title: Combining programmed intracavernous PGE1 injections and sildenafil on demand to salvage sildenafil nonresponders Nocturnal tumescence: a parameter for postoperative erectile integrity after nerve sparing 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 Use of intraoperative video documentation to improve sexual function after radical retropubic prostatectomy. Sildenafil citrate after radical retropubic prostatectomy. Recovery of spontaneous erectile function after nerve-sparing radical retropubic prostatectomy with and without early intracavernous injections of alprostadil: results of a prospective, randomized trial. Early combination therapy: intracavernosal injections and sildenafil following radical prostatectomy increases sexual activity and the return of natural erections The use of an erectogenic pharmacotherapy regimen following radical prostatectomy improves recovery of spontaneous erectile function. Tadalafil in the treatment of erectile dysfunction following bilateral nerve sparing radical retropubic prostatectomy: a randomized, double-blind, placebo controlled trial. Penile weight and cell subtype specific changes in a post-radical prostatectomy model of erectile dysfunction. Return of nocturnal erections and erectile function after bilateral nerve-sparing radical prostatectomy in men treated nightly with sildenafil citrate: subanalysis of a longitudinal randomized double-blind placebo-controlled trial. Clinical efficacy of sildenafil citrate based on etiology and response to prior treatment. Pilot study of changes in stretched penile length 3 months after radical retropubic prostatectomy. Prognostic Factors for Response to Sildenafil in Patients with Erectile Dysfunction Role of sildenafil citrate in treatment of erectile dysfunction after radical retropubic prostatectomy. A prospective study measuring penile length in men treated with radical prostatectomy for prostate cancer. Treatment of erectile dysfunction with sildenafil. Rationale for combination therapy of intraurethral prostaglandin E1 and sildenafil in the salvage of erectile dysfunction patients desiring noninvasive therapy Vardenafil improved patient satisfaction with erectile hardness, orgasmic function and sexual experience in men with erectile dysfunction following nerve sparing radical prostatectomy. Factors predicting recovery of erections after radical prostatectomy. Safety and efficacy of vardenafil for the treatment of men with erectile dysfunction after radical retropubic prostatectomy. Preserved postoperative penile size correlates well with maintained erectile function after bilateral nerve-sparing radical retropubic prostatectomy. Acetyl-L-carnitine plus propionyl-L-carnitine improve efficacy of sildenafil in treatment of erectile dysfunction after bilateral nerve-sparing radical retropubic prostatectomy. Efficacy, safety and patient acceptance of sildenafil citrate as treatment for erectile dysfunction.
abstract: In a prospect i ve , placebo-controlled , one group crossover design study , we tested whether adding programmed intracavernous PGE1 injections ( IC-PGE1 ) can improve the effectiveness of sildenafil  in erectile dysfunction ( ED ) patients unresponsive to monotherapy with this drug . In all , 40 ED patients who had experienced unsatisfactory erections with both the 50 and 100 mg sildenafil doses were treated with four bi-weekly 20 μg IC-PGE1 injections given in the clinic and provided with either placebo or 50 mg sildenafil capsules for the next 4 weeks . Thereafter , they were crossed over to the other oral treatment for an additional 4-week period . The IIEF-Erectile Function domain score ( IIEF-EFS ) , the main outcome measure , was found considerably higher ( P<0.001 ) with the combined IC-PGE1–50 mg sildenafil treatment than with IC-PGE1–placebo or sildenafil alone ( 50 or 100 mg ) in a subset of 26 subjects ( 65 % ) . They thus shifted from the ‘ severe ’ or ‘ moderate ’ to the ‘ mild ’ grading of ED classification PURPOSE The exact process and time required for rehabilitation of erectile function after nerve sparing prostatectomy remain unclear to date . Different theories of the pathophysiology of postoperative erectile dysfunction are currently being discussed . In a prospect i ve study we performed recordings of nocturnal penile tumescence and rigidity during the acute phase after nerve sparing radical prostatectomy , ie in the first night after removal of the catheter , to assess the organic penile integrity . MATERIAL S AND METHODS In 27 patients with local prostate carcinoma who had been sexually active before the intervention , we performed unilateral or bilateral nerve sparing radical prostatectomy . Preoperative sexual function of all patients was evaluated by the International Index of Erectile Function-5 question naire . On the day of catheter removal ( postoperative day 7 to 14 ) an  NPTR recording  was performed on the following night with an erectometer ( RigiScan ) . RESULTS All patients had a preoperative IIEF score greater than 18 . After removal of the catheter 25 of 27 patients ( 93 % ) showed 1 to 5 nocturnal rigidity increases by greater than 70 % for at least 10 minutes . In a control group of 4 patients who underwent radical prostatectomy without nerve sparing , no nocturnal erections were recorded . CONCLUSIONS NPTR recording during the acute phase after nerve sparing radical prostatectomy showed residual erectile function as early as the first night after catheter removal . These results are significant for selecting adequate pharmacological treatment for optimal therapy and rehabilitation of satisfactory erections and sexual function . In cases of early nocturnal tumescence , application of a PDE5 inhibitor can support successive organ rehabilitation . However , if tumescence does not occur , penile injection therapy is recommended 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 OBJECTIVES To determine whether arbitrary minor variances in surgical technique can have a major impact on the recovery of sexual function  after radical retropubic prostatectomy . METHODS The surgical procedures of 62 potent men were videotaped prospect ively . Eighteen months after the study was initiated , the videotapes were review ed and specific steps in the surgical procedure correlated with patient-reported potency rates . RESULTS Four steps were identified that appeared to correlate with the recovery of sexual function : over-sewing back-bleeders from the proximal dorsal vein on the anterior surface of the prostate , division of the striated sphincter when placing urethral sutures , division of the posterior striated sphincter , and hemostasis at the end of the case . CONCLUSIONS We believe that retrospective review of intraoperative videotapes has great promise . Because many surgeons use different techniques , it is likely that each individual may be able to identify other important arbitrary variations that may improve their patients ' outcomes . Similarly , for surgeons with less than optimal outcomes , the review of early successful cases may enable them to identify ways that modification of their surgical technique can improve the outcome of future patients . To the best of our knowledge , the use of retrospective review of intraoperative videotapes has not been commonly used in any other surgical field PURPOSE Erectile dysfunction continues to be a significant problem for men after radical retropubic prostatectomy  despite nerve sparing techniques . Sildenafil citrate ( Viagra ) has proved effective for erectile dysfunction in many men . We determine the efficacy of sildenafil in men with erectile dysfunction after radical retropubic prostatectomy  and examine variables that may impact the response to treatment . MATERIAL S AND METHODS A total of 84 men were prescribed sildenafil after radical retropubic prostatectomy  and asked to complete a series of question naires , including the International Index of Erectile Function ( IIEF ) , on erectile function before and after sildenafil administration . The importance of factors , such as patient age , time since surgery , degree of cavernous nerve sparing , preoperative prostate specific antigen , Gleason score , clinical and pathological stage , and baseline postoperative erectile function , was examined . RESULTS Of the 84 patients 45 ( 53 % ) had improved erections and 34 ( 40 % ) had improved ability for intercourse while taking sildenafil .  Mean IIEF score for the erectile function domain increased from 9 to 14 ( p < 0.001 ) . Orgasmic function ( p = 0.004 ) and intercourse satisfaction ( p = 0.009 ) also significantly improved . The degree of nerve sparing and baseline postoperative erectile dysfunction had a significant impact on the ability of sildenafil to improve erectile function ( p = 0.010 and p < 0.001 , respectively ) and total IIEF question naire responses ( p = 0.031 and p < 0.001 , respectively ) . Age and pathological stage also appeared to have a significant effect . CONCLUSIONS Sildenafil improved erectile function and the ability to have intercourse in more than half of men after radical retropubic prostatectomy . Baseline postoperative erectile function , which is dependent on the degree of nerve sparing technique , significantly impacts the likelihood that patients will respond to sildenafil PURPOSE This study was aim ed at assessing prospect ively the effect of postoperative intracavernous injections of alprostadil on the recovery of spontaneous erectile function after nerve-sparing radical retropubic prostatectomy . MATERIAL S AND METHODS A total of 30 potent patients with clinical ly localized prostate cancer ( clinical stage B1 or B2 , Gleason sum 7 or greater , prostatic specific antigen less than 20 ng./ml . ) underwent nerve-sparing radical retropubic prostatectomy  and was subsequently r and omized to alprostadil injections 3 times per week for 12 weeks ( group 1 , 15 patients ) or  observation without any erectogenic treatment ( group 2 , 15 patients ) . Patients were assessed at the 6-month followup by sexual history , physical examination , color Doppler sonography of the cavernous arteries and polisomnographic recording of nocturnal erections . RESULTS In group 1 , 12 patients ( 80 % ) completed the entire treatment schedule and were evaluated at the long-term followup . Eight patients in this group ( 67 % ) reported the recovery of spontaneous erection sufficient for satisfactory sexual intercourse , compared with 3 patients ( 20 % ) in group 2 . The difference between the 2 groups was statistically significant ( p < 0.01 ) . In group 1 , all but 1 patient reporting normal postoperative erections also showed normal erections at nocturnal testing , whereas color Doppler sonography demonstrated normal penile hemodynamics in all of them . In these patients , failures were the result of cavernous veno-occlusive dysfunction ( 2 cases , 17 % ) and cavernous nerve injury ( 2 cases , 17 % ) . In group 2 , patients with normal erections showed both normal nocturnal testing and penile hemodynamics , whereas failures were the result of cavernous veno-occlusive dysfunction ( 8 cases , 53 % ) , cavernous arterial insufficiency ( 2 cases , 13 % ) or cavernous nerve injury ( 3 cases , 20 % ) . Complications in patients treated with alprostadil injections accounted for 2 cases ( 13 % ) of a penile nodule and 1 further case ( 6 % ) of prolonged penile erection . Complications were not seen in group 2 patients . CONCLUSIONS Early postoperative administration of alprostadil injections significantly increases the recovery rate of spontaneous erections after nerve-sparing radical retropubic prostatectomy . It is our belief that programmed vasoactive injections improve cavernous oxygenation , thereby limiting the development of hypoxia-induced tissue damage . The potential complications related to the use of intracavernous injections must be clearly explained to patients Early pharmacological prophylaxis has been reported to increase the return of spontaneous erections following radical prostatectomy ( RP ) . In this study , we evaluated the role of intracavernosal alprostadil ( PGE1 ) combined with sildenafil in stimulating early recovery of spontaneous erections following RP . In this prospect i ve study , we included 22 patients who underwent bilateral nerve-sparing RP after October 2004 .  Sildenafil dose of 50 mg/day was started at the time of hospital discharge . Of 22 patients , 18 started on PGE1–4 μg ( 1–8 ) and four started on low-dose Trimix ( 20 U ) 2–3 times/week . These patients are followed up at regular intervals ( 3 , 6 , 9 and 12 months ) with abridged version of the International Index for Erectile Function-5 question naire . Patient compliance , return of sexual activity and return of natural erection , adverse effects and reasons for discontinuation were recorded . Penile doppler studies were performed during followup visits to assess the vascular status . After a mean followup of 6 months ( 3–8 months ) , 11/22 ( 50 % ) patients had return of spontaneous partial erections . Of the 18 PGE1 users , six continued 4 μg PGE1 , four increased the dose to 8 μg , six decreased the dose to 2 μg and two patients further reduced the dose to 1 μg . Of four low-dose Trimix users , three increased the dose to 30 U and one reduced the dose to 15 U. Of 22 patients , 21 were sexually active : 12/21 ( 57 % ) with the injections alone and 9/21 ( 42.9 % ) with combination therapy ( injections ( PGE1 ) and sildenafil ) . Penile doppler studies revealed arterial insufficiency in 77 % ( 17/22 ) patients and venous insufficiency in one patient . Early intracavernosal injections following RP facilitated early sexual intercourse , patient satisfaction and potentially earlier return of natural erections . Early combination therapy with sildenafil allowed a lower dose of intracavernous injections , minimizing the penile discomfort PURPOSE It has been suggested that postradical prostatectomy ( RP ) erectile function outcomes are improved by early use of erectogenic medications . This analysis was design ed to assess the ability of a post-RP vasoactive drug program to improve long-term spontaneous erectile function . METHODS Men with functional preoperative erections who underwent RP were challenged early postoperatively with oral sildenafil . Nonresponders were switched to intracavernosal injection therapy ( ICI ) . Patients were instructed to inject three times a week . Only patients who presented within 6 months post RP , who completed the International Index of Erectile Function ( IIEF ) question naire on at least three separate occasions after surgery , and who had been followed for at least 18 months were included . Data from men who were committed to rehabilitation were compared with those of men who did not follow the protocol but continued to be followed serially following RP . RESULTS There were 58 patients in the rehabilitation ( R ) group and 74 in the nonrehabilitation ( NR ) group . No differences existed in mean patient age , comorbidity profile , intraoperative nerve sparing status , or postoperative erectile hemodynamics between the two groups . At 18 months post RP , there were statistically significant differences between the two groups in the percentage of patients who were capable of having medication-unassisted intercourse ( R=52 % vs. NR=19 % , P<0.001 ) ; mean erectile rigidity ( R=53+/-21 % vs. NR=26+/-43 % , P<0.01 ) ; mean IIEF erectile function ( EF ) domain scores ( R=22+/-6 vs. NR=12+/-14 , P<0.01 ) ; the percentage of patients with normal EF domain scores ( R=22 % vs. NR=6 % , P<0.01 ) ; the percentage of patients responding to sildenafil ( R=64 % vs. NR=24 % , P<0.001 ) ; the time to become a sildenafil responder ( R=9+/-4 vs. NR=13+/-3 months , P=0.02 ) ; and the percentage of patients responding to ICI ( R=95 % vs. NR=76 % , P<0.01 ) . CONCLUSIONS The data generated from this nonr and omized study indicate that a pharmacologic penile rehabilitation protocol results in higher rates of spontaneous functional erections and erectogenic drug response after RP 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 PURPOSE We evaluated neurogenic erectile dysfunction , focusing on the post-radical prostatectomy model . We investigated changes in DNA , protein and apoptotic cells of the rat penis after  denervation . Gross morphometry was measured to eluci date the impact of chemical changes . MATERIAL S AND METHODS Postpubertal male Sprague-Dawley rats were r and omized to bilateral or unilateral cavernous nerve transection , or sham operation .  Wet weight , DNA content and protein content were measured . Tissue sections were stained for apoptosis by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling and the apoptotic index was calculated . Dual staining was performed for endothelial and smooth muscle cells to identify apoptotic cells . RESULTS Penile wet weight was significantly decreased at all time points after bilateral neurotomy ( p < 0.0005 ) . Unilateral neurotomy allowed much greater preservation of penile weight . DNA content was significantly decreased in bilaterally denervated penes and unchanged in unilaterally operated penes . Protein content was not significantly altered in the bilateral or unilateral cohorts . Bilateral neurotomy induced significant apoptosis , while unilateral surgery caused significantly less apoptosis . Each population had apoptotic clustering just beneath the tunica albuginea , which was mostly smooth muscle cells . CONCLUSIONS These data suggest the importance of neural integrity to maintain penile homeostasis . The loss in penile weight was consistent with the anecdotal experience of many clinicians . Decreased DNA content may have been due to significant levels of apoptosis in smooth muscle cells . Preserved protein content may suggest an increase in extracellular protein , as postulated in corporeal fibrosis . The subtunical population of apoptotic smooth muscle cells revealed a mechanism for veno-occlusive dysfunction observed after radical prostatectomy . These effects were significantly moderated in the unilateral model , reinforcing the critical nature of neural integrity INTRODUCTION After bilateral nerve-sparing radical retropubic prostatectomy ( BNSRRP ) , nocturnal and sexually mediated erections may help to preserve normal erectile function ( EF ) . AIM To investigate nocturnal penile tumescence and rigidity ( NPTR ) in a subset ( N = 54 men ) from a r and omized , double-blind trial ( N = 76 ) of nightly sildenafil after BNSRRP . METHODS Inclusion required preoperative " normal " EF ( defined as a combined score of > /=8 for International Index of Erectile Function questions 3 ( penetration ) and 4 ( maintained erection after penetration ) and NPTR testing ( > /=10 continuous minutes of > /=55 % rigidity [ R > /= 55 % ] at the base ) . Postoperative assessment s were at weeks 4 ( pretreatment ) , 16 , 28 , 40 ( during 36 weeks of nightly prophylaxis : sildenafil 50 mg [ N = 17 ] , 100 mg [ N = 18 ] or placebo [ N = 19 ] ) , and 48 ( after 8 weeks of no erectile dysfunction therapy , when " responders " were delineated by the defined normal EF and a " yes " response to " Over the past 4 weeks , have your erections been good enough for satisfactory sexual activity ? " ) . Base and tip rigidity and tumescence were measured using penile plethysmography . MAIN OUTCOME MEASURES Duration of R > /= 55 % and area under the curves for rigidity and tumescence . RESULTS Postoperatively , rapid profound reduction in nocturnal EF was noted in all groups . There was a gradual dose-dependent improvement in base and tip rigidity in the sildenafil groups but little improvement in the placebo group . Eight weeks after treatment termination ( 48 weeks postoperatively ) , 24 % ( 4/17 ) of 50-mg sildenafil recipients , 33 % ( 6/18 ) of 100-mg sildenafil recipients , and 5 % ( 1/19 ) of placebo recipients were responders . Tip R > /= 55 % was the most discriminating NPTR measure between nonresponders and responders to sildenafil , in whom it regained baseline ( preoperative ) levels ( whereas base R > /= 55 % did not ) . It was most prolonged in responders to sildenafil 100 mg . CONCLUSIONS In our subset analysis , nightly sildenafil for 9 months post-BNSRRP objective ly improved nocturnal erections and pharmaceutically unassisted EF PURPOSE We assess the clinical efficacy of sildenafil citrate and predictors of satisfactory outcome . MATERIAL S AND METHODS All patients treated with sildenafil citrate within the first 6 weeks of its release were evaluated with a self-administered question naire before and at completion of therapy to assess etiology of erectile dysfunction , level of sexual function , libido , response to previous therapies , response to therapy with sildenafil citrate and quality of life . Sexual function was measured before and during therapy using an abbreviated version of the International Index of Erectile Function , with a successful outcome defined as a level of satisfaction of 4 or 5 on a 5-point scale . RESULTS Followup was obtained in 267 of the 308 patients who entered the study . Mean age plus or minus st and ard deviation was 61+/-9.6 years and duration of erectile dysfunction was 4.1+/-3 years .  Overall satisfaction with sildenafil citrate for the entire patient population was 65 % and response to prior therapies did not affect satisfaction . There was a significant positive correlation between baseline sexual function and response to sildenafil citrate but even patients with severe erectile dysfunction had a 41 % satisfaction rate . Etiology of erectile dysfunction had a significant impact on satisfaction rate , with neurogenic causes of erectile dysfunction ( diabetes , prostate surgery and so forth ) having significantly lower rates than psychogenic or vasculogenic erectile dysfunction . CONCLUSIONS Sildenafil citrate is a highly effective oral agent for the treatment of erectile dysfunction in clinical practice . The best predictors for response to sildenafil citrate therapy are baseline sexual function and etiology of erectile dysfunction . However , we could not identify any patient characteristic that would predict absolute failure for sildenafil citrate therapy . Therefore , all patients with erectile dysfunction who do not have specific contraindications should be considered for sildenafil citrate therapy OBJECTIVES To evaluate changes in stretched penile length after  radical retropubic prostatectomy ( RRP )  in a prospect i ve penile measurement study because an occasional complaint from patients after RRP is that their penis is shortened . METHODS Thirty-one patients undergoing RRP by one surgeon were enrolled . The same physician completed measurements with a paper ruler to the nearest 0.5 cm . The stretched penile length was measured from the tip of the glans to the pubopenile skin junction . The measurements were taken in the preoperative holding area before the patient received anesthetic medication for the RRP and again 3 months postoperatively . The reliability and reproducibility of this measurement were confirmed . RESULTS All 31 patients were measured at 3 months postoperatively . Of the 31 patients , 22 ( 71 % ) had a decrease in stretched penile length ( range 0.5 to 4.0 cm ) . Seven were shortened 0.5 cm , 11 were shortened 1.0 to 2.0 cm , and 4 were shortened more than 2.0 cm . Five patients had no change , and in four the penile length was longer ( range 0.5 to 1.0 cm ) . CONCLUSIONS The results of this pilot study appear to show that the stretched penile length decreases after RRP at 3 months of follow-up in most men ; 48 % ( 15 of 31 ) had considerable shortening greater than 1.0 cm . If confirmed by other investigators , the cause of this change needs to be eluci date Objective : To assess the clinical efficacy of sildenafil as treatment for erectile dysfunction ( ED ) the factors associated with treatment failure were investigated . Methods : Open , prospect i ve study including 244 patients suffering from ED who were evaluated by anamnesis , physical exploration , blood test , dynamic penile color duplex ultrasonography and Sexual Health Inventory for Male ( SHIM ) . The efficacy of sildenafil was assessed by repeating the SHIM 2 months after therapy , independent of the final dose used . Side effects were also recorded . Factors influencing treatment outcome were evaluated by univariate and multivariate statistical analysis . Results : Overall , sildenafil was effective in 56.8 % of 213 eligible patients . When the etiologic diagnosis was not included in the multivariate analysis , antecedents of diabetes mellitus , non – nerve – sparing radical prostatectomy and SHIM basal score were selected as predictors of a poor response . In a second analysis including etiologic diagnosis , only SHIM basal score and etiological diagnosis proved to be of prognostic value . Side effects were noticed by 24.4 % of patients , none of them being severe . Conclusions : Sildenafil is a rather effective and well – tolerated treatment for ED . The basal severity of ED and etiological diagnosis are the prognostic factors most significantly associated with treatment outcome BACKGROUND Sildenafil citrate was introduced as a treatment for  erectile dysfunction  in April 1998 in the United States and has been available since March 1999 in Japan . In this article , we assess the efficacy of sildenafil in the treatment of  erectile dysfunction in Japanese men after radical retropubic prostatectomy for localized prostate cancer . METHODS Of 106 men who underwent radical retropubic prostatectomy between January 1994 and March 2000 , 43 were prescribed sildenafil at their request after radical retropubic prostatectomy .  Medication was initiated at 25 mg , and if this was ineffective , the dose was increased to 50 mg . Of the patients , 18 underwent bilateral and 21 unilateral nerve sparing ( NS ) procedures , while in 4 patients , a non-NS procedure was performed . These patients were interviewed using a question naire about their response to sildenafil and using the 5-item International Index of Erectile Function ( IIEF-5 ) question naire . RESULTS Thirty-three of the 43 patients were eligible for evaluation of the  efficacy of sildenafil and 27 completed the IIEF-5 question naires . Sildenafil at 50 mg had a better effect on sexual function than 25 mg in most Japanese patients . Of the 16 patients who underwent bilateral NS procedures , 10 ( 62.5 % ) had improved ability for intercourse and 3 ( 18.8 % ) had improved erections . Of the 13 patients who underwent unilateral NS procedures , 7 ( 53.8 % ) had improved ability for intercourse and 4 ( 30.8 % ) had improved erections . None of the 4 patients who underwent non-NS procedures had a positive response . Of 24 patients with positive response to sildenafil , 3 ( 12.5 % ) did not have to take sildenafil after receiving it because they did not require it for intercourse . Mean IIEF-5 score increased from 4.3 to 11.4 ( P < 0.0001 ) . Patient age , time since surgery , PSA and pathological stage did not have statistically significant effects on outcome . The most commonly cited adverse effect was headache ( 21 % ) . CONCLUSION Sildenafil is equally effective for erectile dysfunction in Japanese patients who have undergone bilateral and unilateral NS procedures , and aids recovery of natural erectile function after radical retropubic prostatectomy . However , non-NS procedure patients had no response to sildenafil . This study suggested that sildenafil is well tolerated and should be initially used for treatment of Japanese men with erectile dysfunction  after radical retropubic prostatectomy PURPOSE Some patients report that the penis is smaller after radical retropubic prostatectomy for prostate cancer . We performed a prospect i ve study which measured penile length before and after radical retropubic prostatectomy . MATERIAL S AND METHODS A total of 124 men consented to penile measurements before radical prostatectomy performed by the same surgeon . Repeat measurements were performed at 3-month intervals following surgery . Penile measurements ( cm . ) consisted of flaccid length , stretched length , depth of prepubic fat pad and circumference . Statistical analysis of penile measurements was performed using the paired sample s and independent Student 's t test , Pearson 's correlation and analysis of variance . RESULTS Mean patient age was 59.1 ( range 42 to 76 ) . No patient had a penile abnormality , for example Peyronie 's disease , or history of penile or urethral surgery . The size of the penis was significantly smaller after prostatectomy , and there was a significant difference for flaccid ( p < 0.001 ) , stretched ( p < 0.001 ) , prepubic fat pad ( p = 0.02 ) and circumference measurements ( p < 0.01 ) . Twelve patients ( 19 % ) had a 15 % or greater decrease in stretched penile length . When dichotomizing groups at the cut point of 15 % decrease , the independent t test of prostate size was not significant ( t[df 36.7 ] = -1.83 , p = 0.076 ) . Nerve sparing was not significant in relation to change in penile stretched length , ( F[df 2 , 62 ] = 0.501 , p = 0.609 ) . CONCLUSIONS Our findings support observations of decreased penile length after radical prostatectomy . Men should be counseled before radical prostatectomy that penile shortening may occur OBJECTIVES To determine the efficacy of sildenafil for the treatment of erectile dysfunction ( ED ) in a clinical practice setting ; to evaluate the correlation between patient and partner perceptions of treatment outcomes ; and to assess the relation between the severity of ED and response to treatment . METHODS Among the first 100 men to receive sildenafil in a urology practice setting , 74 ( mean + SD age 64+/-11 years ) completed a vali date d sexual function question naire ( International Index of Erectile Function [ IIEF ] ) before and after a 4 to 6-week treatment period . A modified version of the same question naire was independently completed by partners . ED was categorized into a severity class of I to IV . RESULTS Sildenafil treatment improved erections by 71 % to 95 % , according to responses in key IIEF questions 3 and 4 . Overall , 57 ( 77 % ) of 74 patients desired to continue treatment after the test period . Patient score on the IIEF was correlated with partner score on the modified question naire before and after treatment ( r = 0.67 to 0.81 , P < 0.01 ) . IIEF scores were reflected in a simple severity classification system . Men with the best preservation of erections ( severity class I ) exhibited the best responses to sildenafil , whereas men with no erections ( severity class IV ) were much less likely to respond to the drug and desire continuation of treatment ( P < 0.01 ) . Patients with a radical prostatectomy were relatively refractory to sildenafil , except for 2 of 5 who had undergone a nerve-sparing operation . CONCLUSIONS In clinical practice , sildenafil is an effective treatment of ED , according to partner-vali date d question naire responses ; and the results of treatment are predictable with an ED severity classification system Corpus cavernosum smooth muscle relaxation and hence penile erection are regulated in part by increases in smooth muscle synthesis of the second messengers cyclic adenosine monophosphate ( cAMP ) and cyclic guanosine monophosphate ( cGMP ) . The object of this study was to determine 30-month follow-up results in motivated patients desiring noninvasive medical therapy using sildenafil citrate ( Viagra ) in combination with intraurethral prostagl and in E1 ( PGE1 ) ( Medicated Urethral System for Erection [ MUSE ] ) .  Twenty-eight patients ( mean±s.d . age , 59±7.3 y ; 17 who had undergone radical prostatectomy and 11 who had a diagnosis of organic erectile dysfunction ) were included in this study . Detailed history taking and physical examinations were performed and vascular risk factors noted . In these patients , treatment with either 100 mg of sildenafil citrate and /or 1000 μg of MUSE had failed . None of these patients desired intracavernosal injection . Duplex Doppler ultrasonography  after redosing was carried out on all patients . Dynamic infusion corpus cavernosography/cavernosometry was obtained in 17 of 28 patients , and combination therapy was initiated using 100 mg of sildenafil citrate orally 60 min before intercourse and 500 μg of MUSE intraurethrally immediately before intercourse . Independently , either 100 mg of sildenafil citrate or 1000 μg of MUSE was not efficacious in inducing an erection sufficient for vaginal penetration in any of the 28 patients . After initiating a combination therapy , at 30 months , all 28 patients were reporting erections sufficient for vaginal penetration , with 3.6 intercourse episodes per month . None of the patients crossed over to intracavernosal therapy or penile prosthesis . During therapy , eight of 28 patients reduced the dose of sildenafil citrate to 50 mg . Combination therapy with MUSE and sildenafil  may be more efficacious in the salvage of patients who desire noninvasive therapy but in whom single-treatment modalities fail . Although both cAMP- and cGMP-mediated vasodilation can lead to penile erection , combining therapies that incorporate both pathways may succeed when single therapies fail 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 Because preservation of functioning penile erections is a major concern for many patients considering treatment for localized prostate cancer , we analyzed various factors determined before and after radical retropubic prostatectomy to identify those significantly associated with recovery of erectile function . MATERIAL S AND METHODS Our prospect i ve data base of patients undergoing pelvic lymphadenectomy and radical retropubic prostatectomy  was used to determine factors predictive of erection recovery after radical prostatectomy . The study included 314 consecutive men with prostate cancer treated with radical retropubic prostatectomy between November 1993 and December 1996 . Preoperative potency satisfactory for intercourse and degree of neurovascular bundle preservation during the operation were documented . RESULTS Patient age , preoperative potency status and extent of neurovascular bundle preservation but not pathological stage were predictive of potency recovery after radical prostatectomy . At 3 years after the operation 76 % of men younger than age 60 years with full erections preoperatively who had bilateral neurovascular bundle preservation would be expected to regain erections sufficient for intercourse . Compared to the younger men , those 60 to 65 years old were only 56 % ( 95 % confidence interval [ CI ] 37 to 84 ) and those older than 65 years were 47 % ( 95 % CI 30 to 73 ) as likely to recover potency . Patients with recently diminished erections were only 63 % ( 95 % CI 38 to 100 ) as likely to recover potency as men with full erections preoperatively , and those with partial erections were only 47 % ( 95 % CI 23 to 96 ) as likely to recover potency . Resection of 1 neurovascular bundle reduced the chance of recovery to 25 % ( 95 % CI 10 to 61 ) compared to preserving both nerves . CONCLUSIONS Knowledge of preoperative erectile function and patient age before the operation and the degree of neurovascular bundle preservation afterward may aid in patient counseling regarding potency recovery after radical prostatectomy 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 OBJECTIVES Controversial data on penile length after  radical retropubic prostatectomy  are available . We hypothesised that postoperative penile size correlates to erectile function following bilateral nerve-sparing radical retropubic prostatectomy  ( BNSRRP ) . METHODS Thirty-three consecutive patients with a preoperative erectile function domain of the International Index of Erectile Function ( IIEF-EF ) score indicating full potency ( > or = 26 ) were prospect ively enrolled . All patients underwent BNSRRP performed by one high-volume surgeon . All patients were preoperatively evaluated by IIEF-EF ,  analysis of comorbidities , physical examination  , and  penile power colour Doppler ultrasound using intracavernosal injection of prostagl and in E(1 ) ( PGE(1 ) ) 20 microg plus audiovisual and manual genital stimulation .  Penile length and circumference were measured in flaccidity and at maximum erection . Six months postoperative , patients were assessed with the same protocol plus general assessment questions investigating penile structure and function . Statistical analysis was performed with an independent sample t test . RESULTS Mean patient age was 56.5 yr . We found no difference between the preoperative and the 6-mo postoperative mean IIEF-EF domain score ( 27.2 vs , 26.7 , respectively ; p = 0.35 ) . No difference was found in penile colour Doppler evaluation between the preoperative and postoperative periods ( all p values > or = 0.3 ) . We found no differences in penile length and circumference between the preoperative and postoperative evaluation either in the flaccid or in the erect state . Mean flaccid penile length ( cm ; preop vs. postop ) : 13.2 vs. 13 ( p = 0.6 ) . Mean flaccid penile circumference ( cm ; preop vs. postop ) : 11.1 vs. 11 ( p = 0.7 ) . Mean erect penile length ( cm ; preop vs. postop ) : 16.8 vs. 16.5 ( p = 0.08 ) . Mean erect penile circumference ( cm ; preop vs. postop ) : 15.6 vs. 15.3 ( p = 0.2 ) . CONCLUSIONS This is the first report on penile changes in flaccidity and at maximum erection after BNSRRP in patients treated by one high-volume surgeon . The postoperative preservation of erectile function positively correlated with the maintenance of penile length following surgery . We found no change in penile size after surgery OBJECTIVES To determine whether propionyl-L-carnitine ( PLC ) plus acetyl-L-carnitine ( ALC ) improves the effectiveness of sildenafil in restoring sexual potency after bilateral nerve-sparing radical retropubic prostatectomy . METHODS We analyzed the data from 96 patients who had undergone bilateral nerve-sparing radical retropubic prostatectomy : 33 were given placebo ( group 1 ) , 32 used PLC 2 g/day plus ALC 2 g/day plus sildenafil 100 mg when needed ( group 2 ) , and 35 used sildenafil alone ( group 3 ) . The studied variables were sexual function ( assessed through sexual behavior interviews and the International Index of Erectile Function ) , peak systolic velocity and end-diastolic velocity of cavernosal arteries ( assayed by dynamic echo-color Doppler ) , the percentage of patients able to achieve a positive intracavernous injection test , and side effects . RESULTS Placebo proved ineffective and sildenafil and sildenafil plus ALC and PLC proved effective . The International Index of Erectile Function-15 scores of the group 2 patients were significantly greater than those of group 3 in the following domains : erectile function , sexual intercourse satisfaction , orgasm , and general sexual well-being . The drugs did not significantly modify the score in the sexual desire domain or in the peak systolic velocity or end-diastolic velocity of the cavernosal arteries . Sexual behavior interviews revealed that 2 of 29 in group 1 , 28 of 32 in group 2 , and 20 of 39 in group 3 attained satisfactory sexual intercourse ( P < 0.01 ) . Only group 2 had a significantly increased percentage of patients with a positive intracavernous injection test after therapy ( 36.4 % versus 63.6 % ; P < 0.01 ) . ALC plus PLC did not significantly improve the side effects of sildenafil . CONCLUSIONS PLC and ALC proved to be safe and reliable in improving the efficacy of sildenafil in restoring sexual potency after bilateral nerve-sparing radical retropubic prostatectomy PURPOSE We assessed the efficacy and safety of sildenafil citrate as treatment for erectile dysfunction . MATERIAL S AND METHODS A total of 433 completely evaluated men with chronic erectile dysfunction were treated with sildenafil citrate . Response was assessed prospect ively by baseline and followup physician interviews , and by a patient self-administered 15-item question naire on the domains of patient treatment response and satisfaction , partner treatment satisfaction , comparative previous treatment satisfaction , adverse effects , and patient and partner quality of life . RESULTS Of the 304 men ( 70.2 % ) who completed the question naire 278 received sildenafil , including 186 who previously had undergone treatment for erectile dysfunction , principally involving intracavernous injection therapy . A response was elicited by a median dose of 100 mg . in 188 patients ( 67.6 % ) who achieved erection suitable for sexual intercourse . Those with psychogenic erectile dysfunction responded significantly better than those with organic dysfunction ( p < 0.001 ) . Erection suitable for intercourse was attained by 30.8 % of patients with erectile dysfunction after radical prostatectomy and 80 % with cavernous veno-occlusive dysfunction . Of previous intracavernous injection responders 29.9 % were refractory to sildenafil , while 33 . 3 % of previous intracavernous injection nonresponders responded to sildenafil . The sildenafil response was considered inferior to the intracavernous injection response by 43.6 % of the men who previously responded to intracavernous injection , of whom 51.5 % continued to receive intracavernous injection as the only treatment ( 19.5 % ) or as an alternative to sildenafil ( 32 % ) . Adverse effects in 53.6 % of cases were assessed as mild in 56.4 % , moderate in 38.3 % and severe in 5.3 % . Multiple adverse effects were reported by 62.4 % of patients , while 17 ( 6.1 % ) discontinued sildenafil as a direct result of intolerable adverse effects . The most common adverse effects were facial flushing in 33.5 % of cases , headaches in 23.4 % , nasal congestion in 12.6 % , dyspepsia in 10.1 % and dizziness in 10.8 % . Baseline patient and partner quality of life scores significantly improved after sildenafil treatment ( p < 0.001 ) , while significantly improved quality of life was noticed by 51.5 % and 43.1 % , respectively . CONCLUSIONS Sildenafil citrate is effective oral first line treatment for erectile dysfunction . Although more than 50 % of men reported adverse effects , most were considered mild and rarely result ed in treatment cessation . There was a trend in those on intracavernous injection who responded to sildenafil to continue intracavernous injection as the only therapy or as an alternative to sildenafil . Also , we noted that some cases refractory to sildenafil responded to intracavernous injection . These findings imply that intracavernous injection remains an effective erectile dysfunction treatment option
target: Experimental data support the concept of cavernosal damage and suggest a protective role for daily dosage of a PDE5-I ; however , similar data have not yet been replicated in humans .
  Penile rehabilitation programs are common in clinical practice , but there is no definitive evidence to support their use or the best treatment strategy .
  PDE5-Is are efficacious and safe in young patients with normal preoperative erectile function who have undergone bilateral nerve-sparing radical prostatectomy .
  On-dem and use of a PDE5-I may be at least as efficacious as daily use .
  PDE5-I use in penile rehabilitation programs is not supported by rigorous level 1 evidence -based medicine .
  PDE5-Is are an efficacious and safe treatment for post-RP ED in properly selected patients .
  The experimental results on the protective role of daily dosages of PDE5-Is , while robust , have not been replicated in humans .
background: CONTEXT  Erectile dysfunction ( ED ) after radical prostatectomy ( RP ) has a significant negative impact on a patient 's health-related quality of life .
  Phosphodiesterase type 5 inhibitors ( PDE5-Is ) have recently been utilized not only as a treatment of ED in this population but also as a preventive strategy in penile rehabilitation programs .
  OBJECTIVE To eluci date the pathophysiologic mechanisms of post-RP ED , to assess the need for rehabilitation following surgery , and to analyze the basic scientific evidence and clinical applications of PDE5-Is for the prevention and treatment of ED .
  EVIDENCE SYNTHESIS Post-RP ED has many factors .
  Cavernosal nerve injury induces pro-apoptotic factors ( ie , loss of smooth muscle ) and pro-fibrotic factors ( ie , an increase in collagen ) within the corpora cavernosa .