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 A randomized, placebo-controlled study to assess safety and efficacy of vardenafil 10 mg and tamsulosin 0.4 mg vs. tamsulosin 0.4 mg alone in the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia. Effects of tadalafil on lower urinary tract symptoms secondary to benign prostatic hyperplasia and on erectile dysfunction in sexually active men with both conditions: analyses of pooled data from four randomized, placebo-controlled tadalafil clinical studies. The effect of benign lower urinary tract symptoms on subsequent prostate cancer testing and diagnosis. Sexual function in men with lower urinary tract symptoms and prostatic enlargement secondary to benign prostatic hyperplasia: results of a 6-month, randomized, double-blind, placebo-controlled study of tadalafil coadministered with finasteride. Efficacy and safety of the coadministration of tadalafil once daily with finasteride for 6 months in men with lower urinary tract symptoms and prostatic enlargement secondary to benign prostatic hyperplasia. The effects of dutasteride, tamsulosin and combination therapy on lower urinary tract symptoms in men with benign prostatic hyperplasia and prostatic enlargement: 2-year results from the CombAT study. Tadalafil 2.5 or 5 mg administered once daily for 12 weeks in men with both erectile dysfunction and signs and symptoms of benign prostatic hyperplasia: results of a randomized, placebo-controlled, double-blind study. Decision tree analyses of key patient characteristics in Middle Eastern/North African and Latin American men treated with long-acting and short-acting PDE5 inhibitors for erectile dysfunction The relationship among lower urinary tract symptoms, prostate specific antigen and erectile dysfunction in men with benign prostatic hyperplasia: results from the proscar long-term efficacy and safety study. Aquablation among novice users in Canada: A WATER II subpopulation analysis. Combination therapy with doxazosin and finasteride for benign prostatic hyperplasia in patients with lower urinary tract symptoms and a baseline total prostate volume of 25 ml or greater. Tadalafil once daily improves ejaculatory function, erectile function, and sexual satisfaction in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia and erectile dysfunction: results from a randomized, placebo- and tamsulosin-controlled, 12-week double-blind study.
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 INTRODUCTION Safety and efficacy of tamsulosin and vardenafil are well established : however , there is no report regarding combined therapy with these drugs for  lower urinary tract symptoms ( LUTSs ) secondary to benign prostatic hyperplasia ( BPH ) . AIM To compare the safety and efficacy of tamsulosin 0.4 mg/day vs. tamsulosin 0.4 mg/day plus vardenafil 10 mg/day in patients with LUTS/BPH in a r and omized trial with 12-week follow-up . METHODS We conducted a r and omized , double-blind , placebo-controlled study on 60 men with persistent storage LUTS after 2-week run-in with tamsulosin .  MAIN OUTCOME MEASURES International Prostate Symptom Score ( IPSS ) , IPSS-bother , International Index of Erectile Function , Version 5 ( IIEF-5 ) and Over Active Bladder question naire ( OAB-q ) scores , uroflowmetry data ( Qmax , Qave ) , and postvoiding residual urine were recorded after run-in ( baseline ) , and 2 and 12 weeks after treatment . Differences between vardenafil and placebo at different times were calculated with unpaired sample s t-test . Between-group differences in change from baseline to 2 and 12 weeks were evaluated with analysis of variance . RESULTS We found a between-group significant difference from baseline to 12 weeks in the following : ( i ) Qmax ( placebo : + 0.07 , vardenafil : + 2.56 , P = 0.034 ) ; ( ii ) Qave  ( placebo : -0.15 , vardenafil : + 1.02 , P = 0.031 ) ; ( iii ) irritative-IPSS subscores ( placebo : -1.67 , vardenafil : -3.11 , P = 0.039 ) ; and ( iv ) IIEF ( placebo : + 0.06 , vardenafil : + 2.61 , P = 0.030 ) . No patient reported any serious ( grade ≥ 2 ) adverse event ( AE ) . There were no differences in the incidence of common , treatment-related AEs between men undergoing combined therapy or tamsulosin alone . CONCLUSIONS The combination of tamsulosin and vardenafil for 12 weeks was well tolerated and more effective to improve both LUTS and erectile function , as compared with tamsulosin alone . Further studies are needed to assess the role of combined therapy of phosphodiesterase type 5 inhibitors and alpha blockers in treating LUTS/BPH INTRODUCTION Erectile dysfunction ( ED ) and lower urinary tract symptoms suggestive of benign prostatic hyperplasia ( LUTS/BPH ) are common in aging males and frequently occur together . Tadalafil has demonstrated efficacy in treating both conditions . AIM The study aims to evaluate the efficacy and safety of tadalafil 5 mg once daily vs. placebo over 12 weeks in treating both LUTS/BPH and ED in sexually active men . We also assessed relationships of baseline disease severity and prostate specific antigen ( PSA ) to outcomes . METHODS Data were pooled from four multinational , r and omized studies of men ≥45 years with LUTS/BPH , with analyses restricted to sexually active men with ED . R and omization ( baseline ) followed a 4-week placebo run-in ; changes from baseline were assessed vs. placebo using analysis of covariance . MAIN OUTCOME MEASURES International Prostate Symptom Score ( IPSS ) , IPSS subscores , Quality -of-Life Index ( IPSS-QoL ) , BPH Impact Index ( BII ) , and International Index of Erectile Function-Erectile Function ( IIEF-EF ) Domain score were used in this study . RESULTS Tadalafil ( N = 505 ) significantly improved total IPSS vs. placebo ( N = 521 ) ; mean changes from baseline were -6.0 and -3.6 , respectively ( P < 0.001 ) . Improvements in IIEF-EF Domain score  ( tadalafil , 6.4 ; placebo , 1.4 ) were also significant vs. placebo , as were the IPSS storage and voiding subscores , IPSS-QoL , and BII ( all P < 0.001 ) . No significant impact of baseline ED severity or PSA category on IPSS response was observed ( interaction P values , 0.463 and 0.149 , respectively ) . Similarly , improvement in IIEF-EF Domain score was not significantly impacted by baseline LUTS/BPH severity or PSA category ( interaction P values , 0.926 and 0.230 , respectively ) . Improvements in IPSS and IIEF-EF Domain score during treatment were weakly correlated ( r = -0.229 ) . Treatment-emergent adverse events were consistent with previous reports . CONCLUSIONS Tadalafil was efficacious and well tolerated in treating ED and LUTS/BPH in sexually active men with both conditions . Improvements in both conditions were significant regardless of baseline severity . Improvements in the total IPSS and the IIEF-EF Domain score were weakly correlated BACKGROUND Lower urinary tract symptoms ( LUTS ) are common and have been associated with the subsequent diagnosis of prostate cancer ( PCa ) in population cohorts . OBJECTIVE To determine whether the association between LUTS and PCa is due to the intensity of PCa testing after LUTS diagnosis . DESIGN , SETTING , AND PARTICIPANTS We prospect ively followed a representative , population -based cohort of 1922 men , aged 40 - 79 yr , from 1990 until 2010 with interviews , question naires , and abstract ing of medical records for prostate outcomes . Men were excluded if they had a previous prostate biopsy or PCa diagnosis .  Self-reported LUTS was defined as an American Urological Association symptom index score > 7 ( n=621 ) . Men treated for LUTS ( n=168 ) were identified from review of medical records and /or self report . Median follow-up was 11.8 yr ( interquartile range : 10.7 - 12.3 ) . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Associations between self-reported LUTS , or treatment for LUTS , and risk of subsequent prostate biopsy and PCa were estimated using Cox proportional hazard models . RESULTS AND LIMITATIONS Fifty-five percent of eligible men enrolled in the study . Men treated for LUTS were more likely to undergo a prostate biopsy ( hazard ratio [ HR ] : 2.4 ; 95 % confidence interval [ CI ] , 1.7 - 3.3 ) . Men younger than 65 yr who were treated for LUTS were more likely to be diagnosed with PCa ( HR : 2.3 , 95 % CI , 1.5 - 3.5 ) , while men aged > 65 yr were not ( HR : 0.89 , 95 % CI , 0.35 - 1.9 ) . Men with self-reported LUTS were not more likely to be biopsied or diagnosed with PCa . Neither definition of LUTS was associated with subsequent intermediate- to high-risk cancer . The study is limited by lack of histologic or prostate-specific antigen level data for the cohort . CONCLUSIONS These results indicate that a possible cause of the association between LUTS and PCa is increased diagnostic intensity among men whose LUTS come to the attention of physicians . Increased symptoms themselves were not associated with intensity of testing or diagnosis INTRODUCTION Tadalafil ( TAD ) 5 mg coadministered with finasteride ( FIN ) 5 mg significantly improves lower urinary tract symptoms ( LUTS ) in men with benign prostatic hyperplasia ( BPH ) and prostatic enlargement . However , its effects on erectile/sexual function have yet to be fully described . AIM Assess the effects of TAD/FIN coadministration ( compared with placebo [PBO]/FIN ) on erectile and sexual function in sexually active men with LUTS and prostatic enlargement secondary to BPH with or without baseline comorbid erectile dysfunction ( ED ) . METHODS A r and omized , double-blind , PBO-controlled study of 695 men ( 610 sexually active ; 450 with baseline ED ; 404 sexually active with baseline ED ) conducted at 70 sites in 13 countries .  TAD 5 mg or PBO once daily coadministered with FIN 5 mg once daily for 26 weeks . MAIN OUTCOME MEASURES International Index of Erectile Function ( IIEF ) domain and single-item scores ; proportions of patients who demonstrated minimal clinical ly important differences ( MCIDs ) in IIEF-Erectile Function domain scores ( IIEF-EF ; MCID defined as ≥4-point improvement ) ; and sexual dysfunction adverse events ( AEs ) . RESULTS Compared with PBO/FIN , TAD/FIN result ed in improvements for all IIEF domain and single-item scores assessed among patients with baseline ED ( P ≤ 0.002 for all measures ) and among patients without baseline ED ( P ≤ 0.041 for all measures ) . Compared with PBO/FIN , significantly larger percentages of sexually active men with baseline ED treated with TAD/FIN achieved an IIEF-EF MCID after 4 , 12 , and 26 weeks of therapy ( P < 0.001 for odds ratio comparisons between TAD/FIN and PBO/FIN at all 3 three postbaseline timepoints ) . The incidence of sexual AEs was low : five TAD/FIN patients and seven PBO/FIN patients reported sexual AEs , including ED , decreased/lost libido , and ejaculation disorders . CONCLUSIONS TAD/FIN coadministration for the treatment of men with LUTS and prostatic enlargement secondary to BPH concurrently leads to statistically significant improvements in erectile/sexual function and is well-tolerated , regardless of the presence/absence of ED at treatment initiation PURPOSE Medical treatment for men with lower urinary tract symptoms and prostatic enlargement secondary to benign prostatic hyperplasia is 5α-reductase inhibitor monotherapy or coadministration with an α-blocker . We assessed the effects of tadalafil 5 mg coadministered with finasteride 5 mg during 26 weeks on lower urinary tract symptoms and sexual symptoms . MATERIAL S AND METHODS In an international , r and omized , double-blind , parallel study of men 45 years old or older who were 5α-reductase inhibitor naïve and had an I-PSS ( International Prostate Symptom Score ) of 13 or greater and prostate volume 30 ml or greater , 350 were treated with placebo/finasteride  and 345 received tadalafil/finasteride for 26 weeks . Changes in lower urinary tract symptoms secondary to benign prostatic hyperplasia were assessed with the I-PSS , erectile dysfunction improvements were assessed with the IIEF-EF ( International Index of Erectile Function-Erectile Function ) in sexually active men and safety was assessed by evaluating adverse events . RESULTS Least squares mean changes from baseline in I-PSS after 4 , 12 and 26 weeks of tadalafil/finasteride coadministration were -4.0 , -5.2 and -5.5 , respectively . Corresponding values for placebo/finasteride coadministration were -2.3 , -3.8 and -4.5 ( p ≤ 0.022 at all visits favoring tadalafil/finasteride  coadministration ) . I-PSS subscores ( storage and voiding ) and quality of life index were also numerically improved with tadalafil/finasteride coadministration . Least squares mean changes from baseline in IIEF-EF  with tadalafil/finasteride coadministration were 3.7 after 4 weeks , and 4.7 after 12 and 26 weeks . Corresponding values for placebo/finasteride coadministration were -1.1 , 0.6 and -0.0 ( p < 0.001 at all visits favoring tadalafil/finasteride coadministration ) . Tadalafil/finasteride coadministration was well tolerated and most adverse events were mild/moderate . CONCLUSIONS The coadministration of tadalafil/finasteride provides early improvement in lower urinary tract symptoms in men with benign prostatic hyperplasia and prostatic enlargement . Tadalafil/finasteride coadministration also improves erectile function in men who have comorbid erectile dysfunction PURPOSE We investigated whether combination therapy with dutasteride and tamsulosin is more effective than either monotherapy alone for improving symptoms and long-term outcomes in men with moderate to severe lower urinary tract symptoms and prostatic enlargement ( 30 cc or greater ) . We report preplanned 2-year analyses . MATERIAL S AND METHODS The CombAT study is an ongoing , multicenter , r and omized , double-blind , parallel group study . Men 50 years or older with a clinical diagnosis of benign prostatic hyperplasia , International Prostate Symptom Score 12 points or greater , prostate volume 30 cc or greater , total serum prostate specific antigen 1.5 ng/ml or greater to 10 ng/ml or less and peak urinary flow greater than 5 to 15 ml per second or less with a minimum voided volume of 125 ml or greater were r and omized to 0.5 mg dutasteride , 0.4 mg tamsulosin or the combination once daily for 4 years . Symptoms were assessed every 3 months and peak urinary flow was assessed every 6 months . The primary end point at 2 years was the change in International Prostate Symptom Score from baseline . RESULTS Combination therapy result ed in significantly greater improvements in symptoms vs dutasteride from month 3 and tamsulosin from month 9 , and in benign prostatic hyperplasia related health status from months 3 and 12 , respectively . There was a significantly greater improvement from baseline in peak urinary flow for combination therapy vs dutasteride and tamsulosin monotherapies from month 6 . There was a significant increase in drug related adverse events with combination therapy vs monotherapies , although most did not result in the cessation of therapy . CONCLUSIONS In men with moderate to severe lower urinary tract symptoms and prostate enlargement ( 30 cc or greater ) combination therapy provides a significantly greater degree of benefit than tamsulosin or dutasteride monotherapy INTRODUCTION Erectile dysfunction ( ED ) and lower urinary tract symptoms suggestive of benign prostatic hyperplasia ( BPH-LUTS ) commonly coexist in aging men .  Tadalafil , a phosphodiesterase type 5 inhibitor approved for treating ED , is currently being evaluated for treating BPH-LUTS . AIMS This multinational Phase 3 study assessed effects of tadalafil 2.5 or 5 mg once daily on ED and BPH-LUTS in men with both conditions during 12 weeks of double-blinded therapy . METHODS Men were ≥ 45 years old , sexually active , and experiencing ED for ≥ 3 months and BPH-LUTS for > 6 months . R and omization ( baseline ) followed a 4-week placebo lead-in ; changes from baseline were assessed via analysis of covariance and compared to placebo . A gatekeeping procedure controlled for multiple comparisons of co- primary and key secondary measures at end point ( last post-baseline observation ) . MAIN OUTCOME MEASURES The co- primary measures were the International Index of Erectile Function-erectile function ( IIEF-EF ) domain and International Prostate Symptom Score ( IPSS ) score ; key secondary measures were the Sexual Encounter Profile Question 3 ( SEP Q3 ) and BPH Impact Index ( BII ) . Treatment-emergent adverse events , serious adverse events , orthostatic vital signs , clinical laboratory and uroflowmetry parameters , and postvoid residual volume were assessed . RESULTS Tadalafil 2.5 mg ( N = 198 ) and 5 mg ( N = 208 ) significantly improved IIEF-EF domain scores ( both P < 0.001 ) vs. placebo ( N = 200 ) at end point . For IPSS , improvements were significant with tadalafil 5 mg ( P < 0.001 ) , but not 2.5 mg , for observations from 2 weeks through end point ( least-squares mean ± st and ard error change from baseline at end point , placebo -3.8 ± 0.5 , tadalafil 2.5 mg -4.6 ± 0.4 , and 5 mg -6.1 ± 0.4 ) . Tadalafil 5 mg significantly improved SEP Q3 and BII ( P < 0.001 ) . Overall , tadalafil was well tolerated with no clinical ly adverse changes in orthostatic vital signs or uroflowmetry parameters . CONCLUSIONS Tadalafil 5 mg significantly improved both ED and BPH-related outcomes through 12 weeks and was well tolerated Abstract Background : Phosphodiesterase type 5 ( PDE5 ) inhibitors have discontinuation rates as high as 60 % in men with erectile dysfunction . Treatment satisfaction has been significantly associated with treatment continuation . Underst and ing key characteristics in terms of treatment preference , relationship , and lifestyle issues could provide direction on how to improve compliance with PDE5 inhibitor treatment globally . Objective : The objective was to identify subgroups of interest in the pooled data base of two observational studies conducted in Latin America ( LA ) and Middle East/North Africa ( MENA ) exploring patient characteristics and prescription of either a long- or short-acting PDE5 inhibitor at baseline . Methods : Two identical prospect i ve , non-interventional , observational , studies in MENA ( N = 493 ) and LA ( N = 511 ) treated men with an ‘ on dem and ’ ( pro re nata , PRN ) PDE5 inhibitor ( sildenafil , tadalafil , vardenafil , or lodenafil ) during 6 months . In this post-hoc meta- analysis of two observational studies with equal design , pooled data were analyzed to determine patient characteristics and PDE5 inhibitor prescribed/used most likely to be associated with patient expectations , satisfaction , self-esteem , and patient – partner relationships . Decision tree analyses , with and without weighting , were used to identify and describe key features . Results : In each analysis of patient expectations , patient – partner relationship , and self-esteem , we describe the two major subgroups at baseline for each decision tree . Analyses of patient expectations and sexual self-esteem revealed that patients prescribed long-acting PDE5 inhibitors ( 59 % ) highlighted the importance of treatment effect duration , second to partner satisfaction with treatment , while patients prescribed short-acting PDE5 inhibitors ( 32 % ) placed less importance on treatment effect duration but considerable importance on treatment effect lasting until intercourse completion . Further insights regarding patients , partner relationship characteristics , and treatment expectations were identified . Conclusion : Our analyses have described key characteristics , such as self- and partner perceptions , sexual attitudes , and treatment expectations in relation to the patients ’ country and prescribed treatment , which might guide treatment decisions in MENA and LA men with ED PURPOSE We evaluated the associations among lower urinary tract symptoms , prostate specific antigen ( PSA ) and erectile dysfunction ( ED ) in men with benign prostatic enlargement enrolled in the Proscar ( Merck , Whitehouse Station , New Jersey ) Long-Term Efficacy and Safety Study . MATERIAL S AND METHODS The Proscar Long-Term Efficacy and Safety Study was a 4-year , r and omized , double-blind , placebo controlled study that enrolled 3,040 men with moderate to severe lower urinary tract symptoms and an enlarged prostate gl and . Two questions assessed ED . A logistic regression model , including the effect of patient age , was used to examine the relationships among  quasi-American Urological Association Symptom Score ( AUASS ) , PSA , and ED at baseline . Changes in ED scores from baseline to study closeout were analyzed with ANOVA . RESULTS A total of 2,981 patients had baseline data available for analysis . Mean age was 64 years , mean  quasi-AUASS  was 15 , mean  PSA was 2.8 ng/ml and mean prostate volume was 55 cm . At baseline every 1 point increase in quasi-AUASS was associated with a 2 % increased risk of ED even after controlling for age ( p < 0.001 ) . At 48 months in placebo but not in finasteride treated men a 1-unit decrease in quasi-AUASS was associated with a slight but statistically significant decrease in ED . No association existed between increasing PSA and ED on baseline or longitudinal analysis . CONCLUSIONS We found a moderately strong association between baseline quasi-AUASS and the ED rate in men with an enlarged prostate , a finding that was supported by longitudinal data in the placebo arm . The absence of a relationship between PSA and ED highlights the need for further investigation into the mechanisms of benign prostatic hyperplasia related sexual dysfunction INTRODUCTION Surgical management options for lower urinary tract symptoms/benign prostatic hyperplasia ( LUTS/BPH ) associated with prostates of small to moderate volume ( < 80 cc ) are numerous ; however , for men with enlarged prostates ( > 80 cc ) , many of these options are neither safe nor effective . Recently , Aquablation ( PROCEPT BioRobotics , Inc. , U.S. ) , a precise ultrasound-guided , robotically executed prostatic ablative procedure , has become available with U.S. Food and Drug Administration approval . Herein , we present three-month safety and efficacy data from the cohort of Canadian men included in the WATER II trial . METHODS WATER II is a prospect i ve clinical trial of the Aquablation system for the treatment of BPH in men with prostate volumes between 80 and 150 cc . Only patients from Canada were included for this analysis . At baseline , subjects completed International Prostate Symptom Score ( IPSS ) , as well as several vali date d question naires , uroflowmetry and post-void residual volume measurements , and underwent st and ard laboratory blood assessment . These were repeated at one and three months post-Aquablation . RESULTS A total of 19 subjects who met inclusion and exclusion criteria were enrolled at three Canadian academic sites . Mean pre- , one-month , and three-month post-treatment IPSS scores were 21.2±5.5 , 9.9±6.9 ( p<0.0001 ) , and 5.0±4.5 ( p<0.0001 ) , respectively . Mean pre- , one-month , and three-month post-treatment maximum urinary flow rates ( Qmax ) were 6.6±3.1 ml/s , 19.5±6.1 ml/s ( p<0.0001 ) , and 23.1±9.2 ml/s ( p<0.0001 ) , respectively . The Clavien-Dindo grade 2 or higher event rate at three months was 31.6 % ( six events ) . CONCLUSIONS In this short-term , three-month analysis of Canadian men , Aquablation appears to provide a strong surgical alternative in patients with LUTS/BPH due to larger prostate volumes , with impressive functional outcomes , relatively short operative time and length of hospital stay , and acceptable complication and low transfusion rates PURPOSE We examined data from the Medical Therapy of Prostatic Symptoms trial to determine the relationship between baseline TPV and the effect of medical therapy in men with LUTS secondary to BPH . MATERIAL S AND METHODS A total of 3,047 patients with LUTS were r and omized to placebo , 4 to 8 mg doxazosin , 5 mg finasteride or the combination of doxazosin and finasteride . Average treatment duration was 4.5 years The primary outcome was time to overall clinical progression of BPH , defined as a confirmed 4 point or greater increase in AUA SS , acute urinary retention , incontinence , renal insufficiency or recurrent urinary tract infection . Secondary outcomes were the need for invasive therapy for BPH , and changes in AUA SS and the maximum urinary flow rate with time . TPV was measured by transrectal ultrasound at baseline and study end . RESULTS In patients with a small prostate ( baseline TPV less than 25 ml ) combination therapy was no better than doxazosin alone for decreasing the risk of clinical progression of BPH and need for invasive therapy as well as improving AUA SS and the maximum urinary flow rate . However , in patients with moderate size ( 25 to less than 40 ml ) or enlarged ( 40 ml or greater ) gl and s combination therapy led to a clinical benefit in these outcomes that was superior to that of doxazosin or finasteride . CONCLUSIONS Combination therapy with doxazosin and finasteride led to a greater decrease in the risk of clinical progression of BPH than either drug alone in patients with LUTS with a baseline TPV of 25 ml or greater INTRODUCTION Tadalafil , a long-acting phosphodiesterase type 5 inhibitor , is approved for treating signs and symptoms of benign prostatic hyperplasia ( BPH ) and erectile dysfunction ( ED ) ; tamsulosin , an alpha-blocker , is approved for treating signs and symptoms of BPH . AIM To determine the effects of tadalafil or tamsulosin on sexual function , including ejaculation and orgasm , satisfaction , and erectile function , in sexually active men with ED and lower urinary tract symptoms suggestive of BPH ( LUTS/BPH ) . METHODS A r and omized , double-blind , placebo-controlled study of tadalafil 5 mg once daily for 12 weeks in men with LUTS/BPH ; tamsulosin 0.4 mg once daily was an active control . MAIN OUTCOME MEASURES The International Index of Erectile Function ( IIEF ) question naire was administered at baseline and 4 , 8 , and 12 weeks . Analysis of orgasm and ejaculation was post hoc based on the IIEF-Orgasmic Function ( OF ) domain ( IIEF-Q9 [ ejaculatory frequency ] and Q10 [ orgasmic frequency ] ) . Other measures included IIEF-Intercourse Satisfaction ( IS ) , Overall Satisfaction ( OS ) , and Erectile Function ( EF ) domains . Changes from baseline to 12 weeks ( or last observation ) vs. placebo were analyzed using analysis of covariance . Higher IIEF scores indicate better functioning . RESULTS Of 511 study participants , 310 ( 60.7 % ) had ED and were sexually active . The IIEF-OF increased significantly through 12 weeks with tadalafil vs. placebo ( P = 0.048 ) , as did IIEF-Q9 ( P = 0.045 ) but not IIEF-Q10 ( P = 0.100 ) . Compared with placebo , IIEF-OF , Q9 , and Q10 decreased significantly with tamsulosin ( all P < 0.05 ) . The IIEF-IS and OS increased significantly at end point with tadalafil ( both P < 0.001 ) ; for tamsulosin , change was not significant for IS , while OS decreased significantly ( P = 0.009 ) . The IIEF-EF domain increased significantly vs. placebo with tadalafil ( P < 0.001 ) but not tamsulosin ( P = 0.699 ) . CONCLUSIONS Tadalafil 5 mg once daily significantly improved ejaculation and orgasm , intercourse and overall satisfaction , and erectile function . Men receiving tamsulosin 0.4 mg once daily experienced a decrease in both ejaculatory/orgasmic frequency and overall satisfaction vs. placebo , with no significant effect on erectile function
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 .