Penile weight and cell subtype specific changes in a post-radical prostatectomy model of erectile dysfunction. Sildenafil: an orally active type 5 cyclic GMP-specific phosphodiesterase inhibitor for the treatment of penile erectile dysfunction. The use of an erectogenic pharmacotherapy regimen following radical prostatectomy improves recovery of spontaneous erectile function. Nocturnal tumescence: a parameter for postoperative erectile integrity after nerve sparing radical 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. Erectile function following brachytherapy, external beam radiotherapy, or radical prostatectomy in prostate cancer patients Effect of nightly versus on-demand vardenafil on recovery of erectile function in men following bilateral nerve-sparing radical prostatectomy. The multinational Men's Attitudes to Life Events and Sexuality (MALES) Study Phase II: understanding PDE5 inhibitor treatment seeking patterns, among men with erectile dysfunction. Return to work and sick leave after radical prostatectomy: A prospective clinical study Early use of vacuum constriction device following radical prostatectomy facilitates early sexual activity and potentially earlier return of erectile function Penile rehabilitation therapy following radical prostatectomy Tadalafil rehabilitation therapy preserves penile size after bilateral nerve sparing radical retropubic prostatectomy. Effects of nonlinear aerobic training on erectile dysfunction and cardiovascular function following radical prostatectomy for clinically localized prostate cancer. Changes in health utilities and health-related quality of life over 12 months following radical prostatectomy. The Effect of Salvage Radiotherapy and its Timing on the Health-related Quality of Life of Prostate Cancer Patients. A 6-month, prospective, observational study of PDE5 inhibitor treatment persistence and adherence in Middle Eastern and North African men with erectile dysfunction 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 Effects of Early Pelvic-Floor Muscle Exercise for Sexual Dysfunction in Radical Prostatectomy Recipients A return to normal erectile function with tadalafil once daily after an incomplete response to as-needed PDE5 inhibitor therapy. Effects of tadalafil treatment on erectile function recovery following bilateral nerve-sparing radical prostatectomy: a randomised placebo-controlled study (REACTT). 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. 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 PDE5 inhibitors blunt inflammation in human BPH: a potential mechanism of action for PDE5 inhibitors in LUTS. Efficacy and safety of tadalafil for erectile dysfunction in patients with multiple sclerosis.
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 Sildenafil ( Viagra , UK-92,480 ) is a novel oral agent under development for the treatment of  penile erectile dysfunction .  Erection is dependent on nitric oxide and its second messenger , cyclic guanosine monophosphate ( cGMP ) . However , the relative importance of phosphodiesterase ( PDE ) isozymes is not clear . We have identified both cGMP- and cyclic adenosine monophosphate-specific phosphodiesterases ( PDEs ) in human corpora cavernosa in vitro . The main PDE activity in this tissue was due to PDE5 , with PDE2 and 3 also identified . Sildenafil is a selective inhibitor of PDE5 with a mean IC50 of 0.0039 microM. In human volunteers , we have shown sildenafil to have suitable pharmacokinetic and pharmacodynamic properties ( rapid absorption , relatively short half-life , no significant effect on heart rate and blood pressure ) for an oral agent to be taken , as required , prior to sexual activity . Moreover , in a clinical study of 12 patients with erectile dysfunction without an established organic cause , we have shown sildenafil to enhance the erectile response ( duration and rigidity of erection ) to visual sexual stimulation , thus highlighting the important role of PDE5 in human penile erection . Sildenafil holds promise as a new effective oral treatment for penile erectile dysfunction 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 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 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 Background and purpose For localized prostate cancer , treatment options include external beam radiotherapy ( EBRT ) , radical prostatectomy ( RP ) , and brachytherapy ( BT ) .  Erectile dysfunction ( ED ) is a common side-effect . Our aim was to evaluate penile erectile function ( EF ) before and after BT , EBRT , or RP using a vali date d self-administered quality -of-life survey from a prospect i ve registry . Material and methods Analysis included 478 patients undergoing RP ( n = 252 ) , EBRT ( n = 91 ) , and BT ( n = 135 ) with at least 1 year of follow-up and EF documented using IIEF-5 scores at baseline , 6 weeks , 6 months , 1 year , and annually thereafter . Results Differences among treatments were most pronounced among patients with no or mild initial ED ( IIEF-5 ≥ 17 ) . Overall , corrected for baseline EF and age , BT was associated with higher IIEF-5 scores than RP ( + 7.8 IIEF-5 score ) or EBRT ( + 3.1 IIEF-5 score ) . EBRT was associated with better IIEF-5 scores than RP ( + 4.7 IIEF-5 score ) . In patients undergoing EBRT or RP with bilateral nerve sparing ( NS ) , recovery of EF was observed and during follow-up , the differences to BT were not statistically significant . Overall age had a negative impact on EF preservation ( corrected for baseline IIEF ) . Conclusion In our series , EF was adversely affected by each treatment modality . Considered overall , BT provided the best EF preservation in comparison to EBRT or RP.ZusammenfassungHintergrund und ZielDie externe Radiotherapie ( EBRT ) , die radikale Prostatektomie ( RP ) sowie die Brachytherapie ( BT ) stellen Beh and lungsoptionen für das lokalisierte Prostatakarzinom dar . Die erektile Dysfunktion ( ED ) ist eine häufige Nebenwirkung dieser Therapien . Unser Ziel war es , die penile erektile Funktion ( EF ) vor und nach BT , EBRT und RP mit Hilfe eines validierten , vom Patienten ausgefüllten Lebensqualitätsfragebogens aus einer prospektiven Date nbank zu beurteilen . Material und Method enMit einer minimalen Nachbeobachtungszeit von einem Jahr wurden 478 Patienten analysiert , die eine RP ( n = 252 ) , EBRT ( n = 91 ) oder BT ( n = 135 ) erhalten hatten und deren EF mit dem IIEF-5-Score vor Therapie sowie nach 6 Wochen , 6 Monaten , nach einem Jahr und danach jährlich ermittelt worden sind . ErgebnisDie größten therapiebedingten Unterschiede wurden bei Patienten ohne oder nur mit milder initialer ED beobachtet ( IIEF-5 ≥ 17 ) . Korrigiert für die EF und das Alter bei Therapie , war die BT mit höherem IIEF-5-Score assoziiert als die RP ( + 7,8 IIEF-5-Score ) oder die EBRT ( + 3,1 IIEF-5-Score ) . Die EBRT war mit einem besseren IIEF-5-Score assoziiert als die RP ( + 4,7 IIEF-5-Score ) . Bei Patienten mit bilateraler nervenschonender RP oder einer EBRT wurde eine Erholung der EF beobachtet ; i m Verlauf war der Unterschied zur BT nicht mehr statistisch signifikant . Insgesamt hatte ein höheres Alter einen negativen Einfluss auf die Erhaltung der EF ( korrigiert für Ausgangs-EF).SchlussfolgerungIn unserer Serie verschlechterte sich die EF durch alle Therapieformen . Insgesamt bot die BT die beste EF-Erhaltung verglichen mit der EBRT oder RP BACKGROUND To date , no data have been available from large , well- design ed trials comparing on dem and and nightly dosing of phosphodiesterase type 5 ( PDE5 ) inhibitors on recovery of erectile function in postprostatectomy patients with erectile dysfunction ( ED ) . OBJECTIVE To investigate the effect of early postoperative dosing with vardenafil , administered either nightly or on dem and , compared with placebo on recovery of erectile function in men with ED following bilateral nerve-sparing radical prostatectomy ( NSRP ) surgery . DESIGN , SETTING , AND PARTICIPANTS A r and omised , double-blind , double-dummy , multicentre , parallel group study conducted at 87 centres across Europe , Canada , South Africa , and the United States . For inclusion , patients had to be scheduled to undergo bilateral NSRP within 1 mo of screening and have a normal International Index of Erectile Function erectile function domain ( IIEF-EF ) score of > or = 26 at screening . A total of 628 men , aged 18 - 64 yr , were r and omised to treatment . Study design consisted of a 9-mo double-blind treatment period , a 2-mo single-blind washout period , and an optional 2-mo open-label period . INTERVENTION Patients received placebo , nightly vardenafil , or on dem and vardenafil . MEASUREMENTS Primary outcome measure was the percentage of subjects with an IIEF-EF score of > or = 22 after the 2-mo washout period . Secondary variables included mean per-patient success rates for Sexual Encounter Profile ( SEP ) questions 2 and 3 . RESULTS AND LIMITATIONS No statistically significant differences were observed among treatment groups in the proportion of patients with an IIEF-EF score of > or = 22 or in SEP3 success rates after the washout period . On-dem and vardenafil treatment result ed in significantly greater IIEF-EF scores and better SEP3 response rates than placebo over the entire treatment period . CONCLUSIONS In this study of men with ED following bilateral NSRP , vardenafil was efficacious when used on dem and , supporting a paradigm shift towards on dem and dosing with PDE5 inhibitors in this patient group . TRIAL REGISTRATION European clinical trials data base ( EudraCT ; available at http://eudract.emea.europa.eu/ ) . TRIAL REGISTRATION NUMBER 11336 OBJECTIVE The aim of Phase II of the Men 's Attitudes to Life Events and Sexuality ( MALES ) Study is to explore PDE5 inhibitor treatment seeking among men with erectile dysfunction ( ED ) . METHODS Phase II of the MALES study involved 2,912 men , aged 20 - 75 years , from 8 countries ( U.S. , U.K. , Germany , France , Italy , Spain , Mexico , and Brazil ) , who reported ED . Participants were recruited from the MALES Phase I sample [ 1 ] and via booster methods ( e.g. , physician referral , street interception ) , and completed self-report question naires concerning the characteristics of their ED , their efforts to seek PDE5 inhibitor treatment for their sexual dysfunction , and attitudinal and referent influences that potentially affect treatment-seeking . Statistical analyses focus on identification of correlates of PDE5 inhibitor treatment seeking . RESULTS PDE5 inhibitor utilization is strongly associated with ED sufferers ' assessment of the severity of their sexual dysfunction , with their belief that medication for ED is dangerous , and with their perceptions of whether physicians , other professionals , and spouses or family members are supportive of their seeking treatment . ED sufferers who evaluate their sexual dysfunction as severe , who believe that medication for ED is not dangerous , and who perceive support for treatment seeking from referent others , are more likely to utilize PDE5 inhibitor treatment . CONCLUSION Findings indicate that perceived ED severity , beliefs about ED medication , and referent influences are strongly correlated with utilization of PDE5 inhibitor therapy . These findings aid our underst and ing of factors that may incline men with ED to seek-or to avoid-PDE5 inhibitor therapy for their sexual dysfunction , and provide a basis for clinical and educational interventions to assist men with ED to seek appropriate treatment Abstract Background . To evaluate work status at three months after  radical prostatectomy ( RP ) in patients with prostate cancer ( PCa ) in relation to socio-demographics , urinary incontinence and bother , medical complications health-related quality of life ( HRQOL ) and surgical methods . To identify pre-RP available factors that can predict the duration of immediate post-RP sick leave . Material and methods . This prospect i ve question naire-based study included 264 men with PCa < 65 years , who were active in the work force before RP . Urinary incontinence and bother were assessed using the Exp and ed Prostate Cancer Index Composite-50 ( EPIC-50 ) . HRQOL was measured using SF-12 . Medical complications comprised self- reported new morbidities and re-hospitalizations within three months after RP . Patients ’ work status was defined as either “ stable/improved ” or “ declined ” at three months compared to work status at baseline . Duration of immediate post-RP sick leave was considered as prolonged when lasting > 6 weeks . Associations were analyzed using logistic regression analyses . Results . Almost 30 % of the patients had declined work status three months after RP . Change of physical HRQOL was the only factor remaining significantly associated with declined work status in the multivariate analysis . Half of the patients had prolonged immediate sick leave . Having physically strenuous work was the strongest predictor for this outcome . Conclusions . Long periods of sick leave and reduced workforce participation after RP should be considered potential adverse effects of this treatment To assess the efficacy of vacuum constriction devices ( VCD ) following radical prostatectomy ( RP ) and determine whether early use of VCD facilitates early sexual activity and potentially earlier return of erectile function . This prospect i ve study consisted of 109 patients who underwent nerve-sparing ( NS ) or non-nerve-sparing ( NNS ) RP between August 1999 and October 2001 and developed erectile dysfunction following surgery . The patients were r and omized to VCD use daily for 9 months ( Group 1 , N=74 ) or observation without any erectogenic treatment ( Group 2 , N=35 ) . Treatment efficacy was analyzed by responses to the Sexual Health Inventory of Men ( SHIM ) ( abridged 5-item International Index of Erectile Function ( IIEF-5 ) ) , which were stratified by the NS status . Patient outcome regarding compliance , change in penile length , return of natural erection , and ability for vaginal intercourse were also assessed . The mean patient age was 58.2 years , and the minimum follow-up was 9 months . Use of VCD began at an average of 3.9 weeks after RP . In Group 1 , 80 % ( 60/74 ) successfully used their VCD with a constriction ring for vaginal intercourse at a frequency of twice/week with an overall spousal satisfaction rate of 55 % ( 33/60 ) . In all , 19 of these 60 patients ( 32 % ) reported return of natural erections at 9 months , with 10/60 ( 17 % ) having erections sufficient for vaginal intercourse . The abridged IIEF-5 score significantly increased after VCD use in both the NS and NNS groups . After a mean use of 3 months , 14/74 ( 18 % ) discontinued treatment . In Group 2 , 37 % ( 13/35 ) of patients regained spontaneous erections at a minimum follow-up of 9 months after surgery . However , only four of these patients ( 29 % ) had erections sufficient for successful vaginal intercourse and rest of patients ( 71 % ) sought adjuvant treatment . Of the 60 successful users , 14 ( 23 % ) reported a decrease in penile length and circumference at 9 months ( range , 4–8 months ) compared to 12/14 ( 85 % ) among the nonresponders . However , in control group 22/35 reported decrease in penile length and circumference . Early use of VCD following RP facilitates early sexual intercourse , early patient/spousal sexual satisfaction , and potentially an earlier return of natural erections sufficient for vaginal penetration 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 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 UNLABELLED Erectile dysfunction ( ED ) is a major adverse effect of radical prostatectomy ( RP ) . We conducted a r and omized controlled trial to examine the efficacy of aerobic training ( AT ) compared with usual care ( UC ) on ED prevalence in 50 men ( n=25 per group ) after RP . AT consisted of five walking sessions per week at 55 - 100 % of peak oxygen uptake ( VO2peak ) for 30 - 60 min per session following a nonlinear prescription . The primary outcome was change in the prevalence of ED , as measured by the International Index of Erectile Function ( IIEF ) , from baseline to 6 mo . Secondary outcomes were brachial artery flow-mediated dilation ( FMD ) , VO2peak , cardiovascular ( CV ) risk profile ( eg , lipid profile , body composition ) , and patient-reported outcomes ( PROs ) . The prevalence of ED ( IIEF score ≤ 21 ) decreased by 20 % in the AT group and by 24 % in the UC group ( difference : p=0.406 ) . There were no significant between-group differences in any erectile function subscale ( p>0.05 ) . Significant between-group differences were observed for changes in FMD and VO2peak , favoring AT . There were no group differences in other markers of CV risk profile or PROs . In summary , nonlinear AT does not improve ED in men with localized prostate cancer in the acute period following RP . TRIAL REGISTRATION Clinical trials.gov identifier NCT00620932 INTRODUCTION Although radical prostatectomy ( RP ) is an effective treatment for prostate cancer , it has potentially deleterious effects on health-related quality of life ( HRQoL ) . Utility is an important global measure of HRQoL. This utility is also used in decision-making models and economic evaluations . There are no published prospect i ve data characterizing men 's utilities for health outcomes post-RP . METHODS From July 2003 to June 2006 , patients undergoing RP at the University Health Network in Toronto , Ontario , Canada , completed the Patient-Oriented Prostate Utility Scale ( PORPUS )  , a disease-specific HRQoL and utility instrument . Men were included if they had clinical ly localized prostate cancer and had completed HRQoL measures prior to surgery and at least once within 9 to 18 months after the RP .  Health-related quality of life was measured prior to surgery and at 4 stages after surgery : 0 to 3 months , 3 to 9 months , 9 to 18 months , and 18 to 30 months . Statistical analyses included pairwise t-tests and multivariable linear regression comparing changes in scores between baseline and the 9- to 18-month range . RESULTS Two hundred and thirteen men ( mean age 60.9 , median Gleason score 7 ) met the inclusion criteria . At baseline , HRQoL was high ( mean PORPUS-P [ psychometric ] = 83.8 ) . Scores declined sharply by 3 months ( 65.5 , p < 0.001 ) and improved but did not reach baseline by 9 - 18 months ( 75.1 , p < 0.001 ) . Utility scores ( PORPUS-U[utility ] ) showed the same pattern : 0.94 at baseline ; 0.81 at 3 months ( p < 0.001 ) ; and 0.88 at 9 to 18 months ( p < 0.001 ) . Predictors of HRQoL , including baseline PORPUS score , nerve-sparing surgery and smoking status , decline after RP . CONCLUSION Symptom scores are known to be affected up to 12 months after RP . Our study demonstrates that global health status also declines and remains affected 1 year after surgery BACKGROUND The impact of salvage radiotherapy ( SRT ) and its timing on health-related quality of life ( HRQoL ) in prostate cancer patients is still unclear . OBJECTIVE To compare the HRQoL of patients who underwent SRT with that of patients who underwent radical prostatectomy ( RP ) only and to investigate whether SRT timing is associated with HRQoL. DESIGN , SETTING , AND PARTICIPANTS All SRT patients ( n=241 ) and all RP-only patients ( n=1005 ) were selected from a prospect i ve data base ( 2004 - 2015 ) . The data base contained HRQoL and prostate problem assessment s up to 2 yr after last treatment . OUTCOME MEASUREMENT AND STATISTICAL ANALYSIS Mixed effects growth modelling adjusting for significant differences in patient characteristics and baseline HRQoL was used to analyze the association between : ( 1 ) " treatment " ( RP-only vs SRT ) and ( 2 ) " timing of SRT " with changes in HRQoL. RESULTS AND LIMITATIONS SRT patients showed significantly ( p<0.05 ) poorer recovery from urinary , bowel , and erectile function after their last treatment ( clinical ly meaningful difference for urinary and erectile function ) . Patients with a longer interval ( ≥ 7 mo ) between RP and SRT reported significantly better sexual satisfaction after SRT ( p=0.02 ) , and a better urinary function recovery ( p=0.03 ) . Limitations of the study include the nonr and om design and the variability in timing of HRQoL measurements . CONCLUSIONS Up to 2 yr after treatment , SRT patients reported poorer HRQoL in several HRQoL domains compared with RP-only patients , but not in overall HRQoL. Delaying the start of SRT after RP may limit the incidence and duration of urinary and sexual problems . Nevertheless , decisions regarding SRT timing should also be based on the potential benefits in disease recurrence . PATIENT SUMMARY Patients who receive radiotherapy after surgery may experience poorer urinary , bowel , and erectile function compared with patients who undergo surgery only . Although more research is needed , delaying radiotherapy seems to limit its impact on urinary and sexual functioning 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 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 Background : Sexual dysfunction is common after radical prostatectomy ( RP ) . Although pelvic-floor muscle exercise ( PFME ) has been recommended for sexual dysfunction , the optimal time for starting exercises after this surgery and the effects of exercise still need to be examined . Objectives : The present study was intended to explore the prevalence of sexual dysfunction and to assess the efficacy of PFME in sexual dysfunction following RP . Methods : Participants were r and omly distributed into an experimental group ( n = 35 ) or a control group ( n = 27 ) . The experimental group took part in PFME as part of regular daily activities after catheter removal post-RP . The control group was taught the exercise in the third month after RP . We followed up the participants at 1 , 3 , 6 , 9 , and 12 months . Results : All of the patients experienced a severe degree of sexual dysfunction after receiving RP . A t test showed a significant difference in the sexual function mean score between the experimental and control groups at 6 and 12 months . A mixed-model analysis indicated that , after a controlled surgical approach , there was a significant difference in group effect . The experimental group ’s sexual function was better than the control group ’s sexual function . Conclusion : This study demonstrates that early PFME is an effective intervention for sexual dysfunction in prostatectomy patients . The results can help healthcare providers to include this intervention in patients ’ discharge plans . Implication s for Practice : Patient sexual dysfunction after an RP is common . Nurses should evaluate and manage patients ’ sexual dysfunction and promote the early return of patients ’ potency INTRODUCTION An optimal outcome of an erectile dysfunction ( ED ) treatment is to enable a return to normal erectile function ( as defined by an International Index of Erectile Function-Erectile Function [ IIEF-EF ] domain score ≥ 26 ) . As-needed ( PRN ) phosphodiesterase type 5 ( PDE5 ) inhibitor treatment does not always result in a return-to-normal erectile function . AIM The combined studies evaluated whether treatment with tadalafil once daily would allow men to return to normal erectile function who had less than normal IIEF-EF domain scores while using a maximum dose of a PRN PDE5 inhibitor treatment . METHODS Men were ≥ 18 years of age , sexually active , reported a ≥ 3-month history of ED , and had been taking the maximum dose of sildenafil citrate , vardenafil , or tadalafil PRN . R and omization to once-daily therapy with tadalafil 2.5 mg to 5 mg ( N = 207 ) , tadalafil 5 mg ( N = 207 ) , or placebo  ( N = 209 ) for 12 weeks followed a 4-week maximum dose PRN PDE5 treatment and 4-week nondrug lead periods . Two identical double-blind , r and omized , placebo-controlled studies were conducted ; combined results are reported . MAIN OUTCOME MEASURE The main outcome measure was the percentage of subjects with a return-to-normal erectile function ( IIEF-EF domain score ≥ 26 ) when treated with tadalafil once daily compared with placebo . RESULTS In subjects not achieving normal erectile function with the maximum dose of a PRN PDE5 inhibitor , a higher percentage of subjects treated with tadalafil  had an IIEF-EF domain score ≥ 26 at end point ( tadalafil 2.5- to 5-mg group [ 39 % ] ; tadalafil 5-mg group [ 40 % ] ) compared with the placebo group ( 12.1 % ; P < 0.001 ) . Tadalafil was generally well tolerated and adverse events observed were consistent with previous reports of tadalafil once daily . CONCLUSIONS Treatment with tadalafil once daily significantly improved erectile function in men with mild to mild-moderate impairments in erectile function following PRN PDE5 inhibitor treatment 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 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 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 BACKGROUND Metabolic syndrome ( MetS ) and benign prostate hyperplasia (BPH)/low urinary tract symptoms ( LUTS ) are often comorbid . Chronic inflammation is one of the putative links between these diseases . Phosphodiesterase type 5 inhibitors ( PDE5i ) are recognized as an effective treatment of BPH-related LUTS . One proposed mechanism of action of PDE5 is the inhibition of intraprostatic inflammation . In this study we investigate whether PDE5i could blunt inflammation in the human prostate . METHODS Evaluation of the effect of tadalafil and vardenafil on secretion of interleukin 8 ( IL-8 , a surrogate marker of prostate inflammation ) by human myofibroblast prostatic cells ( hBPH ) exposed to different inflammatory stimuli . We preliminary evaluate histological features of prostatic inflammatory infiltrates in BPH patients enrolled in a r and omized , double bind , placebo controlled study aim ed at investigating the efficacy of vardenafil ( 10 mg/day , for 12 weeks ) on BPH/LUTS . RESULTS In vitro treatment with tadalafil or vardenafil on hBPH reduced IL-8 secretion induced by either TNFα or metabolic factors , including oxidized low-density lipoprotein , oxLDL , to the same extent as a PDE5-insensitive PKG agonist Sp-8-Br-PET-cGMP . These effects were reverted by the PKG inhibitor KT5823 , suggesting a cGMP/PKG-dependency . Treatment with tadalafil or vardenafil  significantly suppressed oxLDL receptor ( LOX-1 ) expression . Histological evaluation of anti-CD45 staining ( CD45 score ) in prostatectomy specimens of BPH patients showed a positive association with MetS severity . Reduced HDL-cholesterol and elevated triglycerides were the only MetS factors significantly associated with CD45 score . In the MetS cohort there was a significant lower CD45 score in the vardenafil-arm versus the placebo-one INTRODUCTION Data are sparse concerning the effects of phosphodiesterase type 5 ( PDE5 ) inhibitors for erectile dysfunction ( ED ) in subjects with multiple sclerosis ( MS ) . AIM To evaluate the efficacy and safety of tadalafil use in subjects with ED because of MS . METHODS Ninety-six MS patients with ED after a 4-week treatment-free period were given tadalafil  10 mg . All patients were re-evaluated after 4 weeks . Those with a score lower than 26 on the International Index of Erectile Function ( IIEF-15 ) and with less than 75 % of total successful sexual attempts assessed by the Sexual Encounter Profile Questions 2 and 3 ( SEP2 - 3 ) had their dosage of tadalafil increased to 20 mg , whereas responding subjects continued with 10 mg . Subsequently , all patients had a final follow-up visit after 8 weeks . MAIN OUTCOME MEASURES SEP2 - 3 , IIEF-15 question naire . The Life Satisfaction Checklist ( LSC ) question naire composed of eight questions was used prior to starting tadalafil and at the end of the 12-week treatment . RESULTS Ninety-two subjects completed the study . Seventy-two responded , 30 of whom used 10 mg . Two subjects discontinued the therapy because of moderate side effects : one suffered from headache and one from tachycardia . Responding patients reached a significant statistical improvement in all follow-ups compared with baseline on the erectile domain and overall sexual satisfaction scores of the IIEF-15 using the Wilcoxon test P < 0.01 . Furthermore , they showed statistical improvement through the Wilcoxon test P < 0.01 on the sexual life , family life , and partner relationship questions of the LSC compared with baseline . CONCLUSION Tadalafil is an effective and safe treatment for males with MS suffering from ED . Further studies are needed on MS patients to evaluate the efficacy and safety of long-term use , and to detect predictable parameters for the success of PDE5 inhibitors
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 .
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 .