Survey of patient and partner satisfaction following collagenase Clostridium histolyticum treatment for Peyronie's disease.

Intralesional injection of collagenase Clostridium histolyticum (CCH) is a minimally invasive, Food and Drug Administration-approved, effective treatment for Peyronie's disease (PD). To assess the satisfaction of patients and their female sexual partners (FSP) following CCH therapy for PD, we conducted a retrospective review of the records of all patients treated with CCH for PD between 04/2014 and 03/2016. Collected variables included demographics, pre- and post-treatment sexual function, penile curvature, penile vascular findings, and treatment outcomes. Patients and their FSPs were subsequently contacted by telephone and queried regarding their ability to have intercourse and their satisfaction with treatment. A total of 24 couples responded to our questionnaire and constitute the subjects of this analysis. Patient and FSP satisfaction with treatment were 67% and 71%, respectively. Significant predictors of FSP satisfaction with treatment included recall of penile trauma during prior sexual intercourse, improved ability to have sexual intercourse following treatment, and absence of post-procedural glans hypoesthesia. In conclusion, CCH imparts a significant benefit on a couple's sexual health. Partner satisfaction with treatment is correlated with improved ability to have sexual intercourse and absence of patient glans hypoesthesia.

Characterisation of pomegranate juice effects on human corpus cavernosum.

Pomegranate (POM) juice may benefit the erectile process, but the scientific evidence is lacking. This study evaluates the molecular characterisation and confirmation of POM's action on human corpus cavernosum (HCC) obtained from patients (n = 16) undergoing penile prosthesis implantation. After phenylephrine contraction, the relaxant effects of POM with various inhibitors in the presence and absence of palmitic acid (PA)-induced acute oxidative stress were investigated. Electrical field stimulation (EFS)- and acetylcholine (ACh)-induced relaxation were performed using organ bath preparation. Expression of neuronal nitric oxide synthase (nNOS), endothelial (eNOS), phosphodiesterase (PDE)-5A and cGMP levels were assessed in cells from ex vivo organ cultures of HCC, using RT-PCR, ELISA and immunohistochemistry techniques. POM induced marked relaxation of HCC (maximum response: 97.0 ± 3.1%) and reversed the PA-induced decrease of EFS (20 Hz). nNOS transcription was increased by 7-fold in POM-treated cells without influencing eNOS and PDE5A expressions. We conclude that POM induced marked relaxation of HCC via: (i) nNOS stimulation, and (ii) downstream relaxation stimulated by nNOS and cGMP and bypassing the NO and PDE5. This action provides a rationale for the therapeutic or preventative use of POM in men with erectile dysfunction who do not respond well to PDE5 inhibitors.

Failure to attain stretched penile length after intracavernosal injection of a vasodilator agent is predictive of veno-occlusive dysfunction on penile duplex Doppler ultrasonography.

Penile duplex Doppler ultrasound (PDDU) assesses the etiology of erectile dysfunction. Peak systolic velocity (PSV), end-diastolic velocity (EDV), and resistive index (RI) are common PDDU parameters. We assessed whether stretched penile length (SPL) in the flaccid state and measured penile length at peak erection after intracavernosal injection (ICI) of a vasodilator during PDDU correlated with the etiology of erectile dysfunction. We performed a retrospective review of 93 patients who underwent PDDU for erectile dysfunction. Normal and stretched penile length were measured, both at a flaccid state prior to ICI and at peak erection during PDDU. Collected data included patient demographics, vascular, and anatomic parameters. The mean age was 52 years. SPL was equivalent to peak penile length after ICI in 60 patients (65%, group 1) and did not match in 33 (35%, group 2). There were no significant differences between the two groups in terms of flaccid, stretched, and post-ICI erect penile lengths, IIEF score, PSV, percent rigidity or tumescence, and vasodilator dose used. Patients in group 2 had less of a change in penile length from flaccid to erect state (36% vs. 44%, p = 0.02), higher EDV (12.0 vs. 8.5, p = 0.041), lower RI (0.6 vs. 1.0, p = 0.046), and more veno-occlusive dysfunction (82% vs. 53%, p = 0.001). On multivariate analysis, failure to reach maximum SPL at peak ICI erection (OR 2.255, CI 1.191-4.271, p = 0.0126), EDV (OR 1.281, CI 1.115-1.471, p < 0.001) and RI (OR 0.694, CI 0.573-0.723, p = 0.009) predicted veno-occlusive dysfunction. Failure to reach maximal SPL during PDDU using ICI with a vasodilator agent predicted veno-occlusive dysfunction, which is independent of both penile rigidity and tumescence. This measurement could serve as another diagnostic tool for predicting veno-occlusive dysfunction when PDDU is not readily available. Limitations include the subjective nature of penile measurements and different PGE1 doses used.

Differential expression of novel biomarkers (TLR-2, TLR-4, COX-2, and Nrf-2) of inflammation and oxidative stress in semen of leukocytospermia patients.

Chronic genitourinary inflammation results in Leukocytospermia (LCS), an elevated number of white blood cells (WBCs) in semen, which, in association with oxidative stress, may suppress sperm function, and manifest as male factor infertility. The current clinical diagnosis of LCS employs manual enumeration of WBCs and requires complex staining and laboratory skills or measurement of inflammatory cytokines and chemokines levels. Many patients with idiopathic infertility are asymptomatic. In search of better inflammatory markers for LCS, we evaluated expression of toll-like receptors 2 and 4 (TLR-2/4), cyclooxygenase-2 (COX-2), and nuclear factor (erythroid-derived 2)-like 2 (Nrf-2) in semen samples of age-matched infertile patients with and without LCS. We employed the usage of specific Western blot evaluation, cytokine array; immunofluorescence microscopy (IFM) followed by computer-based analysis, and other molecular approaches. As compared with non-LCS patients (n = 38), semen samples from LCS patients (n = 47) displayed significantly lower total sperm count (p < 0.01), motility (p < 0.0001), normal head count (p < 0.0001), and a significantly higher white blood cell count (p < 0.0001). Differential cytokine profiling of seminal plasma by antibody array revealed up-regulation of several pro-inflammatory chemokines in LCS samples. Western blot analysis of LCS seminal plasma (n = 15) also showed a significant increase in expression of TLR-2 (p < 0.001) and 4 (p < 0.01), COX-2 (p < 0.001), and Nrf-2 (p < 0.001) as compared with semen samples from non-LCS patients (n = 15). Computer-based objective IFM analysis of spermatozoa from LCS patients showed increased expression of TLR-4 (p < 0.001), Cox-2 (p < 0.01), and (Nrf-2) (p < 0.01). Significant differences in the subcellular localization of these proteins were evident in the sperm head and tail segments of LCS samples. Altogether, these observations suggest that TLR-2/4, COX-2, and Nrf-2 can serve as novel biomarkers of inflammation and oxidative stress. Therefore, developing a rapid assay for these biomarkers may facilitate early diagnosis and management of LCS especially in idiopathic and asymptomatic male infertility patients.

Therapeutic advances in the treatment of Peyronie's disease.

Peyronie's disease (PD) is an under-diagnosed condition with prevalence in the male population as high as 9%. It is a localized connective tissue disorder of the penis characterized by scarring of the tunica albuginea. Its pathophysiology, however, remains incompletely elucidated. For the management of the acute phase of PD, there are currently numerous available oral drugs, but the scientific evidence for their use is weak. In terms of intralesional injections, collagenase clostridium histolyticum is currently the only Food and Drug Administration-approved drug for the management of patients with PD and a palpable plaque with dorsal or dorsolateral curvature >30°. Other available intralesional injectable drugs include verapamil and interferon-alpha-2B, however, their use is considered off-label. Iontophoresis, shockwave therapy, and radiation therapy have also been described with unconvincing results, and as such, their use is currently not recommended. Traction therapy, as part of a multimodal approach, is an underused additional tool for the prevention of PD-associated loss of penile length, but its efficacy is dependent on patient compliance. Surgical therapy remains the gold standard for patients in the chronic phase of the disease. In patients with adequate erectile function, tunical plication and/or incision/partial excision and grafting can be offered, depending on degree of curvature and/or presence of destabilizing deformity. In patients with erectile dysfunction non-responsive to oral therapy, insertion of an inflatable penile prosthesis with or without straightening procedures should be offered.

Erectile dysfunction in urethral stricture and pelvic fracture urethral injury patients: diagnosis, treatment, and outcomes.

Urethral stricture disease, pelvic fracture urethral injury (PFUI), and their various treatment options are associated with erectile dysfunction (ED). The etiology of urethral stricture disease is multifactorial and includes trauma, inflammatory, and iatrogenic causes. Posterior urethral injuries are commonly associated with pelvic fractures. There is a spectrum in the severity of both conditions and this directly impacts the treatment options offered by the surgeon. Many published studies focus on the treatment outcomes and the relatively high recurrence rates after surgical repair. This communication reviews the current knowledge of the association between ED and urethral stricture disease, as well as PFUI. The incidence, pathophysiology, and clinical ramifications of both conditions on sexual function are discussed. The treatment options for ED in those patients are reviewed and summarized.

Comparison of infrapubic versus transcrotal approaches for inflatable penile prosthesis placement: a multi-institution report.

Inflatable penile prostheses (IPP) are associated with excellent long-term outcomes. To date, no study has evaluated the significance of surgical approach on IPP intraoperative variables. High-volume surgeons placing the Titan 0-degree prosthesis from March-July 2012 completed questionnaires including pre-/intraoperative variables. Intraoperative data were compared between surgeons performing an infrapubic versus transcrotal approach for total length of prosthesis, proximal and distal measurements, rear-tip extender (RTE) length, reservoir size and fill volume and ability to place the reservoir in the space of Retzius. Forty-six surgeons placed 256 IPPs, with a median of 5 (range 1-10) inserted. Transcrotal placement was performed most commonly (80%). Revision procedures accounted for 13% of cases, with 19% previously undergoing robotic-assisted prostatectomy. Compared with infrapubic, transcrotal placement resulted in a longer total prosthesis (22.3 cm vs 20.6 cm, P < 0.0001), increased proximal dilation (10.1 cm vs 8.6 cm, P < 0.0001), longer RTEs (1.9 cm vs 1.2 cm, P < 0.0001) and larger reservoir fill volume (79 cc vs 71 cc, P = 0.0003). No differences were noted in distal measurements or ability to place the reservoir in the space of Retzius. Compared with the infrapubic approach, high-volume surgeons placing the Titan 0-degree IPP transcrotally achieved increased proximal dilation with an ~1-2-cm-longer prosthesis inserted.

Effect of avanafil on rat and human corpus cavernosum.

We compared the activity of a new phosphodiesterase-5 inhibitor (PDE5i) avanafil with sildenafil and tadalafil in human and rat corpus cavernosum (CC) tissues. The effect of avanafil with several inhibitors and electrical field stimulation (EFS) was evaluated on CC after pre-contraction with phenylephrine. With the PDE5i, sildenafil and tadalafil, concentration-response curves were obtained and cyclic guanosine monophosphate (cGMP) levels were measured in tissues. Avanafil induced relaxation with maximum response of 74 ± 5% in human CC. This response was attenuated by NOS inhibitor and soluble guanylate cyclase (sGC) inhibitor. Avanafil potentiated relaxation responses to acetylcholine and EFS in human CC and enhanced SNP-induced relaxation and showed 3-fold increase in cGMP levels. When compared with sildenafil, avanafil and tadalafil were effective at lower concentrations in human CC. In addition, Sprague-Dawley rats underwent in vivo intracavernosal pressure (ICP) and mean arterial pressure (MAP) measurements. Avanafil increased ICP/MAP that was enhanced by SNP and cavernous nerve (CN) stimulation in rat CC tissues. Also avanafil showed maximum relaxation response of 83 ± 7% in rat CC with 3-fold increase in cGMP concentration. Taken together, these results of our in vivo and in vitro studies in human and rat suggest that avanafil promotes the CC relaxation and penile erection via NO-cGMP pathway.

The direction and severity of penile curvature does not have an impact on concomitant vasculogenic erectile dysfunction in patients with Peyronie's disease.

Although the association between Peyronie's disease (PD) and erectile dysfunction (ED) is well established, limited data are available correlating penile curvature and penile hemodynamic parameters. We sought to examine this association in a cohort of PD men undergoing penile duplex Doppler ultrasound (PDDU). PD patients were retrospectively evaluated to correlate the extent and direction of penile curvature with measured vascular parameters. Demographic variables, disease characteristics and PDDU parameters were tabulated and statistically compared based on extent (≤ 45° and >45°) and direction (dorsal, ventral, lateral, ventrolateral, dorsolateral) of curvature. A total of 220 PD patients (mean age of 55.0 ± 9.2 years) underwent PDDU at one institution from January 2008 to December 2010. Overall, 69.5% of patients were found to have vasculogenic ED (arterial insufficiency (AI): 10%; veno-occlusive dysfunction (VOD): 43.2%; AI + VOD: 16.4%). Mean curvature was similar among all PDDU groups (AI: 41.7 ± 5.2°; VOD: 41.3 ± 2.5°; AI+VOD: 37 ± 4.1°; no-ED: 37.3 ± 3°; P > 0.85). No significant differences were noted in the presence or type of ED among various directions of curvature (P = 0.34) or when curvatures were stratified by ≤ 45° and >45°. The direction and extent of penile curvature are not associated with altered rates of vasculogenic ED on PDDU in PD patients.

The pre-treatment prevalence and types of sexual dysfunction among patients diagnosed with prostate cancer.

Erectile dysfunction (ED) following prostate cancer therapy is a common condition that is well documented in literature. Despite the significant focus placed on ED and prostate cancer, very little is known regarding the baseline prevalence of other aspects of sexual dysfunction (SD) in this specific cohort of patients. The objective of the current manuscript was to assess the prevalence of subtypes of SD, including ED, ejaculatory dysfunction (EjD) and decreased libido among men with newly diagnosed prostate cancer. To achieve this objective, patients presenting to our clinic with a new diagnosis of prostate cancer from July 2011 and May 2012 completed the Male Sexual Health Questionnaire (MSHQ) to assess baseline sexual function. A total of 60 patients completed an MSHQ, with a mean age of 60.28 ± 6.25 (range 44-73 years). Of patients surveyed, 14% reported no sexual activity within the previous month, while 53% had sex at least once weekly. The percentage of patients reporting ED, EjD and decreased sexual desire ≥50% of the time was 37, 26 and 48% respectively. Eleven to 18% of patients reported that these symptoms were 'very' or 'extremely' bothersome. Patients noted dissatisfaction with the quality of their sexual relationship, frequency of sexual activity and quality of sex in 18, 31 and 20%, respectively. Overall findings suggest that patients with newly diagnosed prostate cancer experience a high rate of SD at baseline. Knowledge of these prevalence rates may assist physicians managing patient's expectations with planned therapies.

Understanding the course of Peyronie's disease.

AIMS: To correct common misconceptions about Peyronie's disease (PD) that present obstacles to early recognition and treatment. METHODS: The prevalence, natural disease course, psychosocial effects and treatment considerations for patients with PD were reviewed. RESULTS: Studies over the past decade have shown that the prevalence of PD may be higher (up to 20%) than previously thought. PD can lead to emotional and relationship distress. Nearly 10% of men who present with PD are younger than 40. Both younger age and comorbid vascular disease have been associated with more severe and progressive PD. In the majority of patients, symptoms will either deteriorate or remain stable. PD is often associated with erectile dysfunction (ED). Effective, minimally invasive treatments used early in the disease course include unapproved and/or investigational intralesional injection therapy with verapamil, interferon (IFN) α-2b, or collagenase clostridium histolyticum (CCH). Surgical intervention is considered in patients with ED and/or penile deformity that impairs sexual functioning; however, preoperative discussion of appropriate expectations is important. DISCUSSION: The availability of effective minimally invasive and surgical therapies for PD suggests that active management should be considered over a 'wait-and-see' approach. CONCLUSION: Providing early intervention and improved education/awareness of PD as a chronic and progressive disorder may result in improved physical and psychosocial outcomes for PD patients. As general practitioners are often the first contact for men with PD, they are well positioned to recognise symptoms early and promptly refer patients for further evaluation and treatment.

Does a replacement or revision of an inflatable penile prosthesis lead to decreased patient satisfaction?

To analyze the reason for replacement, revision and overall satisfaction of a cohort who underwent surgical replacement of an inflatable penile prosthesis (IPP). A cohort of 105 patients who underwent IPP replacement from 2005-2007 was retrieved from the prosthesis database. Approximately 21.9% (23) underwent replacement or revision of their prosthesis because of complications, and were further analyzed. Reason for removal was stratified into infectious and non-infectious (erosion, non-function and patient discomfort). Age, race (African American vs non-African American), smoking history, hypertension, diabetes, coronary artery disease and hyperlipidemia were stratified by reason for removal. Finally, we contacted patients and recorded subjective satisfaction with their IPP. The reason for removal was most commonly because of a non-functional IPP (47.8%), followed by infection (30.4%), erosion (17.4%) and patient discomfort (4.3%). Age and race did not show a significant difference when analyzing reason for replacement (P > 0.05). Patients who were smokers (P = 0.907) had hypertension (P = 0.554), diabetes (P = 0.591) or hyperlipidemia (P = 0.219) did not have significantly higher infection rates. Approximately 58.3% were satisfied with their prosthesis, 75% would have the surgery performed again and 91.7% would still recommend prosthesis surgery. Device malfunction was the primary reason for replacement/removal at our institution. Despite the complications of prosthesis reoperation, the majority of patients were still satisfied with their prosthesis, would have the surgery performed again and would recommend prosthesis surgery to a friend.

Update on treatments for premature ejaculation.

Current and upcoming treatment options for premature ejaculation (PE) are of global clinical interest. In 2008, the International Society for Sexual Medicine published an evidence-based definition for PE. While there are no US Food and Drug Administration-approved therapies for PE, the American Urological Association 2004 guidelines state the serotonergic antidepressants paroxetine, sertraline, fluoxetine and clomipramine and the topical lidocaine-prilocaine cream are effective treatment options. However, there are limitations associated with their use, which may be overcome by PE-specific therapies currently in development. Two agents that are in advanced stages of clinical development include: (i) dapoxetine, an on-demand short-acting selective serotonin reuptake inhibitor, and (ii) PSD502, a metered-dose aerosol containing lidocaine and prilocaine, also for on-demand treatment. Another on-demand agent in development is tramadol, a weak opioid that is currently approved for treating pain. Coupled with efficient diagnosis, it is hoped that these newer agents will improve the quality of life for patients who suffer from PE.

Dapoxetine for premature ejaculation.

Premature ejaculation (PE) is the most common form of male sexual dysfunction, with an estimated worldwide prevalence of 20­30%.1 Although PE is not life threatening, it has significant impact on quality of life. The fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR)defines PE as "persistent or recurrent ejaculation with minimal sexual stimulation before, on, or shortly after penetration and before the person wishes it" that "causes marked distress or interpersonal difficulty" and "is not due exclusively to the direct effects of a substance."2 The International Society for Sexual Medicine, which recently modified the definition to include the threshold ejaculatory latency time, defines PEas "male sexual dysfunction characterized by ejaculation which always or nearly always occurs prior to or within 1 min of vaginal penetration; the inability to delay ejaculation on all or nearly all vaginal penetrations; and negative personal consequences such as distress, bother, frustration, and/or the avoidance of sexual intimacy."3 The lack of ejaculatory control is consistent among all clinical definitions of PE and is a highly sensitive predictor of the condition.

Available and future therapies for premature ejaculation.

Premature ejaculation (PE), the most common male sexual dysfunction, impacts the quality of life of not only the affected male but also his partner. Despite its prevalence, there are currently no United States Food and Drug Administration-approved therapies for PE. In 2004, the American Urological Association published treatment guidelines for PE that recommended the serotonergic antidepressants paroxetine, sertraline, clomipramine and fluoxetine, as well as topical lidocaine-prilocaine cream. None of these treatments were developed for PE, and all have limitations associated with their use. Therapies in development may have advantages over the currently available treatments. These include PSD-502, a metered-dose aerosol of lidocaine and prilocaine used as an on-demand local treatment, and dapoxetine, an on-demand short-acting selective serotonin reuptake inhibitor. Together with a recent, evidence-based definition of PE, these novel therapies should improve sexual function and quality of life in men suffering from PE.

Clinical applications of centrally acting agents in male sexual dysfunction.

Currently available agents for erectile dysfunction (ED) share the same mechanism of action and pharmacologic properties. Therefore, they share the same limitations, including a principal focus on erection as an end-organ process. One of the relatively unexplored areas of research has been the potential for centrally acting agents to improve male sexual response. A variety of neurohormones and neurotransmitter systems are involved in the male sexual response, including testosterone, dopamine, serotonin and the melanocortin systems. Investigations to determine the utility of centrally acting agents as monotherapy or adjunctive therapy in men with ED or other forms of sexual dysfunction are underway. Bremelanotide, a melanocortin agonist, has been tested in men with ED and may prove to be one of the first centrally acting agents to have clinical utility in male sexual dysfunction.

Current safety and tolerability issues in men with erectile dysfunction receiving PDE5 inhibitors.

AIMS: Treatment of erectile dysfunction (ED) has been greatly advanced by the advent of phosphodiesterase type-5 (PDE5) inhibitors. Upon the introduction of these agents, their cardiovascular (CV) safety was a major concern, mainly due to their vasodilatory effects. We conducted an electronic literature review of data concerning the safety and tolerability issues of men with ED receiving PDE5 inhibitors. RESULTS: Although safety concerns have been raised, evaluation of CV safety and related adverse events in clinical trials has not revealed any atypical safety issues. DISCUSSION: No causal association has been established to date between non-arteritic anterior ischaemic optic neuropathy (NAION) and PDE5 inhibitors. In addition, there are established guidelines which provide recommendations for the safe and effective use of these agents in treating men with ED and associated comorbidities. CONCLUSIONS: Clinical trial and postmarketing surveillance data confirm the safety and tolerability profile of the PDE5 inhibitors, even in patients with endothelial dysfunction-associated comorbidities.

Gene and stem cell therapy for erectile dysfunction.

Erectile dysfunction (ED) is defined as the inability to attain and/or maintain penile erection sufficient for satisfactory sexual performance. ED is a highly prevalent health problem with considerable impact on the quality of life of men and their partners. Although the treatment of ED with oral phosphodiesterase type V (PDE5) inhibitors is effective in a wide range of individuals, it is not efficacious in all patients. The failure of PDE5 inhibitors happens mainly in men with diabetes, non-nerve sparing radical prostatectomy, and high disease severity. Therefore, improved therapies based on a better understanding of the fundamental issues in erectile physiology and pathophysiology have recently been proposed. Here, we summarize studies on ED treatment using gene and stem cell therapies. Adenoviral-mediated intracavernosal transfer of therapeutic genes, such as endothelial nitric oxide synthase (eNOS), calcitonin gene-related peptide (CGRP), superoxide dismutase (SOD), and RhoA/Rho kinase and mesenchymal stem cell-based cell and gene therapy strategy for the treatment of age- and diabetes-related ED are the focus of this review.