***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Objective To assess the efficacy and safety of sildenafil citrate ( Viagra ® , Pfizer Inc. , USA ) in a double‐blind , placebo‐controlled , dose‐escalation study over a period of 26 weeks in men with erectile dysfunction of a broad spectrum of aetiology The experience of pain arises from both physiological and psychological factors , including one 's beliefs and expectations . Thus , placebo treatments that have no intrinsic pharmacological effects may produce analgesia by altering expectations . However , controversy exists regarding whether placebos alter sensory pain transmission , pain affect , or simply produce compliance with the suggestions of investigators . In two functional magnetic resonance imaging ( fMRI ) experiments , we found that placebo analgesia was related to decreased brain activity in pain-sensitive brain regions , including the thalamus , insula , and anterior cingulate cortex , and was associated with increased activity during anticipation of pain in the prefrontal cortex , providing evidence that placebos alter the experience of pain PURPOSE Although the effect of phosphodiesterase type 5 inhibitors on endothelial function in the systemic circulation has been extensively studied , its effect on penile endothelial function remains unexplored . Therefore , we evaluated the effect of daily sildenafil on penile endothelial function . MATERIAL S AND METHODS A total of 60 patients with erectile dysfunction were r and omized blindly to daily placebo or 50 mg sildenafil for 4 weeks . Penile and forearm blood flow as well as endothelial function indices were measured at baseline and after 4 weeks using venoocclusive strain gauge plethysmography for both organs . Sequential changes in flow , maximal blood flow and area under the curve induced by reactive hyperemia after 5 minutes of transient ischemia were considered indices of endothelial function . RESULTS There were 34 patients treated with sildenafil and 19 on placebo who completed the study . The general characteristics of both groups were comparable . Mean + /- SEM baseline penile blood flow was 6.2 + /- 1.4 and 7.0 + /- 0.6 ml/dl per minute for the placebo and sildenafil groups , respectively ( p = 0.54 ) . Baseline forearm blood flow was similar in both groups . At baseline penile AUC was 420 + /- 50 and 520 + /- 50 ( p = 0.18 ) , and in the forearm it was 445 + /- 40 and 410 + /- 40 ( p = 0.45 ) for the placebo and sildenafil groups , respectively . After 4 weeks on the assigned drug penile blood flow increased to 11.2 + /- 2 ml/dl per minute in the sildenafil group ( p = 0.02 ) and remained unchanged in the placebo group . After 4 weeks penile AUC increased to 720 + /- 65 in the sildenafil group ( 0.04 ) and remained unchanged in the placebo group . Placebo and sildenafil did not affect the indices of forearm endothelial function . CONCLUSIONS Daily sildenafil significantly improves penile blood flow and penile endothelial function indices without causing any relevant systemic effects 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 It is well recognized that sexual stimulation leading to penile erection is controlled by different areas in the brain . Animal erection studies have shown that apomorphine ( a D2>D1 dopamine receptors nonselective agonist ) seems to act on neurons located within the paraventricular nucleus and the medial preoptic area of the hypothalamus . Yet , only recently , was a central ly acting agent , apomorphine sublingual , approved for the treatment of erectile dysfunction . The present functional magnetic resonance imaging placebo-controlled study presents the first in vivo demonstration of the apomorphine-induced  modulation of cortical and subcortical brain structures in patients with psychogenic erectile dysfunction .  Noteworthy , patients in comparison with potent controls , showed an increased activity in frontal limbic areas that was downregulated by apomorphine . This suggests that psychogenic impotence may be associated with previously unrecognized underlying functional abnormalities of the brain BACKGROUND Tadalafil is being investigated for the treatment of lower urinary tract symptoms ( LUTS ) suggestive of benign prostatic hyperplasia ( BPH-LUTS ) . OBJECTIVE To assess efficacy , including onset , and safety of tadalafil on BPH-LUTS and the subject 's and clinician 's perception of changes in urinary symptoms . DESIGN , SETTING , AND PARTICIPANTS This r and omized , double-blind , placebo-controlled , 12-week trial enrolled men ≥45 yr of age with BPH-LUTS for > 6 mo , International Prostate Symptom Score ( IPSS ) ≥13 , and maximum urine flow rate ( Q(max ) ) ≥4 to ≤15 ml/s . INTERVENTION Tadalafil 5 mg ( n=161  ) or placebo ( n=164 ) , once daily . MEASUREMENTS Analysis of covariance ( ANCOVA ) modeling evaluated change from baseline in continuous efficacy variables . Categoric efficacy variables were analyzed with the Cochran-Mantel-Haenszel test , and between-group differences in treatment-emergent adverse events ( TEAEs ) were assessed using the Fisher exact test . RESULTS AND LIMITATION : Tadalafil significantly improved IPSS results , from baseline to endpoint , compared to placebo ( -5.6 vs -3.6 ; p=0.004 ) . Reduction in IPSS results was apparent after 1 wk and significant after 4 wk ( tadalafil -5.3 vs placebo -3.5 ; p=0.003 ) . The BPH Impact Index ( BII ) was not assessed at week 1 ; however , BII improvement was apparent at 4 wk ( tadalafil -1.8 vs placebo -1.2 ; p=0.029 ) and continued at 12 wk ( tadalafil -1.8 vs placebo -1.3 ; p=0.057 ) . Tadalafil  significantly improved the International Index of Erectile Function-Erectile Function score in sexually active men with erectile dysfunction ( ED ; 6.7 vs 2.0 ; p<0.001 ) at 12 wk ( not assessed at week 1 ) . Few subjects reported one TEAE or more ( p=0.44 ) . For tadalafil , the most common TEAEs were headache ( 3.7 % ) and back pain ( 3.1 % ) . Tadalafil did not significantly improve Q(max ) or reduce postvoid residual volume . CONCLUSIONS Tadalafil 5 mg once daily for 12 wk result ed in a clinical ly meaningful reduction in total IPSS results as early as 1 wk and achieved statistical significance at 4 wk in men with BPH-LUTS . The adverse event profile was consistent with that previously reported in men with ED . TRIAL REGISTRATION This clinical trial is registered on the clinical trials.gov website ( http://www . clinical trials.gov ) . The registration number is NCT00827242 A multi-center , r and omized , double-blind , placebo-controlled study was conducted with 158 subjects who were r and omized to placebo or avanafil 50 , 100 , and 200 mg on dem and for 8 weeks to evaluate the safety , tolerability , and efficacy of avanafil in the treatment of erectile dysfunction ( ED ) in Korean men . The primary outcome was the erectile function ( EF ) domain score of the International Index of Erectile Function ( IIEF ) question naire . Secondary outcomes included changes in the scores of IIEF questions 3 and 4 ( IIEF Q3 , Q4 ) from baseline , changes in all domain scores in the IIEF from baseline , Sexual Encounter Profile questions 2–5 ( SEP2–5 ) , the Global Efficacy Assessment Question ( GEAQ ) , and the number of subjects whose EF domain score at the 8th week visit was ≥ 26 . After 8 weeks of treatment , the dose groups except avanafil 50 mg scored significantly higher on the IIEF-EF domain from baseline than the placebo group . The changes from baseline in the avanafil group in IIEF Q3 ( all doses ) and Q4 ( 200 mg alone ) were higher than the placebo group . The differences between avanafil and placebo groups were significant in SEP2 ( 100 and 200 mg ) and SEP3–5 ( 200 mg ) . The differences in the GEAQ “ Yes ” response were also significant in the avanafil 100 and 200 mg groups . Regarding the ratio of normal EF at the end of the study , avanafil 200 mg differed significantly from the placebo . Most treatment-associated adverse events were mild and resolved spontaneously . This is a clinical trial study and was registered at www . Clinical Trials.gov ( Identifier : NCT02477436 ) INTRODUCTION Udenafil is a potent selective phosphodiesterase type 5 ( PDE5 ) inhibitor newly developed for the treatment of erectile dysfunction ( ED ) . AIM This study was performed to evaluate the efficacy and safety of udenafil therapy in patients with ED . METHODS In this multicenter , double-blind , placebo-controlled , fixed-dose , parallel-group phase III trial , 167 patients with ED of diverse origin and severity were r and omized to take placebo or udenafil at fixed doses of 100 or 200 mg as needed for 12 weeks . MAIN OUTCOME MEASURES Primary efficacy variable was change from baseline in erectile function ( EF ) domain scores of the International Index of Erectile Dysfunction ( IIEF ) question naire . Secondary efficacy variables include change from baseline in scores on the IIEF Questions 3 and 4 ( IIEF Q3 and Q4 ) , change from baseline in all domain scores of the IIEF , patients ' responses to questions 2 and 3 of the Sexual Encounter Profile ( SEP2 and SEP3 ) , and patients ' responses to the Global Assessment Question ( GAQ ) . Any adverse events were also recorded during the trial . RESULTS After 12 weeks of treatment , the patients treated with udenafil showed significantly greater change from baseline in the IIEF-EF domain score compared with placebo ( placebo , 0.20 ; 100-mg udenafil , 7.52 ; and 200-mg udenafil , 9.93 , respectively ) ( P < 0.0001 ) . Compared with placebo , udenafil significantly enhanced the rates of successful penetration ( SEP Q2 ) and maintenance of erection ( SEP Q3 ) ( P < 0.0001 ) . Furthermore , significantly greater proportions of udenafil treatment groups responded positively to the GAQ compared with the placebo group ( GAQ : placebo , 25.9 % ; 100-mg udenafil , 81.5 % ; and 200-mg udenafil , 88.5 % , respectively ) ( P < 0.0001 ) . Treatment-related adverse events were generally mild to moderate with facial flushing and headache being the most common . CONCLUSIONS Udenafil is an effective and well-tolerated therapy for ED of broad-spectrum etiology and severity PURPOSE We evaluated the improvement in  erectile dysfunction and lower urinary tract symptoms  as well as the safety of once daily administration of 50 mg mirodenafil in men with erectile dysfunction . MATERIAL S AND METHODS A total of 226 patients visited for treatment of erectile dysfunction and were recruited for the study . Of these men 180 met the study inclusion criteria after completing a 2-week screening period ( visit [V]1 ) . The patients were r and omly allocated into 2 groups . Group 1 ( 90 patients ) received 50 mg mirodenafil once daily and group 2 ( 90 patients ) received a placebo daily . Blood pressure , heart rate , IIEF-5 ( 5-item version of the International Index of Erectile Function ) , and SEP ( Sexual Encounter Profile ) questions 2 and 3 were assessed at 4 ( V2 ) , 8 ( V3 ) and 12 weeks after the start of treatment ( V4 ) . I-PSS ( International Prostate Symptom Score ) , maximal flow rate and post-void residual volume were also assessed for the evaluation of lower urinary tract symptoms . RESULTS Of the 180 patients 71 in group 1 and 63 in group 2 completed the 12-week clin 
    Output:
    
Conclusions and Relevance In this study , placebo was associated with improvement of ED , especially among men with ED-related posttraumatic stress disorder .
No difference was found between placebo and PDE5I among men treated for ED after prostate surgery