Value of prolonged scrotal drainage after penile prosthesis implantation: a multicenter prospective nonrandomized pilot study.

We aimed to understand the risks and benefits of post-inflatable penile prosthesis (IPP) implantation drainage and optimal duration. Our patients were divided into 3 groups: Group 1 (n = 114) had no drain placed, Group 2 had a drain placed for 24 h (n = 114) and Group 3 had a drain placed for 72 h (n = 117). Postoperative scrotal hematoma and prosthesis infection rates were compared between the groups. The patients from Group 3 demonstrated a statistically significant lower incidence of hematoma on the 10th postoperative day: (n = 1, 0.9%) compared to Group 2: (n = 11, 9.6%) and Group 1: (n = 8, 7%), (p = 0.013). However, on the 3rd postoperative day, there was a statistically significant lower incidence of hematoma in both Groups 3 and 2: (0.9% and 6.1%, respectively) vs. Group 1: (11.4%), (p = 0.004). Hematoma rates followed the same group order after the first day of surgery: 1.7% (n = 2), 5.3% (n = 6), and 8.8% (n = 10), respectively, (p = 0.05). Five patients (4.4%) in Group 1 and four patients (3.5%) in Group 2 developed an IPP associated infection, opposed to only a single patient (0.85%) in Group 3, (p = 0.210). We concluded that prolonged scrotal drainage for 72 h after virgin IPP implantation significantly reduces hematoma and infection rates.

Physicians' attitudes towards androgen replacement therapy for male and female sexual dysfunction.

Androgen deficiency syndrome is a commonly diagnosed condition. The aim of this study was to investigate common clinical practices of specialists in the field of sexual medicine regarding androgen replacement treatment for men and women. Attendees of the 16th Annual Congress of the European Society of Sexual Medicine held in January 2014 in Istanbul, Turkey, were asked to participate in a survey during the congress days. A 24-item self-report, closed-question questionnaire was distributed. Three sections were accessed: sociodemographic data, professional background and personal practice patterns regarding androgen substitution in men and women. A total of 133 physicians (mean age 47 years; range 25-79) completed the survey. Responses were inconsistent regarding the lab tests used for primary evaluation of male androgen deficiency. The majority of participants (62%) recommended testosterone replacement therapy for symptomatic men with testosterone levels <8 nmol l(-1) (231 ng dl(-1)). Similarly, most physicians (88%) recognized a correlation between libido and testosterone levels in women. Only 42% and 53% reported they would prescribe testosterone to women with low libido, premenopausal and postmenopausal, respectively. This survey showed discrepancies among physicians regarding testosterone replacement therapy for men and women.

Results from an online survey investigating ED patients' insights and treatment expectations.

Data suggest that the currently available therapies for erectile dysfunction (ED) do not meet all the patients' and their partners' expectations. The aim was to assess ED patients' treatment expectations for a variety of sex- and drug-related aspects such as importance of spontaneity, partner satisfaction, ideal onset of action and ideal duration of action. A total of n=1124 men with ED and n=410 healthy men, aged 30-75, participated in this online survey. The ED sample was further divided into patients currently undergoing treatment (CTG), patients who had been undergoing treatment in the past (PTG) and naïve patients (NG). The International Index of Erectile Function as well as a mix of study-specific questions was used. All groups considered 'maintaining an erection until the partner reaches orgasm' the most important aspect regarding erectile function. 'Being able to please the partner' was considered as the most important aspect for a fulfilled sex life. The majority of men (38.1%) further considered an onset of action of about 15 min to be desirable. In all, 95.9% further considered a duration of action up to 4 h to be desirable whereas approximately 71% of men considered a duration of more than 12 h to be too long. It seems that once the basic functional aspects related to erectile function have been covered, additional benefits such as 'spontaneity' and 'pleasing the partner' become important and may be critical for choosing the optimum individual treatment, to improve the sexual satisfaction and the adherence to the treatment.

Continuation and effectiveness of tadalafil once daily during a 6-month observational study in erectile dysfunction: the EDATE study.

AIMS: This was the first observational study evaluating treatment continuation, effectiveness and tolerability of tadalafil 5 mg once daily (TAD-OaD) in patients who chose and paid for treatment of erectile dysfunction (ED) in routine clinical practice. METHODS: Men ≥ 18 years with ED, treated previously with phosphodiesterase type 5 (PDE5)-inhibitor on-demand (PRN) or treatment-naïve, were enrolled at 59 sites. For patients prescribed TAD-OaD at baseline (T1), change in erectile function (IIEF-EF and GAQ) was documented after 1-3 (T2) and 4-6 (T3) months. The primary outcome was the probability to switch/discontinue from TAD-OaD, estimated by Kaplan-Meier (KM) product-limit method. Changes in IIEF-EF were evaluated using a mixed model for repeated measures adjusting for patient baseline characteristics. RESULTS: Of 975 men enrolled (median age 56.8 years, 33.7% with previous PDE5-inhibitor use), 778 were prescribed TAD-OaD, 135 TAD-PRN and 62 sildenafil or vardenafil PRN. During the 6-month longitudinal observation, 107 patients (13.8% of 778) switched or discontinued TAD-OaD-treatment. KM-rates (95%CI) for continuing TAD-OaD at 2, 4 and 6 months were 94.0% (92.3, 95.7), 88.3% (85.9, 90.6) and 86.3% (83.7, 88.9), respectively. The 25th percentile of time to switch/discontinuation of TAD-OaD was estimated as 31.1 weeks (lower 95%CI 30.3 weeks). At T3, IIEF-EF scores had increased by 7.1 (LSmean; 95%CI 5.8, 8.5) points; 91.3% of patients reported improved erections. The most frequently reported AE was headache (10 patients; 1.3%); no new/unexpected safety signals were observed. CONCLUSION: Under routine conditions, and when patients were involved in treatment decision-making, more than 86% of men starting/switching to tadalafil once daily (OaD) at baseline continued tadalafil OaD treatment for ≥ 6 months.

Genetic association study of the GNB3 C825T, the ACE I/D and the eNOS G894T polymorphisms and the risk to develop erectile dysfunction in a German ED population.

Erectile dysfunction (ED) is often associated with cardiovascular disorders such as hypertension, coronary heart disease, hypercholesterolaemia and diabetes mellitus. The genotypes in the GNB3 C825T, the ACE I/D and the eNOS G894T polymorphisms have been identified as genetic risk factors for cardiovascular disorders. The association between the genotypes in these polymorphisms and the risk to develop ED was analysed. In 455 German ED patients and 111 age-matched healthy controls genotyping in the candidate polymorphisms was performed after DNA extraction from whole blood. Association studies between the genotype distribution in the control group in comparison with the ED-group and age of onset of the disease as well as erectile response to intracorporal prostaglandin injection in dependence of candidate polymorphism genotype were performed using the SPSS-Software(R). Genotype distribution of the GNB3 C825T, the ACE I/D and the eNOS G894T polymorphisms was similar in the ED population and the healthy control group. The age of onset of the disease as well as the erectile response to intracorporal prostaglandin injection was independent of the genotypes in the three candidate polymorphisms. In contrast to the previous studies in this analysis, the risk to develop ED is not influenced by the genotypes in the GNB3 C825T, the ACE I/D and the eNOS G894T polymorphisms.

[Chronic PDE-5 inhibition in patients with erectile dysfunction: new treatment approach using once daily Tadalafil]. / Chronische PDE-5-Hemmung bei erektiler Dysfunktion : Neuer Therapieansatz mit täglicher Einmalgabe von Tadalafil.

Erectile dysfunction (ED) is often associated with increased cardiovascular risk. There is increasing evidence suggesting that dysfunction of the vascular endothelium with reduced bioavailability of nitric oxide (NO) may be the pathogenetic link between ED and cardiovascular disease. The crucial importance of the NO-guanylatecyclase-cGMP-phosphodiesterase pathway for penile erection is mirrored by the efficacy of phosphodiesterase-5 (PDE5) inhibitors in the treatment of ED. In contrast to other currently available PDE5 inhibitors with a half-life time of about 4 h Tadalafil has a half-life time of about 17.5 h resulting in erectile responsiveness for up to 36 h after 1 single dose. Most clinical experience has been reported with on-demand use of PDE-5 inhibitors, but meanwhile several studies were able to demonstrate that Tadalafil given daily in low (2.5 and 5 mg) doses is both highly effective and well-tolerated. In three randomized, double-blind, placebo-controlled multi-center trials, various validated measures of erectile function indicated that once daily Tadalafil at doses of 2.5, 5, and 10 mg was significantly superior to placebo.In another mono-center trial, once daily Tadalafil has shown significant efficacy even after failure of on-demand treatment. In a controlled cross-over study of on-demand versus daily Tadalafil treatment, 72% of the patients preferred once daily administration, mainly because of superior and longer efficacy allowing a more spontaneous sexual life. Interestingly in a pilot study of on-demand versus chronic administration of Tadalafil for 4 weeks, only regular dosing improved several markers of endothelial function.

[Premature ejaculation]. / Der vorzeitige Samenerguss (Ejaculatio praecox).

With prevalence rates of 20%-25% premature ejaculation (PE) represents the most frequent sexual dysfunction in men. Whereas genetically determined changes in the serotonin receptor-/transporter mechanism seem to be responsible for lifelong PE, acquired PE is often associated with other conditioning diseases such as erectile dysfunction, prostatitis or thyroid dysfunctions. Typical features of PE are a short intravaginal ejaculatory latency time (IELT) <1-2 min, lack of control over ejaculation, personal distress and partner problems. Treatment of PE subdivides into sexual therapy as well as drug therapy. Among the medications considered for PE, oral therapy with selective serotonin re-uptake inhibitors (SSRI), Dapoxetine (the first officially approved medication for PE) and topical therapy with lidocaine/prilocaine-containing medications are given priority.

Cardiovascular outcomes among sildenafil users: results of the International Men's Health Study.

AIM: To assess the incidence of serious cardiovascular disease (CVD) events [i.e. myocardial infarction (MI) and stroke] and all-cause mortality in men with erectile dysfunction (ED) who received prescriptions for sildenafil. METHODS: The International Men's Health Study (IMHS) was a prospective, observational cohort study of patients with ED and a new or existing prescription for sildenafil. Baseline and follow-up questionnaires provided information on demographics, CVD risk factors and ED. Postevent questionnaires were mailed to patients following possible nonfatal CVD events to collect information related to exposure to sildenafil/ED treatments before the event. RESULTS: Thirty-five CVD events were reported in 30 patients in the analysis set (n = 3813). The incidence of all-cause mortality, MI and stroke was 0.4, 0.6 and 0.1 per 100 patient-years of observation respectively. Among the six men who reported using sildenafil in the month before a nonfatal CVD event, two reported use in the 24 h before the event. CONCLUSION: The results of the IMHS support previous reports that ED and CVD are often comorbid and share risk factors.

[Efficacy and tolerability of vardenafil within the time window of 6 hours after administration and beyond. Results of a clinical study carried out in 233 urological offices]. / Die Wirksamkeit und Verträglichkeit von Vardenafil im Zeitfenstervon sechs Stunden nach Einnahme und darüber hinaus. Ergebnisse einer klinischen Studie in 233 urologischen Praxen.

UNLABELLED: In the multicenter STEADY-(safety, tolerability, efficacy and impact on quality of life of vardenafil 10 mg in patients with erectile dysfunction)-study, 996 patients with erectile dysfunction were treated with vardenafil for a period of 12 weeks. The results within a time window of up to 6 hours post-administration and beyond (up to 12 hours) were evaluated. The effectiveness of vardenafil was analysed on the basis of the parameters Sexual Encounter Profile (SEP) 2 (vaginal penetration) and SEP3 (erection maintenance) as also the "erectile function score" and overall satisfaction. RESULTS: On the occasion of the first follow-up 4 weeks after the administration of vardenafil there was an appreciable improvement in all four parameters. Very high success rates were observed not only during the primarily investigated time window of 6 hours, but also beyond this (up to 12 hours). Satisfaction with sexual intercourse (SI) increased from 24.6% prior to treatment to 87.6% at the end of the 12-week treatment period. CONCLUSION: Under doctor's office conditions vardenafil was reliable and highly effective, already at the 10 mg dose, when the patients utilized its effect within a time window ranging from < 0.5 to 12 hours (tablet ingestion to SI). In addition, vardenafil was very well tolerated. Patient satisfaction with the treatment was reportedly very high.

[Acute liver failure caused by phenprocoumon -- three case reports]. / Akutes Leberversagen durch Phenprocoumon -- drei Fallberichte.

We report on three women with phenprocoumon-induced liver failure. In all three, jaundice was the main symptom. Liver failure was manifest 6 months after initial exposure to phenprocoumon in two women and 18 months in the third. None received corticosteroids. The course was prolonged in each patient, but all three finally recovered. Liver failure associated with oral anticoagulation is rare. Most published reports describe only individual cases. Instances of fatal outcome and instances requiring liver transplantation for survival have been seen. Coumarin treatment should be considered as a possible etiology of acute liver failure, even if the drug has been administered for a longer period without any previous problems. While cross-reactions with other coumarin substances have been reported, if coumarin anticoagulation is absolutely required, use of a congener under close monitoring seems justifiable.

[Erectile dysfunction. New drugs with special consideration of the PDE 5 inhibitors]. / Erektile Dysfunktion. Neue Medikamente unter besonderer Berücksichtigung der PDE-5-Inhibitoren.

Erectile dysfunction (ED) tends to be associated with other diseases, the common basis of which is endothelial dysfunction. ED is also frequently combined with LUTS and the common basis for both conditions seems to be elevation of Rho-kinase activity and decrease of NO concentration. Because all three PDE 5 inhibitors sildenafil, tadalafil, and vardenafil have a common mode of action, i.e., inhibition of PDE 5, they are not different in terms of their efficacy and safety profile except for color vision disturbances which are more common after sildenafil and back pain/myalgia more often observed after tadalafil. The main differentiating characteristics among the three PDE 5 inhibitors are their pharmacokinetics. These are ultimately responsible for the observation that in head-to-head comparative trials depending on the respective study design the overwhelming majority of the patients opted either for tadalafil as the longest acting PDE 5 inhibitor (36 h) or for vardenafil as a relatively rapidly acting drug. All published studies so far have shown that in terms of the cardiovascular risk profile (myocardial infarction rate) all three PDE 5 inhibitors performed better than placebo although the results were not statistically significant. Without any exception it applies to all three PDE 5 inhibitors that they are absolutely contraindicated in patients taking nitrate- or molsidomine-containing medications and that they may interact in particular with non-uroselective alpha-adrenoceptor blockers. This is why their simultaneous application with PDE 5 inhibitors has to be avoided.In the near future chronic (daily) application of a PDE 5 inhibitor may show advantages, at least in those 50-60% of all patients in whom there is a high likelihood of endothelial dysfunction due to the diagnostic (penile duplex Doppler) outcome. Possible new developments in the management of ED with a time frame of 5-8 years until their market approval are guanylate cyclase activators, Rho-kinase inhibitors, melanocortin receptor agonists, gene therapy, and tissue engineering.

Sustained efficacy and tolerability with vardenafil over 2 years of treatment in men with erectile dysfunction.

This randomised, double-blind study assessed the long-term efficacy and tolerability of vardenafil 10 and 20 mg in men with erectile dysfunction (ED). A total of 566 men who completed an initial 12-month treatment period entered a 12-month extension. In these men, both doses of vardenafil produced improvement in scores for the 'erectile function' Domain of the International Index of Erectile Function, evident from week 4 and maintained through 2 years. Sexual Encounter Profile diary responses indicated that following treatment, penetration was achieved on 92-94% of attempts and erections that lasted long enough for successful intercourse were achieved on 87-89% of attempts. In response to the General Assessment Question, 90-92% of patients reported improved erections with vardenafil. Most treatment-emergent events were mild and transient with no cardiovascular safety concerns. These results support the long-term efficacy, reliability and tolerability of vardenafil 10 and 20 mg in men with ED.

The 'effectiveness' scale--therapeutic outcome of pharmacologic therapies for ED: an international consensus panel report.

Despite availability of outcome measures and scales for assessing erectile dysfunction (ED) treatment efficacy, guidelines are not available for assessing broader therapeutic outcomes or defining treatment failure in ED. An International Consensus Advisory Panel was convened to develop guidelines, definitions and a new algorithm for evaluating treatment effectiveness in ED. These new guidelines are recommended for use in both research and clinical practice. A multidisciplinary, international panel, consisting of 11 senior researchers and clinicians, was convened to address pertinent issues concerning therapeutic outcome assessment for ED. The panel utilized a modified Delphi method of consensus development and proposed a new model for outcomes assessment. This model is inherently testable, using existing instruments and current methods of assessment. Following a comprehensive literature review and discussion, the Panel recommended adoption of a new treatment effectiveness conceptual framework or theoretical model for assessing therapeutic outcomes in ED. Treatment effectiveness is presumed to be a combined function of two other factors, treatment response and treatment satisfaction. Treatment response is based on the combined assessment of efficacy and tolerability, and treatment satisfaction on the combined assessment of patient and partner satisfaction. Taken together, these two domains define an overall domain of treatment effectiveness. This therapeutic index would be derived by independently assessing treatment efficacy and satisfaction by means of event logs, questionnaires or the more typical patient interview methods. In conclusion, the Ad Hoc Advisory Consensus Panel recommends adoption of a new framework or conceptual model for conducting ED outcome trials or clinical research. The concept of 'treatment effectiveness' is proposed as a new 'umbrella concept' or distal outcome to be evaluated.

[Therapy of erectile dysfunction in 2005]. / Therapie der erektilen Dysfunktion im Jahr 2005.

Erectile dysfunction (ED) management in the following 3-5 years will be dominated by substances targeting the L-arginine-NO-guanylate cyclase-cGMP-PDE-5 pathway, resulting in an intracellular elevation of the cGMP concentrations. Promising alternatives to the PDE-5 inhibitors, such as guanylate cyclase activators and Rho-kinase inhibitors, may also effectively compliment a PDE-5 inhibitor. Intranasal application of the melanocortin agonist PT 141 (Melanotan II) seems to be promising. As scheduled sexual activities are not preferred by the majority of couples, the future of ED-therapy will focus on drugs with a 1-2 day long efficacy window, or a daily bedtime application of low dosage agents which result in nocturnal reoxygenation of the cavernous bodies and in turn in functional improvement. Elevation of the cGMP levels and improvement of endothelial function as a result of this approach also promises benefits in cardiovascular diseases and in LUTS.

IC351 (tadalafil, Cialis): update on clinical experience.

IC351 (tadalafil, trade name Cialis) is a new representative compound of the second generation of selective phosphodiesterase 5 (PDE-5) inhibitors. The selectivity ratio vs PDE-5 is more than 10 000 for PDE-1 through PDE-4 and PDE-7 through PDE-10 and 780 for PDE-6. In the European daily-dosing trial, the efficacy rates were up to 93% for successful intercourses with completion in the 50-mg dose in patients with mild to moderate erectile dysfunction (ED). In two different dose-ranging studies with 2-25 mg taken as needed, efficacy rates of up to 88% improvement in erections and up to 73% successful intercourses with completion were achieved. In a placebo-controlled, fixed-dose (10- and 20-mg) trial in diabetic patients, improved erections of 56% and 64% were reported compared with 25% after placebo. Drug-related adverse effects, with headache in up to 23% of patients (placebo, up to 17%), dyspepsia in up to 11% (placebo, up to 7%), back pain in up to 4.7% (placebo, 0%), and myalgia in up to 4.1% (placebo, up to 2.4%), were mostly mild to moderate. Neither drug-related serious cardiovascular adverse events nor color vision disturbances were encountered. The long half-life (>17 h), with a comfortably long window of opportunity, releases couples from the need to plan sexual activities and therefore provides the highest amount of spontaneity for sexual activities.

The efficacy and tolerability of vardenafil, a new, oral, selective phosphodiesterase type 5 inhibitor, in patients with erectile dysfunction: the first at-home clinical trial.

Vardenafil, a novel selective phosphodiesterase type 5 inhibitor, was evaluated in its first large-scale at-home trial. A total of 601 men with mild to severe erectile dysfunction (ED) were enrolled in this multi-centre, randomized, double-blind, placebo-controlled trial of 12 weeks of treatment with either placebo or 5, 10 and 20 mg of vardenafil. Primary endpoints were Q3 (vaginal penetration) and Q4 (maintenance of erection) of the International Index of Erectile Function (IIEF). In the intent-to-treat population (n=580), the changes from baseline for 5, 10 and 20 mg vardenafil (1.2, 1.3 and 1.5, respectively) were all improved (P<0.001) over placebo (0.2) for Q3 and were similarly improved for Q4 (1.4, 1.5 and 1.7) compared to placebo (0.5) (P<0.001). All vardenafil doses improved all IIEF domains compared to placebo (P<0.001). The percentage of successful intercourses was between 71 and 75% for the three vardenafil doses. For the 20 mg dose, 80% of the patients experienced improved erections (GAQ) compared to 30% for placebo. Most frequent treatment-emergent adverse events were headache (7-15%), flushing (10-11%) and up to 7% for dyspepsia or rhinitis. Vardenafil treatment resulted in a high efficacy and low adverse-event profile in a population with mixed ED etiologies.