Epidémiologie de la dysfonction érectile (1ère partie). Prévalence et incidence mondiales

Many studies have provided epidemiological data on erectile dysfunction over the last ten years. Surveys performed in several countries in the world include a single question and a detailed questionnaire, usually the IIEF (International index of erectile function). However, the results are difficult to compare because of methodological differences. Prevalence estimates of moderate or severe erectile dysfunction range between 11 and 19% in France, 3 and 11% in Europe (Germany, Italy, Netherlands, Spain and Sweden) and in USA, according to the MMAS (Massachusetts male aging study), this prevalence is 35%. Prevalence estimates increase with age and the threshold is situated between 50 and 60 years. Incidence data are lacking, but data have recently become available from the MMAS. According to this study, the annual incidence rate for erectile dysfunction is 25.9 cases per 1,000 men. This rate increases with each decade of age.     

Resultats preliminaires d’injections intracaverneuses d’un donneur d’oxyde d’azote (NO), la linsidomine,dans le traitement de l’impuissance

Recent experimental studies showed an important role of endothelium derived relaxing factor (EDRF) for cavernous smooth muscle relaxation. Since nitric oxide (NO) seems to account for the biological actions of EDRF, a study was done to examine a possible role of the NO-donor SIN-1 in the treatment of erectile dysfunction. To determine the therapeutic range, 0.1, 0.2, 0.5 and 1 mg SIN-1 were injected intracavernously in 2 patients with erectile dysfunction each. Then, 40 patients were injected 1 mg SIN-1 including 4 patients that had prolonged erections to minimal doses of papaverine-phentolamine and 4 patients that did not respond with a full erection to other pharmacologic agents. Intracavernous injection of SIN-1 induced a dose dependent erectile response by increasing the arterial inflow and relaxing cavernous smooth muscle. To 1 mg SIN-1, 19 patients had a full, 14 an almost full and 7 a moderate erection. There were no systemic or local side effects. In the patients with prolonged erections to papaverine-phentolamine, the mean duration of a full erection to SIN-1 was 68 minutes. Compared to a papaverine (15 mg/ml)-phentolamine (0.5 mg/ml) mixture, the erectile response to SIN-1 was superior in 8, comparable in 29 and inferior in 3 patients. Our preliminary data suggest a possible role of SIN-1 for the treatment of erectile dysfunction. The absence of prolonged erections by its spontaneous intracavernous decomposition, a maximal smooth muscle relaxation by a receptor independant action and its low cost indicate its potential to become a standard drug for intracavernous pharmacotherapy.     

Cavernous nerve reconstruction to preserve erectile function following non-nerve-sparing radical retropubic prostatectomy: a prospective study

Erectile dysfunction following radical prostatectomy for treatment of clinically localized prostate cancer remains a problem that deters many men from seeking surgical treatment. Sparing the cavernous nerves has been popularized as a method of preserving potency, but men with locally advanced disease may be at increased risk for positive margins with this technique. In this study, sural nerve grafting of the cavernous nerve bundles, to preserve postoperative potency while potentially maximizing cancer control, was examined. Thirty men were enrolled in this prospective phase I study and underwent non-nerve-sparing radical prostatectomy performed by one of two protocol surgeons. Preoperative erectile function was assessed both objectively, using a RigiScan (Timm Medical Technologies, Inc., Eden Prairie, Minn.), and subjectively. The cavernous nerves were identified and resected during the operation with the use of an intraoperative mapping device (CaverMap; Alliant Medical Technologies, Norwood, Mass.). Bilateral autologous sural nerve grafting to the cavernous nerve stumps was performed by one of two protocol plastic surgeons. Postoperative erectile dysfunction therapy, using intracorporeal injection, a vacuum pump, and/or oral sildenafil therapy, was instituted 6 weeks after the operation. Spontaneous erectile activity was subjectively and objectively measured every 3 months after the operation. Follow-up periods ranged from 13 to 33 months (mean, 23 months). Overall, 18 of 30 patients (60 percent) demonstrated both objective and subjective evidence of spontaneous erectile activity. Of those 18 men, 13 (72 percent) were able to have intercourse (seven unassisted and six with the aid of sildenafil). No disease or biochemical recurrences have been noted in this group of patients with locally advanced disease. In conclusion, autologous sural nerve grafting after non-nerve-sparing radical prostatectomy is an effective means of preserving spontaneous erectile activity after the operation while maximizing cancer control potential.     

Advances in the Management of Post-Radical Prostatectomy Erectile Dysfunction: Treatment Strategies When PDE-5 Inhibitors Don't Work

Phosphodiesterase type-5 (PDE-5) inhibitors have revolutionized the treatment of post-radical prostatectomy erectile dysfunction. For those patients who undergo a non-nerve-sparing radical prostatectomy or whose condition fails to respond to PDE-5 inhibitors, alternative treatment with intracavernous injection therapy, transurethral alprostadil, vacuum erection devices, and recently described combination therapy is available. The goals of therapy are to provide the patient with a means of obtaining an erection so that the patient and his partner may resume sexual relations as soon as possible following radical prostatectomy. There is evidence that early institution of treatment may promote improvement in the return of spontaneous erections in patients who have undergone nerve preservation. In patients who undergo non-nerve-sparing procedures, therapy may improve penile rigidity. Intracavernous injection therapy, transurethral alprostadil, and vacuum devices are highly effective in the management of post-prostatectomy erectile dysfunction. High dropout rates, which are not related to adverse effects, have been described with all 3 modalities. Pre- and postoperative counseling may improve patient and partner satisfaction.     

Neuroregenerative strategies after radical prostatectomy

Patients with erectile dysfunction (ED) following radical prostatectomy (RP) continue to present to practicing urologists. Although nerve-sparing RP has decreased the rates of ED significantly, new therapies for cavernosal nerve protection and recovery are now being developed. This report discusses the many agents available in neuroregeneration and neuroprotection to aid in the recovery of erectile function. Multiple agents and strategies have been used for neuroprotection and neuroregeneration of the cavernosal nerve following RP and in nerve injury models. Many of these agents display promise for the treatment of impotence. Early treatment for patients recovering from RP is becoming the standard of care. Natural recovery of erections may take as long as 18 to 24 months post RP; however, treatment plans may reduce the time to erectile recovery.     

Nonpharmacologic treatment of erectile dysfunction

Nonpharmacologic treatment for erectile dysfunction (ED) includes sex therapy, the use of vacuum erection devices, penile prosthesis implantation, and penile vascular surgery. Sex therapy is indicated for psychogenic ED and is at times a useful adjunct for other treatments in men with mixed psychogenic and organic ED. Vacuum erection devices produce usable erections in over 90% of patients; however, patient and partner acceptability is an issue. Three-piece inflatable penile prostheses create flaccidity and an erection that comes close to that which occurs naturally. Penile vascular surgery has shown greatest efficacy in young men with vasculogenic ED resulting from pelvic or perineal trauma.     

Gene transfer of extracellular SOD to the penis reduces O2-* and improves erectile function in aged rats

Increased superoxide anion (O(2)(-).) may contribute to vascular dysfunction in aging. In aged cavernosal tissue, lucigenin-enhanced chemiluminescence demonstrated a threefold increase in superoxide formation, and the oxidative fluorescent probe hydroethidine indicated higher superoxide levels throughout the aged penis. This increase in superoxide was associated with impaired cavernosal nerve-mediated and agonist-induced erectile responses, increased nitrotyrosine staining, and lower cGMP levels, but no compensatory change in cavernosal extracellular (EC)-superoxide dismutase (EC-SOD) mRNA or protein. In vivo adenoviral (Ad) gene transfer of EC-SOD to the penis resulted in higher expression of EC-SOD mRNA, protein, SOD activity, cGMP levels, and lower nitrotyrosine staining. Transfection with AdCMVEC-SOD resulted in a significant increase in erectile response to cavernosal nerve stimulation, ACh, and zaprinast to a magnitude similar to young rats. These data provide evidence in support of the hypothesis that erectile dysfunction associated with aging is related in part to an increase in cavernosal O(2)(-). formation. Gene-transfer of EC-SOD reduces superoxide formation and restores age-associated erectile function and may represent a novel therapeutic target for the treatment of erectile dysfunction.     

Les traitements pharmacologiques de l'insuffisance érectile

About 10 to 20% of men are affected by erectile dysfunction in France. The prevalence of erectile dysfunction increases with age and has a multifactorial etiology in the great majority of cases. The recent availability of oral treatments has improved the medical approach to erectile dysfunction. After a clinical presentation of erectile dysfunction and its causes, this article deals with the general principle of medical therapy for erectile dysfunction. Oral therapy with sildenafil and other compounds and local therapy by intracavernous injections (papaverine, moxisylyte, prostaglandin E1) or intraurethral administration of PGE1 are reviewed.     

Dysfonction érectile et traitement antihypertenseur

Fifteen to 20% of hypertensive patients suffer from erectile dysfunction prior to initiation of antihypertensive therapy and the frequency of erectile dysfunction increases to 40–50% after initiation of antihypertensive therapy. Clinical studies conducted according to a rigorous methodology have shown that diuretics are the main cause of erectile dysfunction. Antihypertensive combination therapy is an aggravating factor. Phosphodiesterase-5 inhibitors can be used in hypertensive patients with erectile insufficiency in the absence of any contraindications.     

The molecular basis of erectile dysfunction: from bench to bedside

Erectile dysfunction is a common problem affecting many men across all age groups. Its etiology is multifactorial. Hormonal, vascular, neurogenic, lifestyle, and psychological entities have all been implicated as causative agents. The molecular basis underlying its etiology and progression is complex and still challenges researchers in the field. Nonetheless, newly discovered common pathways and targets of its pathogenesis have opened a new era for both prevention and active treatment of the disease. This review describes some of the known molecular mechanisms contributing to erectile dysfunction and discusses the future of gene therapy for the disease.     

Définition du seuil de la pathologie nommée “dysfonctions érectiles”. Où commence l’insuffisance érectile?

“Erectile dysfunction” is a poor term and should be replaced by “erectile insufficiency”, as although everybody knows the function of erections obtained in response to sexual excitation, the role of nocturnal erections (about 95% of erection time) is unknown. Although erectile insufficiency is generally experienced as a cruel handicap, it may not justify the status of a disease. It is also questionable to make it a psychiatric illness. Finally, erection and sexuality in general, should not be confined within certain norms, even when these norms are defined by the medical profession. However, the physician is faced with all these problems presented by this normal man who consults for impotence at a time when drugs are now available on the market, which are able to induce or facilitate erection (this latter group was previously called aphrodisiacs).     

Phosphodiesterase type 5 inhibitors for the treatment of male lower urinary tract symptoms

Both lower urinary tract symptoms due to benign prostatic hyperplasia (BPH) and erectile dysfunction have a very high prevalence among aging men, and there is some clinical evidence that they may share a common pathophysiology. Consequently, several preliminary studies of phosphodiesterase type 5 inhibitors-sildenafil and tadalafil-have recently been conducted in men with concomitant erectile dysfunction and lower urinary tract symptoms to determine whether these agents are effective for the treatment of symptomatic BPH. These studies have demonstrated efficacy, both alone and in combination with an alpha-blocker, in treating lower urinary tract symptoms along with sexual dysfunction. However, larger-scale randomized studies are necessary to determine long-term safety, efficacy, and cost effectiveness.     

Oral and non-oral combination therapy for erectile dysfunction

An estimated 30 million men in the United States suffer from varying degrees of erectile dysfunction. Increasing age and comorbidities are likely to increase the number of men who are initially refractory or become refractory to phosphodiesterase (PDE)-5 inhibitors, the most popular oral therapy. Combination therapy, a concept well proved in other areas of medicine, is therefore of increasing importance. Combination oral and non-oral (intracavernosal injection and intraurethral application) therapies have been shown to salvage monotherapy. The early introduction of combination therapy has been shown to expedite both the return of natural function and PDE-5 inhibitor responsiveness in post-prostatectomy patients with no reports of serious adverse events. Larger controlled studies are needed to corroborate those encouraging findings.     

Erectile dysfunction in patients with cardiovascular disease

Erectile dysfunction is a highly prevalent disease, especially in cardiovascular-compromised men. Many of the well-established risk factors for cardiovascular disease are also risk factors for erectile dysfunction. A correlation between erectile dysfunction and endothelial dysfunction is well established. It is postulated that erectile dysfunction with an arteriovascular aetiology can predate and be an indicator of potential coronary artery disease. In this paper we will attempt to increase awareness among cardiologists for the predictive value of erectile dysfunction for future cardiovascular disease in order to optimise cardiovascular risk management. The treatment of erectile dysfunction and cardiovascular interactions is also discussed in detail.     

Gene therapy strategies for urological dysfunction.

Novel molecular techniques such as conventional and ex vivo gene therapy, and tissue engineering have only recently been introduced to the field of urology. The lower urinary tract is ideally suited for minimally invasive therapy, and also ex vivo approaches would limit the risk of systemic side effects. Muscle-derived stem cells have been used successfully to treat stress incontinence, and rats with diabetic bladder dysfunction benefited from nerve growth factor (NGF)-based gene therapy. Nitric oxide synthase and capase-7 might provide suitable gene therapy targets for erectile dysfunction and benign prostatic hyperplasia, respectively.     

Gene transfer of prepro-calcitonin gene-related peptide restores erectile function in the aged rat.

Erectile dysfunction in the aging male is caused, in part, by inadequate relaxation of the corpora cavernosal smooth musculature. Calcitonin gene-related peptide (CGRP), a peptide neurotrasmitter localized in the corpora cavernosa, is down-regulated in the aging rat penis. We examined the hypothesis that this reduction in CGRP may contribute to decreased cavernosal smooth muscle relaxation. Therefore, we sought to determine whether adenoviral-mediated gene transfer of prepro-CGRP (AdRSVCGRP) could enhance erectile responses in aged rats. We found a significant decrease in CGRP concentrations and in cAMP and cGMP levels in aged rat cavernosal tissue compared to younger rats. Aged rats also had significantly lower erectile function as determined by cavernosal nerve stimulation compared to younger rats. Five days after transfection with AdRSVCGRP, these aged rats had an approximately threefold increase in cavernosal CGRP levels compared to animals transfected with adenoviruses encoding nuclear-targeted beta-galactosidase (AdRSV beta gal). The AdRSVCGRP-transfected animals also demonstrated an increase in CGRP mRNA and immunohistochemical localization of CGRP in the smooth muscle of the corpora cavernosa. In addition, cAMP levels in the corpora cavernosa were significantly increased, whereas cGMP levels remained unchanged. Adenoviral transduction efficiency of beta-galactosidase reporter gene was measured by chemiluminescence and was observed in cavernosal tissue 5 days after transfection with AdRSV beta gal. More importantly, 5 days after administration of AdRSVCGRP, a significant increase was observed in the erectile response to cavernosal nerve stimulation in the aged rat, similar to the response observed in younger rats. These data suggest that in vivo adenoviral gene transfer of CGRP can physiologically improve erectile function in the aged rat.     

Apport de la Prostaglandine E1 dans l’exploration et le traitement de l’impuissance: A propos de 980 cas dont 510 traites par auto-injections

Since 1982, many substances have been injected intracavernosally to produce erections in impotent men. Because the first-generation drugs (phenoxybenzamine, papaverine) were associated with severe side-effects, including priapism and penile fibrosis, it was essential that a safe and effective substance be found for this application. In a series of 980 patient with erectile dysfunction who received prostaglandin E1 intracavernosal injections, 70 % developped an erection lasting more than 30 minutes with minimal side-effects. All the 510 men who entered a self-administration protocol were capable of engaging in intercourse and experienced no major sideeffects. Prostaglandin E1 is effective, safe and preferable to all other drugs currently used for intracavernosal injection.     

La dysfonction éréctile au Sénégal: Profil épidemiologique

Methodology

This was a transverse randomized survey of subjects over the age of 18 years. Subjects completed a self-administered questionnaire composed of two parts. The first part contained information on demographic characteristics, associated diseases, erectile dysfunction and associated sexual disorders and the second part was based on IIEF5. Two groups were identified: a group with erectile dysfunction (ED group) and another group without erectile dysfunction (No ED group). Differences between the two groups were considered to be statistically significant for p ≤ 0.05 on the Chi-square test.

Results

The global prevalence of erectile dysfunction was 26%. The prevalence by age-group revealed a progressive increase of ED with age from 11% between 20 and 30 years to 76% between 70 and 80 years. The rate of polygamous men was significantly higher in the group with ED (29.2%) compared to the group without ED (6.6%) (p < 0.0001) and the severity of ED increased in relation to the number of wives. Chronic alcoholism was significantly more frequent in the group with ED (p = 0.023). The frequency of ED increased with the duration of cigarette smoking from 11.9% for less than 5 years, 16.9% between 5 years and 10 years and 71.2% for more than 10 years. Some diseases (diabetes, hypertension and depression) were significantly more frequent in the group with ED. Analysis of the type of ED revealed that secondary erectile dysfunction was more frequent (95.6%) than primary erectile dysfunction (4.4%). Associated sexual disorders were significantly more frequent in the group with ED.     

La dysfonction érectile au Congo : premières données sur la fréquence de ce motif de consultation et profil clinique au centre hospitalier universitaire de Brazzaville

Objective

To study risk factors and diagnostic investigations results of erectile dysfunction in urologic consultation in Brazzaville.

Method

It was a prospective study, which included 40 patients between 25 and 80 year-old seen for erectile dysfunction in the external urology-andrology consultation of the teaching hospital of Brazzaville, from December 2009 to August 2010. Information obtained from the investigation form included age, past history, risk factors, clinical and nonclinical characteristics and the international index of erectile function (IIEF-5) in its French translation. Epi Info software version 3.5.1 and SPSS 11.5 were used for data analysis. The Chi squared test was used to compare quantitative results and the analysis of variance (ANOVA) for qualitative results. The significance level was 0.05.

Results The frequency of erectile dysfunction was 14.7%, with an average age of 50.7 + 12.3 year-old (27?C77 years). The group 40 to 50 year-old was the most affected. The mean duration was 2.6 + 2.2 years (three months to nine years). Associated diseases were hypertension (22.5%) and diabetes (15%). The risk factors observed were alcoholism (75%), tobacco use (25%) and obesity (12.5%). The erectile dysfunction was severe in 47.5% of cases and severity was correlated with age. It was unbearable in 40% of cases

Conclusion

Erectile dysfunction was found in 14.7% of patients seen in urologic consultation. This number is underestimated because of modesty and taboos.