PDE5 inhibitors blunt inflammation in human BPH: a potential mechanism of action for PDE5 inhibitors in LUTS. Effects of daily low-dose treatment with phosphodiesterase type 5 inhibitor on cognition, depression, somatization and erectile function in patients with erectile dysfunction: a double-blind, placebo-controlled 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 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. Hypogonadal men nonresponders to the PDE5 inhibitor tadalafil benefit from normalization of testosterone levels with a 1% hydroalcoholic testosterone gel in the treatment of erectile dysfunction (TADTEST study). Inhibition of phosphodiesterase type 5 with tadalafil is associated to an improved activity of circulating angiogenic cells in men with cardiovascular risk factors and erectile dysfunction. Comparison of 25 and 75 mg/day naftopidil for lower urinary tract symptoms associated with benign prostatic hyperplasia: a prospective, randomized controlled study. Effects of phosphodiesterase-5 inhibitor on ischemic kidney injury during nephron sparing surgery: quantitative assessment by NGAL and KIM-1 Eliciting preferences for drug treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia. 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. 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. Physical activity and PDE5 inhibitors in the treatment of erectile dysfunction: results of a randomized controlled study. A 6-month, prospective, observational study of PDE5 inhibitor treatment persistence and adherence in Middle Eastern and North African men with erectile dysfunction 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. Combination therapy with dutasteride and tamsulosin in men with moderate-to-severe benign prostatic hyperplasia and prostate enlargement: the CombAT (Combination of Avodart and Tamsulosin) trial rationale and study design. Randomized Controlled Trial to Assess the Efficacy of the Combination Therapy of Alfuzosin and Tadalafil in Patients with Lower Urinary Tract Symptoms Due to Benign Prostatic Hyperplasia. A comparative randomized prospective study to evaluate efficacy and safety of combination of tamsulosin and tadalafil vs. tamsulosin or tadalafil alone in patients with lower urinary tract symptoms due to benign prostatic hyperplasia.
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 Phosphodiesterase type 5 ( PDE5 ) inhibitors have recently been shown to have cognitive-enhancing effects in animal models and in our previous pilot study . To investigate the efficacy of daily low-dose treatment with a PDE5 inhibitor on cognitive function , depression and somatization in patients with erectile dysfunction ( ED ) , 8-week , double-blind , placebo-controlled study enrolled 60 male patients with ED for ≥3 months without cognitive impairment . Forty-nine patients completed the study . Patients were r and omized to receive either daily low-dose udenafil 50 mg or placebo for 2 months . The International Index of Erectile Function-5 ( IIEF-5 ) , the Korean version of the Mini-Mental State Examination ( K-MMSE ) for general cognitive function and the Seoul Neuropsychological Screening Battery for comprehensive neuropsychological examination , the Physical Health Question naire-9 ( PHQ-9 ) for depression and the Physical Health Question naire-15 ( PHQ-15 ) for somatization were administered at baseline and at 2 months . The change in the mean IIEF-5 was significantly higher in the udenafil group than the placebo group ( 6.08±4.72 vs 2.20±3.50 , P=0.008 ) . The changes in the PHQ-9 and PHQ-15 were −2.04±3.14 and −2.17±2.87 in the udenafil group , and 1.20±1.63 and 0.56±2.48 in the placebo group ( both , P<0.001 ) . The changes in the K-MMSE and Digit Span Forward were 1.25±1.26 and 0.92±1.02 in the udenafil group , and −0.52±1.19 and −0.24±1.13 in the placebo group ( both , P<0.001 ) . However , there were no differences in the other neuropsychological tests . Daily dosing with a PDE5 inhibitor seems to improve cognitive function , depression and somatization , as well as erectile function , in patients with ED 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 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 INTRODUCTION Addition of testosterone ( T ) may improve the action of phosphodiesterase type 5 inhibitors ( PDE5-Is ) in patients with erectile dysfunction not responding to PDE5-Is with low or low-normal T levels . AIMS To confirm this add-on effect of T in men optimally treated with PDE5-Is  and to specify the baseline T levels at which such an effect becomes significant . METHODS A multicenter , multinational , double-blind , placebo-controlled study of 173 men , 45 - 80 years , nonresponders to treatment with different PDE5-Is , with baseline total T levels ≤ 4 ng/mL or bioavailable T ≤ 1 ng/mL. Men were first treated with tadalafil 10 mg once a day ( OAD ) for 4 weeks ; if not successful , they were r and omized in a double-blind , placebo-controlled design to receive placebo or a 1 % hydroalcoholic T gel ( 50 mg/5 g gel ) , to be increased to 10 mg T if results were clinical ly unsatisfactory . Main Outcomes Measures . Mean change from baseline in the Erectile Function Domain Score of the International Index of Erectile Function and rate of successful intercourses ( Sexual Encounter Profile 3 question ) . RESULTS Erectile function progressively improved over a period of at least 12 weeks in both the placebo and T treatment groups . In the overall population with a mean baseline T level of 3.37 ± 1.48 ng/mL , no additional effect of T administration to men optimally treated with PDE5-Is was encountered . The differences between the T and placebo groups were significant for both criteria only in the men with baseline T ≤ 3 ng/mL. CONCLUSIONS The maximal beneficial effects of OAD dosing with 10 mg tadalafil may occur only after as many as 12 weeks . Furthermore , addition of T to this PDE5-I regimen is beneficial , but only in hypogonadal men with baseline T levels ≤ 3 Circulating angiogenic cells ( CACs ) contribute to repair of the vessel wall and dysfunctional CACs are associated to endothelial dysfunction in men with vascular risk factors ( VRFs ) . We investigated whether inhibition of phosphodiesterase type 5 ( PDE5 ) in men with erectile dysfunction ( ED ) and VRFs is accompanied to changes of CACs and to changes of endothelial function . Thirty-six men with ED and VRFs were r and omised to 4 weeks of tadalafil ( 20mg/other day ) or placebo treatment . The number of ex vivo exp and ed functional CAC 's , identified by uptake of 1,1'-dioctadecyl-3 , 3,3 ' , 3'-tetramethylindocarbocyanine-labelled acetylated low-density lipoprotein ( DiLDL ) and concomitant Ulex europaeus agglutinin I ( UEA-1 ) binding , was determined at baseline and after treatment . The number of cells double positive for DiLDL and for UEA-1 , per high-power field fluorescence microscopy was significantly reduced in patients compared to 10 controls ( 26.88+/-6.3 and 74.41+/-17.1 , respectively ; P<0.0001 ) and was markedly increased after tadalafil treatment ( 40.69+/-13.07 versus 25.82+/-6.49 ; P<0.0001 ) . The percentage variation of CACs number and of flow-mediated dilation in the brachial artery by ultrasound after treatment was significantly associated to the presence of endothelial dysfunction at baseline . In conclusion , the increased number of functional CACs after tadalafil treatment suggests a beneficial effect of prolonged PDE5 inhibition on vascular homeostasis BACKGROUND The present study investigated the efficacy , safety , and utility of starting an alpha(1d)-selective antagonist , naftopidil , at 75 or 25 mg/day in patients with lower urinary tract symptoms ( LUTS ) associated with benign prostatic hyperplasia ( BPH ) . METHODS In this prospect i ve comparative study , the subjects comprised 153 patients with LUTS associated with BPH . Patients were r and omized to receive either 25 mg/day ( Group LD ) or 75 mg/day ( Group HD ) of naftopidil for 4 weeks . The lower urinary tract disease symptom score ( LUTDSS ) , the International Prostate Symptom Score ( IPSS ) , the Quality of life assessment index , the maximum flow rate ( Q(max ) ) , and the residual urine volume were compared between the groups . RESULTS In both groups , the LUTDSS and the IPSS were significantly improved at the endpoint and no significant intergroup differences were identified . However , the improvement in the Q(max ) was significantly better for Group HD than for Group LD . The overall efficacy did not differ significantly between the groups . The degree of improvement in voiding symptoms and LUTDSS among patients with moderate symptoms was significantly greater for Group HD than for Group LD . The frequency of adverse reactions did not differ significantly between the groups . CONCLUSIONS Starting administration at 75 mg/day rather than 25mg/day is helpful for LUTS associated with BPH for patients with moderate symptoms , particularly in improving voiding symptoms . The 75 mg/day administration was considered to be a recommendable therapeutic dose in some patients Abstract Purpose Interruption of renal blood flow is often necessary during nephron sparing surgery ( NSS ) and can induce renal injury . This study examines whether tadalafil , a phosphodiesterase-5 ( PDE-5 ) inhibitor and well-known vasodilator , exerts nephroprotective effects in patients undergoing NSS . Methods This non-r and omized study included 49 patients with enhancing solid renal mass . All patients were subjected to open NSS during which clamping the renal artery was performed . Twenty-two patients were pretreated with tadalafil 1 day prior NSS and 2 days following surgery . The other 27 patients underwent the same surgical procedure but did not receive tadalafil ( controls ) . Urine sample s were collected before surgery and following renal pedicle clamp removal . Urine levels of NGAL and KIM-1 , two novel biomarkers for acute kidney injury ( AKI ) , were determined . Results Clamping the renal artery induced kidney dysfunction as reflected by increases in urinary NGAL and KIM-1 in all participants . These increases in urinary NGAL and KIM-1 excretion were evident 1 h after renal ischemia and lasted for 72 and 24 h , respectively . Pretreatment with tadalafil reduced the absolute urinary excretion of KIM-1 , but not of NGAL . Although the incidence of AKI was comparable between tadalafil-treated and untreated NSS subjects , the elevation in serum creatinine ( SCr ) was significantly attenuated in tadalafil-treated group as compared with NSS controls . Conclusions Tadalafil exerts nephroprotective effects in AKI following NSS , as was evident by reduced urinary excretion of KIM-1 and attenuation of SCr elevation . Carefully controlled large clinical studies are needed before defining the role of PDE-5 inhibition therapy in these patients PURPOSE There are 2 main medical preparations available for lower urinary tract symptoms result ing from benign prostatic hyperplasia ( BPH ) . Choosing between an alpha-blocker and a 5alpha-reductase inhibitor requires trade-offs between their attributes or characteristics . We investigated the relative importance of and trade-offs between the attributes of the 5alpha-reductase inhibitor dutasteride and alpha-blockers in community dwelling men using a vali date d technique . MATERIAL S AND METHODS A discrete choice experiment was administered to 211 men older than 40 years who were r and omly selected from the general United Kingdom population . Attributes investigated in the discrete choice experiment were time to symptom improvement , sexual and nonsexual side effects , the risks of acute urinary retention ( AUR ) and surgery , cost and prostate size decrease . Using regression analysis the relative importance of these attributes , the trade-offs that men are willing to make between these attributes and the willingness to pay for each attribute were estimated . RESULTS All attributes were important to respondents . The most important attribute was side effects . The least preferred side effects was impotence , followed by decreased libido and dizziness . Respondents were willing to wait 13 , 2 and 8 months longer for symptom improvement in exchange for decreased prostate size , and the risks of AUR and surgery , respectively . Men reporting moderate symptoms were less concerned about sexual side effects , time to symptom improvement and the risk of AUR compared with men reporting mild symptoms . CONCLUSIONS Given the attribute levels of BPH medical treatment , overall community dwelling men preferred the 5alpha-reductase inhibitor over alpha-blockers . In the interests of shared decision making it is important to consider the importance of eliciting the preferences of patients with BPH 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 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 INTRODUCTION Physical activity ( PhA ) has proven to be a protective factor for normal erectile function in numerous epidemiological studies . AIM The aim of this study was to establish if PhA could have a therapeutic role in the treatment of  erectile dysfunction ( ED ) . METHODS This was a r and omized , open-label study . A total of 60 patients complaining of ED were studied . Patients were assessed at baseline and after 3 months of study treatment . At baseline , patients were r and omized to receive phosphodiesterase type 5 inhibitor ( PDE5i ) alone ( group A ) or PDE5i plus regular ( ≥3 hours/week ) , aerobic , non-agonistic PhA ( group B ) . MAIN OUTCOME MEASURES All subjects completed the International Index of Erectile Function ( IIEF-15 ) question naire and performed total testosterone ( TT ) . RESULTS Mean PhA was 3.4 hours/week in group B vs. 0.43 in group A ; mean energy expenditure in group B was 1,868 kcal/ week or 22.8 metabolic equivalent (MET)/week . IIEF restoration of ED occurred in 77.8 % ( intervention group ) vs. 39.3 % ( control ) ( P < 0.004 ) . The IIEF-15 score result ed in statistical improvement in intervention group in all the domains but one ( orgasm ) : erectile function 24.7 vs. 26.8 ( P = 0.003 ) ; confidence ( Q15 ) 3.53 vs. 4.07 ( P = 0.006 ) ; sexual desire 6.46 vs. 7.18 ( P = 0.028 ) ; intercourse satisfaction 9.85 vs. 11.25 ( P = 0.001 ) ; total satisfaction 7.17 vs. 8.07 ( P = 0.009 ) ; total score 56.2 vs. 61.07 ( P = 0.007 ) . TT was statistically similar in the two groups ; separate analysis in each group showed statistical increase in group B 4.24 vs. 4.55 ( P = 0.012 ) . At multivariate logistic regression analysis , PhA was the only independent variable for normal erection ( P = 0.010 ) ( 95 % confidence interval [ CI ] 0.036 - 0.643 ) , higher sexual satisfaction ( P = 0.022 ) ( 95 % CI 0.084 - 0.821 ) and normal total IIEF-15 score ( P = 0.023 ) ( 95 % CI 0.85 - 0.837 ) . CONCLUSION In this r and omized controlled pilot study , PDE5i plus PhA was more effective than PDE5i alone in the treatment of ED Abstract Background : Erectile dysfunction ( ED ) negatively impacts quality of life .  Phosphodiesterase type 5 inhibitors ( PDE5Is ) are effective in treating ED ; however , rates of discontinuation remain high . Objectives : To assess on-dem and PDE5I treatment persistence and adherence through 6 months in Middle Eastern and North African ( MENA ) men with ED in a prospect i ve , non-interventional , observational trial . Research design and methods : Enrolled men were ≥18 years old from Saudi Arabia , Egypt , and the United Arab Emirates , PDE5I naïve , and sexually active .  PDE5Is were selected per routine clinical practice . Persistence was defined as use of ≥1 dose during the prior 4 weeks , adherence as compliance with dosing instructions during the most recent dose . Logistic regression models were used to identify factors associated with persistence and adherence . Main outcome measures : Persistence and Adherence Question naire ; Partner Relationship Question naire ; Self-Esteem and Relationship Question naire ; International Index of Erectile Function ( IIEF ) ; Erectile Dysfunction Inventory of Treatment Satisfaction . Results : Patients ’ ( n = 493 ) mean age was 49.8 years , mean BMI was 29.3 , and the majority ( n = 354 , 71.8 % ) were from Saudi Arabia .  Tadalafil was the most prescribed PDE5I ( 69.6 % ) , versus sildenafil ( 15.4 % ) , or vardenafil ( 15.0 % ) . Patients ’ mean IIEF – Erectile Function scores improved from moderate to mild and Erection Hardness Scores ( SD ) improved from 1.8 ( 1.0 ) at baseline to 3.5 ( 0.7 ) at 6 months . At 6 months , 64.9 % of patients were treatment persistent ( tadalafil , 68.8 % , sildenafil , 65.8 % , and vardenafil , 45.9 % ) and 59.6 % were adherent . Factors significantly predictive ( p < 0.05 ) of persistence at 6 months included age , employment status , and ED severity . Factors significantly predictive of adherence were age , employment status , and duration of ED . Interpretation of differences between drugs was limited by substantial differences in prescription rates between countries . Conclusions : At 6 months , 64.9 % of men were treatment persistent . In this study , age , employment status , ED severity , and duration of ED were associated with persistence and /or adherence 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 Benign prostatic hyperplasia ( BPH ) is a highly prevalent condition in aging men , which can be progressive and lead to acute urinary retention ( AUR ) and the need for surgery . It is commonly treated with alpha-blockers and 5alpha-reductase inhibitors ( 5ARIs ) , both of which improve the symptoms of BPH . Long-term treatment with 5ARIs can also reduce the risk of developing AUR and the need for surgery . The l and mark Medical Therapy of Prostatic Symptoms ( MTOPS ) trial demonstrated that over 4 years the combination of the type 2-specific 5ARI , finasteride and the alpha-blocker doxazosin was more effective than either agent alone in reducing overall clinical progression . Since the initiation of MTOPS , it has been shown that patients with larger prostates and higher prostate-specific antigen ( PSA ) levels are at greater risk of BPH progression , and are therefore arguably more likely to benefit from combination therapy . The Combination of Avodart and Tamsulosin ( CombAT ) trial is a 4-year , global , multicenter , r and omized , double-blind , parallel-group study design ed to investigate the benefits of combination therapy with the dual 5ARI dutasteride and the alpha-blocker tamsulosin compared with each monotherapy in improving symptoms and long-term outcomes in men with moderate-to-severe symptoms of BPH and prostate enlargement .  Symptoms and long-term outcomes ( AUR and surgery ) will be assessed as separate primary endpoints at 2 and 4 years , respectively . Eligible patients were at least 50 years old with prostate volume > or = 30 cm(3 ) and PSA level > or = 1.5 ng/mL. A total of 4838 subjects have been enrolled . This paper describes the rationale , design and baseline data of the CombAT study OBJECTIVE The purpose of our study was to evaluate the effect of alfuzosin and tadalafil as combination therapy compared with each monotherapy , in patients with lower urinary tract symptoms ( LUTS ) due to benign prostatic hyperplasia ( BPH ) . METHODS Men over the age of 50 years with LUTS secondary to BPH and an International Prostate Symptom Score ( IPSS ) 8 or higher , were r and omized to receive 10 mg alfuzosin ( n = 25 ) , 10 mg tadalafil ( n = 25 ) or the combination of both the drugs ( n = 25 ) once daily for 3 months . Symptoms were assessed at baseline , 6 weeks and 3 months . The primary endpoint was the change in IPSS from the baseline . Secondary endpoints were changes in IPSS storage and voiding subscores , peak urinary flow rate , residual urine volume , IPSS quality of life score and erectile domain score . RESULTS There were significant improvements in all IPSS scores , peak urinary flow rate and IPSS quality of life score from baseline at both 6 weeks and 3 months in all the three groups ( P < 0.003 ) . Combination therapy was better than monotherapy in improving IPSS scores and reducing post-void residual urine volume ( P < 0.005 ) . Combination therapy was similar to alfuzosin regarding improvement in maximum urine flow rate ( P = 0.22 ) , similar to tadalafil in improvement on erectile function ( P = 0.22 ) and better than each monotherapy in improving the IPSS quality of life ( P ≤ 0.015 ) . CONCLUSION Alfuzosin and tadalafil combination therapy provides greater symptomatic improvement as compared to either monotherapy in men with LUTS due to BPH INTRODUCTION Lower urinary tract symptoms ( LUTS ) associated with benign prostatic hyperplasia ( BPH ) and erectile dysfunction are common disorders of advancing age . AIM To evaluate the efficacy and safety of tamsulosin and tadalafil in patients with LUTS due to BPH . METHODS In this prospect i ve r and omized study , 133 men complaining of LUTS due to BPH were included . Forty-five patients received tamsulosin 0.4 mg/day alone ( Group A ) , 44 patients received tadalafil 10 mg/day ( Group B ) , and combination therapy ( tamsulosin and tadalafil both ) was instituted in 44 patients ( Group C ) . After a 2-week medication free run-in period , they were evaluated for International Prostatic Symptom Score ( IPSS ) , International Index of Erectile Function score ( IIEF5 ) , quality of life ( IPSS QoL ) , maximum urinary flow rate ( Qmax ) , post-void residual urine ( PVR ) volume , and safety parameters before and at 3 months of treatment . MAIN OUTCOME MEASURES There were primary ( IPSS , IPSS QoL index , Qmax , and PVR ) and secondary ( erectile function [ EF ] domain scores from IIEF5 ) efficacy end points . Safety assessment included laboratory tests and patient 's reporting of adverse event . RESULTS A significant improvement in IPSS score was observed in all the 3 groups A , B , and C ( -50.90 % , P < 0.05 ; -33.50 % , P < 0.05 ; and -53.90 % , P < 0.05 , respectively ) . IIEF5 score increased significantly in these three groups ( + 39.28 % , P < 0.05 ; + 45.96 % , P < 0.05 ; and + 60.23 % , P < 0.05 , respectively ) . A significant increase in Qmax and decrease in PVR were also observed ( 33.99 % , P < 0.05 ; 29.78 % , P < 0.05 ; and 37.04 % , P < 0.05 ) and ( -60.90 % , P < 0.05 ; -49.45 % , P < 0.05 ; and -62.97 % , P < 0.05 , respectively ) . The QoL scores improved significantly ( -73.35 % , P < 0.05 ; -70.26 % , P < 0.05 ; and -79.65 % , P < 0.05 , respectively ) . Side effects were dyspepsia , heartburn , headache , flushing , myalgia , and backache . Adverse effect dropout was 3.7 % . No participant experienced any severe or serious adverse events . CONCLUSIONS In patients with LUTS due to BPH , tamsulosin and tadalafil alone or in combination cause a significant improvement in patients with LUTS . Their EF also improves with these medications . The improvement is better with combination therapy compared with single agent alone
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 .