Effect of Tadalafil Once Daily on Penile Length Loss and Morning Erections in Patients After Bilateral Nerve-sparing Radical Prostatectomy: Results From a Randomized Controlled Trial.

OBJECTIVE: To report penile integrity measures, including stretched penile length (SPL), from a randomized, double-blind, double-dummy, placebo-controlled trial evaluating treatment with tadalafil initiated after nerve-sparing radical prostatectomy (nsRP). METHODS: Patients aged ≤ 68 years were randomized after nsRP 1:1:1 to 9-month double-blind treatment (DBT) with tadalafil 5 mg once daily (OaD), 20-mg tadalafil on-demand ("pro-re-nata"; PRN), or placebo, followed by 6-week drug-free washout and 3-month open-label OaD treatment. Secondary outcome measures included the change in SPL from pre-nsRP to the end of DBT (analysis of covariance adjusting for treatment, country, baseline, age, and nerve-sparing score), responses to Sexual Encounter Profile (SEP) questions 1-3 (mixed models for repeated measures adjusting for treatment, country, visit, visit-treatment-interaction, age), and Standardized Morning Erection Question (Cochran-Mantel-Haenszel test adjusted for age and country). RESULTS: Four hundred twenty-three patients were randomized to tadalafil OaD (N = 139), tadalafil PRN (N = 143), and placebo (N = 141). Greater retainment of SPL was observed with tadalafil OaD vs placebo at the end of DBT (least-square mean [95% confidence interval] difference OaD vs placebo, 4.1 mm [0.4 to 7.8 mm]; P = .032). No significant effects on SPL were found for tadalafil PRN vs placebo, or for the nerve-sparing score. Penile tumescence (SEP1) and ability for vaginal insertion (SEP2) significantly improved vs placebo at the end of double-blind and open-label treatment for patients randomized to tadalafil OaD only. The ability for successful sexual intercourse (SEP3) significantly improved with tadalafil OaD vs placebo only during DBT. The distribution of Standardized Morning Erection Question responses was different at the end of DBT (P = .045); 34.2% of patients on tadalafil OaD, 50.0% on tadalafil PRN, and 56.5% on placebo reported absence of morning erections. CONCLUSION: These data suggest the early initiation of tadalafil OaD protects from penile length loss and may contribute to protection from structural cavernosal changes after nsRP.

Do men with mild erectile dysfunction have the same risk factors as the general erectile dysfunction clinical trial population?

OBJECTIVE: • To compare the underlying risk for diseases associated with erectile dysfunction (ED; i.e. cardiovascular disease and diabetes) in a population of men with mild ED relative to a general ED clinical trial population. PATIENTS AND METHODS: • Men enrolled in a randomized, double-blind placebo-controlled (DBPC) trial of sildenafil for the treatment of mild ED were compared with a database of men enrolled in 67 of the manufacturer's other DBPC sildenafil trials. • The main outcome measures were baseline demographics, comorbidities and concomitant medications. RESULTS: • In both populations, most men were white, approximately one quarter were smokers, and most had an organic component to their ED etiology. • In the mild ED population (N = 176) versus the database population (N = 14,537), mean ± sd (range) age was 50 ± 12 (19-84) versus 55 ± 11 (18-89) years, body mass index was 29 ± 5 (20-48) versus 28 ± 5 (11-64) kg/m² and ED duration was 3.5 ± 3.2 (< 1-18) versus 4.6 ± 4.7 (< 1-45) years. • The prevalence of comorbidities associated with ED was similar (hypertension 26.1% (n = 46) vs 32.8%; diabetes mellitus 13.6% (n = 24) vs 22.1%; dyslipidemias 12.5% (n = 22) vs 11.7%; hypercholesterolemia 12.5% (n = 22) vs 9.5%; gastro-esophageal reflux disease 10.8% (n = 19) vs 6.0%; benign prostatic hyperplasia 9.7% (n = 17) vs 9.9%; depression 6.3% (n = 11) vs 5.6%; and anxiety 4.0% (n = 7) vs 1.6%), as was the rate of use of medications for those comorbidities. CONCLUSIONS: • Men with mild ED have similar risk factors to a general ED clinical trial population. Thus, mild ED is an important indicator of risk for underlying disease associated with ED. • Inquiry into ED should be part of routine clinical evaluation to facilitate rapid identification and early intervention. • Men complaining of mild ED should be evaluated adequately for underlying cardiovascular risk.

Men with mild erectile dysfunction benefit from sildenafil treatment.

INTRODUCTION: Sildenafil treatment has not been evaluated in a double-blind, placebo-controlled (DBPC) trial specific to men with mild erectile dysfunction (ED), defined by a 22-25 score on the International Index of Erectile Function-erectile function domain (IIEF-EF). AIM: To assess sildenafil efficacy in sexually dissatisfied men with mild ED. MAIN OUTCOME MEASURES: Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS), IIEF, Quality of Erection Questionnaire (QEQ), Erection Hardness Score (EHS 4=completely hard/fully rigid), general efficacy questions (GEQs), event log questions (hardness sufficient for penetration, duration sufficient for successful intercourse, ejaculation/orgasm, and second erection within 24 hours), and analog scales (erection firmness, reliability, and maintenance, and general sexual performance). METHODS: Eight-week DBPC flexible-dose (25, 50, or 100 mg) trial with 6-week, open-label (OL) extension. RESULTS: One hundred and seventy-six men were randomized (mean±standard deviation: age, 50±12 year; ED duration, 3.5±3.2 year). Most had organic or mixed ED. For sildenafil vs. placebo, 66% vs. 89% titrated to 100 mg and efficacy at DBPC end was better, including the EDITS Index score (least squares mean [standard error], 80.3 [2.3] vs. 62.1 [2.5]; P<0.0001); treatment satisfaction (EDITS Index score >50 in 89% vs. 63%; P=0.0001); no ED (IIEF-EF ≥26 in 58% vs. 39%; P<0.05); GEQs (≥4.9-fold greater odds of improved erections and ability to have sexual intercourse); and EHS 4 (47.2% vs. 25.2% of occasions; P<0.0001). At OL end, 93% of men were satisfied (EDITS Index score>50), 77% had no ED, and ≥89% were GEQ responders; mean scores on IIEF domains, the QEQ, and analog scales were >80% of the maximum; 60% of occasions had EHS 4; and event log responses were positive on >80% of occasions, except for second erections (41.9%). Headache, nasal congestion, and flushing, mostly mild to moderate, were the most common adverse events. CONCLUSION: Men with mild ED derive substantial benefit from sildenafil treatment.

Vardenafil improves erectile function in men with erectile dysfunction and associated underlying conditions, irrespective of the use of concomitant medications.

INTRODUCTION: Men with erectile dysfunction (ED) are also likely to have associated underlying conditions. AIM: This retrospective analysis evaluated the efficacy and safety of vardenafil in men with ED and underlying conditions, including those taking concomitant medications. METHODS: A total of 13 randomized, double-blind, placebo-controlled clinical studies were included. Vardenafil was administered at a starting dose of 10 mg, adjustable to 5 or 20 mg after 4 weeks. Efficacy analyses were performed on the intent-to-treat (ITT) population, using a last observation carried forward approach. Efficacy was assessed for subgroups of patients with diabetes, hypertension, dyslipidemia, or metabolic syndrome (as defined by International Diabetes Federation criteria). Incidence rates of treatment-emergent adverse events were analyzed overall and by subgroup for patients in the safety population. MAIN OUTCOME MEASURES: Primary efficacy measures were the erectile function domain of the International Index of Erectile Function (IIEF-EF), and Sexual Encounter Profile questions 2 and 3 (SEP2, SEP3). RESULTS: In total, 4,326 patients were randomized to treatment; the ITT population included 4,143 patients, with 4,266 patients valid for safety. At 12 weeks, vardenafil therapy was associated with statistically significant improvements from baseline in IIEF-EF scores, and SEP2 and SEP3 success rates, including patients with ED and diabetes, hypertension, dyslipidemia, or metabolic syndrome. These improvements were irrespective of level of glycemic control, or use of concomitant medications for the treatment of diabetes, hypertension, or dyslipidemia. Across all subgroups, the number and type of treatment-emergent adverse events were consistent with results from previous studies of phosphodiesterase type 5 inhibitors in men with ED and underlying conditions. CONCLUSIONS: Vardenafil demonstrated favorable efficacy and tolerability in this large pool of patients with ED and underlying conditions. Importantly, the use of concomitant medications was not associated with any noteworthy changes in the efficacy or safety profile of vardenafil.

Canadian male sexual health council survey to assess prevalence and treatment of premature ejaculation in Canada.

INTRODUCTION: This study evaluated the prevalence of complaints of premature ejaculation (PE) among a cross-sectional sample of Canadian males and their partners. AIM: It sought to quantify measures of behavior and attitudes as they relate to PE. It evaluated the level of patient knowledge, physician engagement, and patient satisfaction with treatment options for PE, a common sexual complaint. It also explored the patient and partner-reported impacts on quality of life and well-being. MAIN OUTCOME MEASURE: The main outcome measure for the study was the statistical analysis of data on different facets of PE and associated factors from a comprehensive population-based survey conducted in Canada. METHODS: A web-based survey was carried out among adults in Canada (phase 1, N = 3,816) followed by a focused telephone interview in phase 2 for those who met the criteria for PE (phase 2, N = 1,636). Men were classified as having PE based on self-report of low or absent control over ejaculation, irrespective of the duration of the ejaculation time, resulting in distress for them or their sexual partner or both, or reporting that they "climaxed too soon". RESULTS: The prevalence of PE in the survey, diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders-III criteria, ranged from 16% to 24% depending on the definition of PE utilized, and did not vary significantly with age. Ninety percent of those with a determination of PE in this survey had not discussed alternatives to prolong time to ejaculation with a physician, pointing to gaps in patient/physician communication around sexual health. CONCLUSIONS: PE is a prevalent sexual problem that poses special challenges to clinicians and causes considerable burden to Canadian men and their partners. There remains a stigma associated with PE, resulting in the existence of significant barriers to obtaining assistance from physicians for this problem. The majority of those interviewed who sought and received treatment have not been satisfied with the results.

Time to treatment of prostate cancer through the Calgary Prostate Institute rapid access clinic.

PURPOSE: To determine the wait time between initial referral, biopsy, diagnosis and individual treatment modalities of prostate cancer treatment through the Calgary Prostate Institute rapid access clinic (RAC) and compare to historical data estimates in Alberta and to suggested standards. Biopsy rate, rate of confirmed prostate cancer and the distribution of treatment modality for patients seen through the RAC is included. MATERIALS AND METHODS: A non-consented, retrospective chart review of 1103 patients from the Calgary Health Region referred to the RAC between September 2005 and August 2006 was completed. RESULTS: Patients experienced a median wait time of 21 days between referral from their family doctor and prostate biopsy. A total of 31.4% of patients referred to the clinic were requested to have a prostate biopsy performed and 50.8% of biopsies resulted in confirmed prostate cancer requiring treatment. Median wait time between diagnosis and treatment for all treatment types was 52.0 days with a 90th percentile of 146.2 days. Median wait time between referral and treatment for all treatment modalities was 101 days with a 90th percentile of 187.2 days. CONCLUSION: Calgary rapid access clinic reduces wait time between referral and biopsy by 78%. Stratifying across treatment type indicates that watchful waiting is the shortest time duration and radiation with hormone therapy is the longest.

Natural history of urinary tract infection in a primary care environment in Canada.

OBJECTIVE: To characterize the natural history of uncomplicated urinary tract infection (uUTI) in a Canadian primary care environment from the patient's perspective. MATERIALS AND METHODS: Female patients (n = 2323) with symptoms of uUTI were recruited by 581 family physicians who collected baseline demographic and clinical data and prescribed 500 mg/day extended release ciprofloxacin (Cipro XL). Follow-up data were collected 4 and 10 days later by patient telephone interview assessing uUTI symptoms, medication compliance, time to symptom resolution, impact on usual activities and overall satisfaction. RESULTS: Patients (mean age 40) had on average 3.56 uUTI symptoms at baseline, the most common of which was frequency (94% of patients). The mean duration of symptoms was 4.9 days. Sixty-three percent of patients reported an impact of uUTI on usual activities prior to antibiotic therapy with a mean impact score of 4.33 {scale 0 to 10 (maximum)}. At day 4, uUTI symptoms had decreased to 0.74/patient, 71.5% of patients reported symptom resolution, while medication compliance was 97%. By day 10, uUTI symptoms had decreased further to 0.42/patient, 84.3% of patients had symptom resolution and only 13% reported a residual impact on usual activities (mean impact score, 0.76). Patients showed high levels of satisfaction (> 80%) with all aspects of therapy. CONCLUSIONS: Patients wait almost 5 days before seeking medical attention for uUTI and by that time symptoms can significantly impact normal activities. This assessment of symptoms and outcomes of uUTI provides physicians with a better view of the impact of infection on patient's lives.

Intravesical potassium chloride sensitivity test in men with chronic pelvic pain syndrome.

PURPOSE: Intravesical potassium chloride has been reported to cause pain in patients with interstitial cystitis and male chronic prostatitis (CP)/chronic pelvic pain syndrome (CPPS). We performed the potassium chloride sensitivity test (PST) in subjects with CP/CPPS and healthy men without pelvic pain. MATERIALS AND METHODS: We recruited 40 men with CP/CPPS and 63 healthy men. The National Institutes of Health CPPS symptom index was used to measure the severity of symptoms. We instilled 100 ml physiological saline (NaCl 0.9%) intravesically. The bladder was emptied and 100 ml potassium chloride solution (KCl 40 mEq) were instilled. The subjects were asked to score urgency (0 to 10) and pain (0 to 10) sensations after each instillation. A positive PST was defined by 5 different cut-off points as the difference in score between KCl and NaCl instillations. Logistic regression analyses and area under the receiver operating characteristics curve were used to determine the predictive power of PST in CP/CPPS. RESULTS: There was no difference in pain and urgency scores between the men with CP/CPPS and controls (p >0.05 for each). Men with CP/CPPS had higher pain and urgency scores with KCl than with NaCl (p = 0.011 and 0.033, respectively). The rates of positive PST were 50% and 36.5% in the CP/CPPS and control groups, respectively (p = 0.160). There was no significant correlation of potassium chloride sensitivity scores with National Institutes of Health symptom scores (p >0.05 for each). The sensitivity, specificity, and positive predictive and negative predictive values of PST were 50%, 63.5%, 46.5% and 66.7%, respectively. CONCLUSIONS: Although there was a significant increase in pain and urgency scores following KCl instillation in patients with CP/CPPS, these scores and the rate of positive PST were not statistically different from those of healthy subjects. Thus, PST does not have a good predictive value in the diagnosis of CP/CPPS.

Pain sensitization in male chronic pelvic pain syndrome: why are symptoms so difficult to treat?

PURPOSE: Male chronic pelvic pain syndrome (CPPS) is a chronic and debilitating symptom complex, and inconsistent outcomes of antibiotic and anti-inflammatory treatments have created an interest in investigating the neurological mechanisms of CPPS pain. Because chronic pelvic pain likely results in hyperexcitability of dorsal horn neurons, ie central sensitization, thermal algometry may be useful in the assessment of CPPS. We evaluated men with and without CPPS to determine if there were differences between the 2 groups in their responses to noxious heat stimuli. MATERIALS AND METHODS: We recruited 66 healthy men without CPPS and 36 men with a history of CPPS for the study. Mean age of CPPS subjects was 43.1 years (range 18 to 62) and mean age of controls was 35.1 (range 21 to 61). All subjects with pain completed a National Institutes of Health-Chronic Prostatitis Symptom Index. We conducted thermal sensory tests with a small thermode programmed to deliver 2 series of 4 rapid bursts of noxious heat stimuli to the perineum and the anterior thigh. The subjects reported sensation on a computerized visual analog scale (COVAS) with a manual sliding lever. The average peak COVAS values and time to peak values from thigh and perineum of each series of thermal bursts were compared between CPPS and controls. RESULTS: The mean pain score on questionnaires was 9.7 (4 or greater indicating significant pain), mean urinary score was 4.7 (range 0 to 10) and mean quality of life impact score was 7.3 (range 3 to 13). Compared to controls men with CPPS reported higher mean peak COVAS values in the perineum. There was no difference between groups in the peak COVAS value on the thigh. CONCLUSIONS: Men with CPPS have altered heat sensation/pain sensitization in the perineum compared to controls. This finding is another that supports the resemblance of CPPS to other chronic pain syndromes and may help explain why CPPS is often refractory to treatment. Further investigations into male CPPS should focus on the mechanisms inducing and maintaining pain in an effort to treat this condition effectively.

Prostate biopsy culture findings of men with chronic pelvic pain syndrome do not differ from those of healthy controls.

PURPOSE: Previous reports have identified bacteria in the prostate of men with chronic pelvic pain syndrome. To examine whether prostatic bacteria are more prevalent among patients with chronic pelvic pain syndrome than among those without pelvic pain, we compared 4-glass urine test and prostate biopsy results. MATERIALS AND METHODS: A total of 120 patients with types IIIa and IIIb chronic pelvic pain syndrome and 60 asymptomatic controls underwent a standard 4-glass urine test, examination of expressed prostatic secretion leukocytes by hemocytometer and transperineal, digitally guided prostate biopsies. Tissue was cultured for aerobes, anaerobes, Trichomonas vaginalis, Chlamydia trachomatis and herpes simplex virus. Skin cultures were performed on a subset of patients and controls. RESULTS: Positive prostate biopsy cultures were obtained from patients and controls. Bacteria were found in 45 of 118 pain patients (38%) and in 21 of 59 controls (36%) (p = 0.74). Older men were more likely to have positive cultures. Men with type IIIa chronic pelvic pain syndrome were more likely than those with type IIIb to have positive prostate biopsy cultures. CONCLUSIONS: Bacteria cultured from transperineal prostatic biopsies do not differ between men with and without chronic pelvic pain syndrome. Prostatic bacteria obtained by biopsy are probably not etiologically related to the symptoms in the majority of men with chronic pelvic pain syndrome.