Efficacy and safety of tadalafil 5 mg once daily for lower urinary tract symptoms suggestive of benign prostatic hyperplasia: subgroup analyses of pooled data from 4 multinational, randomized, placebo-controlled clinical studies. PDE5 inhibitors blunt inflammation in human BPH: a potential mechanism of action for PDE5 inhibitors in LUTS. Efficacy and safety of combined oral therapy with tadalafil and alfuzosin: an integrated approach to the management of patients with lower urinary tract symptoms and erectile dysfunction. Preliminary report. Effects of tadalafil on nighttime voiding (nocturia) in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia: a post hoc analysis of pooled data from four randomized, placebo-controlled clinical studies Update on AUA guideline on the management of benign prostatic hyperplasia. A comparison of the efficacy of naftopidil and tamsulosin hydrochloride in medical treatment of benign prostatic enlargement Efficacy of alfuzosin and sildenafil combination in male patients with lower urinary tract symptoms Continued improvement in pressure-flow parameters in men receiving finasteride for 2 years. Finasteride Urodynamics Study Group. Tadalafil Administered Once Daily for Treatment of Lower Urinary Tract Symptoms in Korean men with Benign Prostatic Hyperplasia: Results from a Placebo-Controlled Pilot Study Using Tamsulosin as an Active Control. Photoselective vaporization of prostate vs. transurethral resection of prostate: A prospective, randomized study with one year follow-up Prostate Volume and Serum Prostate–Specific Antigen as Predictors of Acute Urinary Retention
OBJECTIVE To assess the efficacy and safety of tadalafil , a phosphodiesterase 5 ( PDE5 ) inhibitor efficacious for erectile dysfunction and lower urinary tract symptoms suggestive of benign prostatic hyperplasia ( LUTS/BPH ) , in population subgroups , using pooled data from 4 international , r and omized , placebo-controlled studies in men with LUTS/BPH . METHODS The safety data base included 1500 men r and omized to tadalafil 5 mg once daily or placebo for 12 weeks . Changes in total International Prostate Symptom Score ( IPSS ) , IPSS- quality of life index , and BPH impact index were examined overall , and changes in IPSS or adverse events ( AEs ) were examined across subgroups of interest . Treatment-group differences were assessed using analysis of covariance . RESULTS Results of pooled data confirmed that tadalafil ( N = 752 ) result ed in significant improvements from baseline vs placebo ( N = 746 ) in IPSS ( mean difference -2.3 ; P < .001 ) , and also in BPH impact index and IPSS- quality of life index ( both P < .001 ) . Subgroup analyses demonstrated that IPSS improvements were significant regardless of baseline LUTS severity ( IPSS < 20/≥20 ) , age ( ≤65/>65 years ) , recent previous use of α-blockers or PDE5 inhibitors , total testosterone level ( < 300/≥300 ng/dL ) , or prostate-specific antigen predicted prostate volume ( < 40/≥40 mL ) . [ corrected ] Rates of treatment emergent AEs were comparable between subgroups of baseline age ( ≤65/>65 years ) , previous PDE5 inhibitor use , and the presence or absence of pre-existing diabetes , hypertension , or cardiovascular disease ( including hypertension ) , but somewhat higher for recent previous α-blocker use . CONCLUSION In these pooled data analyses , tadalafil 5 mg improved LUTS/BPH across subgroups of age , LUTS severity , testosterone levels , and prostate volume . Rates of AEs were similar across the subgroups assessed BACKGROUND Metabolic syndrome ( MetS ) and benign prostate hyperplasia (BPH)/low urinary tract symptoms ( LUTS ) are often comorbid . Chronic inflammation is one of the putative links between these diseases . Phosphodiesterase type 5 inhibitors ( PDE5i ) are recognized as an effective treatment of BPH-related LUTS . One proposed mechanism of action of PDE5 is the inhibition of intraprostatic inflammation . In this study we investigate whether PDE5i could blunt inflammation in the human prostate . METHODS Evaluation of the effect of tadalafil and vardenafil on secretion of interleukin 8 ( IL-8 , a surrogate marker of prostate inflammation ) by human myofibroblast prostatic cells ( hBPH ) exposed to different inflammatory stimuli . We preliminary evaluate histological features of prostatic inflammatory infiltrates in BPH patients enrolled in a r and omized , double bind , placebo controlled study aim ed at investigating the efficacy of vardenafil ( 10 mg/day , for 12 weeks ) on BPH/LUTS . RESULTS In vitro treatment with tadalafil or vardenafil on hBPH reduced IL-8 secretion induced by either TNFα or metabolic factors , including oxidized low-density lipoprotein , oxLDL , to the same extent as a PDE5-insensitive PKG agonist Sp-8-Br-PET-cGMP . These effects were reverted by the PKG inhibitor KT5823 , suggesting a cGMP/PKG-dependency . Treatment with tadalafil or vardenafil  significantly suppressed oxLDL receptor ( LOX-1 ) expression . Histological evaluation of anti-CD45 staining ( CD45 score ) in prostatectomy specimens of BPH patients showed a positive association with MetS severity . Reduced HDL-cholesterol and elevated triglycerides were the only MetS factors significantly associated with CD45 score . In the MetS cohort there was a significant lower CD45 score in the vardenafil-arm versus the placebo-one INTRODUCTION Alpha1-blockers ( AB ) are the first-line monotherapy for lower urinary tract symptoms ( LUTS ) .  Phosphodiesterase type 5 ( PDE5 ) inhibitors are the first-line treatment for erectile dysfunction ( ED ) . Numerous studies have supposed a significant association between ED and LUTS , but a causal relationship can not be established . AIM The aim was to evaluate the efficacy of a combined therapy with an AB ( alfuzosin ) and PDE5 inhibitors ( tadalafil ) in patients with LUTS and ED . METHODS This was a r and omized , open-label , three-arm study . A total of 66 men complaining of ED and LUTS were included in the study . Patients were assessed at baseline and after 12 weeks of study treatment , and then underwent r and omized allocation to either alfuzosin 10 mg once a day ( 22 patients ) or tadalafil 20 mg on alternative days ( 21 patients ) , or a combination of both ( 23 patients ) . MAIN OUTCOME MEASURES All participants completed the erectile function domain of the International Index of Erectile Function ( IIEF-EF ) and the International Prostatic Symptom Score ( IPSS ) . Other efficacy variables included maximum urinary flow rate ( Qmax ) and medium urinary flow rate ( Qave ) . RESULTS IIEF-EF tended to improve with alfuzosin alone ( + 15 % ) , while it was clearly improved with tadalafil alone ( + 36.3 % ) . The greatest improvement was experienced with the combination therapy ( + 37.6 % ) . Improvement in Qmax was observed in all groups , but patients receiving combination therapy had greater improvement ( 29.6 % ) than patients receiving either only alfuzosin ( 21.7 % ) or only tadalafil ( 9.5 % ) . IPSS was significantly improved in alfuzosin group ( 27.2 % ) , was more marked with the combination therapy ( 41.6 % ) , and a small increase , although not significant , was also observed with tadalafil ( 8.4 % ) . CONCLUSIONS Combined therapy improved ED and LUTS as demonstrated by the significant improvement in uroflowmetry measures and in IPSS and IIEF-EF scores . A significant improvement was also observed in quality of life assessment s. The beneficial effects of tadalafil on LUTS similar to the benefits of alfuzosin on ED , although present , were smaller Purpose The phosphodiesterase type 5 inhibitor tadalafil is approved for the treatment of signs and symptoms of benign prostatic hyperplasia ( BPH ) . While tadalafil significantly improves overall lower urinary tract symptoms suggestive of BPH ( LUTS/BPH ) , improvements in nocturia were not significant in individual studies . We therefore sought to further assess nocturia based on data integrated from four tadalafil registration al studies . Methods Data were integrated from four r and omized , placebo-controlled  , double-blind , 12-week registration al studies of tadalafil for LUTS/BPH . Nocturia was assessed as nighttime voiding frequency using the International Prostate Symptom Score question 7 ( IPSS Q7 ) . Efficacy results were analyzed using analysis of covariance . Results For the tadalafil 5 mg once daily ( N = 752 ) and placebo ( N = 748 ) groups , baseline characteristics were well balanced , and the overall severity of nocturia per mean IPSS Q7 was 2.3 ± 1.2 . The mean treatment change was −0.4 with placebo and −0.5 with tadalafil ; the least-squares mean ( st and ard error ) treatment difference was −0.2 ( 0.05 ) , p = 0.002 . For patients receiving placebo and tadalafil , respectively , the proportion with improved nocturnal frequency was 41.3 and 47.5 % , with no change was 44.8 and 41.0 % , and with worsening was 13.9 and 11.5 % . Conclusions A statistically significant improvement in nocturnal frequency was seen with tadalafil over placebo ; however , the treatment difference was small and not considered clinical ly meaningful . Further studies using voiding diaries and excluding patients with nocturnal polyuria would be needed to more precisely estimate the impact of tadalafil on nocturia associated with LUTS/BPH PURPOSE To revise the 2003 version of the American Urological Association 's ( AUA ) Guideline on the management of benign prostatic hyperplasia ( BPH ) . MATERIAL S AND METHODS From MEDLINE ® search es of English language publications ( January 1999 through February 2008 ) using relevant MeSH terms , articles concerning the management of the index patient , a male ≥45 years of age who is consulting a healthcare provider for lower urinary tract symptoms ( LUTS ) were identified . Qualitative analysis of the evidence was performed . Selected studies were stratified by design , comparator , follow-up interval , and intensity of intervention , and meta-analyses ( quantitative synthesis ) of outcomes of r and omized controlled trials were planned . Guideline statements were drafted by an appointed expert Panel based on the evidence . RESULTS The studies varied as to patient selection ; r and omization ; blinding mechanism ; run-in periods ; patient demographics , comorbidities , prostate characteristics and symptoms ; drug doses ; other intervention characteristics ; comparators ; rigor and intervals of follow-up ; trial duration and timing ; suspected lack of applicability to current US practice ; and techniques of outcomes measurement . These variations affected the quality of the evidence review ed making formal meta- analysis impractical or futile . Instead , the Panel and extractors review ed the data in a systematic fashion and without statistical rigor . Diagnosis and treatment algorithms were adopted from the 2005 International Consultation of Urologic Diseases . Guideline statements concerning pharmacotherapies , watchful waiting , surgical options and minimally invasive procedures were either up date d or newly drafted , peer review ed and approved by AUA Board of Directors . CONCLUSIONS New pharmacotherapies and technologies have emerged which have impacted treatment algorithms . The management of LUTS/BPH continues to evolve Introduction : Lower urinary tract symptoms in men , over age of 50 years is suggestive of benign prostatic enlargement ( BPE ) . Different alpha-blockers have been evaluated for the treatment of benign prostatic hyperplasia for over last 30 years . This study was conducted in a tertiary care institution during the period of year between June 2011 and August 2013 to compare the effect of naftopidil and tamsulosin in reducing the obstructive and irritable symptoms of BPE . Subjects and Methods : A prospect i ve r and omized comparative study was carried on 60 patients of BPE by assigning half of them to treatment with tamsulosin and rest with naftopidil .  Pre- and post-treatment uroflowmetry ( UFM ) , post-void residue ( PVR ) , International Prostate Symptoms Score ( IPSS ) , were obtained at 15 and 30 days after starting treatment . Results : The age of patients ranged from 51 to 78 . At base line there was no statistical difference between UFM parameter , PVR and IPSS in the two groups . UFM and PVR showed significantly better response at both intervals with naftopidil . Comparison of IPSS showed better improvement in Group A both at 15 and 30 days . It was seen that the obstructive symptoms showed a significantly better response with tamsulosin and symptoms of irritability was seen better response with naftopidil . Conclusion : It was seen that during the period of follow-up of 30 days naftopidil had a better effect on UFM , PVR , IPSS compared with tamsulosin . In general , obstructive symptoms showed better improvement in tamsulosin and irritative symptoms showed better improvement in naftopidil Lower urinary tract symptoms ( LUTS ) and erectile dysfunction ( ED ) are frequently encountered in ageing males . We compared the efficacy of alfuzosin 10 mg alone or in combination with sildenafil 50 mg in the treatment of LUTS due to benign prostatic hyperplasia . One hundred male patients older than 45 years were r and omized to two groups containing 50 patients each ; one group receiving alfuzosin 10 mg and the other group alfuzosin 10 mg combined with sildenafil 50 mg  . International Prostate Symptom Score ( IPSS ) , quality of life ( QoL ) , maximum flow rate ( Qmax ) , prostate volume and post‐void residual urine were evaluated . The mean age was 60.2 ± 17.8 . Mean data of evaluated parameters in both groups at the end of 3rd month compared with baseline values are given respective order as ; 5.1 ( 26.8 % ) and 5.8 ( 28.2 % ) points decreases in IPSS ; 1.6 ( 41.1 % ) and 1.8 ( 45 % ) points decreases in QoL ; and 3.4 ( 29.6 % ) and 3.4 ( 33 % ) points increases in Qmax . The outcomes of our study can not be interpreted in such a way to report that alpha blocker‐PDE5 inhibitor combination  has a better efficacy than alpha blocker treatment alone in patients with LUTS OBJECTIVES To assess the long-term effects of finasteride on pressure-flow parameters in men with urodynamically documented bladder outflow obstruction ( BOO ) . METHODS One hundred twenty-one men with benign prostatic enlargement ( BPE ) and lower urinary tract symptoms ( LUTS ) underwent a pressure-flow study ( PFS ) at 1 of 11 clinical centers . The PFS technique was st and ardized , and all tracings were read by a single reader unaware of the treatment group . Patients who were obstructed according to a modified Abrams-Griffiths nomogram  were r and omized to 5 mg finasteride ( n = 81 ) or placebo ( n = 40 ) for 12 months ; all patients continuing into an open extension received finasteride during the second 12 months of therapy . Results of the initial 12-month study demonstrated the benefit of finasteride treatment on PFS parameters . To examine the continuing effects over time , an analysis of the data from 54 patients who completed 24 months of treatment with finasteride is provided . RESULTS Detrusor pressure at maximum flow ( PdetQmax ) continued to decrease during the second 12 months of therapy ( decreases of 5.3 and 11.7 cm H2O at months 12 and 24 , respectively ) . The percentage of patients obstructed by Abrams-Griffiths classification decreased from 76.2 % at baseline to 66.7 % at month 12 and 59.6 % at month 24 . An intention-to-treat analysis yielded similar results . CONCLUSIONS Finasteride improves urodynamic measures of obstruction in men with BPE and LUTS , with continued improvement during the second 12 months of therapy OBJECTIVES Assess the efficacy and safety of once-daily tadalafil or tamsulosin versus placebo during 12 weeks on lower urinary tract symptoms ( LUTS ) in Korean men with benign prostatic hyperplasia ( BPH ) . METHODS Following a 4-week placebo run-in period , 151 Korean men were r and omly assigned to receive once-daily tadalafil 5 mg , tamsulosin 0.2 mg , or placebo for 12 weeks . RESULTS The International Prostate Symptom Score ( IPSS ) least squares mean changes from baseline to endpoint were numerically but not significantly improved in the tadalafil ( -5.8 ) and tamsulosin ( -5.4 ) groups compared with placebo ( -4.2 , P > 0.05 ) . Decreases in IPSS obstructive and irritative subscores , IPSS Quality of Life score , and BPH Impact Index from baseline to endpoint were largest in the tadalafil group followed by tamsulosin , though none separated significantly from placebo . Increases in maximum urinary flow rate were small and not significantly different than placebo ; the increase was largest in the tadalafil group ( 2.5 mL/sec ) , followed by the placebo ( 2.3 mL/sec ) and tamsulosin ( 2.1 mL/sec ) groups . The percentage of subjects reporting at least one treatment-emergent adverse event was 26.5 , 13.7 and 3.9 % in the tamsulosin , tadalafil and placebo groups , respectively . CONCLUSIONS In this pilot study in Korean men , those with BPH and treated with tadalafil 5 mg or tamsulosin 0.2 mg once daily experienced a reduction in LUTS , which was numerically ( but not statistically ) significant compared with the placebo . Tadalafil was well tolerated and few subjects discontinued the study due to treatment-emergent adverse events . Larger studies in Asian men with BPH and LUTS treated with phosphodiesterase type 5 inhibitors are needed Objectives : To evaluate in a prospect i ve , r and omized study , the efficacy and safety profile of photoselective vaporization of prostate ( PVP ) using a 80W potassium titanyl phosphate ( KTP ) laser when compared to st and ard transurethral resection of prostate ( TURP ) in patients with lower urinary tract symptoms ( LUTS ) due to benign prostatic enlargement ( BPE ) . Material s and Methods : Between February 2009 and August 2009 , 117 patients satisfying the eligibility criteria underwent surgery [ 60 PVP{Group A } ; 57 TURP{Group B } ] . The groups were compared for functional outcome ( both subjective and objective parameters ) , perioperative parameters and complications , with a follow up of one year . P value<0.05 was considered statistically significant . Results : The baseline characteristics of the two groups were comparable . Mean age was 66.68 years and 65.74 years , mean IPSS score was 19.98 and 20.88 , mean prostate volume was 44.77 cc and 49.02 cc in Group A and B , respectively . Improvements in IPSS , QOL , prostate volume , Q max and PVRU at 12 months were similar in both groups . PVP patients had longer operating time , lesser perioperative blood loss , shorter catheterization time and a higher dysuria rate when compared to TURP patients . The overall complication rate was similar in the two groups . Conclusions : In patients with LUTS due to BPE , KTP-PVP is an equally efficacious alternative to TURP with durable results at one year follow up with additional benefits of lesser perioperative blood loss , lesser transfusion requirements and a shorter catheterization time . Long term comparative data is awaited to clearly define the role of KTP-PVP in such patients Objectives : We evaluated prostate volume and  prostate – specific antigen ( PSA ) as predictors of acute urinary retention ( AUR ) in men with benign prostatic enlargement ( BPE ) . Methods : Data were pooled from 3 identical 2–year , multinational , multicenter , non – US , placebo – controlled finasteride trials in 4,222 men with BPE and no evidence of prostate cancer . Results : The 2–year incidence of spontaneous AUR was higher in placebo patients with enlarged prostates ( 4.2 % in men with prostate volume ≥40 ml vs 1.6 % in the < 40 ml group ) and higher PSA levels ( 3.9 % in men with PSA ≥1.4 ng/ml vs. 0.5 % in the < 1.4 ng/ml group ) at baseline . Finasteride reduced AUR incidence by 61 % in men with larger prostates , by 63 % in men with higher PSA levels , and by 47 % in men with smaller prostates , compared with placebo . Conclusions : BPE patients with larger prostate volumes , higher PSA levels and no evidence of prostate cancer have an increased risk of developing AUR and therefore derive the greatest benefit from the risk reduction seen with finasteride therapy
Pooled data analyses revealed that tadalafil 5 mg once daily allows the clinical ly-meaningful improvement of LUTS and nocturnal voiding frequency independent of both erectile dysfunction severity and improvement .
PDE5-Is are safe and effective in improving both LUTS and erectile function in appropriately selected men with LUTS/BPE .
We found evidence to confirm that phosphodiesterase type 5 inhibitors are a valid treatment option for men affected by bothersome urinary symptoms with or without erectile dysfunction
CONTEXT Several pre clinical reports , r and omized controlled trials , systematic review s , and posthoc analyses corroborate the role of phosphodiesterase type 5 inhibitors ( PDE5-Is ) in the treatment of men with lower urinary tract symptoms ( LUTS ) associated with benign prostatic enlargement ( BPE ) .
OBJECTIVE Up date of the latest evidence on the mechanisms of action , evaluate the current meta-analyses , and emphasize the results of pooled data analyses of PDE5-Is in LUTS/BPE .
PATIENT SUMMARY We review ed recent literature on phosphodiesterase type 5 inhibitors in men with lower urinary tract symptoms associated with prostatic enlargement .