Pharmacotherapy For Erectile Dysfunction Research Articles

Současné trendy ve farmakoterapii erektilní dysfunkce

Současné trendy ve farmakoterapii erektilní dysfunkce

Acute Ischemic Priapism: An AUA/SMSNA Guideline.

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. Acute ischemic priapism, characterized by little or no cavernous blood flow and abnormal cavernous blood gases (ie, hypoxic, hypercarbic, acidotic) represents a medical emergency and may lead to cavernosal fibrosis and subsequent erectile dysfunction. A comprehensive search of the literature was performed by Emergency Care Research Institute for articles published between January 1, 1960 and May 1, 2020. Searches identified 2948 potentially relevant articles, and 2516 of these were excluded at the title or abstract level for not meeting inclusion criteria for any key question. Full texts for the remaining 432 articles were reviewed, and ultimately 137 unique articles were included in the report. This Guideline was developed to inform clinicians on the proper diagnosis and surgical and non-surgical treatment of patients with acute ischemic priapism. This Guideline addresses the role of imaging, adjunctive laboratory testing, early involvement of urologists when presenting to the emergency room, discussion of conservative therapies, enhanced data for patient counseling on risks of erectile dysfunction and surgical complications, specific recommendations on intracavernosal phenylephrine with or without irrigation, the inclusion of novel surgical techniques (eg, tunneling), and early penile prosthesis placement. 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. Treatment of the acute ischemic patient must be based on patient objectives, available resources, and clinician experience. As such, a single pathway for managing the condition is oversimplified and no longer appropriate. Using a diversified approach, some men may be treated with intracavernosal injections of phenylephrine alone, others with aspiration/irrigation or distal shunting, and some may undergo non-emergent placement of a penile prosthesis.

Considerations for prescribing pharmacotherapy for the treatment of erectile dysfunction

ABSTRACT Introduction: The effectiveness of phosphodiesterase type 5 inhibitors (PDE5i) in treating erectile dysfunction (ED) creates a new field of both medical practice and pharmaceutical manufacturing. Both paved the way for emerging minimally invasive therapies to restore male sexual function. However, what is the best drug to achieve the optimum outcome is still a challenging question to be answered. Areas covered: The general viewpoint of matching the pharmacotherapeutic characteristics with the patient’s medical, social, and psychological variables, in order to balance between efficacy and safety. Several studies had investigated considerations for preference and long-term adherence for PDE5i. However, a thorough investigation of considerations for prescribing ED pharmacotherapy is still lacking in the literature. This is the aim of this manuscript. Expert opinion: Several issues should be considered in the planning of ED management such as the patient’s and partner’s expectations, etiologic considerations, performance status, safety, adverse effects, ease of administration, compliance, bad experiences with previous treatment, availability, cost, social factors, satisfaction, and finally, regimen considerations. Addressing the patient’s and partner’s individual needs help to tailoring treatment in order to minimize compromises and optimize gains.

The Use of Vasoactive Drugs in the Treatment of Male Erectile Dysfunction: Current Concepts.

It is widely accepted that disorders of the male (uro)genital tract, such as erectile dysfunction (ED) and benign diseases of the prostate (lower urinary tract symptomatology or benign prostatic hyperplasia), can be approached therapeutically by influencing the function of both the vascular and non-vascular smooth muscle of the penile erectile tissue or the transition zone/periurethral region of the prostate, respectively. As a result of the discovery of nitric oxide (NO) and cyclic guanosine monophosphate (GMP) as central mediators of penile smooth muscle relaxation, the use of drugs known to increase the local production of NO and/or elevate the intracellular level of the second messenger cyclic GMP have attracted broad attention in the treatment of ED of various etiologies. Specifically, the introduction of vasoactive drugs, including orally active inhibitors of the cyclic GMP-specific phosphodiesterase (PDE) 5, has offered great advantage in the pharmacotherapy of ED and other diseases of the genitourinary tract. These drugs have been proven efficacious with a fast on-set of action and an improved profile of side-effects. This review summarizes current strategies for the treatment of ED utilizing the application of vasoactive drugs via the oral, transurethral, topical, or self-injection route.

Ингибиторы ФДЭ-5: предпочтения пациентов

To date, multidisciplinary approach is commonly used to treat erectile dysfunction (ED), and the first line of ED pharmacotherapy, despite its multiple causes, is phosphodiesterase inhibitors of type 5 (PDE-5). They are considered an effective and well tolerated treatment option [1-4]. Concurrently, sildenafil has the largest evidence base for efficacy and safety [5]. The satisfaction of patients with ED therapy is a complex and personal matter, and there are no clearly established and reliable criteria for showing preferences when choosing a PDE-5. Adherence of patients to the PDE-5 therapy is determined not only by the erectile response and side effects, but also by how well the treatment meets the needs and expectations of patients and how it affects the relationship between the partners. This review examines the tolerability and efficacy of the various types of PDE-5 available for treating ED, with a special emphasis on the patient's preferences, and in particular on the new sildenafil orodispersible films. As an alternative route of drug administration, films quickly dissolve in the mouth [6] and have several advantages, improve sexual health and the sense of psychological well-being of patients and their partners.

Research in pharmacotherapy for erectile dysfunction.

Although oral phosphodiesterase-5 (PDE5) inhibitors are generally accepted as an effective therapy for erectile dysfunction (ED), men with ED from diabetes or radical prostatectomy respond poorly to these drugs. Many researchers have tried to develop novel therapeutics that target alternative molecular pathways. A group of therapeutics belongs to centrally acting agents that target dopamine and melanocortin receptors. The other one is the peripherally acting agents that target soluble guanylate cyclase, Rho-kinase pathway, and Maxi-K channel, etc. Also, a variety of preclinical studies by the application of biotherapies in the concept of therapeutic angiogenesis or neural regeneration as well as anti-fibrosis to regenerate damaged erectile tissue have been reported. This article will address the current therapeutic targets for ED under clinical or preclinical development, including pharmacotherapy and biotherapy which comprises protein therapy and gene therapy. In spite of numerous clinical trials that target alternative pathways, these agents have yet to reach the market. The results from preclinical studies targeting therapeutic angiogenesis, neural regeneration, and anti-fibrosis are promising.

PD69-10 DOES SURGICAL APPROACH AFFECT RATES OF ERECTILE DYSFUNCTION TREATMENT FOLLOWING RADICAL CYSTECTOMY: ANALYSIS OF A NATIONWIDE INSURANCE CLAIMS DATABASE

You have accessJournal of UrologySexual Function/Dysfunction: Medical, Hormonal & Non-surgical Therapy II1 Apr 2017PD69-10 DOES SURGICAL APPROACH AFFECT RATES OF ERECTILE DYSFUNCTION TREATMENT FOLLOWING RADICAL CYSTECTOMY: ANALYSIS OF A NATIONWIDE INSURANCE CLAIMS DATABASE Meera Chappidi, Max Kates, Gregory Joice, Phillip Pierorazio, and Trinity Bivalacqua Meera ChappidiMeera Chappidi More articles by this author , Max KatesMax Kates More articles by this author , Gregory JoiceGregory Joice More articles by this author , Phillip PierorazioPhillip Pierorazio More articles by this author , and Trinity BivalacquaTrinity Bivalacqua More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.3151AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES As survival following radical cystectomy (RC) improves, it is important to increase focus on survivorship issues such as sexual function. Therefore, our objective was to determine the rates of erectile dysfunction (ED) treatment use in bladder cancer patients prior to and following RC and to determine if surgical approach affects these treatment rates in order to better understand current patterns of care. METHODS Male bladder cancer patients undergoing RC were identified in the MarketScan database (2010-2014). ED treatment was defined as use of phosphodiesterase-5 inhibitors, intracavernosal injections, vacuum erection devices, urethral suppositories, or implantable penile prosthesis. ED treatment use was assessed at baseline (in the year prior to RC) and at 6-month intervals (0-6, 7-12, 13-18, 19-24 months) following RC. At each time point, ED treatment use was compared between patients who underwent open RC (ORC) and minimally-invasive RC (MIRC). Multivariable logistic regression models were used to identify predictors of ED treatment use at 6-month intervals following RC. RESULTS In the cohort of 1176 patients, at baseline, 6.5% (n=77) of patients used ED treatments. The rates of ED treatment use at 0-6, 7-12, 13-18, and 19-24 months following RC were 15.2%, 12.7%, 8.1%, and 10.1% respectively. At baseline and all follow-up time points assessed, the rates of ED pharmacotherapy use between the ORC (n=1009) and MIRC (n=167) groups were comparable. In the multivariable model, predictors of ED treatment use in 0-6 months following RC were age <50 (OR=3.17 95% CI [1.68, 6.01]), baseline ED treatment use (OR=5.75 95%CI [3.08, 10.72]), neoadjuvant chemotherapy (OR=1.72 95%CI [1.13, 2.61]), and neobladder diversion (OR=2.40 95%CI [1.56, 3.70]). Baseline ED treatment use continued to be associated with ED treatment use at 6-12 months (OR=5.63 95%CI [2.42, 13.10]) and 13-18 months (OR=8.99 95%CI [3.05, 26.51]) following RC. Surgical approach (MIRC vs. ORC) was not associated with ED treatment use at any of the follow-up points. CONCLUSIONS ED treatment use following RC is quite low, and is not associated with surgical approach. The strongest predictor of ED treatment use following RC is baseline treatment use followed by younger age. These findings suggest either ED treatment is of low priority for RC patients or sexual function issues may not be commonly discussed with patients following RC. Urologists should consider discussing sexual function more frequently with their RC patients. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e1348 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Meera Chappidi More articles by this author Max Kates More articles by this author Gregory Joice More articles by this author Phillip Pierorazio More articles by this author Trinity Bivalacqua More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Smooth muscle myosin expression, isoform composition, and functional activities in rat corpus cavernosum altered by the streptozotocin-induced type 1 diabetes

Diabetes mellitus (DM) is a quite common chronic disease, and the prevalence of erectile dysfunction (ED) is three times higher in this large population. Although diabetes-related ED has been studied extensively, the actin-myosin contractile apparatus was not examined. The mRNAs encoding smooth muscle myosin (SMM) heavy chains (MHC) and essential light chains (LC(17)) exist as several different alternatively spliced isoforms with distinct contractile properties. Recently, we provided novel data that blebbistatin (BLEB), a specific myosin II inhibitor, potently relaxed corpus cavernosum smooth muscle (CCSM). In this study, we examine whether diabetes alters SMM expression, alternative splicing, and/or functional activities, including sensitivity to BLEB. By using streptozotocin (STZ)-induced 2-mo diabetic rats, functional activities were tested in vivo by intracavernous pressure (ICP) recording during cavernous nerve stimulation and in vitro via organ bath contractility studies. SMM isoform composition was analyzed by competitive RT-PCR and total SMM, myocardin, and embryonic SMM (SMemb) expression by real-time RT-PCR. Results revealed that the blood glucose level of STZ rats was 407.0 vs. 129.5 mg/dl (control). STZ rats exhibited ED confirmed by significantly increased CCSM contractile response to phenylephrine and decreased ICP response. For STZ rats, SM-B, LC(17a) and SM2 isoforms, total SMM, and myocardin expression increased, whereas SM-A, LC(17b), and SM1 isoforms were decreased, with SMemb unchanged. BLEB was significantly more effective in relaxing STZ CCSM both in vitro and in vivo. Thus we demonstrated a novel diabetes-specific effect on alternative splicing of the SMM heavy chain and essential light chain genes to a SMM isoform composition favoring a heightened contractility and ED. A switch to a more contractile phenotype was supported further by total SMM expression increase. Moreover, the change in CCSM phenotype was associated with an increased sensitivity to BLEB, which may serve as a novel pharmacotherapy for ED.

1130 STREPTOZOTOCIN-INDUCED TYPE 1 DIABETES IN RAT ALTERS SMOOTH MUSCLE MYOSIN ISOFORM COMPOSITION TO A MORE CONTRACTILE PHENOTYPE AND INCREASES SENSITIVITY TO THE MYOSIN II SPECIFIC INHIBITOR BLEBBISTATIN

You have accessJournal of UrologySexual Function/Dysfunction/Andrology: Basic Research1 Apr 20111130 STREPTOZOTOCIN-INDUCED TYPE 1 DIABETES IN RAT ALTERS SMOOTH MUSCLE MYOSIN ISOFORM COMPOSITION TO A MORE CONTRACTILE PHENOTYPE AND INCREASES SENSITIVITY TO THE MYOSIN II SPECIFIC INHIBITOR BLEBBISTATIN Xinhua Zhang, Arnold Melman, and Michael DiSanto Xinhua ZhangXinhua Zhang Camden, NJ More articles by this author , Arnold MelmanArnold Melman Bronx, NY More articles by this author , and Michael DiSantoMichael DiSanto Camden, NJ More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.727AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The mRNAs encoding smooth muscle myosin (SMM) heavy chains (MHC) and the 17 kDa essential light chains (LC17) exist as several different isoforms with distinct contractile properties, produced via alternative splicing mechanisms. Recently, we provided novel data that blebbistatin (BLEB), a specific myosin II inhibitor, potently relaxed both rat and human corpus cavernosum smooth muscle (CCSM)(J Sexual Med, 2009). In this study, we determine if diabetes alters SMM expression, alternative splicing and/or functional activities including sensitivity to BLEB. METHODS Fisher 344 male streptozotocin (STZ)-induced diabetic rats were kept for 2 months. Functional activities were then tested in vivo by intracavernous pressure (ICP) recording and in vitro via organ bath contractility studies. SMM isoform composition was analyzed by competitive RT-PCR and total SMM, myocardin (a transcriptional regulator of SMM) and embryonic SMM (SMemb) expression by Real-time RT-PCR. RESULTS Average blood glucose levels of STZ rats were 407 vs 129.5 mg/dl in rats injected with saline (SHAM). STZ rats showed severe erectile dysfunction (ED) confirmed by decreased ICP response to electrical stimulation of cavernous nerve. For STZ rats, LC17a and SM-B isoforms (both associated with increased contractility and faster shortening velocity) and total SMM and myocardin expression increased while LC17b and SM-A isoforms (both associated with decreased contractility and slower shortening velocity) were decreased with SM1/2 SMM MHC isoforms and SMemb unchanged. Interestingly, BLEB was more effective in relaxing STZ CCSM both in vitro and in vivo. CONCLUSIONS We show for the first time to our knowledge a diabetes-specific effect on alternative splicing of the SMM heavy chain and essential light chain genes to a SMM isoform composition favoring a heightened contractility and ED. A switch to a more contractile phenotype is further supported by total SMM expression increase. Moreover, we provide novel data that the change in CCSM phenotype is associated with an increased sensitivity to BLEB, which may serve as a novel pharmacotherapy for ED with specificity to the faster type myosin isoforms found in the diabetic rat CCSM. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e454 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Xinhua Zhang Camden, NJ More articles by this author Arnold Melman Bronx, NY More articles by this author Michael DiSanto Camden, NJ More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...

ORIGINAL RESEARCH—ED PHARMACOTHERAPY: Efficacy and Tolerability of Lodenafil Carbonate for Oral Therapy of Erectile Dysfunction: A Phase III Clinical Trial

ABSTRACT Introduction This is a phase III, prospective, randomized, double-blind, placebo-controlled clinical trial on lodenafil carbonate (LC), a novel phosphodiesterase 5 inhibitor developed in Brazil. Aim Expanding information on LC efficacy and safety. Main Outcome Measures International Index of Erectile Function (IIEF) erectile domain, positive answers to the sexual encounter profile (SEP)-2 and SEP-3 questions and incidence of adverse events (AEs). Methods A total of 350 men with erectile dysfunction (ED) of all degrees were randomized to placebo, LC 40 mg or LC 80 mg and followed for 4 weeks. They completed the IIEF and answered the SEP questions 2 and 3 after each intercourse without and with the use of LC. Results IIEF Erectile Domain scores without and with the use of medication were the following (mean [M] ± standard deviation [SD]): placebo=13.9 ± 5.2 and 14.8 ± 7.8; LC 40 mg=13.6 ± 5.3 and 18.6 ± 8.0; LC 80 mg=13.4 ± 4.9 and 20.6 ± 7.7 (analysis of variance [anova]P &amp;lt;0.01). Positive answers to SEP-2 without and with the use of medication were the following (M ± SD): placebo=55.3 ± 43.2% and 52.1 ± 41.4%; LC 40 mg=46.4 ± 44.3% and 63.5 ± 42.0%; LC 80 mg=50.2 ± 40.9% and 80.8 ± 32.3% (anovaP &amp;lt;0.01). Positive answers to SEP-3 were the following: placebo=20.2 ± 32.3% and 29.7 ± 38.1%; LC 40 mg=19.6 ± 34.3% and 50.8 ± 44.4%; LC 80 mg=20.8 ± 33.2% and 66.0 ± 39.3% (anovaP &amp;lt;0.01). The patients with at least one AE were placebo=28.7%, LC 40 mg=40.9%, and LC 80 mg=49.5%. AEs whose incidence was significantly higher with LC than with placebo included rhinitis, headache, flushing, visual disorder, and dizziness. Conclusions LC showed a satisfactory efficacy–safety profile for oral therapy of ED.

ORIGINAL RESEARCH—ED PHARMACOTHERAPY: The Efficacy and Safety of Udenafil [Zydena] for the Treatment of Erectile Dysfunction in Hypertensive Men Taking Concomitant Antihypertensive Agents

Erectile dysfunction (ED) and hypertension are frequent comorbid conditions. The vasodilating properties of type 5 phosphodiesterase inhibitor (PDE5I) are the major concerns for the treatment of ED patients on antihypertensive medications. To evaluate the efficacy and safety of Udenafil [Zydena] (Dong-A, Seoul, Korea), a newly developed PDE5I, for the treatment of ED patients on antihypertensive medication. It was a multicentered, randomized, double-blind, placebo-controlled, fix-dosed clinical trial among 165 ED patients receiving antihypertensive medications. The subjects treated with placebo, 100 mg or 200 mg of Udenafil for 12 weeks were asked to complete the Sexual Encounter Profile (SEP) diary, the International Index of Erectile Function (IIEF), and the Global Assessment Question (GAQ) during the study period. Primary parameter: the change from baseline for IIEF erectile function domain (EFD) score; Secondary parameters: the IIEF Question 3 and 4, SEP Question 2 and 3, the rate of achieving normal erectile function (EFD > or = 26) and the response to GAQ. Compared to placebo, patients receiving both doses of Udenafil showed significantly improved the IIEF-EFD score. The least squares means for the change from baseline in IIEF-EFD scores were 8.4 and 9.8 for 100 mg and 200 mg Udenafil groups, respectively; those values were significantly higher than that of placebo (2.4, P < 0.0001). Similar results were observed in the comparison of Q3 and Q4 of IIEF, SEP diary and GAQ. Headache and flushing were the most common treatment-emergent adverse events, which were transient and mild-to-moderate in nature. No parameters of efficacy and safety were affected among the subsets stratified according to either the number of antihypertensive medication received or the previous experience of PDE5Is treatment. Udenafil significantly improved erectile function among ED patients with hypertensive symptom treated with concomitant antihypertensive medication. The treatment did not increase the frequency or severity of adverse events.

ORIGINAL RESEARCH—ED PHARMACOTHERAPY: Sildenafil Citrate 100 mg Starting Dose in Men with Erectile Dysfunction in an International, Double-Blind, Placebo-Controlled Study: Effect on the Sexual Experience and Reducing Feelings of Anxiety About the Next Intercourse Attempt

ABSTRACT Introduction Sildenafil citrate 50 mg is the recommended starting dose for men with erectile dysfunction (ED); however, most men are later titrated to sildenafil 100 mg for improved efficacy. Aim Assess the tolerability and efficacy of sildenafil initiated at the 100-mg dose in men with ED. Methods Men with ED (score ≤25 on the Erectile Function domain of the International Index of Erectile Function) who had received ≤6 total doses of a phosphodiesterase type 5 inhibitor and none within 4 weeks were randomized to 8 weeks of double-blind, placebo-controlled (DBPC), fixed-dose treatment (50 or 100 mg sildenafil or placebo) followed by 4 weeks of open-label flexible-dose sildenafil (50 or 100 mg). Main Outcome Measures Efficacy, tolerability, treatment satisfaction, and other end points were measured at baseline and/or the end of the double-blind and open-label phases and compared between placebo and sildenafil initiated at doses of 50 and 100 mg. Results Improvements in DBPC patient-reported outcomes from baseline were statistically significant for both sildenafil 50 and 100 mg compared with placebo. At the end of DBPC treatment, 56% of men on the 100-mg dose felt no anxiety about the next intercourse attempt compared with 39% in the 50-mg group (odds ratio 2.03; P = 0.0197). Changes in functional scores from baseline were not statistically significant with the 100-mg dose compared with the 50-mg dose in the DBPC. Measures of treatment satisfaction and sexual experience significantly favored the 100-mg dose compared with the 50-mg dose in the DBPC. There was no increase in adverse events with the higher dose. Conclusions Sildenafil at 50 mg or 100 mg significantly improved erection quality, treatment satisfaction, anxiety levels, and the sexual experience compared with placebo during DBPC. Sildenafil 100 mg improved the sexual experience and treatment satisfaction, and reduced feelings of anxiety compared with the 50-mg dose.

ORIGINAL RESEARCH—ED PHARMACOTHERAPY: Efficacy and Safety of Mirodenafil, A New Oral Phosphodiesterase Type 5 Inhibitor, for Treatment of Erectile Dysfunction

Mirodenafil is a newly developed oral phosphodiesterase type 5 inhibitor, currently under investigation as a treatment for erectile dysfunction (ED). We investigated the efficacy and safety of on demand mirodenafil therapy at fixed doses (50 and 100 mg) in Korean men with a broad range of ED. A multicenter, randomized, double-blind, placebo-controlled, parallel-group, fixed-dose study was conducted with 223 subjects who were randomized to placebo or mirodenafil at fixed doses of 50 or 100 mg for 12 weeks on an "as needed" basis. Primary efficacy measures were scores on the International Index of Erectile Function (IIEF) Question 3 (Q3) and Question 4 (Q4). Secondary efficacy measures included all domain scores of the IIEF, Sexual Encounter Profile Question 2 (SEP2), Sexual Encounter Profile Question 3 (SEP3), the Global Assessment Question (GAQ), and the Life Satisfaction Checklist (LSC). Safety assessments included laboratory tests, vital signs, physical examination, 12-lead electrocardiogram recordings, and patients' reporting of adverse events. Mirodenafil 50 and 100 mg groups showed a significantly greater increase in IIEF Q3 (P = 0.0001, P < 0.0001, respectively) and Q4 scores (both P < 0.0001) at the end point compared with the placebo group. And mirodenafil in both doses significantly improved the scores of all five domains of the IIEF, SEP2, and SEP3 as well as the percentages of patients responding positively to the GAQ compared with the placebo group. As for LSC scores, the two mirodenafil groups showed significantly greater improvements in items regarding life as a whole, sexual life, and partner relationship than the placebo group. Most treatment-associated adverse events were of mild intensity, resolving spontaneously. Mirodenafil, in doses of 50 or 100 mg, significantly improved erectile function and were well tolerated in a representative population of Korean men with broad-spectrum ED of various etiologies and severities.

Pharmacotherapy for erectile dysfunction

Objective: To review advances in the pharmacological treatment of erectile dysfunction (ED) highlighting potential neuro-endocrine and molecular targets. Methods: A comprehensive MEDLINE and PUBMED search was utilized to investigate current novel mechanistic approaches in treating erectile dysfunction. Search criteria included, but were not limited to, erectile dysfunction (ED), cGMP, nitric oxide, Rho-kinase, phosphodiesterase, gene therapy, apomorphine, melanocortin and corpora cavernosa. Articles relating to in vitro, animal and in vivo experimental therapy were evaluated and included in this review and future directions are described. Results: Current first-line ED treatment often involves the use of phosphodiesterase inhibitors. However, many novel pharmacotherapeutic approaches under development including the use of melanocortins and Rho-kinase inhibitors as well as the introduction of gene therapy have demonstrated efficacy in animal as well as early human trials. Conclusions: The success of oral pharmacotherapy for ED has been accompanied by renewed interest into the ED pathophysiology and signal transduction pathways. This has led to the identification of new therapeutic targets, which are poised to change the dynamic of ED management by broadening treatment alternatives to include other oral and genetic therapies.

Penile prosthesis implant: tips and tricks

Erectile Dysfunction (ED) affects nearly 52% of men between the ages of 40 and 70 worldwide, causing overall lifestyle difficulties and is often a symptom of an underlying disease. Although more invasive than some of the other currently available therapies, penile prosthesis surgery has the advantages of high patient satisfaction rates and avoidance of systemic adverse events in the vast majority of cases. After a penoscrotal incision is made, the dissection is carried down through dartos fascia. Two-centimeter corporotomies are made and 2 horizontal mattress sutures are placed on each side of the corporotomy. These sutures are used as guide during dilatation and measurement, and they are also used to close the corporotomy. Dilatation starts with an 10-mm Hegar dilator and proceeds to 14-mm. The dilator are directed laterally to avoid urethral injury. After corporeal measurements are taken, the appropriate cylinder size is selected. The prosthesis components are prepared for implantation and distal cylinder insertion is aided by use of the Furlow cylinder inserter. The Furlow inserter directs the Keith needle (with the device pulling-suture attached) through the glans penis and allows the attached cylinder to be positioned appropriately. If the cylinder fit is proper, the proximal portion is all the way down to the attachment of the crus to the pelvic bone and the distal portion is in the distal corpus cavernosum under the midglans penis. The corporotomies are closed and in preparation for pump placement, a pouch is developed in the scrotal septum. The pump is placed in this pouch and the connections between the pump and each cylinder are made. Safe reservoir insertion into the retropubic space through the primary penoscrotal incision is possible only if the bladder is completely empty. Metzenbaum scissors is used to perforate the transversalis fascia. Using a nasal speculum, the empty reservoir is introduced into the retropubic space and it is then filled with the requisite amount of saline solution. Dartos fascia and skin are then closed. Penile prostheses were first developed 30 years ago; despite ongoing advances in the pharmacotherapy for ED, prosthetic surgery continues to occupy an important therapeutic role. Improvements in reducing the incidence of infection, treating infection with antiseptic washes, enhancing device longevity, and instituting new techniques to manage complicated implantation procedures have made them more acceptable to patients. Although penile implants are the least often chosen and most invasive treatment for erectile dysfunction, they have the highest satisfaction rate among both patients and partners.

ORIGINAL RESEARCH—ED PHARMACOTHERAPY: Can an Educational Program Optimize PDE5i Therapy? A Study of Canadian Primary Care Practices

The importance of patient instructions, designed to optimize therapy with phosphodiesterase type 5 inhibitors for the treatment of erectile dysfunction (ED), has recently been demonstrated. To evaluate the impact of an educational program for new sildenafil users against usual ED management in Canadian primary care practices. This multicenter, 6-month cluster randomized prospective study was conducted across Canada in general practitioners' offices where sites were randomized to receive a treatment optimization program (TOP) tool at visit 1 (TOP sites) or not to receive the TOP tool (non-TOP sites) while continuing with usual practice. Study participants were men seeking medical attention for ED and who were sildenafil naïve. The TOP tool consisted of a tear-off sheet, a brochure, and a video. Study drug was not provided to the patients. Sildenafil samples and prescriptions were dispensed as per usual care practices. The Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) questionnaire was used to determine treatment satisfaction at visit 2 (month 3) and visit 3 (month 6). Patient and physician satisfaction with the TOP tool was assessed using self-reported questionnaires. The intent-to-treat (ITT) population consisted of 2,573 patients from 231 primary care sites. At visits 2 and 3, treatment satisfaction with sildenafil was high with almost 9 patients out of 10 satisfied with treatment. No significant statistical differences were observed in the EDITS scores between the TOP and the non-TOP groups at visits 2 and 3. More than 80% of the participants were satisfied or very satisfied with the video and the brochure. More than 8 out of 10 participating physicians (84%) would use the TOP tool in their current practice if available. TOP is a valuable and time-efficient ED management tool providing benefits to newly diagnosed ED patients and to their physicians.

ORIGINAL RESEARCH—ED PHARMACOTHERAPY: The South Australian Couples Sildenafil Study: Double-Blind, Parallel-Group Randomized Controlled Study to Examine the Psychological and Relationship Consequences of Sildenafil Use in Couples

ABSTRACT Introduction The South Australian Couples Sildenafil (SACS) study sought to look more closely at the role of sexual functioning in couples by exploring the impact of treatment for erectile dysfunction (ED) with sildenafil. Aim The SACS study investigated the individual and dyadic impact of the drug sildenafil (Viagra) on couples over a 6-month period. Main Outcome Measures A range of outcome measures were utilized including the Dyadic Adjustment Scale (DAS), the International Index of Erectile Function (IIEF), and the Erectile Dysfunction Inventory of Treatment Satisfaction. Methods Couples were recruited through the use of local media and general practitioners. Couples were randomly allocated to placebo or active drug with the option of using up to one study tablet per day for 6 months. Couples were reviewed at 2 weeks, 4 weeks, 8 weeks, 3 months, and 6 months. Results There were 108 couples who were eligible for the study with the eventual analysis including 49 couples in the active treatment group and 47 in the placebo group with similar demographic and background profiles found in both groups. A large number of psychosocial, quality-of-life, and sexual measures were recorded at the end of the trial for both male subjects and their female partners. Predictably, the erectile response in the active treatment group showed a significant improvement as measured by the IIEF although no change was found between the active and placebo groups in relationship functioning as measured by the DAS scores. Conclusions The SACS study found no difference between treatment arms with regard to relationship functioning after the use of sildenafil for ED. Potential contributing factors to a “no change” result are discussed. The SACS study adds to the available literature on psychological and interpersonal factors in the treatment of ED which have not been sufficiently investigated until recently.

ORIGINAL RESEARCH—ED PHARMACOTHERAPY: The Treatment Satisfaction Scale (TSS) is a Sensitive Measure of Treatment Effectiveness for both Patients and Partners: Results of a Randomized Controlled Trial with Vardenafil

ABSTRACT Introduction Erectile dysfunction (ED) treatment studies do not routinely measure “treatment effectiveness,” a function of treatment response (based on efficacy and tolerability) and treatment satisfaction (both patient and partner satisfaction). The ED Treatment Satisfaction Scale (TSS) is a brief, comprehensive self-report measure of patient and partner satisfaction. Aim To measure, for the first time in an ED treatment study, pre- and post-treatment patient and partner satisfaction with the TSS. Methods A randomized, double-blind, placebo-controlled, parallel-group, multi-institutional comparison of the efficacy and safety of flexible-dose vardenafil was performed in 229 couples (treated man with ED &amp;gt;6 months and untreated woman partner aged ≥18 years without sexual dysfunction [defined as a total Female Sexual Function Index score &amp;gt;26.55]). Main Outcome Measures Couples completed the TSS throughout the trial. Couples also completed the modified Sexual Life Quality Questionnaire–Quality of Life domain (mSLQQ-QoL) and men completed the International Index of Erectile Function-erectile function domain (IIEF-EF). Analysis of covariance produced least squares (LS) mean domain scores. Post hoc Pearson correlation coefficients were calculated for patient and partner TSS scores, and for TSS scores with other outcomes. Results TSS domain scores increased from baseline to last observation carried forward (LOCF) in the vardenafil-treated men and untreated women partners, but exhibited little change for the placebo group (P &amp;lt; 0.0001 vs. placebo). For both patients and partners in the vardenafil group, correlations between TSS domains, the IIEF-EF and the mSLQQ-QoL scores at LOCF were moderate to strong. Conclusions The TSS detected that vardenafil was superior to placebo on treatment satisfaction from both patient and partner perspectives. The TSS holds promise for evaluating “treatment effectiveness” by measuring more general treatment satisfaction.

Endothelial dysfunction, erectile dysfunction and phosphodiesterase 5 inhibitors. An update of the current data and future perspectives.

Endothelial dysfunction is a pathological entity that multiply affects the health status. Erectile dysfunction is being recognized as a condition that is strongly interrelated with endothelial dysfunction, being a vascular event itself. Oral pharmacotherapy for erectile dysfunction has provided us with a new armamentarium on this condition. Phosphodiesterase 5 inhibitors have been investigated and proved useful in clinical practice for erectile dysfunction but in addition to this, the results seem promising of a beneficial effect on endothelial dysfunction, as well.

ORIGINAL RESEARCH—ED PHARMACOTHERAPY: A Comparison of the Efficacy and Tolerability of Tadalafil 10 mg and 20 mg in Japanese Patients with Severe Erectile Dysfunction

Tadalafil is a phosphodiesterase type 5 inhibitor with documented efficacy in the treatment of erectile dysfunction (ED). To compare the efficacy and tolerability of tadalafil 10 mg and 20 mg in men with severe ED. A prespecified subgroup analysis was conducted to compare the efficacy of tadalafil 10 and 20 mg measured by the International Index of Erectile Function (IIEF) erectile function (EF) domain and Sexual Encounter Profile (SEP) among patients with severe ED (EF domain score = 1-10) in a Japanese placebo-controlled study (PCT). We also analyzed the efficacy of the two doses in men with severe ED post hoc by pooling data from three tadalafil clinical trials that evaluated these doses using a similar study design (three placebo-controlled trials), and evaluated (post hoc) the presence of organic comorbidities in patients with different levels of response to tadalafil 10 or 20 mg. Mean change in the IIEF-EF domain and mean per-patient changes in percent "yes" responses to SEP Question 2 (SEP2) and Question 3 (SEP3). Patients with severe ED in the Japanese study experienced numerically greater increases (improvements) when taking tadalafil 20 mg compared with 10 mg in the IIEF-EF domain (14.3 vs. 12.4; P = 0.355), SEP2 (60% vs. 57%; P = 0.781), and SEP3 (61% vs. 49%, P = 0.196). When sufficiently powered, these observations reached statistical significance in the three PCTs: patients with severe ED experienced greater increases when taking tadalafil 20 mg compared with 10 mg in the IIEF-EF domain (13.6 vs. 10.4; P = 0.014) and SEP3 (56% vs. 43%, P = 0.019). Both doses were well tolerated. Patients with severe ED, and especially those with an organic comorbidity, may derive greater clinical benefits from tadalafil 20 mg compared with 10 mg.