based on a palpable penile plaque or acquired penile curvature. Patients underwent routine laboratory investigation in addition to testosterone and prolactin assessment. RESULTS: Mean ages +/-SD were 54.1 +/- 6.9 (range 42-71) and 52.5 +/- 11.9 (range 20-84) years for patients with and without PD respectively. Of the patients, 11.8% had mild, 38.3% had moderate and 49.9% had severe ED. 7.9% of the patients had PD. Significant associations between PD and both the longer duration and the increased severity of ED were detected. There were also significant associations between PD and the following socio-demographic risk factors of ED: age, obesity, smoking, duration and number of cigarettes smoked per day. Concomitant diseases and medical comorbidities such as diabetes, dyslipidemia, psychological disorders and the presence of at least one risk factor were significantly associated with PD in patients with ED. CONCLUSIONS: Peyronie's disease was not rare among the study population. There were significant associations between ED risk factors and PD. Further studies are needed to investigate how much ED and PD influence each other.

Adult↗

[The microstructure studies of penile cavernous tissue of erectile dysfunction rat models with chronic renal failure].

OBJECTIVE: To investigate the mechanism of erectile dysfunction (ED) in rat models with chronic renal failure (CRF). METHODS: Chronic renal failure was induced by adult male Sprague-Dawley rats, which were subjected to an excisional 5/6 nephrectomy. The rats in NCRF group and CRF group were divided into three groups randomly. Injected with apomorphine(APO, 80 microg/kg), penile erections of three groups were observed and noted by the 2nd week, 4th week respectively and 6th week from the 14th day of 5/6 nephrectomy and experimental models of ED with CRF were selected; NOS activity was examined and the microstructures of penile were observed under optical microscope with computer configuration image analysis system in selected rat models. RESULTS: Compared with the controls, the areas of smooth muscle and NOS activity in the penile cavernous tissue of ED rats with CRF decreased significantly (P < 0.01 or P < 0.05) , and collagen fibers slightly increased, and these alterations had close correlations with the duration of CRF. The CONCLUSIONS: Penile erection is seriously affected in rats with CRF. The decreases of areas of blood sinus had no obvious changes. the number of smooth muscles and NOS activity might be the most important factors.

Animals↗

Erectile dysfunction following nerve-sparing radical retropubic prostatectomy and its treatment with sildenafil.

BACKGROUND: We retrospectively evaluated the erectile function after nerve-sparing radical retropubic prostatectomy (RRP) and the efficacy of sildenafil for erectile dysfunction (ED) following RRP according to the preoperative erectile function. METHODS: We evaluated 48 Japanese patients who underwent nerve-sparing RRP at the Sapporo Medical University School of Medicine, Sapporo, Japan, between January 1996 and December 2001. Erectile function following nerve-sparing RRP was assessed by a simple mailed questionnaire that was constructed for the study. RESULTS: Of the 48 patients, 36 had normal erectile function preoperatively, but for 12, function was not sufficient to penetrate. The overall estimated recovery rates of any degree of erection were 50.6% at 36 months and 94.3% at 60 months. However, that of erection sufficient to penetrate was only 17.7% at 36 months and was only seen in bilateral nerve-sparing patients. Sildenafil was effective in 9 of 13 ED patients (69.2%) in both nerve-sparing groups. When patients were divided according to preoperative erectile function, no difference was found in the efficacy rate between patients with normal function and those with ED. CONCLUSIONS: Even bilateral nerve-sparing RRP can not always guarantee a sufficient erection. However, sildenafil is effective for ED following nerve-sparing RRP regardless of the nerve-sparing procedure or preoperative erectile function. Thus, preoperative function alone, although depending on its severity, may not necessarily be a reason for exclusion from receiving nerve-sparing RRP if patients want to have the operation.

Aged↗

[Diagnosis and therapy of erectile dysfunction: a function of legal health insurance?].

From the medical point of view erectile dysfunction (ED) is accepted as a disease. However, there is a difference between the medical definition and the definition used by the official health insurance companies. This means that these health insurance companies have sometimes refused payment to the urologists for work done in the diagnosis and treatment of ED, especially in elderly men. Studies on the sexual behavior of elderly men show that 53-80% of men older than 75 years are still interested in sex and that 26% of this group have intercourse several times a month. Therefore, no one can say that sexual interest and activity decrease in elderly men to the point of complete inactivity. For this reason, the basic principle of maintaining the health of the individual is just as applicable in this case as it is in elderly people who are hard-of-hearing or who have weak eyesight. Thus, the diagnosis and therapy of ED must, strictly speaking, be considered a medical service that is recognized and paid for by the official health insurance companies. The substances used have not been licensed for this indication by the German BGA (German equivalent of the FDA), but this does not influence the possibility of prescribing them. Generally speaking papaverine, papaverine/phentolamine and prostaglandin E1 can be prescribed. In our opinion, prostaglandin E1 is to be preferred.

Aged↗