Vasculogenic Erectile Dysfunction: The Impact of Diet and Lifestyle.

Vasculogenic erectile dysfunction has been aptly called the "canary in the coal mine" for cardiovascular disease because it almost always precedes other manifestations of atherosclerotic cardiovascular disease, including myocardial infarction and stroke. It is common, associated with the presence of modifiable cardiovascular risk factors, and impacted by diet and lifestyle choices. This concise review provides an update on the use of dietary and other lifestyle interventions to improve vasculogenic erectile dysfunction and atherosclerotic cardiovascular disease.

Epidemiology regarding penile prosthetic surgery.

With the onset of a metabolic syndrome epidemic and the increasing life expectancy, erectile dysfunction (ED) has become a more common condition. As incidence and prevalence increase, the medical field is focused on providing more appropriate therapies. It is common knowledge that ED is a chronic condition that is also associated with a myriad of other disorders. Conditions such as aging, diabetes mellitus, hypertension, obesity, prostatic hypertrophy, and prostate cancer, among others, have a direct implication on the onset and progression of ED. Characterization and recognition of risk factors may help clinicians recognize and properly treat patients suffering from ED. One of the most reliable treatments for ED is penile prosthetic surgery. Since the introduction of the penile prosthesis (PP) in the early seventies, this surgical procedure has improved the lives of thousands of men, with reliable and satisfactory results. The aim of this review article is to characterize the epidemiology of men undergoing penile prosthetic surgery, with a discussion about the most common conditions involved in the development of ED, and that ultimately drive patients into electing to undergo PP placement.

[Penile revascularization using laparoscopic mobilization of the inferior epigastric artery].

The article presents a case of successful penile revascularization using laparoscopic mobilization of the inferior epigastric artery in a 35 y. o. patient with penile arteriovenous insufficiency.

Dynamic and morphologic evaluation of erectile dysfunction on penile doppler sonography and contrast cavernosography.

BACKGROUND: Penile erection is a complex phenomenon that involves coordinated interaction of the psychologic, hormonal, nervous, arterial, venous, and sinusoidal systems. Erectile dysfunction (ED) is the persistent inability to attain or maintain penile erection sufficient for sexual intercourse. This study aims to determine the real-time morphologic vascular abnormalities in men with ED using penile Doppler sonography in Kano, Nigeria. MATERIALS AND METHODS: Twenty-one patients who were referred from urology clinics on account of suspected vasculogenic ED were reviewed. The cavernorsal arteries were examined with 7.5 MHz linear transducer in gray scale and duplex Doppler modes before and after intracavernosal injection of 60 mg papevarine. Serial peak systolic velocity (PSV), end diastolic velocity (EDV), and diameter measurements were performed at 5-min intervals for 30 min. RESULTS: The mean age of the patients was 43.14 ± 9.84 years. Out of the 21 patients examined, 5 showed normal findings while 10 had evidence of venous leakage. Five patients had arterial insufficiency; out of which 3 patients showed calcifications of the tunica albuginea, suggesting Peyronie's disease. Interestingly, 1 patient showed combining features of arterial insufficiency and of venous leakage. Those with arterial insufficiency were relatively older than other patients. They also had compounding medical conditions of diabetes and hypertension. CONCLUSION: Vascular etiologies are important contributors of ED in our setting. Papavarine-induced Doppler sonography and cavernosography shows promise in accurate assessment and overall care of these patients.

Vessel-sparing Radiotherapy for Localized Prostate Cancer to Preserve Erectile Function: A Single-arm Phase 2 Trial.

BACKGROUND: Erectile dysfunction remains the most common side effect from radical treatment of localized prostate cancer. We hypothesized that the use of vessel-sparing radiotherapy, analogous to the functional anatomy approach of nerve-sparing radical prostatectomy (RP), would improve erectile function preservation while maintaining tumor control for men with localized prostate cancer. OBJECTIVE: To determine erectile function rates after vessel-sparing radiotherapy. DESIGN, SETTING, AND PARTICIPANTS: Men with localized prostate cancer were enrolled in a phase 2 single-arm trial (NCT02958787) at a single academic center. INTERVENTION: Patients received vessel-sparing radiotherapy utilizing a planning MRI and MRI-angiogram to delineate and avoid the erectile vasculature. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Both physician- and patient-reported inventories were used to capture erectile function at baseline and at 2 and 5 yr after treatment. Validated model-based comparisons were performed to compare vessel-sparing results to nerve-sparing RP and conventional radiotherapy. RESULTS AND LIMITATIONS: From 2001 to 2009, 135 men underwent vessel-sparing radiotherapy. After a planned interim analysis, the trial was stopped after meeting the primary endpoint. The median follow-up was 8.7 yr, with a ≥94% response rate to all inventories at each time point. At 5 yr, 88% of patients were sexually active with or without the use of sexual aids. The 2-yr erectile function rates were significantly improved with vessel-sparing radiotherapy (78%, 95% confidence interval [CI] 71-85%) compared to modeled rates for convention radiotherapy (42%, 95% CI 38-45%; p<0.001) or nerve-sparing prostatectomy (24%, 95% CI 22-27%; p<0.001). At 2 yr after treatment, 87% of baseline-potent men retained erections suitable for intercourse. The 5- and 10-yr rates of biochemical relapse-free survival were 99.3% and 89.9%, and at 5 yr the biochemical failures were limited to the National Comprehensive Cancer Network high-risk group. The single-arm design is a limitation. CONCLUSIONS: Vessel-sparing radiotherapy appears to more effectively preserve erectile function when compared to historical series and model-predicted outcomes following nerve-sparing RP or conventional radiotherapy, with maintenance of tumor control. This approach warrants independent validation. PATIENT SUMMARY: In this interim analysis we looked at using a novel approach to spare critical erectile structures to preserve erectile function after prostate cancer radiotherapy. We found that almost 90% of patients at 5 yr after treatment remained sexually active, significantly higher than previous studies with surgery or radiotherapy.

The vascular and neurogenic factors associated with erectile dysfunction in patients after pelvic fractures

ABSTRACT Erectile dysfunction (ED) is a common complication of pelvic fractures. To identify the vascular and neurogenic factors associated with ED, 120 patients admitted with ED after traumatic pelvic fracture between January 2009 and June 2013 were enrolled in this study. All patients answered the International Index of Erectile Function (IIEF-5) questionnaire. Nocturnal penile tumescence (NPT) testing confirmed the occurrence of ED in 96 (80%) patients on whom penile duplex ultrasound and neurophysiological testing were further performed. Of these ED patients 29 (30%) were demonstrated only with vascular abnormality, 41 (42.7%) were detected only with neural abnormality, 26 (27.1%) revealed mixed abnormalities. Of the 55 patients (29+26) with vascular problems, 7 patients (12.7%) with abnormal arterial response to intracavernous injection of Bimix (15mg papaverine and 1mg phentolamine), 31 (56.4%) with corporal veno-occlusive dysfunction and 17 (30.9%) had both problems. Of the 67 (41+26) patients with abnormal neurophysiological outcomes, 51 (76.1%) with abnormal bulbocavernosus reflex (BCR), 20 (29.9%) with pathological pudendal nerve evoked potentials (PDEPs) and 25 (37.3%) with abnormal posterior tibial somatosensory nerve evoked potentials (PTSSEPs). Our observation indicated that neurogenic factors are important for the generation of ED in patients with pelvic fracture; venous impotence is more common than arteriogenic ED.

Pudendal nerve and internal pudendal artery damage may contribute to radiation-induced erectile dysfunction.

PURPOSE/OBJECTIVES: Erectile dysfunction is common after radiation therapy for prostate cancer; yet, the etiopathology of radiation-induced erectile dysfunction (RI-ED) remains poorly understood. A novel animal model was developed to study RI-ED, wherein stereotactic body radiation therapy (SBRT) was used to irradiate the prostate, neurovascular bundles (NVB), and penile bulb (PB) of dogs. The purpose was to describe vascular and neurogenic injuries after the irradiation of only the NVB or the PB, and after irradiation of all 3 sites (prostate, NVB, and PB) with varying doses of radiation. METHODS AND MATERIALS: Dogs were treated with 50, 40, or 30 Gy to the prostate, NVB, and PB, or 50 Gy to either the NVB or the PB, by 5-fraction SBRT. Electrophysiologic studies of the pudendal nerve and bulbospongiosus muscles and ultrasound studies of pelvic perfusion were performed before and after SBRT. The results of these bioassays were correlated with histopathologic changes. RESULTS: SBRT caused slowing of the systolic rise time, which corresponded to decreased arterial patency. Alterations in the response of the internal pudendal artery to vasoactive drugs were observed, wherein SBRT caused a paradoxical response to papaverine, slowing the systolic rise time after 40 and 50 Gy; these changes appeared to have some dose dependency. The neurofilament content of penile nerves was also decreased at high doses and was more profound when the PB was irradiated than when the NVB was irradiated. These findings are coincident with slowing of motor nerve conduction velocities in the pudendal nerve after SBRT. CONCLUSIONS: This is the first report in which prostatic irradiation was shown to cause morphologic arterial damage that was coincident with altered internal pudendal arterial tone, and in which decreased motor function in the pudendal nerve was attributed to axonal degeneration and loss. Further investigation of the role played by damage to these structures in RI-ED is warranted.

Initial evidence demonstrating the association between the vascular status in surgically resected renal parenchymal pathology and sexual function.

Our goal is to evaluate the association between histopathology of glomerulosclerosis (GS) and atherosclerosis (AS) in the nephrectomized normal parenchyma together with patients' background, and erectile dysfunction (ED) of patients treated with radical nephrectomy (RN) for renal cell carcinoma (RCC). ED was assessed with the International Index of Erectile Function in 65 patients who were less than age 70 years at the time of questionnaire. Glomeruli status was assessed by the extent of global GS. AS was graded based on lumen occlusion and frequency of involvement. Patients' backgrounds included any comorbidities, post-RN renal insufficiency, tumor pathology, demographics and social status. The presence of diabetes mellitus and lack of a spouse were independent predictors for severe ED, whereas G0/1 AS was an independent predictor for mild/no ED. The extent of global GS was significantly lower in patients with mild/no ED than in other patients. Our study represents the first report identifying healthy arterial status in the renal parenchyma as a significant indicator of favorable erectile function and that the evaluation of AS severity is not a superior indicator of severe ED in the presence of comorbidities or social status among patients treated with RN.

Embolization of the periprostatic venous plexus for erectile dysfunction resulting from venous leakage.

PURPOSE: To evaluate retrospectively the safety and efficacy of anterograde embolization of the periprostatic venous plexus (AEPV) via percutaneous access of the deep dorsal vein of the penis for erectile dysfunction (ED) resulting from veno-occlusive dysfunction (VOD). MATERIALS AND METHODS: From September 2009 through December 2012, 18 patients with moderate to severe ED secondary to insufficiency of physiologic venous occlusion as diagnosed by color Doppler evaluation of the penis after direct pharmacologic stimulation were treated. Preliminary diagnoses were also confirmed with dynamic cavernosography. Selective AEPV was achieved using a combination of N-butyl cyanoacrylate and endovascular coils. Follow-up consisted of collecting International Index of Erectile Function questionnaire (IIEF-6) scores and repeated color Doppler evaluation. RESULTS: Immediate technical success was achieved in 16 of 18 patients (88.8%). Follow-up data were obtained at a mean of 13.3 months ± 7.5. In 12 of the patients with technical success, the mean IIEF-6 score improved from 10.5 ± 5.2 to 20.6 ± 8.4 after the procedure (P = .0069). At 3-month short-term follow-up, clinical success defined by an end-diastolic velocity of < 5 cm/s on color Doppler was noted in 81% (13 of 16 patients). Of these 13 patients, 7 patients had continued erectile function at the end of follow-up, and the other 6 patients reported progressive diminishment in the benefit over time. No major complications and two minor complications were encountered. CONCLUSIONS: AEPV for ED secondary to VOD is a safe alternative to surgical treatment that demonstrates promising short-term and midterm efficacy.

The use of PDE-5 inhibitors in the treatment of lower urinary tract symptoms due to benign prostatic hyperplasia.

The relationship between lower urinary tract symptoms secondary to BPH and ED has recently been the subject of significant research due to the prevalence of both conditions concomitantly existing in older men. Many large-scale studies have demonstrated an association between erectile dysfunction and lower urinary tract symptoms. Although the mechanisms underlying the relationship between LUTS and ED are not fully elucidated, several theories are currently proposed in literature: the nitric oxide/cGMP pathway, RhoA/Rho-kinase signaling, pelvic atherosclerosis associated with chronic hypoxia, and autonomic adrenergic hyperactivity. The mechanisms by which these pathways affect the bladder, prostate, pelvic vasculature and spinal cord are also the subject of current research. In this chapter, we examine the randomized, placebo-controlled trials that have evaluated the use of PDE-5Is in LUTS, as well as randomized, controlled trials (RCTs) researching combination PDE-5Is and alpha blockers.

An oral formulation of angiotensin-(1-7) reverses corpus cavernosum damages induced by hypercholesterolemia.

INTRODUCTION: The renin angiotensin system plays a crucial role in erectile function. It has been shown that elevated angiotensin-II levels contribute to the development of erectile dysfunction (ED). Oppositely, angiotensin-(1-7) (Ang-[1-7]) mediates penile erection by activation of receptor Mas. Recently, we have developed a formulation based on Ang-(1-7) inclusion in cyclodextrin (CyD) [Ang-(1-7)-CyD], which allows for the oral administration of Ang-(1-7). AIM: In the present study, we evaluated the effects of chronic treatment with Ang-(1-7)-CyD on penile fibrosis, oxidative stress, and endothelial function in hypercholesterolemic mice. METHODS: Apolipoprotein(Apo)E-/- mice fed a Western-type diet for 11 weeks received Ang-(1-7)-CyD or vehicle during the final 3 weeks. Collagen content and reactive oxygen species (ROS) production within the corpus cavernosum were evaluated by Sirius red and dihydroethidium staining, respectively. Protein expression of neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS), nicotinamide adenine dinucleotide phosphate (NADPH) subunits (p67-phox and p22-phox), and AT1 and Mas receptors in the penis was assessed by Western blotting. Nitric oxide (NO) production was measured by Griess assay in the mice serum. Cavernosal strips were mounted in an isometric organ bath to evaluate the endothelial function. MAIN OUTCOME MEASURES: The effect of Ang-(1-7)-CyD treatment on penile fibrosis, oxidative stress, and endothelial function in hypercholesterolemia-induced ED. RESULTS: Ang-(1-7)-CyD treatment reduced collagen content in the corpus cavernosum of ApoE-/- mice. This effect was associated with an attenuation of ROS production and a diminished expression of NADPH. Furthermore, Ang-(1-7)-CyD treatment augmented the expression of nNOS and eNOS in the penis and elevated vascular NO production. Importantly, these effects were accompanied by an improvement in cavernosal endothelial function. CONCLUSION: Long-term treatment with Ang-(1-7)-CyD reduces penile fibrosis associated with attenuation of oxidative stress. Additionally, cavernosal endothelial function in hypercholesterolemic mice was markedly improved. These results suggest that Ang-(1-7)-CyD might have significant therapeutic benefits for the treatment of erectile dysfunction.

The link between vasculogenic erectile dysfunction, coronary artery disease, and peripheral artery disease: role of metabolic factors and endovascular therapy.

Erectile dysfunction (ED) is estimated to affect 150 million people worldwide and may indicate diffuse systemic macrovascular disease. Endothelial dysfunction represents the probable pathophysiological link between vasculogenic ED, coronary artery disease (CAD), and peripheral artery disease (PAD), and the artery size hypothesis along with evidence-based research support ED as the incident clinical event. Given that many common risk factors for atherosclerosis, including smoking, diabetes mellitus, hyperlipidemia, and obesity are prevalent and causative in patients with ED, it is likely that metabolic factors play a crucial role in the link between the two disorders. The interplay of these factors provides a unifying physiological, endocrinological, and behavioral model for the association between ED, CAD, and PAD. Current therapy is unlikely to reverse the natural history of ED. Percutaneous revascularization may improve ED symptoms, and thereby quality of life, in a select group of patients. Large prospective studies are needed to define male pelvic arterial anatomy and thus enhance the utilization of internal pudendal angiography and revascularization. In this review, we provide an overview of normal erectile anatomy and physiology, the pathophysiology of ED, currently accepted diagnostic imaging modalities and treatments for ED, and recently investigated endovascular therapies for ED.

A review of outcomes of an intracavernosal injection therapy programme.

UNLABELLED: Study Type--Therapy (outcomes research) Level of Evidence 2b. What's known on the subject? and What does the study add? Intracavernosal injection (ICI) therapy is an important treatment option for erectile dysfunction. However, high discontinuation rates have been reported for ICI therapy, and a risk of priapism has long been a concern. There has never been a large sample study performed with multivariate analysis to characterise outcomes of ICI therapy. The present paper reviews ICI therapy outcomes in a very large population of men at a tertiary care Sexual Medicine Clinic over 5 years. Multivariate analysis was used to further characterise these outcomes. The present study shows that for a large percentage of our sample of patients, ICI therapy is a successful treatment strategy. And, while discontinuation rates are still high, many of those not continuing ICI therapy achieved success with phosphodiesterase inhibitors. Also, the incidence of priapism was less in the present study than previously reported. OBJECTIVES: • To review the outcomes, adverse events and discontinuation rates of intracavernosal injection (ICI) therapy in men with erectile dysfunction (ED) in a sexual medicine practice over a 5-year period at a tertiary referral centre. • Since 1983, ICI has become a staple therapeutic option and high success rates have been reported. However, priapism is a significant concern and discontinuation rates are estimated to be >50%. PATIENTS AND METHODS: • Men presenting with ED who were enrolled in our ICI programme between September 2002 and August 2006 were followed at least annually. • Patient demographic information, agents used, erectile function outcomes and adverse events were recorded. • Failure was defined as the inability to have penetrative sex. Discontinuation was defined as patient declaration of such, failure to attend an annual follow-up visit or failure to call for a repeat prescription. • Multivariable analysis was used to define predictors of failure to respond to ICI therapy, as well as predictors of discontinuation within 36 months of starting ICI in those patients responding. RESULTS: • In all, 1412 patients had complete data and constituted the study population. Most patients were using Trimix and 89% of Trimix users were capable of having sexual intercourse. • Response rates were lower in pelvic radiation and diabetic patients. • However, the discontinuation rate was significant; it was lower in men who had not undergone radical prostatectomy (RP). Of note, many RP patients discontinued ICI because of recovery of natural or phosphodiesterase type 5 inhibitor-assisted erections. CONCLUSIONS: • ICI therapy is associated with very high success rates even in men with high comorbidity profiles; however, the discontinuation rates, even in men who had not undergone RP, by the end of the third year are significant. • Of note, the recorded priapism rate was extremely low (0.5%).

Predicting participation in and successful outcome of a penile rehabilitation programme using a phosphodiesterase type 5 inhibitor with a vacuum erection device after radical prostatectomy.

UNLABELLED: Study Type--Therapy (case series) Level of Evidence 4. What's known on the subject? and What does the study add? The role of the vacuum erection device (VED) has increased with its use in combined therapy with a phosphodiesterase type 5 inhibitor (PDE5i) for penile rehabilitation after radical prostatectomy (RP) and radiotherapy. The advantages of the VED are non-invasive, cost-effective, and a possibility of preventing shrinkage of penis length. Albeit current widespread use of penile rehabilitation programmes for post-RP erectile dysfunction, independent predictors for the rehabilitation participants, as well as for its treatment success have not been fully investigated. In the present study, we have added several new predictors for rehabilitation participation, e.g. African-Americans and higher preoperative sexual function. Conversely, higher preoperative PSA concentrations and the presence of positive surgical margins were predictors for avoidance of rehabilitation. Notably, there was a primary surgeon difference, which had a trend for predicting outcome of the rehabilitation among the participants, implying their surgical technique and follow-up might influence success of the rehabilitation. OBJECTIVES: • To investigate baseline demographic and clinicopathological characteristics of men who participate in our penile rehabilitation programme after radical prostatectomy (RP). • To determine predictors for participation in rehabilitation, as well as successful rehabilitation outcome using multivariable logistic regression analyses. PATIENTS AND METHODS: • We analysed data on 2345 consecutive patients who underwent RP between 2001 and 2009 in our institution. • The decision to participate in penile rehabilitation using phosphodiesterase type 5 inhibitor (PDE5i) with a vacuum erection device (VED) was based on the patient's choice after post-RP discussions. • Rehabilitation success was defined using the following criteria: (i) patients who continued the penile rehabilitation programme and did not switch treatment from PDE5i to other erectile aids, (ii) success was noted in men who had an Expanded Prostate Cancer Index Composite (EPIC) sexual function (SF) score of >75% of the patient's baseline EPIC score, and (iii) patients who answered that they achieved adequate erections with a PDE5i. • Logistic regression analysis was used to identify factors associated with treatment participation and its success. RESULTS: • Of 676 patients, 354 (53.2%) men participated in a penile rehabilitation programme. Among 329 rehabilitation participants with available data, 96 (29.2%) had treatment success. • In multivariable regression analysis, African-Americans (odds ratio [OR] 3.47, P < 0.001), and higher preoperative SF (OR 1.02, P < 0.001) were associated with participation in rehabilitation. • Higher preoperative PSA concentration (OR 0.50, P = 0.004) and presence of positive surgical margins (OR 0.68, P = 0.042) were found to be independent predictors for non-participation in the rehabilitation. • For rehabilitation outcomes, being older at surgery (OR 0.93, P = 0.001) and adjuvant therapy (OR 0.34, P = 0.047) had a negative association with successful outcome. • There was a trend in the relationship between primary surgeon and rehabilitation success (OR 1.05, P = 0.053) CONCLUSIONS: • Those patients who have risk factors, e.g. adverse prostate cancer features, need to be carefully counselled and encouraged to participate in the penile rehabilitation programme. • Clinicians could lead patients toward successful outcomes if appropriate surgical techniques and rehabilitation are provided.

The cumulative effects of medication use, drug use, and smoking on erectile dysfunction among men who have sex with men.

INTRODUCTION: Erectile dysfunction (ED) is highly prevalent among human immunodeficiency virus-seropositive (HIV+) men who have sex with men (MSM). There is a need for additional research to determine the correlates of HIV+ and HIV-seronegative (HIV-) MSM, especially regarding nonantiretroviral medication use. AIMS: This study examined the prevalence of ED and the sociodemographic, medical conditions, medication use, and substance use correlates of ED among HIV+ and HIV- MSM. METHODS: A modified version of the International Index of Erectile Function (IIEF) for MSM was self-administered by participants enrolled in the Multicenter AIDS Cohort Study, an ongoing prospective study of the natural and treated histories of HIV infection among MSM in the United States. The study sample included 1,340 participants, including 612 HIV+ and 728 HIV- men. Poisson regression with robust error variance was used to estimate prevalence ratios of ED in multivariable models in combined (HIV+/-) and separate analyses. MAIN OUTCOME MEASURE: ED was determined by the summed scores of a modified version of the IIEF validated among MSM. RESULTS: Twenty-one percent of HIV+ MSM and 16% of HIV- MSM reported ED. Being >55 years of age, black race, cumulative pack years of smoking, cumulative antihypertensive use, and cumulative antidepressant use had significant positive associations with the prevalence of ED in the total sample. Among HIV+ men, duration of antihypertensive use and antidepressant use were significantly associated with increasing prevalence of ED. Among HIV- men, being >55 years of age, black race, and cigarette smoking duration were associated with increased prevalence of ED. CONCLUSION: Predictors of ED may differ by HIV status. Although smoking cessation and effective medication management may be important as possible treatment strategies for ED among all MSM, there may be a burden on sexual functioning produced by non-HIV medications for HIV+ men.

Vasogenic erectile dysfunction Topiramate-induced.

Reversible erectile dysfunction due to Topiramate has been linked to the effect of this antiepileptic drug on reproductive hormones levels. We described two epileptic male patients which experienced erectile dysfunction during Topiramate treatment. Serum sexual hormones were tested during treatment and at several time intervals following drug discontinuation. Topiramate did not seem to affect plasma levels of total, free and bioavailable testosterone and sex hormone-binding globulin. Since Topiramate erectile dysfunctions could not be related to changes in reproductive hormones levels, a vasogenic mechanism must be considered.

Erectile function and sexual satisfaction before and after penile prosthesis implantation in radical prostatectomy patients: a comparison with patients with vasculogenic erectile dysfunction.

INTRODUCTION: Patients with erectile dysfunction (ED) after radical prostatectomy (RP) may benefit from penile prosthesis (PP) implantation after failure of less invasive treatments. Aim. To assess surgical outcomes and satisfaction after PP implantation in RP patients and compare the results with those in patients with vasculogenic ED (controls). METHODS: A database of 415 consecutive PPs (January 1996-December 2008) was used to collate data on preimplantation ED treatments, surgical complications, satisfaction, and International Index of Erectile Function (IIEF) scores before and 3 months after implantation. The results for 90 post-RP implants (79 primary, 11 secondary) and 131 implants for vasculogenic ED were compared. MAIN OUTCOME MEASURES: The main outcome measures of this study are intra- and postoperative complications and IIEF domain scores. RESULTS: Mean follow-up of RP patients was 37.6 ± 26.8 months. Mean interval between RP and PP implantation was 31.5 ± 28.7 months. Nearly all primary implants (96.2%) were inflatable (3-piece, 70.1%; 2-piece, 24.1%). There was no significant difference between groups in terms of rates of infection (1.1%), mechanical failure (3.3%), and other surgical complications requiring revision surgery (migration, auto-inflation) (4.4%). For primary implants, the mean preimplantation IIEF score (all items) was significantly lower in RP patients than in controls (14.7 ± 5.9 vs. 22.6 ± 10.8, P = 0.003), chiefly because of significantly lower scores for erectile function, intercourse satisfaction, and orgasmic function. After PP implantation in RP patients, the scores for all domains improved, but the total score remained significantly lower than in controls (63.1 ± 7.0 vs. 68.5 ± 6.9, P = 0.005). The orgasmic function score was significantly lower (P < 0.001). Overall satisfaction rate was 86.1% in RP patients and 90.7% in controls (P = 0.3). CONCLUSIONS: PP implantation after RP is associated with low morbidity and high satisfaction. It improves the scores for all IIEF domains and, in particular, erectile function. Fibrosis of the retropubic space may require a second incision for reservoir placement or implantation of a 2-piece PP.

What is the definition of a satisfactory erectile function after bilateral nerve sparing radical prostatectomy?

INTRODUCTION: Different cut-offs of the erectile function (EF) domain of the International Index of Erectile Function (IIEF) have been used as definition of postoperative EF recovery. AIM: To test the correlation between patient satisfaction and IIEF-EF domain score cut-offs. MAIN OUTCOME MEASURE: The IIEF was used to evaluate EF and satisfaction before and after bilateral nerve sparing radical prostatectomy (BNSRP). METHODS: The study included 165 consecutive patients treated with retropubic BNSRP at a single institution. All patients had normal preoperative EF (IIEF-EF ≥ 26) and reached an IIEF-EF ≥ 17 following surgery. Complete data included EF, intercourse (IS), and overall satisfaction (OS) assessed by the corresponding domains of the IIEF administered prior and after surgery. Patients were divided into three groups according to the highest IIEF-EF score reached postoperatively, namely 17-21 (group 1), 22-25 (group 2), and ≥ 26 (group 3). One-way analysis of variance was used to compare IIEF-OS and IIEF-IS domain scores at the time the EF end point was reached. The same analyses were repeated separately in those patients with a complete EF recovery after surgery (group 3). RESULTS: Mean preoperative IIEF-OS and IIEF-IS domain score was 8.4, 8.8, 8.7 and 11.6, 11.8, 11.9 in group 1, 2, 3, respectively (all P ≥ 0.3). After a mean follow-up of 26.7 months, mean postoperative IIEF-OS and IIEF-IS domain scores assessed at the time of EF recovery were comparable for patients reaching an IIEF-EF of 22-25 and for patients scoring postoperatively ≥ 26 (8.1, 8.1, and 10.6, 11.4; all P ≥ 0.3). However, mean IIEF-OS and IIEF-IS domain scores of these patients were significantly higher as compared to patients reaching an IIEF-EF domain score < 22 (6.3 and 8.4, respectively; all P ≤ 0.006). Similar results were achieved considering only those patients (group 3) who had complete EF recovery after surgery. CONCLUSIONS: We demonstrated that in preoperatively fully potent patients treated with BNSRP a lower satisfaction is expected when an IIEF-EF cut-off of 17 is used. Conversely, no difference was found using a cut-off of 22 or 26. Therefore, our results support that a cut-off of IIEF-EF ≥ 22 might represent a reliable score for defining EF recovery after BNSRP.

Randomized, double-blinded, placebo-controlled crossover trial of treating erectile dysfunction with sildenafil after radiotherapy and short-term androgen deprivation therapy: results of RTOG 0215.

INTRODUCTION: Erectile dysfunction (ED) may be the most commonly observed adverse event (AE) associated with the combination of radiation therapy (RT) and androgen deprivation therapy (ADT). A significant number of men are trying phosphodiesterase type 5 inhibitors (PDE5s) such as sildenafil to treat ED, yet sildenafil studies to date shed little light on the response to ED after ADT. AIM: The purpose of this trial was to evaluate sildenafil in the treatment of ED in prostate cancer patients previously treated with external beam RT and neoadjuvant and concurrent ADT. METHODS: In this randomized, double-blinded crossover trial, eligible patients received RT/ADT for intermediate risk prostate cancer and currently had ED as defined by the International Index of Erectile Function (IIEF). Patients were randomized to 12 weeks of sildenafil or placebo followed by 1 week of no treatment then 12 weeks of the alternative. Treatment differences were evaluated using a marginal model for binary crossover data. MAIN OUTCOME MEASURES: The primary end point was improved erectile function, as measured by the IIEF. RESULTS: The study accrued 115 patients and 61 (55%) completed all three IIEF assessments. Sildenafil effect was significant (P = 0.009) with a difference in probabilities of erectile response of 0.17 (95% confidence interval: 0.06, 0.29), and 0.21 (0.06, 0.38) for patients receiving ≤ 120 days of ADT. However, as few as 21% of patients had a treatment-specific response, only improving during sildenafil but not during the placebo phase. CONCLUSIONS: This is the first controlled trial to suggest a positive sildenafil response for ED treatment in patients previously treated with RT/ADT, however, only a minority of patients responded to treatment. ADT duration may be associated with response and requires further study. The overall low response rate suggests the need for study of additional or preventative strategies for ED after RT/ADT for prostate cancer.

PARP inhibition restores erectile function by suppressing corporal smooth muscle apoptosis in diabetic rats.

INTRODUCTION: An important mechanism suggested to be responsible for diabetes-associated erectile dysfunction (ED) involves increased apoptosis, increased collagen deposition, and reduced smooth muscle content in the corpus cavernosum. AIM: To determine whether the activation of the pro-apoptotic poly(adenosine diphosphate ribose) polymerase (PARP) pathway is involved in the induction of corporal apoptosis, and whether the administration of 3-aminobenzamide (3-AB), a specific PARP inhibitor, could ameliorate ED in diabetic rats. METHODS: Male Sprague-Dawley rats (8-weeks-old) were randomly divided into three groups: age-matched controls (C), diabetic controls (DM), and 3-AB-treated diabetic group (DM + 3-AB). Diabetes was induced by intraperitoneal (ip) injection of streptozotocin (50 mg/kg). Eight weeks after the induction of diabetes, DM + 3-AB group treated with 3-AB (30 mg/kg/day, ip) for 4 weeks. MAIN OUTCOME MEASURES: At 12 weeks after diabetes induction, erectile function was assessed by cavernous nerve stimulation. Penile tissue was assessed for apoptosis, Masson's trichrome stain and immunohistochemical analysis for smooth muscle alpha actin. Expression of poly(ADP-ribose), phospho-protein kinase B (Akt), phospho-Bcl-2-associated death promoter (Bad), B-cell leukemia/lymphoma 2 (Bcl-2), Bcl-2-associated X Protein (Bax), and apoptosis-inducing factor (AIF) were evaluated by Western blot. Caspase-3 activity and malondialdehyde (MDA), adenosine triphosphate (ATP), and nicotinamide adenine dinucleotide (NAD+) concentrations were also determined. RESULTS: DM group showed impaired erectile function, increased PARP activity and corporal apoptosis, and decreased smooth muscle contents. Expression of phospho-Akt, phospho-Bad, Bcl-2, and concentrations of ATP and NAD+ were decreased in the DM group, whereas concentrations of MDA, expression of Bax, nuclear translocation of AIF, and caspase-3 activity were increased. Treatment with 3-AB restored erectile function and significantly reversed all molecular and histological alterations except for the increased MDA. CONCLUSION: Over-activation of penile PARP pathway in diabetic rats enhances corporal apoptosis via energy depletion, suppression of Akt phosphorylation, and activation of the mitochondrial apoptotic pathway, which results in ED; these event could be prevented by treatment with 3-AB.