The Diagnosis and Management of Recurrent Ischemic Priapism, Priapism in Sickle Cell Patients, and Non-Ischemic Priapism: An AUA/SMSNA Guideline.

PURPOSE: Priapism is a persistent penile erection that continues hours beyond, or is unrelated to, sexual stimulation and results in a prolonged and uncontrolled erection. Given its time-dependent and progressive nature, priapism is a situation that both urologists and emergency medicine practitioners must be familiar with and comfortable managing. METHODOLOGY: A comprehensive search of the literature on acute ischemic priapism and non-ischemic priapism (NIP) was performed by Emergency Care Research Institute for articles published between January 1, 1960 and May 1, 2020. A search of the literature on NIP, recurrent priapism, prolonged erection following intracavernosal vasoactive medication, and priapism in patients with sickle cell disease was conducted by Pacific Northwest Evidence-based Practice Center for articles published between 1946 and February 19, 2021. Searches identified 4117 potentially relevant articles, and 3437 of these were excluded at the title or abstract level for not meeting inclusion criteria. Full texts for the remaining 680 articles were ordered, and ultimately 203 unique articles were included in the report. RESULTS: This Guideline provides a clinical framework for the treatment (non-surgical and surgical) of NIP, recurrent ischemic priapism, and priapism in patients with sickle cell disease. The treatment of patients with a prolonged erection following intracavernosal vasoactive medication is also included. The AUA guideline on the diagnosis of priapism and the treatment of acute ischemic priapism was published in 2021. CONCLUSIONS: All patients with priapism should be evaluated emergently to identify the sub-type of priapism (acute ischemic versus non-ischemic) and those with an acute ischemic event should be provided early intervention when indicated. NIP is not an emergency and treatment must be based on patient objectives, available resources, and clinician experience. Management of recurrent ischemic priapism requires treatment of acute episodes and a focus on future prevention of an acute ischemic event. Sickle cell disease patients presenting with an acute ischemic priapism event should initially be managed with a focus on urologic relief of the erection; standard sickle cell assessment and interventions should be considered concurrent with urologic intervention. Treatment protocols for a prolonged, iatrogenic erection must be differentiated from protocols for true priapism.

Impact of Baseline Total Testosterone Level on Successful Treatment of Sexual Dysfunction in Men Taking Once-Daily Tadalafil 5 mg for Lower Urinary Tract Symptoms and Benign Prostatic Hyperplasia: An Integrated Analysis of Three Randomized Controlled Trials.

INTRODUCTION: Controversy exists as to whether erectile response to phosphodiesterase type 5 inhibitors is compromised in men with low total testosterone (TT) levels. This is amplified by reports of improved response to phosphodiesterase type 5 inhibitor therapy after coadministration of testosterone replacement therapy in hypogonadal men unresponsive to phosphodiesterase type 5 inhibitors. AIM: To determine whether TT and luteinizing hormone levels influence efficacy of tadalafil for erectile dysfunction in men with concomitant lower urinary tract symptoms and benign prostatic hyperplasia. METHODS: This integrated analysis included 1,075 men randomized to once-daily tadalafil 5 mg (n = 540) or placebo (n = 535) for 12 weeks in three prospective clinical trials who had not received concomitant testosterone replacement therapy. Subjects were categorized at baseline by low vs normal TT levels (n = 1,049; <300 vs ≥300 ng/dL) and normal vs high luteinizing hormone levels (n = 1,058; ≤9.4 vs >9.4 mIU/mL). Treatment-group differences in International Index of Erectile Function (IIEF) by hormone subgroups were assessed using analysis of covariance. MAIN OUTCOME MEASURES: Changes in IIEF erectile function domain and other domain scores. RESULTS: The overall study population was comprised primarily of white men (>86%) with a mean age range of 64 to 70 years. Median baseline TT level in the integrated population was 355 ng/dL; levels were lower than 300 ng/dL (cutoff for normal) in 32.4% of men. Men with low TT levels reported diabetes (21.8%), cardiovascular disease (54.1%), and hypertension (49.1%) numerically more often than men with normal TT levels (10.6%, 43.2%, and 36.7%, respectively). Low TT and high luteinizing hormone levels were associated with numerically, but not statistically significantly, lower 12-week IIEF domain scores compared with those with normal levels. Changes in most 12-week IIEF domain scores showed that tadalafil was significantly more effective than placebo (P < .02). CONCLUSION: Low TT levels at baseline did not negatively influence response to tadalafil in men of advancing age with concomitant lower urinary tract symptoms and benign prostatic hyperplasia and erectile dysfunction.

Proportion of tadalafil-treated patients with clinically meaningful improvement in lower urinary tract symptoms associated with benign prostatic hyperplasia ­ integrated data from 1,499 study participants.

OBJECTIVES: To evaluate the proportion of patients achieving clinically meaningful improvement of lower urinary tract symptoms suggestive of benign prostatic hyperplasia (BPH-LUTS) with tadalafil using two definitions of response. PATIENTS AND METHODS: Post hoc integrated analysis of four placebo-controlled studies in men (aged ≥45 years; International Prostate Symptom Score [IPSS] of ≥13; maximum urinary flow rate [Q(max)] of ≥4 to ≤15 mL/s) with BPH-LUTS randomised to tadalafil 5 mg (752 patients) or placebo (747) for 12 weeks after a 4-week placebo run-in. Responders were defined as having a total IPSS improvement of ≥3 points or ≥25% from randomisation to endpoint (Week 12). Response status was calculated per patient, and relative benefit and odds ratio (OR) with 95% confidence interval (CI) of tadalafil vs placebo was calculated using a logistic Generalised Mixed Model for Repeated Measures. RESULTS: Tadalafil 5 mg once daily resulted in a significantly greater proportion of patients achieving a ≥3-point IPSS improvement (71.1% and 56.0% for tadalafil and placebo patients, respectively [OR 1.9, 95% CI 1.5, 2.4; P < 0.001]) and achieving a ≥25% improvement in total IPSS randomisation to endpoint (61.7% and 45.5% for tadalafil and placebo patients, respectively [OR 2.0, 95% CI 1.6, 2.5; P < 0.001]). CONCLUSION: About two-thirds of tadalafil-treated patients achieve a clinically meaningful improvement in BPH-LUTS symptoms, based on two different definitions of responder status.

Direct effects of tadalafil on lower urinary tract symptoms versus indirect effects mediated through erectile dysfunction symptom improvement: integrated data analyses from 4 placebo controlled clinical studies.

PURPOSE: Tadalafil has regulatory approval for the treatment of men with signs/symptoms of benign prostatic hyperplasia with and without erectile dysfunction. We assessed whether the effects of treatment with tadalafil for lower urinary tract symptoms/benign prostatic hyperplasia are independent of improvements in erectile dysfunction. MATERIALS AND METHODS: Four separate analyses used integrated data from 4 randomized, double-blind, placebo controlled studies in men with lower urinary tract symptoms/benign prostatic hyperplasia with and without erectile dysfunction to test whether total I-PSS (International Prostate Symptom Score) improvement was due to improvement in IIEF-EF (International Index of Erectile Function-Erectile Function domain score). Unidirectional and bidirectional path analysis models determined direct and indirect treatment effects mediated by improvements in lower urinary tract symptoms/benign prostatic hyperplasia and erectile dysfunction symptoms. RESULTS: A total of 1,496 men, of whom 77% had erectile dysfunction, received at least 1 dose of tadalafil 5 mg once daily or placebo. The placebo adjusted treatment effect for men with erectile dysfunction was represented by a mean decrease of -2.3 (p <0.0001) in total I-PSS vs -2.2 (p = 0.0007) for men without erectile dysfunction. The correlation between change from baseline in total I-PSS and IIEF-EF was weak (r(2) = 0.08, p <0.0001). The unidirectional path analysis model suggested that the total treatment effect on total I-PSS score improvement (2.25) was derived from a direct treatment effect of 1.57 (70%, p <0.001) and an indirect treatment effect of 0.67 (30% via IIEF-EF improvement, p <0.001). Bidirectional path analysis showed that total I-PSS improvement was largely attributed to direct (92.5%, p <0.001) vs indirect (7.5%, p = 0.32) treatment effects via IIEF-EF improvement. CONCLUSIONS: Regardless of the analytical approach, self-reported erectile dysfunction status did not appreciably influence tadalafil treatment response in men with lower urinary tract symptoms/benign prostatic hyperplasia, supporting the dual action of tadalafil on lower urinary tract symptoms/benign prostatic hyperplasia and erectile dysfunction.

Three-year outcomes of recovery of erectile function after open radical prostatectomy with sural nerve grafting.

INTRODUCTION: Optimal oncologic control of higher stage prostate cancers often requires sacrificing the neurovascular bundles (NVB) with subsequent postoperative erectile dysfunction (ED), which can be treated with interposition graft using sural nerve. AIMS: To examine the long term outcome of sural nerve grafting (SNG) during radical retropubic prostatectomy (RRP) performed by a single surgeon. METHODS: Sixty-six patients with clinically localized prostate cancer and preoperative International Index of Erectile Function (IIEF) score >20 who underwent RRP were included. NVB excision was performed if the risk of side-specific extra-capsular extension (ECE) was >25% on Ohori' nomogram. SNG was harvested by a plastic surgeon, contemporaneously as the urologic surgeon was performing RRP. IIEF questionnaire was used pre- and postoperatively and at follow-up. MAIN OUTCOME MEASURES: Postoperative IIEF score at three years of men undergoing RRP with SNG. Recovery of potency was defined as postoperative IIEF-EF domain score >22. RESULTS: There were 43 (65%) unilateral SNG and 23 (35%) bilateral SNG. Mean surgical time was 164 minutes (71 to 221 minutes).The mean preoperative IIEF score was 23.4+1.6. With a mean follow-up of 35 months, 19 (28.8%) patients had IIEF score >22. The IIEF-EF scores for those who had unilateral SNG and bilateral SNG were 12.9+4.9 and 14.8+5.3 respectively. History of diabetes (P=0.001) and age (P=0.007) negatively correlated with recovery of EF. 60% patients used PDE5i and showed a significantly higher EF recovery (43% vs. 17%, P=0.009). CONCLUSIONS: SNG can potentially improve EF recovery for potent men with higher stage prostate cancer undergoing RP. The contemporaneous, multidisciplinary approach provides a good quality graft and expedited the procedure without interrupting the work-flow.

Clinical outcomes and patient satisfaction rates among elderly male aged ≥75 years with inflatable penile prosthesis implant for medically refractory erectile dysfunction.

PURPOSE: The purpose of the study is to assess the clinical outcomes and patient satisfaction rate between men aged under and over 75 years who underwent inflatable penile prosthesis (IPP) implantation. METHODS AND MATERIALS: A retrospective review of clinical database and follow-up independent telephone survey was undertaken in all men who underwent first-time IPP implantation between January 2006 and November 2010. Patient demographics, surgical outcomes, and patient satisfaction rate using Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) scores were recorded. RESULTS: A total of 216 first-time IPP were implanted. Of these, 30 patients were aged ≥75 years. In men aged ≥75 years, 3 patients had IPP revision surgery for mechanical malfunction (average 18.6 months; 12-24 months). While the 2-year Kaplan-Meier estimates of mechanical survival showed better outcome in men aged ≥75 years than men aged <75 years (95 vs. 92%; p = 0.38), there was no difference in the IPP mechanical survival between the 2 groups at 3 years follow-up. There were no statistically significant differences in the ease of IPP use, and EDITS scores among the two groups. The majority of men were satisfied and would recommend the IPP surgery to other men. CONCLUSIONS: Men aged ≥75 years reported satisfactory outcome with IPP surgery with no statistical significant difference identified across device survival and satisfaction rates compared to men aged <75 years.

A comparative study of the efficacy of intralesional verapamil versus normal saline injection in a novel Peyronie disease animal model: assessment of immunohistopathological changes and erectile function outcome.

PURPOSE: While intralesional injections improve penile curvature and decrease plaque volume, the exact mechanism of action on Peyronie disease is unknown. We evaluated penile curvature, immunohistology and erectile function outcomes after intralesional injections of verapamil and normal saline in a previously described Peyronie disease animal model. MATERIALS AND METHODS: Peyronie plaque was induced in 12 adult male rats using an established Peyronie disease animal model. At 4 weeks the rats were divided into group 1-5 with 0.1 mg/0.1 ml intralesional verapamil injected every second day for 2 weeks, group 2-5 with 0.1 ml intralesional normal saline injection and group 3-2 that served as controls. At weeks 6 and 8 penile pressure was measured and serial immunohistochemical staining of penile tissue sections was done. RESULTS: Intralesional injection of verapamil and normal saline resulted in macroscopic and microscopic changes to penile curvature and Peyronie plaque size. Decreased collagen and elastin fibers were measured with a significant reduction in smooth muscle α-actin (p <0.05). Changes were greater in group 1 than group 2 (p <0.05). Intralesional verapamil injection was associated with greater recovery of electrostimulated penile pressure, a surrogate of erectile function, than in the saline and control groups. CONCLUSIONS: To our knowledge this novel study offers for the first time histological evidence of cellular changes and improvement in penile pressure studies in rats with Peyronie plaque after intralesional verapamil injection therapy in a Peyronie disease animal model.

Comparison between AMS 700™ CX and Coloplast™ Titan inflatable penile prosthesis for Peyronie's disease treatment and remodeling: clinical outcomes and patient satisfaction.

INTRODUCTION: The implantation of inflatable penile prosthesis (IPP) with simultaneous manual penile remodeling allows for men to undergo a single procedure aimed at correcting both the penile deformity/curvature and erectile dysfunction (ED). AIM: To evaluate the clinical outcomes and patient satisfaction in men with Peyronie's disease (PD) and ED who underwent AMS 700™ CX and the newer Coloplast™ Titan inflatable penile prosthesis (IPP) implant. MAIN OUTCOME MEASURES: Patient demographics, type of IPP, clinical outcomes, post-implant sexual characteristics, and overall patient satisfaction. METHODS: A single-center retrospective review of clinical database and prospective telephone survey were conducted in all men with PD who underwent IPP between January 2006 and November 2010. RESULTS: A total of 138 patients with an average age of 57.7 (32 to 80) underwent AMS 700 CX (88 patients) and Coloplast Titans (50 patients) IPP implantation during the 5-year period. The majority of patients (91%) had only one IPP implantation. The IPP clinical outcomes include eight (6%) revision surgery for device malfunction and three (2%) device explantation for prosthesis infection. While there was no statistically significance in device survival between the two devices, the trend favored AMS 700 CX over Titan (5-year Kaplan-Meier estimates of mechanical survival were 91% vs. 87%, P>0.05) and both IPPs provided similar penile straightening without the need for revision surgery. Most men (79%) reported great satisfaction following CX or Titan implants with greater than two thirds of men reported greater self-confidence and 82% of patients would undergo the same operation again. CONCLUSIONS: AMS 700™ CX and Coloplast™ Titan IPP implantation and penile remodeling appeared to provide permanent penile straightening and high patient satisfaction without an increase risk of revision surgery.

Peyronie's disease and mechanotransduction: an in vitro analysis of the cellular changes to Peyronie's disease in a cell-culture strain system.

INTRODUCTION: Penile traction therapy (PTT) has gained considerable popularity as a noninvasive treatment option in Peyronie's disease (PD) to improve penile curvature and length. However the exact mechanism of action of PTT is unknown and as yet unproven. AIM: Using a cyclic strain culture system, we investigate the cellular changes to the tunical tissues following equibiaxial tractional forces. The observed protein alteration following mechanical traction should replicate the changes observed in tunical tissue following PTT. METHODS: Flexcell FX-5000(TM) Tension Plus system (Flexcell International Corporation, McKee-sport, PA, USA) is a pressurized chamber system that allows for sustained and dynamic application of hydrostatic pressure to cellular culture. Primary cell cultures from PD and normal tunical tissue (control) were sub-cultured on BioFlex-ProNectin plate 1 × 106 (Flexcell International Corporation, Hillsborough, NC, USA) for 24 hours and exposed to Flexcell sinusoidal strain of 18% at 1 Hz (strained group) on the biaxial plates for 24 hours under 37 °C in a 5% CO2 atmosphere. MAIN OUTCOMES MEASURES: Immunohistochemistry (IHC) stains and Western blot assays between strained and nonstrained (control) cells. RESULTS: Significant increase in smooth muscle α-actin, ß-catenin, and Hsp 47 proteins were measured in the PD group compared with control group. IHC staining revealed a decrease in α-actin staining while Western blot assay showed an increase in metalloproteinase-8 expression with no measured change in ß-catenin level in the strained PD group. CONCLUSIONS: This novel study of cells derived from diseased and normal human tunica albuginea cultured in a mechanical strained environment provides good scientific evidence for the use of penile traction device in Peyronie's plaque remodeling.

Daily dosing of PDE5 inhibitors: where does it fit in?

To provide a critical contemporary review of daily PDE5-inhibitor (PDE5-I) use in urological and nonurological conditions. PDE5-Is can be taken up to once a day. However, at present only tadalafil is approved for use in both erectile dysfunction (ED) and benign prostate hyperplasia (BPH) with lower urinary tract symptoms (LUTS). Evolving research in penile rehabilitation, Peyronie's disease, male infertility, pulmonary arterial hypertension, muscular dystrophy and Raynaud's phenomenon shows these therapeutic areas may also benefit from PDE5i therapy. This review examines the role of chronic PDE5 inhibition in ED, BPH-LUTS and other therapeutic targets which may shape our clinical practice in the years to come.

Symptomatic benefits of testosterone treatment in patient subgroups: a systematic review, individual participant data meta-analysis, and aggregate data meta-analysis.

BACKGROUND: Testosterone replacement therapy is known to improve sexual function in men younger than 40 years with pathological hypogonadism. However, the extent to which testosterone alleviates sexual dysfunction in older men and men with obesity is unclear, despite the fact that testosterone is being increasingly prescribed to these patient populations. We aimed to evaluate whether subgroups of men with low testosterone derive any symptomatic benefit from testosterone treatment. METHODS: We did a systematic review and meta-analysis to evaluate characteristics associated with symptomatic benefit of testosterone treatment versus placebo in men aged 18 years and older with a baseline serum total testosterone concentration of less than 12 nmol/L. We searched major electronic databases (MEDLINE, Embase, Science Citation Index, and the Cochrane Central Register of Controlled Trials) and clinical trial registries for reports published in English between Jan 1, 1992, and Aug 27, 2018. Anonymised individual participant data were requested from the investigators of all identified trials. Primary (cardiovascular) outcomes from this analysis have been published previously. In this report, we present the secondary outcomes of sexual function, quality of life, and psychological outcomes at 12 months. We did a one-stage individual participant data meta-analysis with a random-effects linear regression model, and a two-stage meta-analysis integrating individual participant data with aggregated data from studies that did not provide individual participant data. This study is registered with PROSPERO, CRD42018111005. FINDINGS: 9871 citations were identified through database searches. After exclusion of duplicates and publications not meeting inclusion criteria, 225 full texts were assessed for inclusion, of which 109 publications reporting 35 primary studies (with a total 5601 participants) were included. Of these, 17 trials provided individual participant data (3431 participants; median age 67 years [IQR 60-72]; 3281 [97%] of 3380 aged ≥40 years) Compared with placebo, testosterone treatment increased 15-item International Index of Erectile Function (IIEF-15) total score (mean difference 5·52 [95% CI 3·95-7·10]; τ2=1·17; n=1412) and IIEF-15 erectile function subscore (2·14 [1·40-2·89]; τ2=0·64; n=1436), reaching the minimal clinically important difference for mild erectile dysfunction. These effects were not found to be dependent on participant age, obesity, presence of diabetes, or baseline serum total testosterone. However, absolute IIEF-15 scores reached during testosterone treatment were subject to thresholds in patient age and baseline serum total testosterone. Testosterone significantly improved Aging Males' Symptoms score, and some 12-item or 36-item Short Form Survey quality of life subscores compared with placebo, but it did not significantly improve psychological symptoms (measured by Beck Depression Inventory). INTERPRETATION: In men aged 40 years or older with baseline serum testosterone of less than 12 nmol/L, short-to-medium-term testosterone treatment could provide clinically meaningful treatment for mild erectile dysfunction, irrespective of patient age, obesity, or degree of low testosterone. However, due to more severe baseline symptoms, the absolute level of sexual function reached during testosterone treatment might be lower in older men and men with obesity. FUNDING: National Institute for Health and Care Research Health Technology Assessment Programme.

Penile Doppler sonographic and clinical characteristics in Peyronie's disease and/or erectile dysfunction: an analysis of 1500 men with male sexual dysfunction.

UNLABELLED: What's known on the subject? and What does the study add? Penile colour Doppler ultrasonography (CDU) can be an invaluable investigative tool to characterize penile abnormalities to complement clinical history and physical examination in the evaluation of men with Peyronie's disease (PD) and/or erectile dysfunction (ED). Although CDU findings between men with PD and those with ED were not markedly different, subtle differences were observed. The classic penile CDU findings in men with PD comprise tunical thickening, intracavernosal fibrosis, septal fibrosis and intracavernosal calcification, while, in men with ED, low peak systolic velocity and high end-diastolic velocity are found on penile haemodynamics. Previously published studies have focused predominantly on either ED or PD exclusively, or examine the risk of progression to ED in the PD population. To our knowledge, this is the largest and most comprehensive analysis of penile CDU and clinical findings in men with PD and/or ED. The large sample size and multivariable analysis allow meaningful interpretation of the results. This study has found some substantial differences in the penile CDU findings of men with PD and/or ED that have not previously been reported. Although the risk factors of ED may be greater than those for PD, there is crossover in age, cardiovascular risk factors, trauma and penile CDU findings in men with PD and/or ED. OBJECTIVE: To explore the differences in penile colour Doppler ultrasonography (CDU) findings between men with Peyronie's disease (PD) and those with erectile dysfunction (ED). MATERIALS AND METHODS: Patients presenting with PD and/or ED who underwent penile CDU were recruited to the study. Patient demographics, comorbidities, International Index of Erectile Function-5 scores, previous therapies and physical findings were documented. Penile curvature, presence of tunical thickening, septal fibrosis, intracavernosal fibrosis and calcification, and cavernosal vascular status were recorded. RESULTS: A total of 1500 men underwent penile CDU during the 10-year period. Of these men, 891 men presented with PD and 609 men had ED only. Men with ED had higher rates of diabetes and coronary artery disease (P < 0.05). Isolated tunical thickening was more common in older men and in the PD cohort. The presence of intracavernosal fibrosis correlated strongly with difficulty maintaining erection (P < 0.05). Impaired cavernosal arterial flow was observed in men with decrease penile rigidity and penile pain, while higher end-diastolic velocities were found in men with difficulty maintaining erection and tunical thickening on penile CDU. CONCLUSIONS: Men with PD and ED had many similarities and differences on penile CDU. Penile CDU continues to be an invaluable clinical tool in the management of men with male sexual dysfunction.

How to evaluate the efficacy of the phosphodiesterase type 5 inhibitors.

INTRODUCTION: Several methods have been so far proposed to compare the effectiveness of the three available phosphodiesterase type 5 inhibitors (PDE5Is). METHODS: Two urologists (E.C. and G.B.B.), together with the Controversy's Editor (E.A.J.), with expertise in the area of medical treatment of erectile dysfunction (ED) present the various perspectives on the evaluation of PDE5Is in ED. The use of the most popular psychometric tool, the International Index of Erectile Function, is presented by an expert psychologist (L.R.D.). MAIN OUTCOME MEASURES: Expert opinion supported by the critical review of the currently available literature. RESULTS: Trials have demonstrated that the PDE5Is are excellent drugs with a great specificity of action and an almost perfect tolerance profile. Some instruments for comparison of clinical efficacy have to be considered subjective (psychometry, patient's preference, changes in quality of general, or sexual life). Some others are more objective (hardness, hormonal levels, and local circulation). An evidence-based comparison of the three PDE5Is should in the future be rooted in both subjective and objective methods. This will be of paramount importance in the drug trial design of new, forthcoming PDE5Is. CONCLUSIONS: Comparison between PDE5Is using both subjective and objective parameters will permit to individuate, on the basis of the evidence, the subset of couples where one drug, or one dose, or dose regimen, is to be considered of first choice.

Chronic pain associated with penile prostheses may persist despite revision or explantation.

INTRODUCTION: Inflatable penile prosthesis (IPP) implantation is the gold standard treatment for medically refractory erectile dysfunction. New chronic pain after IPP implantation is rarely discussed and the optimal treatment is unclear. We evaluated whether IPP re-operation for a primary indication of chronic pain improves patients' symptoms. Our secondary aim was to explore factors associated with resolution or persistence of pain after IPP reoperation. METHODS: We conducted a retrospective analysis of 315 patients who had an IPP revision or explantation at two high-volume prosthetic centers between May 2007 and May 2017. We excluded patients who had device malfunction, pain for <2 months, pain associated with infection or erosion, and patients without long-term followup data. Persistent pain was diagnosed based on patient self-report. RESULTS: A total of 31 patients met our criteria for having undergone a surgical revision (n=18) or explantation (n=13) for pain relief. Eighteen (58%) patients had persistent pain despite surgical intervention. Only patients who had pain secondary to a device malposition improved after re-operation (n=13). A prior diagnosis of a chronic pain syndrome was associated with persistent pain despite intervention. Pain improvement was not associated with age, comorbid conditions, duration of implant, or the number of surgical revisions performed. CONCLUSIONS: Surgical intervention for chronic penile prosthesis pain is unlikely to relieve symptoms, particularly for patients with chronic pain disorders. Patients should be counselled that IPP reoperative procedures as a treatment for pain should be avoided unless the device is identified to be malpositioned, and consideration of alternative therapeutic options may be more beneficial.

Adverse cardiovascular events and mortality in men during testosterone treatment: an individual patient and aggregate data meta-analysis.

Background: Testosterone is the standard treatment for male hypogonadism, but there is uncertainty about its cardiovascular safety due to inconsistent findings. We aimed to provide the most extensive individual participant dataset (IPD) of testosterone trials available, to analyse subtypes of all cardiovascular events observed during treatment, and to investigate the effect of incorporating data from trials that did not provide IPD. Methods: We did a systematic review and meta-analysis of randomised controlled trials including IPD. We searched MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE Epub Ahead of Print, Embase, Science Citation Index, the Cochrane Controlled Trials Register, Cochrane Database of Systematic Reviews, and Database of Abstracts of Review of Effects for literature from 1992 onwards (date of search, Aug 27, 2018). The following inclusion criteria were applied: (1) men aged 18 years and older with a screening testosterone concentration of 12 nmol/L (350 ng/dL) or less; (2) the intervention of interest was treatment with any testosterone formulation, dose frequency, and route of administration, for a minimum duration of 3 months; (3) a comparator of placebo treatment; and (4) studies assessing the pre-specified primary or secondary outcomes of interest. Details of study design, interventions, participants, and outcome measures were extracted from published articles and anonymised IPD was requested from investigators of all identified trials. Primary outcomes were mortality, cardiovascular, and cerebrovascular events at any time during follow-up. The risk of bias was assessed using the Cochrane Risk of Bias tool. We did a one-stage meta-analysis using IPD, and a two-stage meta-analysis integrating IPD with data from studies not providing IPD. The study is registered with PROSPERO, CRD42018111005. Findings: 9871 citations were identified through database searches and after exclusion of duplicates and of irrelevant citations, 225 study reports were retrieved for full-text screening. 116 studies were subsequently excluded for not meeting the inclusion criteria in terms of study design and characteristics of intervention, and 35 primary studies (5601 participants, mean age 65 years, [SD 11]) reported in 109 peer-reviewed publications were deemed suitable for inclusion. Of these, 17 studies (49%) provided IPD (3431 participants, mean duration 9·5 months) from nine different countries while 18 did not provide IPD data. Risk of bias was judged to be low in most IPD studies (71%). Fewer deaths occurred with testosterone treatment (six [0·4%] of 1621) than placebo (12 [0·8%] of 1537) without significant differences between groups (odds ratio [OR] 0·46 [95% CI 0·17-1·24]; p=0·13). Cardiovascular risk was similar during testosterone treatment (120 [7·5%] of 1601 events) and placebo treatment (110 [7·2%] of 1519 events; OR 1·07 [95% CI 0·81-1·42]; p=0·62). Frequently occurring cardiovascular events included arrhythmia (52 of 166 vs 47 of 176), coronary heart disease (33 of 166 vs 33 of 176), heart failure (22 of 166 vs 28 of 176), and myocardial infarction (10 of 166 vs 16 of 176). Overall, patient age (interaction 0·97 [99% CI 0·92-1·03]; p=0·17), baseline testosterone (interaction 0·97 [0·82-1·15]; p=0·69), smoking status (interaction 1·68 [0·41-6·88]; p=0.35), or diabetes status (interaction 2·08 [0·89-4·82; p=0·025) were not associated with cardiovascular risk. Interpretation: We found no evidence that testosterone increased short-term to medium-term cardiovascular risks in men with hypogonadism, but there is a paucity of data evaluating its long-term safety. Long-term data are needed to fully evaluate the safety of testosterone. Funding: National Institute for Health Research Health Technology Assessment Programme.

Tadalafil administered once daily for lower urinary tract symptoms secondary to benign prostatic hyperplasia: a 1-year, open-label extension study.

OBJECTIVE: • To evaluate the 1-year safety of 5 mg of tadalafil once daily in men with lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH-LUTS); efficacy measures were included to evaluate the maintenance of efficacy after an additional year of treatment. PATIENTS AND METHODS: • In total, 427 men who completed a 12-week, placebo-controlled, dose- finding study assessing once-daily tadalafil (2.5, 5, 10 or 20 mg) or placebo elected to continue into the open-label extension period. Safety and efficacy parameters were assessed after 1 month and every 3 months. RESULTS: • In total, 299 patients (69.9%) completed the 1-year, open-label extension period. Treatment-emergent adverse events (TEAEs) were reported by 57.6% of patients, with most TEAEs being mild (44%) or moderate (45%) in severity; the most common TEAEs (≥ 2%) were dyspepsia, gastro-oesophageal reflux disease, back pain, headache, sinusitis, hypertension and cough. Twenty-two patients (5.2%) discontinued as a result of AEs. During the open-label extension period, mean prostate-specific antigen increased from 1.6 ± 1.3 ng/mL to 1.8 ± 1.4 ng/mL. • Mean post-void residual volume was 61.1 ± 60.4 mL at study entry and 42.2 ± 64.1 mL after the open-label extension period. Changes in the total International Prostate Symptom Score (IPSS), IPSS irritative and obstructive subscores, IPSS health-related quality of life and BPH Impact Index were maintained after 1 year. In sexually-active patients with erectile dysfunction, improvements in the International Index of Erectile Function-Erectile Function domain were maintained after 1 year. CONCLUSION: • In men with BPH-LUTS, 5 mg of tadalafil once daily during 1 year of treatment was well tolerated and efficacy changes were maintained.

The role of PDE5 inhibitors in penile septal scar remodeling: assessment of clinical and radiological outcomes.

INTRODUCTION: Effective oral medication for use in men with Peyronie's disease (PD) has been an area of interest of the medical community and lay public for decades. Isolated septal scars (ISS) without evidence of penile deformity is a relatively new clinical entity, and at present, there is paucity in the published literature regarding its treatment. Current research into the use of phosphodiesterase type 5 (PDE5) inhibitors in regulating penile erectile response has revealed an alternative role for PDE5 inhibitors in decreasing oxidative stress-associated inflammatory change as seen in PD. AIM: To examine the presence of ISS and assess the efficacy of PDE5 inhibitor use in septal scar remodeling. METHODS: Retrospective review of prospective database on all men who underwent penile Doppler ultrasound between December 2007 and December 2009. MAIN OUTCOME MEASURES: Of the 65 men with ultrasonographic-confirmed ISS, 35 men received tadalafil 2.5 mg daily over a 6-month period. The clinical outcomes between the two groups were compared using International Index of Erectile Function (IIEF)-5 score and 6 months penile Doppler ultrasound follow up. RESULTS: The mean age for the tadalafil group was 43.2 (20-65) years, similar to the control group at 44.2 (34-72) years. The length of time from onset to presentation was 22 (6 to 40) months. The majority of ultrasonographic-proven ISS was not clinically palpable and complaint of decreased penile rigidity (66%) was the predominant feature. Treatment with low-dose daily tadalafil did not result in any significant side effects (such as headache and flushing) or discontinuation. The tadalafil group reported higher IIEF-5 score (pretreatment 11/25 to post-treatment 18/25) (P < 0.01) and resolution of septal scar were recorded in 24 patients (69%) compared to three patients (10%) in the control group. CONCLUSION: Low-dose daily tadalafil is a safe and effective treatment option in septal scar remodeling.

Penile duplex ultrasonography in men with Peyronie's disease: is it veno-occlusive dysfunction or poor cavernosal arterial inflow that contributes to erectile dysfunction?

INTRODUCTION: At least 20% of men with Peyronie's disease (PD) suffer from erectile dysfunction (ED). The fundamental mechanism is thought to arise from the progression of penile fibrosis, which was initially limited to the PD plaque within the tunica albuginea. However, recent studies have highlighted the possibility of fibrosis of the cavernosal vessel media wall leading to impairment of arterial inflow. AIM: To evaluate the penile duplex ultrasonographic findings in PD of impotent men and to determine whether early features of PD might predict clinical progression. MAIN OUTCOME MEASURES: Patient demographic, comorbidities, International Index of Erectile Function-5 scores, surgical intervention, and physical findings were documented. Penile curvature, plaque size, and peak systolic velocity (PSV) and end-diastolic velocity (EDV) on color duplex ultrasonography (CDU) were recorded. METHODS: We performed a retrospective review of all men presenting with penile curvature and length loss who underwent penile CDU between January 2001 and January 2010. RESULTS: A total of 1,120 men underwent penile CDU during the 10-year period. Complete information was obtained in 810 men; 250 men complained of decreased penile rigidity, while 150 men were unable to sustain erection. Comorbidities were similar between men with PD with and without ED. Tunical thickening (65%) was the most common CDU feature, and mean cumulative calcifications was 24.2 mm(2) (1-360 mm(2) , standard deviation 76). The PSV and EDV on the right cavernosal artery were 14.2 cm/second and 3.5 cm/second, while the left cavernosal artery measurements were 15.1 cm/second and 3.2 cm/second. Multivariate logistic regression model showed strong correlation between plaque size and development of ED. Both veno-occlusive dysfunction and impaired cavernosal arterial inflow were associated with ED. CONCLUSIONS: Veno-occlusive dysfunction and impaired cavernosal arterial inflow contributed to the development of ED, and larger plaque size is a strong predictor of surgical intervention.

Investigative models in erectile dysfunction: a state-of-the-art review of current animal models.

INTRODUCTION: Erectile dysfunction (ED) is a common male sexual disorder producing a significant negative impact on the physical and psychosocial health of men and their partners. The development of ED is frequently attributable to both psychogenic factors as well as physiological alterations in neural, vascular, hormonal, and endothelial function. While the complex nature of human sexual function cannot possibly be replicated fully, the use of animal models provides a valid alternative to the investigation and evaluation of sexual dysfunction. AIM: To review the existing English literature pertaining to the use of experimental models (predominantly rodent models) for the evaluation of ED. MAIN OUTCOME MEASURES: Summary of relevant animal models of ED and the advantages and disadvantages of each animal model. METHODS: A Medline search using the key words "animal models of erectile dysfunction" was carried out and all relevant peer-reviewed English language was evaluated. RESULTS: While larger animals such as dogs, monkeys, cats, and rabbits were used in the early period of investigation (1960-1990), in recent times, rodents have largely replaced other animals as the predominant animal model for investigating erectile function. The most frequently reported models of ED can be classified as traumatic (cavernous nerve injury and arterial ligation) and metabolic (diabetic, hypercholesterolemia/lipidemia, and castration). Other models that have been studied include organic (smoking, hypertension, and chronic renal failure) and nonorganic (psychological) models. CONCLUSIONS: The development and utilization of the various rodent models has allowed for significant advances in the field of sexual dysfunction. Neurophysiological studies using the various animal models have provided important insights into human sexual dysfunction. At present, animal models play a significant role in evaluating novel therapeutics and surgical techniques and will likely continue to remain a vital research tool in the future.