title: Penile rehabilitation therapy following radical prostatectomy Randomized, double-blind, placebo-controlled study of postoperative nightly sildenafil citrate for the prevention of erectile dysfunction after bilateral nerve-sparing radical prostatectomy Effects of tadalafil treatment on erectile function recovery following bilateral nerve-sparing radical prostatectomy: a randomised placebo-controlled study (REACTT). A phase 3, placebo controlled study of the safety and efficacy of avanafil for the treatment of erectile dysfunction after nerve sparing radical prostatectomy. Tadalafil in the treatment of erectile dysfunction following bilateral nerve sparing radical retropubic prostatectomy: a randomized, double-blind, placebo controlled trial. Tadalafil rehabilitation therapy preserves penile size after bilateral nerve sparing radical retropubic prostatectomy. An evaluation of an alternative dosing regimen with tadalafil, 3 times/week, for men with erectile dysfunction: SURE study in 14 European countries. 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 of tadalafil for the treatment of erectile dysfunction at 24 and 36 hours after dosing: a randomized controlled trial. Vardenafil improved patient satisfaction with erectile hardness, orgasmic function and sexual experience in men with erectile dysfunction following nerve sparing radical prostatectomy. Safety and efficacy of vardenafil for the treatment of men with erectile dysfunction after radical retropubic prostatectomy. Effects of three-times-per-week versus on-demand tadalafil treatment on erectile function and continence recovery following bilateral nerve sparing radical prostatectomy: results of a prospective, randomized, and single-center study.
abstract: Purpose . To compare erectile function ( EF ) recovery of patients treated by early penile rehabilitation therapy ( PRT ) with sildenafil and with control group . Method . Forty men treated by bilateral nerve sparing radical prostatectomy ( NSRP ) and with a normal pre-operative EF were enrolled . Fourteen days after surgery , they were r and omised to a flexible-dose sildenafil group and to a control group . The International Index of Erectile Function ( IIEF ) question naire was completed before surgery and at 3 , 6 , 12 and 24 weeks after NSRP . Results . In the group treated , the mean IIEF score before surgery was 26.2 and 14.1 , 16.2 , 22.5 and 25.2 at 3 , 6 , 12 and 24 weeks after NSRP , respectively . In the control group , the respective scores were 26.5 and 12.4 , 15.8 , 15.3 and 17.4 . There was a significant difference in IIEF mean score ( 25 ± 6 vs. 17 ± 9 , p < 0.05 ) and in the potency rate ( 87 % vs. 56 % ) between the groups at 24 weeks after NSRP . The percentage of patients who were capable of having medication-unassisted intercourse was 54 % vs. 21 % ; 34 % vs. 18 % of patients had a normal EF with 72 % vs. 32 % of responders to sildenafil . Conclusions . PRT with PDE-5 inhibitors should be offered early after RP to allow the recovery of EF Four weeks after bilateral nerve-sparing radical retropubic prostatectomy , men with normal erectile function before surgery were r and omized to double-blind sildenafil ( 50 or 100 mg ) or placebo nightly for 36 weeks , followed by an 8-week drug-free period before assessment of erectile function . Enrollment was prematurely ceased and only 76 men completed because , assuming a placebo response rate similar to the published literature ( for example , 34 % in meta- analysis ) , the 25 % response at blinded interim review suggested a lack of treatment effect . On the contrary , spontaneous erectile function ( a combined score of ⩾8 for questions 3 and 4 of the International Index of Erectile Function and a positive response to ‘ Were erections good enough for satisfactory sexual activity ? ’ ) occurred in only 4 % of the placebo group ( n=1 of 25 ) versus 27 % ( n=14 of 51 , P=0.0156 , Fisher 's exact test ) of the sildenafil group . Nightly sildenafil administration for 36 weeks after surgery markedly increased the return of normal spontaneous erections BACKGROUND The potential rehabilitative and protective effect of phosphodiesterase type 5 inhibitors ( PDE5-Is ) on penile function after nerve-sparing radical prostatectomy ( NSRP ) remains unclear . OBJECTIVE The primary objective was to compare the efficacy of tadalafil 5 mg once daily and tadalafil 20 mg on dem and versus placebo taken over 9 mo in improving unassisted erectile function ( EF ) following NSRP , as measured by the proportion of patients achieving an International Index of Erectile Function-Erectile Function domain ( IIEF-EF ) score ≥ 22 after 6-wk drug-free washout ( DFW ) . Secondary measures included IIEF-EF , Sexual Encounter Profile question 3 ( SEP-3 ) , and penile length . DESIGN , SETTING , AND PARTICIPANTS R and omised , double-blind , double-dummy , placebo-controlled trial in men ≤ 68 yr of age with adenocarcinoma of the prostate ( Gleason ≤ 7 ) and normal preoperative EF who underwent NSRP at 50 centres from nine European countries and Canada . INTERVENTIONS 1:1:1 r and omisation to 9 mo of treatment with tadalafil 5 mg once daily , tadalafil 20 mg on dem and , or placebo followed by a 6-wk DFW and 3-mo open-label tadalafil once daily ( all patients ) . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Logistic regression , mixed-effects model for repeated measures , and analysis of covariance , adjusting for treatment , age , and country , were applied to IIEF-EF scores ≥ 22 , SEP-3 , and penile length . RESULTS AND LIMITATIONS Four hundred twenty-three patients were r and omised to tadalafil once daily ( n=139 ) , on dem and ( n=143 ) , and placebo ( n=141 ) . The mean age was 57.9 yr of age ( st and ard deviation : 5.58 yr ) ; 20.9 % , 16.9 % , and 19.1 % of patients in the tadalafil once daily , on dem and , and placebo groups , respectively , achieved IIEF EF scores ≥ 22 after DFW ; odds ratios for tadalafil once daily and on dem and versus placebo were 1.1 ( 95 % confidence interval [ CI ] , 0.6 - 2.1 ; p=0.675 ) and 0.9 ( 95 % CI , 0.5 - 1.7 ; p=0.704 ) . At the end of double-blind treatment ( EDT ) , least squares ( LS ) mean IIEF-EF score improvement significantly exceeded the minimally clinical ly important difference ( MCID : ΔIIEF-EF ≥ 4 ) in both tadalafil groups ; for SEP-3 ( MCID ≥ 23 % ) , this was the case for tadalafil once daily only . Treatment effects versus placebo were significant for tadalafil once daily only ( IIEF-EF : p=0.016 ; SEP-3 : p=0.019 ) . In all groups , IIEF-EF and SEP-3 decreased during DFW but continued to improve during open-label treatment . At month 9 ( EDT ) , penile length loss was significantly reduced versus placebo in the tadalafil once daily group only ( LS mean difference 4.1 mm ; 95 % CI , 0.4 - 7.8 ; p=0.032 ) . CONCLUSIONS Tadalafil once daily was most effective on drug-assisted EF in men with erectile dysfunction following NSRP , and data suggest a potential role for tadalafil once daily provided early after surgery in contributing to the recovery of EF after prostatectomy and possibly protecting from penile structural changes . Unassisted EF was not improved after cessation of active therapy for 9 mo . TRIAL REGISTRATION Clinical Trials.gov identifier NCT01026818 PURPOSE We evaluated the safety and efficacy of 100 and 200 mg avanafil for the treatment of adult males with erectile dysfunction after bilateral nerve sparing radical prostatectomy . MATERIAL S AND METHODS This was a double-blind , placebo controlled , parallel group , phase 3 study in males age 18 to 70 years with a history of erectile dysfunction of 6 months or more after bilateral nerve sparing radical prostatectomy . Patients were r and omized to 100 or 200 mg avanafil or placebo ( taken 30 minutes before sexual activity ) for 12 weeks . Primary end points included successful vaginal insertion ( Sexual Encounter Profile [ SEP ] question 2 ) , successful intercourse ( SEP3 ) and change in score on the erectile function domain of the International Index of Erectile Function ( IIEF-EF ) question naire . RESULTS A total of 298 patients were r and omized and 84.6 % completed the study . At baseline 16.1 % were age 65 years or older and 71.5 % had severe erectile dysfunction  ( mean overall IIEF-EF domain score 9.2 ) . After 12 weeks there were significantly greater increases in SEP2 and SEP3 and change in mean IIEF-EF domain score with 100 and 200 mg avanafil vs placebo ( p < 0.01 ) . Following dosing with avanafil 36.4 % ( 28 of 77 ) of sexual attempts ( SEP3 ) at 15 minutes or less were successful vs 4.5 % ( 2 of 44 ) for placebo ( p < 0.01 ) . Avanafil was generally well tolerated . No serious adverse events were reported and fewer than 2 % of patients discontinued the study due to an adverse event . CONCLUSIONS Avanafil in 100 and 200 mg doses was effective and well tolerated in improving erectile function after prostatectomy . Results suggest a rapid onset of action and sustained duration of effect , with all 3 primary end points being achieved at both dose levels PURPOSE We evaluated the efficacy and safety of tadalafil 20 mg , taken on dem and , in men with erectile dysfunction following bilateral nerve sparing radical retropubic prostatectomy ( BNSRRP ) . MATERIAL S AND METHODS This r and omized , double-blind , placebo controlled multicenter study consisted of a 4-week treatment-free run-in period ( baseline ) followed by 12 weeks of treatment . A total of 303 men ( mean age 60 years ) with preoperative normal erectile function who had undergone a BNSRRP 12 to 48 months before study were r and omized ( 2:1 ) to tadalafil ( 201 ) or placebo ( 102 ) . The 3 co- primary end points were changes from baseline in the International Index of Erectile Function erectile function domain score , and the percentage of positive responses to Sexual Encounter Profile questions 2 ( successful penetration ) and 3 ( successful intercourse ) . The Global Assessment Question and the Erectile Dysfunction Inventory of Treatment Satisfaction question naire were secondary end points . We defined a priori a subgroup of 201 patients reporting evidence of postoperative tumescence , defined as 50 % or greater " yes " responses to Sexual Encounter Profile question 1 ( ability to achieve at least some erection ) during baseline intercourse attempts and stratified r and omization based on this criterion . RESULTS Patients receiving tadalafil reported greater improvement on all primary and secondary end points ( p < 0.001 ) compared to placebo . For all r and omized patients and for the subgroup with evidence of postoperative tumescence , the mean International Index of Erectile Function erectile function domain score increased for patients receiving tadalafil ( mean + /- SEM 5.3 + /- 0.5 and 5.9 + /- 0.7 , respectively , p < 0.001 vs placebo for both ) . For all r and omized patients who received tadalafil , the mean percentage of successful penetration attempts was 54 % and the mean percentage of successful intercourse attempts was 41 % . For the subgroup with evidence of postoperative tumescence these values were 69 % and 52 % , respectively . Of all patients r and omized to tadalafil 62 % and of the subgroup patients r and omized to tadalafil 71 % reported improved erections . Patients receiving tadalafil reported greater treatment satisfaction on the Erectile Dysfunction Inventory of Treatment Satisfaction than those receiving placebo .  Headache ( 21 % ) , dyspepsia ( 13 % ) and myalgia ( 7 % ) were the most commonly reported adverse events . CONCLUSIONS Tadalafil 20 mg , taken on-dem and , was an efficacious and well tolerated treatment for erectile dysfunction following BNSRRP OBJECTIVE To evaluate the change in penile size r bilateral nerve sparing retropubic radical prostatectomy ( BNSRRP ) and possible effect of Tadalafil . MATERIAL S AND METHODS A total of 65 patients underwent BNSRRP and they were evaluated prospect ively for a whole year of follow-up . The patients were r and omized to control without rehabilitation ( Group 1 ) or Tadalafil rehabilitation group ( Group 2 ) . The patients were evaluated at months 3 , 6 and 12 postoperatively for erectile function , penile measurements ( flaccid penile length , penile length at maximum erection , penile circumference at flaccid status , and penile circumference at maximum erection ) , penile abnormalities and general health status . Statistical analysis was performed by Chi-Square test and significance was defined as p value < 0.05 . RESULTS In Group 1 there was significant decrease in penile measurements at month 3 compared to preoperative measurements . There was decrease in all parameters at month 6 compared to month 3 but only the decrease in penile length at maximum erection was significant . There were no significant differences between postoperative months 6 and 12 for all measurements . In Group 2 there was a tendency to decrease in all measurements at month 3 compared to baseline . There was no significant difference for penile measurements between postoperative 3rd and 6th months and between 6th month and the first year . CONCLUSION Although further large sample d trials are needed to describe the possible positive effect of tadalafil or other PDE5-I 's on penile size after BNSRRP , tadalafil rehabilitation is effective in preserving penile size especially in the early postoperative period after BNSRRP OBJECTIVE To examine the preference for 2 dosing regimens ( on dem and or 3 times/week ) for tadalafil , a phosphodiesterase 5 inhibitor with a duration of effectiveness up to 36 hours in men with erectile dysfunction ( ED ) . DESIGN AND METHODS SURE is a 14 European country , multicenter , crossover , and open-label study . Men with ED ( N=4262 ) were r and omized to tadalafil 20 mg treatment on dem and ( maximum one dose per day and before sexual activity ) or 3 times/week for 5 - 6 weeks . After a 1-week washout period , patients were crossed over to the alternate regimen for 5 - 6 weeks . The patient 's response to a treatment preference question ( TPQ ) was used to determine the preferred treatment regimen . RESULTS The mean age of the r and omized patients was 55 years and 85.2 % reported a history of ED for one year or greater . Overall , the responses of 3861 men to the TPQ assessment showed that 57.8 % preferred the on-dem and regimen and 42.2 % preferred the 3 times/week dosing . Both regimens were efficacious and well tolerated . CONCLUSIONS In this study , while 57.8 % of men preferred the on-dem and regimen of tadalafil 20 mg , a substantial number ( 42.2 % ) preferred the 3 times/week treatment . The two regimens provide additional treatment options by giving men with erectile dysfunction unique flexibility in dosing with tadalafil 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 OBJECTIVES To examine the therapeutic effects of tadalafil on erectile dysfunction ( ED ) at 24 and 36 hours after dosing . METHODS A multicenter , r and omized , double-blind , placebo-controlled , parallel-group study of 348 men ( mean age 57 years ) with ED was conducted in Europe and the United States . Patients were stratified by baseline severity of ED using the Erectile Function domain score of the International Index of Erectile Function and then r and omly allocated within the severity group to receive tadalafil 20 mg ( n = 175 ) or placebo ( n = 173 ) . Subsequently , participants were r and omly assigned to two 4-week treatment intervals , during which they were requested to attempt sexual intercourse approximately 24 or 36 hours after tadalafil or placebo dosing . The primary outcome measure was the proportion of successful sexual intercourse attempts ( completed to ejaculation ) according to patient self-report using the Sexual Encounter Profile diary . RESULTS Of the 348 patients , 327 ( 94 % ) completed the trial ( 163 of 175 in the  tadalafil group and 164 of 173 in the placebo group ) . Thirty-six hours after tadalafil dosing , 59.2 % of intercourse attempts were successful versus 28.3 % in the placebo group ( P < 0.001 ) . The proportion of successful intercourse attempts at approximately 24 hours after treatment was also significantly greater with tadalafil ( 52.9 % ) than with placebo ( 29.1 % ; P < 0.001 ) . Tadalafil was well tolerated . The incidences of four treatment-emergent adverse events were significantly greater in the tadalafil group than in the placebo group ( all P < 0.05 ) : headache , flushing , dyspepsia , and myalgia . CONCLUSIONS Tadalafil 20 mg is an effective and well-tolerated treatment for ED that has a period of responsiveness of up to 36 hours PURPOSE Nerve sparing radical retropubic prostatectomy ( NS-RRP ) results in erectile dysfunction in a significant number of patients . Vardenafil , a potent and selective phosphodiesterase type 5 inhibitor , is generally safe . It improves International Index of Erectile Function erectile function domain scores , and penetration and erection maintenance success rates in patients who have undergone NS-RRP . We report additional parameters important to patient perceptions regarding erection quality and satisfaction with sexual experience following NS-RRP . MATERIAL S AND METHODS A total of 440 men at 58 centers throughout the United States and Canada participated in this r and omized , placebo controlled , double-blind trial with 3 phases , namely baseline ( 4-week untreated period ) , treatment ( 12 weeks ) and followup ( 7 days ) . Participants received placebo ( 145 ) , 10 mg vardenafil ( 146 ) or 20 mg vardenafil ( 149 ) at home on dem and but no more than once per calendar day . Efficacy and satisfaction with erection quality and sexual experience were determined during the trial . RESULTS The 10 and 20 mg vardenafil doses were significantly superior to placebo for the International Index of Erectile Function domains for intercourse satisfaction , orgasmic function and overall satisfaction with sexual experience ( vs placebo p < 0.0009 ) . Significant improvement in the satisfaction rate with erection hardness were demonstrated for each vardenafil dose compared with placebo ( p < 0.0001 ) . Vardenafil was generally well tolerated . Common adverse events were headache , vasodilatation and rhinitis . CONCLUSIONS In this difficult to treat population of men with erectile dysfunction subsequent to NS-RRP on dem and treatment with vardenafil during a 3-month period significantly improved key aspects of the sexual experience important to patient quality of life PURPOSE More than one-third of men may experience erectile dysfunction ( ED ) after nerve sparing radical retropubic prostatectomy . The efficacy and safety of vardenafil , a potent , selective , phosphodiesterase 5 inhibitor , was assessed for the treatment of ED after radical prostatectomy . MATERIAL S AND METHODS In this double-blind study 440 men with ED after nerve sparing radical prostatectomy were r and omized to take placebo , or 10 or 20 mg vardenafil .  Efficacy was measured after 12 weeks using the erectile function domain of the International Index of Erectile Function , diary questions measuring vaginal penetration and intercourse success rates , and a global assessment question ( GAQ ) on erection . RESULTS Of the intent to treat population 70 % had severe ED ( erectile function less than 11 ) at baseline . After 12 weeks both vardenafil doses were significantly superior to placebo ( p < 0.0001 ) for all efficacy variables . Improved erections ( based on GAQ ) were reported by 65.2 % and 59.4 % of patients on 20 and 10 mg vardenafil , respectively , and by only 12.5 % of patients on placebo ( p < 0.0001 ) . Among men with bilateral neurovascular bundle sparing , positive GAQ responses were reported by 71.1 % and 59.7 % of patients on 20 and 10 mg vardenafil , respectively , versus 11.5 % of those on placebo ( p < 0.0001 ) . The average intercourse success rate per patient receiving 20 mg vardenafil was 74 % in men with mild to moderate ED and 28 % in men with severe ED , compared to 49 % and 4 % for placebo , respectively . Few adverse events were observed . They were generally mild to moderate headache , flushing and rhinitis . CONCLUSIONS In men with severe ED after nerve sparing radical retropubic prostatectomy , vardenafil significantly improved key indices of erectile function Erectile dysfunction ( ED ) and urinary incontinence after bilateral nerve-sparing radical prostatectomy ( BNSRP ) still remain major causes of morbidity . Phosphodiesterase type 5 inhibitors ( PDE5-Is ) have a role in the treatment of ED after BNSRP . Several studies in patients with ED and lower urinary tract symptoms demonstrated that PDE5-Is could improve both erectile function and urinary symptoms . The aim of this study was to compare the efficacies of two dosing regimens of 20 mg tadalafil ( on-dem and and 3 times per week ) and to assess the role of tadalafil in recovery of erectile function and continence after BNSRP . We conducted a single-center , prospect i ve , r and omized controlled trial of three times per week versus on-dem and tadalafil 20 mg and a control group after BNSRP . A total of 129 preoperatively potent and continent patients were included in the study . The patients were evaluated at 6 weeks and 12 months postoperatively for erectile function and continence status . There was no significant difference between all three groups with respect to erectile function at 6 weeks after the surgery . Twelve months after the surgery , the International Index of Erectile Function score was significantly higher in the group using tadalafil 20 mg three times per week . However , there was no significant difference between the treated groups and the control group with respect to the continence status at 12 months after the surgery . There was no correlation between incontinence and ED after the surgery in all groups . Tadalafil 20 mg three times per week is an efficacious and well-tolerated treatment option for ED after BNSRP . Treatment with 20 mg tadalafil either three times per week or on dem and can not improve continence recovery after BNSRP compared with the control group
target: By network meta- analysis , sildenafil seems to be the most efficiency with a slightly higher rate of treatment-emergent adverse events ( TEATs ) , whereas tadalafil had the lowest TEATs .
  Compared with placebo , PDE5-Is manifested significantly improved treatment outcomes .
  Overall , regular regimen demonstrated statistically pronounced better potency than on-dem and .
background: Phosphodiesterase type-5 inhibitors ( PDE5-Is ) have been recommended as first line therapy for erectile dysfunction for patients received nerve-sparing radical prostatectomy for prostate cancer .
  We examed the efficiency of PDE5-Is and considered the optimal application .