title: Urodynamic effects of the combination of tamsulosin and daily tadalafil in men with lower urinary tract symptoms secondary to benign prostatic hyperplasia: a randomized, placebo-controlled clinical trial Combined tadalafil and α-blocker therapy for benign prostatic hyperplasia in patients with erectile dysfunction: a multicenter, prospective study. Cardiovascular safety in refractory incontinent patients with overactive bladder receiving add‐on mirabegron therapy to solifenacin (BESIDE) Long-term effects of doxazosin, finasteride and combination therapy on quality of life in men with benign prostatic hyperplasia. The effects of combination therapy with dutasteride and tamsulosin on clinical outcomes in men with symptomatic benign prostatic hyperplasia: 4-year results from the CombAT study. Assessing Preference-Based Outcome Measures for Overactive Bladder: An Evaluation of Patient-Reported Outcome Data from the BESIDE Clinical Trial Effect of combined treatment with phenylpropanolamine and estriol, compared with estriol treatment alone, in postmenopausal women with stress urinary incontinence. Combination treatment with mirabegron and solifenacin in patients with overactive bladder: exploratory responder analyses of efficacy and evaluation of patient-reported outcomes from a randomized, double-blind, factorial, dose-ranging, Phase II study (SYMPHONY) Efficacy and safety of combinations of mirabegron and solifenacin compared with monotherapy and placebo in patients with overactive bladder (SYNERGY study) Combination therapy with solifenacin and tamsulosin oral controlled absorption system in a single tablet for lower urinary tract symptoms in men: efficacy and safety results from the randomised controlled NEPTUNE trial. Solifenacin plus tamsulosin combination treatment in men with lower urinary tract symptoms and bladder outlet obstruction: a randomized controlled trial. Is there a synergistic effect of topical oestrogens when administered with antimuscarinics in the treatment of symptomatic detrusor overactivity? Effects of estrogen with and without progestin on urinary incontinence. Combination treatment with mirabegron and solifenacin in patients with overactive bladder: efficacy and safety results from a randomised, double-blind, dose-ranging, phase 2 study (Symphony). Effects of initial combined tamsulosin and solifenacin therapy for overactive bladder and bladder outlet obstruction secondary to benign prostatic hyperplasia: a prospective, randomized, multicenter study Comparative Effectiveness of Combined Low- and Standard-Dose Trospium and Solifenacin for Moderate Overactive Bladder Symptoms in Elderly Men and Women Does sildenafil enhance the effect of tamsulosin in relieving acute urinary retention? Safety and efficacy of mirabegron as ‘add‐on’ therapy in patients with overactive bladder treated with solifenacin: a post‐marketing, open‐label study in Japan (MILAI study) A comparative randomized prospective study to evaluate efficacy and safety of combination of tamsulosin and tadalafil vs. tamsulosin or tadalafil alone in patients with lower urinary tract symptoms due to benign prostatic hyperplasia. Randomized Controlled Trial to Assess the Efficacy of the Combination Therapy of Alfuzosin and Tadalafil in Patients with Lower Urinary Tract Symptoms Due to Benign Prostatic Hyperplasia. Effect of Improvement in Lower Urinary Tract Symptoms on Sexual Function in Men: Tamsulosin Monotherapy vs. Combination Therapy of Tamsulosin and Solifenacin Treating Overactive Bladder in Older Patients with a Combination of Mirabegron and Solifenacin: A Prespecified Analysis from the BESIDE Study. Clinical efficacy and safety of imidafenacin as add-on treatment for persistent overactive bladder symptoms despite α-blocker treatment in patients with BPH: the ADDITION study. Investigation of the clinical efficacy and safety of pregabalin alone or combined with tolterodine in female subjects with idiopathic overactive bladder. Efficacy of alfuzosin and sildenafil combination in male patients with lower urinary tract symptoms Treatment satisfaction and clinically meaningful symptom improvement in men with lower urinary tract symptoms and prostatic enlargement secondary to benign prostatic hyperplasia: Secondary results from a 6-month, randomized, double-blind study comparing finasteride plus tadalafil with finasteride pl Comparison of Tamsulosin Plus Serenoa Repens with Tamsulosin in the Treatment of Benign Prostatic Hyperplasia in Korean Men: 1-Year Randomized Open Label Study The impact of adding low-dose oral desmopressin therapy to tamsulosin therapy for treatment of nocturia owing to benign prostatic hyperplasia Study design of the Medical Therapy of Prostatic Symptoms (MTOPS) trial. Effects of oral estrogen and progestin on the lower urinary tract among female nursing home residents. Lower Urinary Tract Symptoms Associated with Benign Prostatic Hyperplasia: Combined Treatment with Fesoterodine Fumarate Extended-Release and Tamsulosin - A Prospective Study Serenoa repens, lycopene and selenium versus tamsulosin for the treatment of LUTS/BPH. An Italian multicenter double-blinded randomized study between single or combination therapy (PROCOMB trial). Efficacy and Safety of Mirabegron Add-on Therapy to Solifenacin in Incontinent Overactive Bladder Patients with an Inadequate Response to Initial 4-Week Solifenacin Monotherapy: A Randomised Double-blind Multicentre Phase 3B Study (BESIDE). Population-based survey of urinary incontinence, overactive bladder, and other lower urinary tract symptoms in five countries: results of the EPIC study. Patient-reported outcomes from SYNERGY, a randomized, double-blind, multicenter study evaluating combinations of mirabegron and solifenacin compared with monotherapy and placebo in OAB patients. Add-on anticholinergic therapy for residual nocturia in patients with lower urinary tract symptoms receiving α1-blocker treatment: a multi-centre, prospective, randomised study Efficacy and safety of propiverine and terazosine combination for one year in male patients with luts and detrusor overactivity. Update on AUA guideline on the management of benign prostatic hyperplasia. Estrogens and phenylpropanolamine in combination for stress urinary incontinence in postmenopausal women. A randomized controlled study of the efficacy of tamsulosin monotherapy and its combination with mirabegron for overactive bladder induced by benign prostatic obstruction. Medical therapy versus transurethral resection of the prostate (TURP) for the treatment of symptomatic benign prostatic enlargement (BPE): a cost minimisation analysis Progression of lower urinary tract symptoms after discontinuation of 1 medication from 2-year combined alpha-blocker and 5-alpha-reductase inhibitor therapy for benign prostatic hyperplasia in men--a randomized multicenter study. Solifenacin or mirabegron could improve persistent overactive bladder symptoms after dutasteride treatment in patients with benign prostatic hyperplasia. A randomized, placebo-controlled study to assess safety and efficacy of vardenafil 10 mg and tamsulosin 0.4 mg vs. tamsulosin 0.4 mg alone in the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia. Efficacy and safety of the coadministration of tadalafil once daily with finasteride for 6 months in men with lower urinary tract symptoms and prostatic enlargement secondary to benign prostatic hyperplasia. Long-term safety and efficacy of single-tablet combinations of solifenacin and tamsulosin oral controlled absorption system in men with storage and voiding lower urinary tract symptoms: results from the NEPTUNE Study and NEPTUNE II open-label extension.
abstract: Objectives To evaluate the effect of association of tamsulosin/tadalafil taken daily compared with tamsulosin/placebo in the lower urinary tract with urodynamic study ( UDS ) . Methods All patients underwent baseline UDS before r and omization to tamsulosin 0.4 mg/tadalafil 5 mg ( Group 1 ; n = 20 ) or tamsulosin 0.4 mg/placebo ( Group 2 ; n = 20 ) once daily for 30 days . End-of- study UDS were performed on completion of the treatment period . The primary end point was to demonstrate changes in urodynamic variables in the voiding phase , detrusor pressure at maximum flow ( PdetQmax ) , and maximum flow rate ( Qmax ) , from baseline to week four . Results The primary outcome measure of this clinical trial , PdetQmax , showed a significant reduction in tamsulosin/tadalafil group ( 13 ± 17.0 ) compared to tamsulosin/placebo ( −1.2 ± 14.35 ) group ( P = 0.03 ) . Qmax increased in both groups , tamsulosin/tadalafil ( 1.0 ± 2.4 ) and tamsulosin/placebo ( 1.4 ± 2.4 ) , but the difference was not significant between treatment groups ( P = 0.65 ) . Total IPSS , storage , and voiding sub-score improved significantly in tamsulosin/tadalafil compared with tamsulosin/placebo group . Conclusions The association of tamsulosin/tadalafil reduces detrusor pressure at maximum flow without changing the maximum flow rate during micturition and significantly improves lower urinary tract symptoms compared with the isolated use of tamsulosin This prospect i ve study evaluated the safety of tadalafil 5 mg taken once a day in terms of hypotensive side effects and whether it improves lower urinary tract symptoms ( LUTS ) and restores sexual function in patients with erectile dysfunction who are receiving concomitant α-blocker ( AB ) therapy for benign prostatic hyperplasia ( BPH ) . A total of 158 LUTS/BPH patients receiving AB therapy for ≥3 months were given tadalafil 5 mg once a day . Before treatment with tadalafil ( V1 ) , and 4 weeks ( V2 ) and 12 weeks ( V3 ) after starting  tadalafil , blood pressure , heart rate , International Prostate Symptom Score ( IPSS ) , maximal urine flow rate ( Qmax ) , postvoiding residual urine volume , and International Index of Erectile Function ( IIEF-5 ) score were measured . Of the 158 LUTS/BPH patients , a total of 119 completed the trial . Blood pressure ( systolic and diastolic ) and heart rate did not change . IPSS and IIEF-5 scores improved significantly , but Qmax and postvoiding residual urine volume did not ; however , in the 39 men with a low baseline Qmax ( ≤10 mL/s ) , Qmax rose significantly from 7.97 ± 1.44 mL/s ( baseline ) to 8.91 ± 1.60 mL/s ( V3 ; P = .012 ) . The remaining patients ( baseline Qmax > 10 mL/s ) did not change . At V2 and V3 , adverse side effects were observed in 10 men ( 7.30 % ) and 6 men ( 5.04 % ) , respectively . Facial flushing was the most common adverse side effect ( 6 men at V2 and 4 men at V3 ) , followed by headache ( 2 men each at V2 and V3 ) and dizziness ( 2 men at V2 ) . Two patients dropped out of the study because of adverse side effects . In conclusion , tadalafil 5 mg once a day in combination with AB appeared to have few adverse effects on hypotensive events and can improve LUTS and restore sexual function Summary Aims / objectives : In the BESIDE study , combination therapy ( antimuscarinic [ solifenacin ] and β3‐adrenoceptor agonist [ mirabegron ] ) improved efficacy over solifenacin monotherapy without exacerbating anticholinergic side effects in overactive bladder ( OAB ) patients ; however , a potential synergistic effect on the cardiovascular ( CV ) system requires investigation . Methods OAB patients remaining incontinent despite daily solifenacin 5 mg during 4‐week single‐blind run‐in , were r and omised 1:1:1 to double‐blind daily combination ( solifenacin 5 mg/mirabegron 25 mg , increasing to 50 mg after week 4 ) , solifenacin 5 or 10 mg for 12 weeks . CV safety assessment s included frequency of CV‐related treatment‐emergent adverse events ( TEAEs ) , change from baseline in vital signs ( systolic blood pressure [ SBP ] , diastolic blood pressure [ DBP ] , pulse rate ) and electrocardiogram ( ECG ) parameters . Results The frequency of hypertension , tachycardia and ECG QT prolongation , respectively , was low and comparable across combination ( 1.1 % , 0.3 % , 0.1 % ) , solifenacin 5 mg ( 0.7 % , 0.1 % , 0.1 % ) , and solifenacin 10 mg groups ( 0.8 % , 0 % , 0.1 % ) . Adjusted mean ( SE ) change from baseline to end of treatment ( EoT ) in SBP , DBP , and pulse rate with combination ( 0.07 mm Hg [ 0.38 ] , −0.35 mm Hg [ 0.26 ] , 0.47 bpm [ 0.28 ] ) , solifenacin 5 mg ( −0.93 mm Hg [ 0.38 ] , −0.45 mm Hg [ 0.26 ] , 0.43 bpm [ 0.28 ] ) and solifenacin 10 mg ( −1.28 mm Hg [ 0.38 ] , −0.48 mm Hg [ 0.26 ] , 0.27 bpm [ 0.28 ] ) was generally comparable , with the exception of a mean treatment difference of ~1 mm Hg in SBP between combination and solifenacin monotherapy ; SBP was unchanged with combination and decreased with solifenacin monotherapy . Mean changes from baseline to EoT in ECG parameters were generally similar across treatment groups , except for QT interval corrected using Fridericia 's formula , which was higher with solifenacin 10 mg ( 3.30 mseconds ) vs. combination ( 0.49 mseconds ) and solifenacin 5 mg ( 0.77 mseconds ) . Conclusion The comparable frequency of CV‐related TEAEs , changes in vital signs and ECG parameters indicates no synergistic effect on CV safety outcomes when mirabegron and solifenacin are combined PURPOSE We examined the effects of doxazosin , finasteride and combination therapy among men with benign prostatic hyperplasia on quality of life assessed with MOS-SF-36 ( Medical Outcomes Study Short-Form 36 ) and 2 disease specific instruments ( BII , benign prostatic hyperplasia Impact Index and I-PSS-QoL , International Prostate Symptom Score-QoL ) during 4 years . MATERIAL S AND METHODS The MTOPS ( Medical Therapy of Prostatic Symptoms ) study was a multicenter , r and omized , double-blind , placebo controlled clinical trial with a primary outcome of time to benign prostatic hyperplasia progression . Change in quality of life was a secondary outcome . A total of 2,872 men enrolled in the MTOPS study who had 3 baseline quality of life measures and at least 1 followup measure by any of the quality of life instruments were analyzed . RESULTS Compared with men assigned to placebo , men assigned to doxazosin and combination experienced a statistically significant improvement in the BII at year 4 . Men assigned to each of the drug groups also experienced a significant improvement in the I-PSS-QoL compared with those assigned to placebo . Considering longitudinal changes during 4 years , a significant improvement in BII and I-PSS-QoL scores was observed in men assigned to the drug groups compared with those assigned to placebo . However , there were no significant differences for the MOS-SF-36 subscales and summary scores when drug groups were compared with the placebo group . CONCLUSIONS The quality of life of men treated with doxazosin , finasteride , and the drugs combined generally improved when assessed with the BII and the I-PSS-QoL compared with those treated with placebo .  Quality of life did not show improvement when measured by the MOS-SF-36 BACKGROUND Combination therapy with dutasteride and tamsulosin provides significantly greater benefit than either monotherapy for various patient-reported outcomes in men with moderate-to-severe lower urinary tract symptoms ( LUTS ) due to benign prostatic hyperplasia ( BPH ) and prostatic enlargement . OBJECTIVE To investigate whether combination therapy is more effective than either monotherapy in reducing the relative risk for acute urinary retention ( AUR ) , BPH-related surgery , and BPH clinical progression over 4 yr in men at increased risk of progression . DESIGN , SETTING , AND PARTICIPANTS The Combination of Avodart and Tamsulosin ( CombAT ) study was a 4-yr , multicenter , r and omised , double-blind , parallel-group study in 4844 men > or = 50 yr of age with a clinical diagnosis of BPH , International Prostate Symptom Score > or = 12 , prostate volume > or = 30 cm(3 ) , prostate-specific antigen 1.5 - 10 ng/ml , and maximum urinary flow rate ( Q(max ) ) > 5 and < or = 15 ml/s with minimum voided volume > or = 125 ml . INTERVENTION Oral daily tamsulosin , 0.4 mg ; dutasteride , 0.5 mg ; or a combination of both . MEASUREMENTS The 4-yr primary end point was time to first AUR or BPH-related surgery . Secondary end points included BPH clinical progression , symptoms , Q(max ) , prostate volume , safety , and tolerability . RESULTS AND LIMITATIONS Combination therapy was significantly superior to tamsulosin monotherapy but not dutasteride monotherapy at reducing the relative risk of AUR or BPH-related surgery . Combination therapy was also significantly superior to both monotherapies at reducing the relative risk of BPH clinical progression . Combination therapy provided significantly greater symptom benefit than either monotherapy at 4 yr . Safety and tolerability of combination therapy was consistent with previous experience with dutasteride and tamsulosin monotherapies , with the exception of an imbalance in the composite term of cardiac failure among the three study arms . The lack of placebo control is a study limitation . CONCLUSIONS The 4-yr CombAT data provide support for the long-term use of dutasteride and tamsulosin combination therapy in men with moderate-to-severe LUTS due to BPH and prostatic enlargement . CLINICAL TRIALS.GOV IDENTIFIER : NCT00090103 ( http://www . clinical trials.gov/ct2/show/NCT00090103 ) Objectives The aim of this study was to compare outcomes using two preference-based measures of health status ( EQ-5D-5L and OAB-5D ) in patients with overactive bladder ( OAB ) treated with solifenacin plus mirabegron or solifenacin monotherapy in the BESIDE trial . Methods Patients with OAB who remained incontinent after 4 weeks ’ treatment with solifenacin 5 mg were r and omized 1:1:1 to combination treatment ( solifenacin 5 mg plus mirabegron [ 25 mg for the first 4 weeks/50 mg for the last 8 weeks ] ) , solifenacin 5 mg , or solifenacin 10 mg . EQ-5D-5L and OAB-q were administered at baseline , weeks 4 , 8 , 12 , and end of treatment ( EoT ) . OAB-5D scores were derived from OAB-q results . Responder analysis was carried out using several definitions of minimally important difference . Results A total of 2054 patients received one or more doses of study treatment ( combination , n = 694 ; solifenacin 5 mg , n = 684 ; solifenacin 10 mg , n = 676 ) . EQ-5D-5L Index mean score changes ( from baseline to EoT ) were greater with combination ( 0.059 ) than with solifenacin 5 mg ( 0.040 ) and 10 mg ( 0.044 ) monotherapy , but the differences were not statistically significant . A significantly greater improvement was observed for combination on OAB-5D ( 0.107 vs 0.085 for 5 mg , and 0.087 for 10 mg ; p ≤ 0.01 ) . The dimensions most improved overall were anxiety/depression , pain/discomfort , and usual activities on EQ-5D-5L , and urge , urine loss , and coping on OAB-5D . The proportion of responders was significantly greater with combination compared with monotherapy using OAB-5D only . Conclusions Improvements were observed in all study arms on both the EQ-5D-5L and OAB-5D , although only the OAB-5D showed a statistically significant benefit for combination versus solifenacin monotherapy . Combining generic and condition-specific preference-based health status measures allowed for assessment of dimensions that were particularly relevant to this patient population , while permitting comparison with outcomes from other studies , treatments , and population s via EQ-5D Twenty-nine postmenopausal women with slight to severe stress urinary incontinence and estrogen deficiency symptoms in the urogenital tract were treated with estriol , p.o . 4 mg once daily , and either phenylpropanolamine ( PPA ) , p.o . 50 mg twice daily , or placebo for periods of 6 weeks according to a r and omized double-blind crossover schedule . At urodynamic recordings the maximum urethral closure pressure increased by 22 % with combined treatment ( p less than 0.001 ) and an additional effect of PPA to estriol was shown ( p = 0.022 ) . The pressure transmission ratio increased , by about 15 % , with both treatments ( p less than 0.07 ) . The number of leakage episodes was reduced by 28 % with combined treatment ( p = 0.007 ) , but not with estriol alone ( p = 0.08 ) . Both combined treatment and estriol alone reduced significantly ( p less than 0.01 ) the urinary incontinence complaints . Twelve women ( 43 % ) preferred combined treatment , while 7 ( 25 % ) preferred estriol alone . In women with initially slight to very severe urine loss , combined treatment reduced also ( p = 0.02 ) the amount of urine loss , measured at a st and ardized physical stress test . Signs of estrogen deficiency in vulva , vagina and urethra were reduced , 75 % ( p less than 0.001 ) or 65 % ( p = 0.001 ) with estriol given in combination with PPA or alone . Maturation index of both urethral and vaginal epithelium displayed significant changes . It is concluded that the combined treatment , PPA + estriol , by affecting both the muscular and mucosal factor of the urethra , is more effective than estriol alone for treatment of female stress urinary incontinence in the postmenopausal ages Purpose This large dose-ranging study explored the benefits of different combinations of mirabegron and solifenacin on health-related quality of life ( HRQoL ) , based on patient-reported outcomes ( PROs ) , and patients ( ‘ responders ’ ) achieving clinical ly meaningful improvements in efficacy and HRQoL. Methods SYMPHONY ( NCT01340027 ) was a Phase II , placebo- and monotherapy-controlled , dose-ranging , 12-week trial . Adult patients with overactive bladder ( OAB ) for ≥3 months were r and omized to 1 of 12 groups : 6  combination ( solifenacin 2.5/5/10 mg + mirabegron 25/50 mg ) , 5 monotherapy ( solifenacin 2.5/5/10 mg , or mirabegron 25/50 mg ) , or placebo . Change from baseline to end of treatment was assessed , versus placebo and solifenacin 5 mg in : PROs ( OAB-q [ Symptom Bother/total HRQoL ] and Patient Perception of Bladder Condition score ) , and responders achieving minimally important differences ( MIDs ) in PROs and predetermined clinical ly meaningful improvements in efficacy ( e.g. < 8 micturitions/24 h ) . Changes in PROs and responders were analysed using an ANCOVA model and logistic regression , respectively . Results The Full Analysis Set included 1278 patients . Combination therapy of solifenacin 5/10 mg + mirabegron 25/50 mg significantly improved PROs  versus solifenacin 5 mg and placebo , and significantly more responders achieved MIDs in PROs and efficacy . Micturition frequency normalization was approximately twofold greater with 10 + 25 mg ( OR 2.06 [ 95 % CI 1.11 , 3.84 ; p = 0.023 ] ) and 5 + 50 mg ( OR 1.91 [ 95 % CI 1.14 , 3.21 ; p = 0.015 ] ) versus solifenacin 5 mg . Conclusion Combining mirabegron 25/50 mg and solifenacin 5/10 mg improves objective and subjective efficacy outcomes compared with placebo or solifenacin 5 mg To evaluate the potential of solifenacin 5 mg combined with mirabegron 25 or 50 mg to deliver superior efficacy compared with monotherapy , with acceptable tolerability , in the general overactive bladder ( OAB ) population with urinary incontinence ( UI ) BACKGROUND Storage symptoms are particularly bothersome in men with lower urinary tract symptoms ( LUTS ) but may not be adequately treated by α-blocker monotherapy . OBJECTIVE To assess the efficacy and safety of a fixed-dose combination ( FDC ) of solifenacin and an oral controlled absorption system ( OCAS ) formulation of tamsulosin compared with placebo and compared with tamsulosin OCAS ( TOCAS ) monotherapy in men with moderate to severe storage symptoms and voiding symptoms . DESIGN , SETTING , AND PARTICIPANTS A double-blind 12-wk phase 3 study in 1334 men with storage and voiding LUTS : total International Prostate Symptom Score ( IPSS ) ≥ 13 , maximum urinary flow rate ( Qmax ) 4.0 - 12.0 ml/s , two or more urgency episodes per 24 h of Patient Perception of Intensity of Urgency Scale grade 3 or 4 , and eight or more micturitions per 24h . INTERVENTION Patients were r and omised to placebo , TOCAS 0.4 mg , FDC solifenacin 6 mg plus TOCAS 0.4 mg , or FDC solifenacin 9 mg plus TOCAS 0.4 mg . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Primary efficacy end points were ( 1 ) total IPSS and ( 2 ) Total Urgency and Frequency Score ( TUFS ) . An FDC met the success criteria if it demonstrated superiority compared with placebo and noninferiority compared with TOCAS for total IPSS , as well as superiority compared with TOCAS for TUFS . RESULTS AND LIMITATIONS Reductions in total IPSS and TUFS were observed with both solifenacin 6 mg plus TOCAS ( -7.0 and -8.1 , respectively ) and solifenacin 9 mg plus TOCAS ( -6.5 and -7.6 , respectively ) compared with TOCAS ( -6.2 and -6.7 , respectively ) and placebo ( -5.4 and -4.4 , respectively ) . Solifenacin 6 mg plus TOCAS met all prespecified success criteria for both primary end points , while solifenacin 9 mg plus TOCAS met success criteria compared with placebo but not compared with TOCAS . Both FDCs improved quality of life ( QoL ) measures and were well tolerated , with low incidences of acute urinary retention . CONCLUSIONS The FDC of solifenacin 6 mg plus TOCAS significantly improved storage and voiding symptoms , as well as QoL parameters , compared with placebo . This FDC also improved storage symptoms and QoL compared with TOCAS alone in men with moderate to severe storage symptoms and voiding symptoms  , and it was well tolerated BACKGROUND Alpha blockers are prescribed to manage lower urinary tract symptoms ( LUTS ) associated with benign prostatic hyperplasia ( BPH ) .  Antimuscarinics are prescribed to treat overactive bladder ( OAB ) . OBJECTIVE To investigate the safety of a combination of solifenacin ( SOLI ) and tamsulosin oral controlled absorption system ( TOCAS ) in men with LUTS and bladder outlet obstruction ( BOO ) . DESIGN , SETTING , AND PARTICIPANTS R and omized , double-blind , parallel-group , placebo-controlled study in men aged > 45 yr with LUTS and BOO for ≥3 mo , total International Prostate Symptom Score ( IPSS ) ≥8 , BOO index ≥20 , maximum urinary flow rate ( Q(max ) ) ≤12 ml/s , and voided volume ≥120 ml . INTERVENTIONS Once-daily coadministration of TOCAS 0.4 mg plus SOLI 6 mg , TOCAS 0.4 mg plus SOLI 9 mg , or placebo for 12 wk . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Primary ( safety ) measurements : Q(max ) and detrusor pressure at Q(max ) ( P(det)Q(max ) ) . Other safety assessment s included postvoid residual ( PVR ) volume . Secondary end points included bladder contractile index ( BCI ) score and percent bladder voiding efficiency ( BVE ) . An analysis of covariance model compared each TOCAS plus SOLI combination with placebo . RESULTS AND LIMITATIONS Both active treatment groups were noninferior to placebo at end of treatment ( EOT ) for P(det)Q(max ) and Q(max ) . Mean change from baseline PVR was significantly higher at all time points for TOCAS 0.4 mg plus SOLI 6 mg , and at weeks 2 , 12 , and EOT for TOCAS 0.4 mg plus SOLI 9 mg versus placebo . Both treatment groups were similar to  placebo for BCI and BVE . Urinary retention was seen in only one patient receiving TOCAS 0.4 mg plus SOLI 6 mg . Limitations of the study were that prostate size and prostate-specific antigen level were not measured . CONCLUSIONS TOCAS 0.4 mg plus SOLI 6 mg or 9 mg was noninferior to placebo at EOT for P(det)Q(max ) and Q(max ) in men with LUTS and BOO , and there was no clinical or statistical evidence of increased risk of urinary retention BACKGROUND No authors have investigated whether the administration of local oestrogens in addition to antimuscarinics could have a synergistic effect in the therapy of overactive bladder ( OAB ) . OBJECTIVES To compare the efficacy of antimuscarinics alone versus antimuscarinics in combination with local oestrogens for OAB ; to verify whether risk factors for lower antimuscarinic efficacy can be overcome by the concomitant use of local oestrogens . DESIGN , SETTING , AND PARTICIPANTS Some 229 postmenopausal women with symptomatic urodynamically proven detrusor overactivity were prospect ively enrolled at a tertiary level urogynaecology centre and divided into two groups . INTERVENTION Women in group 1 ( n=129 ) were prescribed tolterodine extended release ( ER ) 4 mg once daily ; women in group 2 ( n=100 ) were prescribed both tolterodine ER 4 mg and concomitant oestriol cream application once daily . MEASUREMENTS All women underwent clinical evaluation and urodynamics in accordance with the Good Urodynamic Practice s Guidelines . After 12 wk of treatment the two groups were compared in terms of subjective efficacy for OAB symptom improvement using a three-point scale . Nonresponders were compared to the patients who improved or were cured in order to identify risk factors for resistance to therapy . RESULTS AND LIMITATIONS There was no significant difference between the two groups in terms of efficacy of therapy : 80.6 % in group 1 versus 82 % in group 2 ( p=0.86 ) . Patients with urodynamically proven detrusor overactivity ( DO ) occurring during provocative manoeuvres and patients with coital incontinence during orgasm reported a higher failure rate both in the overall study population and in group 2 . A possible limitation of the study is the nonr and omised design . CONCLUSIONS No synergistic effect of local oestrogens and antimuscarinics in the treatment of OAB was found . Antimuscarinic treatment has lower cure rates in women with symptomatic DO complaining of incontinence at orgasm or in patients with DO following provocative manoeuvres . The association of local oestrogens does not influence the role of the two mentioned risk factors CONTEXT Menopausal hormone therapy has long been credited with many benefits beyond the indications of relieving hot flashes , night sweats , and vaginal dryness , and it is often prescribed to treat urinary incontinence ( UI ) . OBJECTIVE To assess the effects of menopausal hormone therapy on the incidence and severity of symptoms of stress , urge , and mixed UI in healthy postmenopausal women . DESIGN , SETTING , AND PARTICIPANTS Women 's Health Initiative multicenter double-blind , placebo-controlled , r and omized clinical trials of menopausal hormone therapy in 27,347 postmenopausal women aged 50 to 79 years enrolled between 1993 and 1998 , for whom UI symptoms were known in 23,296 participants at baseline and 1 year . INTERVENTIONS Women were r and omized based on hysterectomy status to active treatment or placebo in either the estrogen plus progestin ( E + P ) or estrogen alone trials . The E + P hormones were 0.625 mg/d of conjugated equine estrogen plus 2.5 mg/d of medroxyprogesterone acetate ( CEE + MPA ) ; estrogen alone consisted of 0.625 mg/d of conjugated equine estrogen ( CEE ) . There were 8506 participants who received CEE + MPA ( 8102 who received placebo ) and 5310 who received  CEE alone ( 5429 who received placebo ) . MAIN OUTCOME MEASURES Incident UI at 1 year among women without UI at baseline and severity of UI at 1 year among women who had UI at baseline . RESULTS Menopausal hormone therapy increased the incidence of all types of UI at 1 year among women who were continent at baseline . The risk was highest for stress UI ( CEE + MPA : relative risk [ RR ] , 1.87 [ 95 % confidence interval { CI } , 1.61 - 2.18 ] ; CEE alone : RR , 2.15 [ 95 % CI , 1.77 - 2.62 ] ) , followed by mixed UI ( CEE + MPA : RR , 1.49 [ 95 % CI , 1.10 - 2.01 ] ; CEE alone : RR , 1.79 [ 95 % CI , 1.26 - 2.53 ] ) . The combination of CEE + MPA had no significant effect on developing urge UI ( RR , 1.15 ; 95 % CI , 0.99 - 1.34 ) , but CEE alone increased the risk ( RR , 1.32 ; 95 % CI , 1.10 - 1.58 ) . Among women experiencing UI at baseline , frequency worsened in both trials ( CEE + MPA : RR , 1.38 [ 95 % CI , 1.28 - 1.49 ] ; CEE alone : RR , 1.47 [ 95 % CI , 1.35 - 1.61 ] ) . Amount of UI worsened at 1 year in both trials ( CEE + MPA : RR , 1.20 [ 95 % CI , 1.06 - 1.36 ] ; CEE alone : RR , 1.59 [ 95 % CI , 1.39 - 1.82 ] ) . Women receiving menopausal hormone therapy  were more likely to report that UI limited their daily activities ( CEE + MPA : RR , 1.18 [ 95 % CI , 1.06 - 1.32 ] ; CEE alone : RR , 1.29 [ 95 % CI , 1.15 - 1.45 ] ) and bothered or disturbed them ( CEE + MPA : RR , 1.22 [ 95 % CI , 1.13 - 1.32 ] ; CEE alone : RR , 1.50 [ 95 % CI , 1.37 - 1.65 ] ) at 1 year . CONCLUSIONS Conjugated equine estrogen alone and CEE + MPA increased the risk of UI  among continent women and worsened the characteristics of UI among symptomatic women after 1 year . Conjugated equine estrogen with or without progestin should not be prescribed for the prevention or relief of UI BACKGROUND Combining the β3-adrenoceptor agonist mirabegron and the antimuscarinic ( AM ) agent solifenacin may improve efficacy in the treatment of overactive bladder ( OAB ) while reducing the AM side effects . OBJECTIVE The primary objective was to evaluate the efficacy of combinations of solifenacin/mirabegron compared with solifenacin 5 mg monotherapy . The secondary objective was to explore the dose-response relationship and the safety/tolerability compared with placebo and monotherapy . DESIGN , SETTING , AND PARTICIPANTS A phase 2 , factorial design , r and omised , double-blind , parallel-group , placebo- and monotherapy-controlled trial , conducted at 141 sites in 20 European countries . Male and female patients were aged ≥18 yr with symptoms of OAB for ≥3 mo . INTERVENTION A total of 1306 patients ( 66.4 % female ) were r and omised to 12 wk of treatment in 1 of 12 groups : 6 combination groups ( solifenacin 2.5 , 5 , or 10 mg plus mirabegron 25 or 50 mg ) , 5 monotherapy groups ( solifenacin 2.5 , 5 , or 10 mg , or mirabegron 25 or 50 mg ) , or placebo . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Change from baseline to end of treatment in mean volume voided per micturition ( MVV ) ( primary end point ) and mean numbers of micturitions per 24 h , incontinence episodes per 24 h , and urgency episodes per 24 h were analysed using an analysis of covariance model . Safety assessment s included treatment-emergent adverse events ( TEAEs ) , blood pressure , pulse rate , postvoid residual ( PVR ) volume , and laboratory and electrocardiography ( ECG ) parameters . RESULTS AND LIMITATIONS Compared with solifenacin 5 mg monotherapy , all combinations with solifenacin 5 or 10 mg significantly improved MVV , with adjusted differences ranging from 18.0 ml ( 95 % confidence interval [ CI ] , 5.4 - 30.0 ) to 26.3 ml ( 95 % CI , 12.0 - 41.0 ) . Three combination groups significantly reduced micturition frequency  compared with solifenacin 5 mg , ranging from -0.80 ( 95 % CI , -1.39 to -0.22 ) to -0.98 ( 95 % CI , -1.68 to -0.27 ) . Five of six combinations significantly reduced urgency episodes compared with solifenacin 5 mg , ranging from -0.98 ( 95 % CI , -1.78 , to -0.18 ) to -1.37 ( 95 % CI , -2.03 to -0.70 ) . No dose-related trends in TEAEs , blood pressure , pulse rate , PVR volume , or laboratory or ECG parameters were observed between combination and monotherapy groups , although the incidence of constipation was slightly increased with combination therapy . CONCLUSIONS Combination therapy with solifenacin/mirabegron significantly improved MVV , micturition frequency , and urgency compared with solifenacin 5 mg monotherapy . All combinations were well tolerated , with no important additional safety findings compared with monotherapy or placebo . PATIENT SUMMARY To improve treatment of overactive bladder ( OAB ) , mirabegron/solifenacin in combination was compared with each drug alone and placebo . Combination therapy improved OAB symptoms and had similar safety and acceptability . TRIAL REGISTRATION Clinical trials.gov : NCT01340027 Purpose The purpose of the study is to evaluate the clinical efficacy of initial combined therapy of an alpha-blocker and anticholinergic agent compared with the alpha-blocker alone in patients with benign prostatic hyperplasia ( BPH ) with overactive bladder ( OAB ) . Methods Hundred and fifty-six BPH patients with International Prostate Symptom Score ( IPSS ) of over 14 ( voiding sub-score ≥8 and storage sub-score ≥6 ) were prospect ively included in Korea . Group 1 ( n = 69 ) was the patients who were treated with Tamsulosin 0.2 mg daily alone for 4 weeks and after 8 weeks they were treated with tamsulosin 0.2 mg and solifenacin 5.0 mg daily combination . Group 2 ( n = 70 ) was the patients who were treated initially with tamsulosin 0.2 mg and solifenacin 5.0 mg combination for 12 weeks . Detailed question naires were used to assess treatment satisfaction at 4th week and at 12th week of treatment in 2 groups . Results Baseline characteristics were not different between the 2 groups . In the 4th week , there was no difference between the 2 groups with regard to IPSS total score and voiding symptom score , although the IPSS storage symptom score was significantly lower in the Group 2 [ −2.0 ( 0.2 ) △ 23.8 vs. −3.0 ( 0.2 ) △ 35.7 ] ( P < 0.001 ) . In the 12th week , there was improvement in storage indices such as IPSS storage symptom score , OABSS , and urgency symptoms compared with baseline in each group ( P < 0.001 ) . No statistical differences in storage indices observed between the two groups at 12 week . Conclusions Earlier treatment with alpha-blocker and anticholinergic agent helped to improve storage symptoms and quality -of-life scores earlier for patients with lower urinary tract symptoms related to BPH and OAB symptoms Objective : To increase the safety and effectiveness of treatments for overactive bladder ( OAB ) with moderate symptoms in elderly patients . Patients and Methods : Patients were examined at the Urodynamic Department of the Regional Diagnostic Center ( Vladivostok , Russian Federation ) from September 1 , 2012 to December 31 , 2012 . The assignment of patients [ n = 177 , average age 69 . 4 years , 98 women ( 55.4 % ) and 79 men ( 44.6 % ) ] was r and om and blind in this placebo-controlled study . Patients were distributed into subgroups according to the method of treatment as follows : group А1 : n = 57 , trospium 30 mg/day + solifenacin 10 mg/day ; group А2 : n = 61 , trospium 15 mg/day + solifenacin 5 mg/day ; group А3 : n = 59 , placebo . All patients underwent a urodynamic examination in accordance with international st and ards before and 2 months after treatment . ICIQ-SF question naires recommended by the International Continence Society ( ICS ) and bladder diaries were used to evaluate the clinical results . The clinical severity of the OAB symptoms and the effectiveness of the treatment were evaluated based on the frequency of episodes of incontinence ( EI ) per day . Three or fewer EI per day were considered moderate dysfunction of the lower urinary tract . Results : Groups of elderly patients with moderate symptoms of OAB who were treated with st and ard- and low-dose trospium and solifenacin demonstrated a significant increase in the median values of reflex volume , bladder capacity , and detrusor compliance and a decrease in the frequency of urination and urinary urgencies . The frequency of EI in both of the main groups decreased by almost 2-fold in comparison to the initial data and reached the following values : group А1 : 1.27 ( -1.08 ) , p ≤ 0.05 ; group A2 : 1.49 ( -1.18 ) , p ≤ 0.05 . The correlation with the decrease in the frequency of EI in these groups was r = 0.85 ( p ≤ 0.01 ) . The percentage of patients with a significant decrease ( EI ≥1.0 ) among those treated with st and ard- and low-dose trospium and solifenacin increased synchronously , prompting us to suppose the absence of a direct correlation between medicine dose and therapeutic effect for moderate OAB symptoms . Conclusion : The combination of low-dose trospium and solifenacin provides good clinical and urodynamic effects in elderly patients with moderate symptoms of OAB . Combination of these drugs in st and ard doses for such patients is excessive OBJECTIVE To compare the safety and efficacy of combined therapy using sildenafil and tamsulosin for management of acute urinary retention ( AUR ) with tamsulosin alone in patients with benign prostate hyperplasia ( BPH ) . MATERIAL S AND METHODS 101 patients were enrolled in a r and omized  placebo-controlled  study from June 2009 to April 2012 . Patients presenting with an initial episode of spontaneous AUR underwent urethral catheterization and then prospect ively r and omized to receive tamsulosin 0.4 mg plus sildenafil 50 mg in group A and tamsulosin 0.4 mg plus placebo in group B for three days . Urethral catheter was removed three days after medical treatment and patient 's ability to void assessed at the day after catheter removal and seven days later . Patients who voided successfully were followed at least for three months . RESULTS Mean age of patients was 59.64 ± 3.84 years in group A and 60.56 ± 4.12 years in group B ( p value = 0.92 ) . Mean prostate volume and mean residual urine were comparable between both groups ( p value = 0.74 and 0.42 , respectively ) . Fifteen patients in group A ( success rate : 70 % ) and nineteen patients in group B ( success rate : 62.7 % ) had failed trial without catheter ( TWOC ) at 7th day following AUR ( p value = 0.3 ) . No significant difference was noted between both groups regarding the rate of repeated AUR at one month and three month follow-up period ( p = 0.07 and p = 0.45 , respectively ) . CONCLUSION It seems that combination therapy by using 5-phosphodiesterase inhibitor and tamsulosin has no significant advantages to improve urinary retention  versus tamsulosin alone To examine the safety and efficacy of mirabegron as ‘ add‐on ’ therapy to solifenacin in patients with overactive bladder ( OAB ) INTRODUCTION Lower urinary tract symptoms ( LUTS ) associated with benign prostatic hyperplasia ( BPH ) and erectile dysfunction are common disorders of advancing age . AIM To evaluate the efficacy and safety of tamsulosin and tadalafil in patients with LUTS due to BPH . METHODS In this prospect i ve r and omized study , 133 men complaining of LUTS due to BPH were included . Forty-five patients received tamsulosin 0.4 mg/day alone ( Group A ) , 44 patients received tadalafil 10 mg/day ( Group B ) , and combination therapy ( tamsulosin and tadalafil both ) was instituted in 44 patients ( Group C ) . After a 2-week medication free run-in period , they were evaluated for International Prostatic Symptom Score ( IPSS ) , International Index of Erectile Function score ( IIEF5 ) , quality of life ( IPSS QoL ) , maximum urinary flow rate ( Qmax ) , post-void residual urine ( PVR ) volume , and safety parameters before and at 3 months of treatment . MAIN OUTCOME MEASURES There were primary ( IPSS , IPSS QoL index , Qmax , and PVR ) and secondary ( erectile function [ EF ] domain scores from IIEF5 ) efficacy end points . Safety assessment included laboratory tests and patient 's reporting of adverse event . RESULTS A significant improvement in IPSS score was observed in all the 3 groups A , B , and C ( -50.90 % , P < 0.05 ; -33.50 % , P < 0.05 ; and -53.90 % , P < 0.05 , respectively ) . IIEF5 score increased significantly in these three groups ( + 39.28 % , P < 0.05 ; + 45.96 % , P < 0.05 ; and + 60.23 % , P < 0.05 , respectively ) . A significant increase in Qmax and decrease in PVR were also observed ( 33.99 % , P < 0.05 ; 29.78 % , P < 0.05 ; and 37.04 % , P < 0.05 ) and ( -60.90 % , P < 0.05 ; -49.45 % , P < 0.05 ; and -62.97 % , P < 0.05 , respectively ) . The QoL scores improved significantly ( -73.35 % , P < 0.05 ; -70.26 % , P < 0.05 ; and -79.65 % , P < 0.05 , respectively ) . Side effects were dyspepsia , heartburn , headache , flushing , myalgia , and backache . Adverse effect dropout was 3.7 % . No participant experienced any severe or serious adverse events . CONCLUSIONS In patients with LUTS due to BPH , tamsulosin and tadalafil alone or in combination cause a significant improvement in patients with LUTS . Their EF also improves with these medications . The improvement is better with combination therapy compared with single agent alone OBJECTIVE The purpose of our study was to evaluate the effect of alfuzosin and tadalafil as combination therapy compared with each monotherapy , in patients with lower urinary tract symptoms ( LUTS ) due to benign prostatic hyperplasia ( BPH ) . METHODS Men over the age of 50 years with LUTS secondary to BPH and an International Prostate Symptom Score ( IPSS ) 8 or higher , were r and omized to receive 10 mg alfuzosin ( n = 25 ) , 10 mg tadalafil ( n = 25 ) or the combination of both the drugs ( n = 25 ) once daily for 3 months . Symptoms were assessed at baseline , 6 weeks and 3 months . The primary endpoint was the change in IPSS from the baseline . Secondary endpoints were changes in IPSS storage and voiding subscores , peak urinary flow rate , residual urine volume , IPSS quality of life score and erectile domain score . RESULTS There were significant improvements in all IPSS scores , peak urinary flow rate and IPSS quality of life score from baseline at both 6 weeks and 3 months in all the three groups ( P < 0.003 ) . Combination therapy was better than monotherapy in improving IPSS scores and reducing post-void residual urine volume ( P < 0.005 ) . Combination therapy was similar to alfuzosin regarding improvement in maximum urine flow rate ( P = 0.22 ) , similar to tadalafil in improvement on erectile function ( P = 0.22 ) and better than each monotherapy in improving the IPSS quality of life ( P ≤ 0.015 ) . CONCLUSION Alfuzosin and tadalafil combination therapy provides greater symptomatic improvement as compared to either monotherapy in men with LUTS due to BPH Purpose To evaluate how much the improvement of lower urinary tract symptoms ( LUTS ) affects sexual function and which storage symptoms or voiding symptoms have the greatest effect on sexual function . Material s and Methods A total of 187 patients were enrolled in this study . Patients were r and omly assigned to receive either tamsulosin 0.2 mg ( group A ) or tamsulosin 0.2 mg and solifenacin 5 mg ( group B ) . At 4 weeks and 12 weeks , the LUTS and sexual function of the patients were evaluated by use of the International Index of Erectile Function-5 ( IIEF5 ) , International Prostate Symptom Score ( IPSS ) , Overactive Bladder Symptom Score ( OABSS ) question naire , uroflowmetry , and bladder scan . Results Both groups A and B showed statistically significant improvements in IPSS , OABSS , and quality of life ( QoL ) . Group A showed improved maximum flow rate , mean flow rate , and residual urine volume by time . Group B did not show an improvement in flow rate or residual urine volume but total voiding volume increased with time . The IIEF5 score was not improved in either group . In group A , the IIEF5 score dropped from 13.66±4.97 to 11.93±6.14 after 12 weeks ( p=0.072 ) . Group B showed a decline in the IIEF5 score from 13.19±5.91 to 12.45±6.38 ( p=0.299 ) . Although group B showed a relatively smaller decrease in the IIEF5 score , the difference between the two groups was not significant ( p=0.696 ) . Conclusions Tamsulosin monotherapy and combination therapy with solifenacin did not improve erectile function despite improvements in voiding symptoms and QoL. The improvement in storage symptoms did not affect erectile function BACKGROUND The BESIDE study demonstrated that combination therapy ( mirabegron and solifenacin 5 mg ) improved  overactive bladder symptoms  versus solifenacin 5 mg or 10 mg , and was well tolerated . OBJECTIVE To ensure efficacy and safety is maintained in older patients ( > 65 yr ) , who usually experience greater symptom severity and comorbidities , a prespecified sub analysis stratified by age group was conducted . DESIGN , SETTING , AND PARTICIPANTS Patients remaining incontinent ( ≥1 episode during 3-d diary ) following 4-wk single-blind daily solifenacin 5 mg were r and omized 1:1:1 to a daily double-blind combination ( solifenacin 5 mg and mirabegron 25 mg , increased to 50 mg at wk 4 ) , solifenacin 5 mg or 10 mg for 12 wk . Four cohorts stratified by age ( < 65 yr , ≥65 yr and < 75 yr , ≥75 yr ) were investigated . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Efficacy assessment s : change from baseline to end of treatment in average daily incontinence ( primary ) and micturition frequency ( key secondary ) , number of incontinence episodes during the 3-d diary ( key secondary ) , and change from baseline in average daily urgency and urgency incontinence episodes . Safety included treatment-emergent adverse events and vital signs . RESULTS AND LIMITATIONS Full analysis set included 2110 patients : 30.9 % aged ≥65 yr and 8.9 % aged ≥75 yr . At the end of treatment , daily , and 3-d incontinence daily micturitions , urgency , and urgency incontinence , were improved in each treatment group and age group ; the largest reductions were observed with combination in each age cohort . There were no notable differences in vital signs or the incidence of treatment-emergent adverse events between treatment and age groups , with the exception of dry mouth , which was highest with solifenacin 10 mg . CONCLUSIONS Efficacy and safety in the overall population is maintained in older ( ≥65 yr ) and elderly ( ≥75 yr ) patients treated with a combination of solifenacin and mirabegron , or solifenacin monotherapy ; irrespective of age , combination was associated with the greatest improvement in overactive bladder symptoms . PATIENT SUMMARY This study investigated the effectiveness and safety of a combination of two different treatments ( mirabegron 50 mg and solifenacin 5 mg ) or solifenacin ( 5 mg or 10 mg ) alone in patients aged < 65 yr or ≥65 yr , and < 75 yr or ≥75 yr with overactive bladder . Symptoms of overactive bladder , such as the urgent need to visit the toilet , incontinence , and frequent urination , were improved with all treatments regardless of the patient 's age , but combination treatment demonstrated the greatest benefit , and was well tolerated OBJECTIVE To evaluate the effects of add-on treatment with an anticholinergic ( imidafenacin ) on persistent overactive bladder ( OAB ) symptoms despite α-blocker ( tamsulosin ) treatment in patients with benign prostatic hyperplasia ( BPH ) . METHODS Patients with BPH ≥50 years old , with urinary urgency at least once per week and total OAB symptom score ( OABSS ) ≥3 points after ≥8-week treatment with tamsulosin were enrolled in a multicenter , open-label study ( not double-blinded ) . Patients were r and omized to receive tamsulosin ( 0.2 mg/day ) alone or tamsulosin ( 0.2 mg/day ) + imidafenacin ( 0.1 mg 2 times a day ) . Primary endpoint was 12-week change in OABSS ; secondary endpoints were changes in OABSS , International Prostate Symptom Score ( IPSS ) , micturition time chart ( MTC ) , hours of undisturbed sleep ( HUS ) , and quality of life ( IPSS-QOL and BPH impact index [ BII ] ) . For statistical analysis , a mixed-effects model and t test were used . RESULTS In total , 308 men were enrolled . The change from baseline to 12 weeks in total OABSS was significantly greater with add-on imidafenacin than tamsulosin alone ( 2.11 , 95 % confidence interval [ CI ] 1.47 - 2.74 , P < .0001 ) . Improvements in frequencies of daytime urination , nighttime urination , urinary urgency , urgency incontinence , IPSS , HUS , IPSS-QOL , and BII , were significantly greater from 4 weeks through 12 weeks in the imidafenacin group . Between-group difference in postvoid residual volume at 12 weeks was not significant ( -1.74 mL , 95 % CI -8.19 to 4.72 ) , and no events of urinary retention were reported . CONCLUSION Combined tamsulosin and imidafenacin treatment is effective and safe in patients with BPH with persistent OAB symptoms  after tamsulosin monotherapy . Furthermore the combination treatment improved the QOL in BPH patients with OAB AIMS To assess the efficacy and safety of pregabalin alone or in combination with tolterodine extended release ( ER ) in subjects with idiopathic OAB . METHODS This 26-week , multicenter , r and omized , double-blind , placebo-controlled , three-period crossover study enrolled women aged ≥ 18 years that were diagnosed with OAB and reported ≥ 8 micturitions/24 hr and ≥ 4 urgency episodes/week on 5-day bladder diary at baseline . Subjects were r and omized to 1 of 10 treatment sequences and received three of five treatments , each for 4 weeks with 4-week washout periods : st and ard-dose pregabalin/tolterodine ER ( 150 mg twice daily [BID]/4 mg once daily [ QD ] , n=102 ) , pregabalin alone ( 150 mg BID , n=105 ) , tolterodine ER alone ( 4 mg QD , n=104 ) , low-dose pregabalin/tolterodine ER ( 75 mg BID/2 mg QD , n=105 ) , and placebo ( n=103 ) . Subjects completed 5-day diaries at the end of treatment and washout periods . The primary endpoint was change from baseline to week 4 in mean voided volume ( MVV ) per micturition . The primary comparison was st and ard-dose pregabalin/tolterodine ER versus tolterodine ER alone ; secondary comparisons were pregabalin alone versus tolterodine ER alone and versus placebo . RESULTS Baseline-adjusted changes in MVV were significantly greater after treatment with st and ard-dose pregabalin/tolterodine ER ( 39.5 ml ) versus tolterodine ER alone ( 15.5 ml ; P<0.0001 ) , and with pregabalin alone ( 27.4 ml ) versus tolterodine ER alone ( P=0.005 ) and placebo ( 11.9 ml ; P=0.0006 ) . Treatments were generally well tolerated ; discontinuation rates due to adverse events were 4 % , 2 % , 5 % , 0 % , and 1 % with st and ard- and low-dose pregabalin/tolterodine ER , pregabalin , tolterodine ER , and placebo , respectively . CONCLUSIONS Pregabalin , alone or with tolterodine ER may offer an alternative treatment option for idiopathic OAB in women Lower urinary tract symptoms ( LUTS ) and erectile dysfunction ( ED ) are frequently encountered in ageing males . We compared the efficacy of alfuzosin 10 mg alone or in combination with sildenafil 50 mg in the treatment of LUTS due to benign prostatic hyperplasia . One hundred male patients older than 45 years were r and omized to two groups containing 50 patients each ; one group receiving alfuzosin 10 mg and the other group alfuzosin 10 mg combined with sildenafil 50 mg  . International Prostate Symptom Score ( IPSS ) , quality of life ( QoL ) , maximum flow rate ( Qmax ) , prostate volume and post‐void residual urine were evaluated . The mean age was 60.2 ± 17.8 . Mean data of evaluated parameters in both groups at the end of 3rd month compared with baseline values are given respective order as ; 5.1 ( 26.8 % ) and 5.8 ( 28.2 % ) points decreases in IPSS ; 1.6 ( 41.1 % ) and 1.8 ( 45 % ) points decreases in QoL ; and 3.4 ( 29.6 % ) and 3.4 ( 33 % ) points increases in Qmax . The outcomes of our study can not be interpreted in such a way to report that alpha blocker‐PDE5 inhibitor combination  has a better efficacy than alpha blocker treatment alone in patients with LUTS OBJECTIVES To report the secondary analyses of treatment satisfaction and clinical ly meaningful improvements in a r and omized study comparing coadministration of tadalafil 5 mg with finasteride 5 mg versus finasteride alone in men with prostatic enlargement secondary to benign prostatic hyperplasia . METHODS An international , r and omized , double-blind , parallel study was carried out in men aged ≥45 years who were 5-alpha reductase inhibitor naïve , and had an International Prostate Symptom Score ≥13 and prostate volume ≥30 mL ; 350 men received placebo/finasteride and 345 received tadalafil/finasteride over 26 weeks . Treatment satisfaction was assessed per protocol using the Treatment Satisfaction Scale-Benign Prostatic Hyperplasia . Responder cut-offs , analyzed post-hoc were total International Prostate Symptom Score improvement ≥3 points or ≥25 % from r and omization . RESULTS Baseline patient characteristics were generally comparable between responders and non-responders . The proportion of patients with an International Prostate Symptom Score improvement ≥3 points with tadalafil/finasteride and placebo/finasteride , respectively , at week 4 was 57.0 % and 47.9 % ( OR 1.45 , 95 % confidence interval 1.07 - 1.97 ) , at week 12 was 68.8 % and 60.7 % ( OR 1.48 , 95 % confidence interval 1.07 - 2.05 ) and at week 26 was 71.4 % and 70.2 % ( OR 1.14 , 95 % confidence interval 0.81 - 1.61 ) ; for IPSS change ≥25 % , the corresponding proportions were 44.8 % and 32.9 % ( OR 1.66 , 95 % confidence interval 1.21 - 2.28 ) , 55.5 % and 51.9 % ( OR 1.18 , 95 % confidence interval 0.87 - 1.62 ) , and 62.0 % and 58.3 % ( OR 1.23 , 95 % confidence interval 0.89 - 1.70 ) . Treatment satisfaction at week 26 was significantly greater with tadalafil/finasteride versus placebo/finasteride  for total treatment satisfaction scale score ( P=0.031 ) and satisfaction with efficacy subscore ( P = 0.025 ) ; scores were not significantly different between treatments for satisfaction with dosing or side-effects ( both P ≥ 0.371 ) . CONCLUSIONS Tadalafil/finasteride results in significantly more patients achieving early clinical meaningful improvements in symptoms , and in greater treatment satisfaction versus placebo/finasteride Introduction : In Korea , increasing attention has recently been given to the use of phytotherapeutic agents to alleviate the symptoms of BPH . Serenoa repens has been shown to have an equivalent efficacy to Finasteride or Tamsulosin in the treatment of BPH in previous studies . The present study was design ed to compare the efficacy and safety of Serenoa repens plus tamsulosin with tamsulosin only over 12 months in men with LUTS secondary to BPH . Material s and Methods : One hundred forty men with symptomatic BPH ( IPSS ≥10 ) were recruited in our hospital for a 12-month , open-label , r and omized trial . Patients were r and omly assigned to either tamsulosin 0.2 mg/day plus Serenoa repens 320 mg/day ( n = 60 ) or tamsulosin 0.2 mg/day only ( n = 60 ) . Prostate volume and PSA were measured at baseline and at end-point , whereas total IPSS , and its storage and voiding subscores , LUTS-related QoL , Qmax , and PVR were evaluated at baseline and later every 6 months . Results : Total 103 patients were finally available : 50 in the TAM + SR group and 53 in the TAM group . At 12 months , total IPSS decreased by 5.8 with TAM + SR and 5.5 with TAM ( p = 0.693 ) ; the storage symptoms improved significantly more with TAM + SR ( -1.7 vs. -0.8 with TAM , p = 0.024 ) . This benefit with regard to storage symptom in the TAM + SR group lasts at 12 months ( -1.9 vs. -0.9 , p = 0.024 ) . The changes of voiding subscore , LUTS-related QoL , Qmax , PVR , PSA , and prostate volume showed no significant differences between the TAM + SR and TAM groups . During the treatment period , 8 patients ( 16.9 % ) with TAM and 10 ( 20 % ) with TAM + SR had drug-related adverse reactions , which included ejaculatory disorders , postural hypotension , dizziness , headache , gastro-intestinal disorders , rhinitis , fatigue and asthenia . Conclusions : The combination treatment of Serenoa repens and tamsulosin was shown to be more effective than tamsulosin monotherapy in reducing storage symptoms in BPH patients after 6 months and up to 12 months of treatment Abstract Purpose To evaluate the efficacy and safety of adding a low-dose oral desmopressin to tamsulosin therapy for treatment of nocturia in patients with benign prostatic hyperplasia ( BPH ) . Methods Eligible patients with BPH and nocturia ≥2/night were r and omly allocated to two treatment groups ; the first of which received 3-month treatment scheme of daily oral dose of tamsulosin OCAS 0.4 mg and desmopressin MELT 60 mcg ( D/T group ) , while the second one received tamsulosin OCAS 0.4 mg only ( T group ) . Patients were followed on monthly basis and changes in the parameters from baseline to 3 months after treatment were assessed on I-PSS/QoL question naire , 7-day voiding diary , urinalysis , serum sodium , abdominal ultrasonography and uroflowmetry . Results A total of 248 patients were included within the study ; 123 patients in the combined D/T group and 125 patients in T group . The frequencies of night voids decreased by 64.3 % in D/T group compared to 44.6 % in T group . The first sleep period , significantly increased from 82.1 to 160.0 min and from 83.2 to 123.8 min in D/T and T group , respectively ; and significant differences between both groups were observed at the end of study ( p < 0.001 ) . I-PSS , QoL score , post-void residual urine volume and Qmax were significantly improved with no statistical difference between both groups . No serious adverse effects were reported in both groups . Conclusion The addition of low-dose oral desmopressin therapy to an α-blocker tamsulosin provides effective treatment for nocturia in patients with LUTS/BPH Alpha-blockers and 5-alpha-reductase inhibitors are medical therapies that are being used as alternatives to surgical interventions to relieve symptoms of  benign prostatic hyperplasia ( BPH )  . Taken as monotherapy , alpha-blockers and 5-alpha-reductase inhibitors have each been shown to provide relief from BPH symptoms . Treatment with finasteride over 4 years has been shown to reduce both BPH symptoms and the likelihood of acute urinary retention and the need for surgery . Direct comparison of the alpha-blocker terazosin with finasteride has been done , but only for a period of 1 year . The Medical Therapy of Prostatic Symptoms ( MTOPS ) trial is a multicenter , r and omized , placebo-controlled , double-masked clinical trial design ed to evaluate the long-term efficacy of the alpha-blocker doxazosin and the 5-alpha-reductase inhibitor finasteride , whether taken as a monotherapy or in combination , in preventing or delaying the progression of BPH . We describe in this paper the design of the MTOPS trial , the concept of BPH progression , the definition and methods of determining the primary outcome events and the proposed statistical analysis methods . A unique feature of MTOPS is the inclusion of prostate biopsies on a subgroup of r and omized participants . Volunteers among r and omized participants are to undergo a biopsy of the prostate at predetermined time points during the trial . Studies that will be conducted using the tissue specimens collected in MTOPS can potentially provide information at the molecular level on the natural history of BPH among medically treated and untreated men with moderate to severe symptoms of BPH OBJECTIVE To examine the effects of oral estrogen/progestin on incontinence and related lower urinary tract conditions among female nursing home ( NH ) residents . DESIGN R and omized placebo-controlled trial . SETTING Five NHs . PARTICIPANTS Thirty-two incontinent female residents of average age 88 . MEASUREMENTS Subjects were r and omized to receive either oral estrogen ( 0.625 mg ) combined with progesterone ( 2.5 mg ) or placebo , daily for 6 months . Measures of incontinence severity , the clinical appearance of the vagina , vaginal and urethral cytology , and urine and vaginal cultures were made at baseline , 3 months , and 6 months . In addition to active drug or placebo , all subjects received regular toileting assistance ( prompted voiding ) by trained research aides during 3-day data - collection periods to compensate for mobility and cognitive impairments . RESULTS At 3 and 6 months there were no significant differences between the groups in the severity of incontinence , the prevalence of bacteriuria , or the results of vaginal cultures . Several clinical findings associated with atrophic vaginitis improved more in the active than the placebo group and vaginal pH and vaginal and urethral cytology exhibited a partial estrogenic effect . CONCLUSIONS Our results must be interpreted with caution because of the size and the select nature of our subject sample . Up to 6 months of oral estrogen had only a partial estrogenic effect on vaginal and urethral epithelium and no clinical effects in this patient population . We believe that future studies of estrogen for urinary incontinence in frail NH residents should utilize a topical preparation and consider targeting urinary tract infection as an additional outcome measure Objective : To evaluate the efficacy and safety of fesoterodine extended-release ( ER ) plus tamsulosin in men with lower urinary tract symptoms ( LUTS ) associated with benign prostatic hyperplasia ( BPH ) . Patients and Methods : Men aged ≥50 years , with LUTS , prostate volume ≤60 ml and International Prostate Symptom Score ( IPSS ) ≥13 were enrolled in this study . 173 consecutive patients were treated initially with tamsulosin ( 0.4 mg ) for 1 week . At the second visit , 47 patients out of the sample of 173 who were still experiencing inconvenient LUTS were r and omized into two groups . The first group received a therapy with tamsulosin and fesoterodine combination ( group 1 , n = 24 ) while the second continued the therapy with the single administration of tamsulosin ( group 2 , n = 23 ) for an additional 4-week period . Results : There was no statistically significant difference in age , prostate volume , Qmax , and postvoid residual urine between the two groups . A statistical significance appeared in the combination group regarding the storage and the total IPSS values among the second and third visits ( 10.5 ± 1.4 to 8.5 ± 1.3 and 16.1 ± 1.8 to 13.7 ± 1.5 respectively ) . Conclusion : Regarding bothersome LUTS and storage symptoms  , fesoterodine ER and tamsulosin combination was significantly more effective than the single administration of tamsulosin BACKGROUND Phytotherapy has been used to treat patients with lower urinary tract symptoms ( LUTS ) . We evaluated the efficacy and tolerability of combination therapy between Serenoa Repens ( SeR ) , Lycopene ( Ly ) , and Selenium ( Se ) + tamsulosin versus single therapies . METHODS PROCOMB trial ( IS RCT N78639965 ) was a r and omized double-blinded , double-dummy multicenter study of 225 patients between 55 and 80 years old , PSA ≤ 4 ng/ml , IPSS ≥12 , prostate volume ≤60 cc , Qmax ≤15 ml/sec , postvoid residual urine ( PVR ) < 150 ml . Participants were r and omized group A ( SeR-Se-Ly ) , group B ( tamsulosin 0.4 mg ) , group C ( SeR-Se-Ly + tamsulosin 0.4 mg ) . The primary endpoints of the study were the reduction of IPSS , PVR , and increase of Qmax in group C versus monotherapy groups . RESULTS The decrease for combination therapy was significantly greater versus group A ( P < 0.05 ) and group B ( P < 0.01 ) for IPSS and versus group A ( P < 0.01 ) for PVR from baseline to 6 months . A greater decrease in IPSS was observed for Group C versus group A ( P < 0.01 ) and increase in Qmax versus group B ( P < 0.01 ) , from 6 months to 12 months . At one year , the changes of IPSS and Qmax were greater for Group C versus monotherapies ( each comparison < 0.05 ) . The proportions of men with a decrease of at least three points ( each comparison P < 0.05 ) and decrease of 25 % for IPSS ( each comparison P < 0.01 ) were greater for Group C. CONCLUSION SeR-Se-Ly + tamsulosin therapy is more effective than single therapies in improving IPSS and increasing Qmax in patients with LUTS BACKGROUND Incontinence has a greater detrimental effect on quality of life than other symptoms of overactive bladder ( OAB ) and is often difficult to treat with antimuscarinic monotherapy . OBJECTIVE To evaluate the efficacy and the safety and tolerability of combination ( solifenacin 5 mg and mirabegron 50 mg ) versus solifenacin 5 or 10 mg in OAB patients remaining incontinent after 4 wk of solifenacin 5 mg . DESIGN , SETTING , AND PARTICIPANTS OAB patients remaining incontinent despite daily solifenacin 5 mg during 4-wk single-blind run-in were r and omised 1:1:1 to double-blind daily combination or solifenacin 5 or 10 mg for 12 wk . Patients receiving the combination were initiated on mirabegron 25 mg increasing to 50 mg after week 4 . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The primary end point was a change from baseline to end of treatment ( EOT ) in the mean number of incontinence episodes per 24h ( stratified rank analysis of covariance [ ANCOVA ] ) . Key secondary end points were a change from baseline to EOT in the mean number of micturitions per 24h ( ANCOVA ) and number of incontinence episodes noted in a 3-d diary at EOT ( mixed-effects Poisson regression ) . A trial ( BESIDE ) comparing combination treatment ( solifenacin plus mirabegron ) with one treatment alone ( solifenacin ) tested the superiority of combination versus solifenacin 5 mg , noninferiority ( and potential superiority ) of combination versus solifenacin 10 mg ( key secondary end points ) , and the safety and tolerability of combination therapy versus solifenacin monotherapy . RESULTS AND LIMITATIONS A total of 2174 patients were r and omised to combination ( n=727 ) , solifenacin 5 mg ( n=728 ) , or solifenacin 10 mg ( n=719 ) . At EOT , combination was superior to solifenacin 5 mg , with significant improvements in daily incontinence ( p=0.001 ) , daily micturitions ( p<0.001 ) , and incontinence noted in a 3-d diary ( p=0.014 ) . Combination was noninferior to solifenacin 10 mg for key secondary end points and superior to solifenacin 10 mg for improving daily micturitions . All treatments were well tolerated . CONCLUSIONS Adding mirabegron 50 mg to solifenacin 5 mg further improved OAB symptoms versus solifenacin 5 or 10 mg , and it was well tolerated in OAB patients remaining incontinent after initial solifenacin 5 mg . PATIENT SUMMARY In this 12-wk study , overactive bladder patients who remained incontinent despite initial solifenacin 5 mg treatment received additional treatment with mirabegron 50 mg . Combining mirabegron 50 mg with solifenacin 5 mg was superior to solifenacin 5 mg alone in improving symptoms of incontinence and frequent urination , and it was well tolerated . TRIAL REGISTRATION Clinical Trials.gov NCT01908829 OBJECTIVE Estimate the prevalence of urinary incontinence ( UI ) , overactive bladder ( OAB ) , and other lower urinary tract symptoms ( LUTS ) among men and women in five countries using the 2002 International Continence Society ( ICS ) definitions . METHODS This population -based , cross-sectional survey was conducted between April and December 2005 in Canada , Germany , Italy , Sweden , and the United Kingdom using computer-assisted telephone interviews .  A r and om sample of men and women aged > /= 18 yr residing in the five countries and who were representative of the general population s in these countries was selected . Using 2002 ICS definitions , the prevalence estimates of storage , voiding , and postmicturition LUTS were calculated . Data were stratified by country , age cohort , and gender . RESULTS A total of 19,165 individuals agreed to participate ; 64.3 % reported at least one LUTS . Nocturia was the most prevalent LUTS ( men , 48.6 % ; women , 54.5 % ) . The prevalence of storage LUTS ( men , 51.3 % ; women , 59.2 % ) was greater than that for voiding ( men , 25.7 % ; women , 19.5 % ) and postmicturition ( men , 16.9 % ; women , 14.2 % ) symptoms combined . The overall prevalence of OAB was 11.8 % ; rates were similar in men and women and increased with age . OAB was more prevalent than all types of UI combined ( 9.4 % ) . CONCLUSIONS The EPIC study is the largest population -based survey to assess prevalence rates of OAB , UI , and other LUTS in five countries . To date , this is the first study to evaluate these symptoms simultaneously using the 2002 ICS definitions . The results indicate that these symptoms are highly prevalent in the countries surveyed AIMS To evaluate patient-reported outcomes ( PROs ) of combinations of solifenacin and mirabegron compared with solifenacin and mirabegron monotherapy and with placebo in patients with overactive bladder ( OAB ) from the SYNERGY trial . METHODS Following a 4-week placebo run-in , period patients ( ≥18 years ) with OAB were r and omized 2:2:1:1:1:1 to receive solifenacin 5 mg + mirabegron 25 mg ( combination 5 + 25 mg ) , solifenacin 5 mg + mirabegron 50 mg , ( combination 5 + 50 mg ) , solifenacin 5 mg , mirabegron 25 mg , mirabegron 50 mg or placebo for 12 weeks , followed by a 2-week washout period . At each visit , PROs related to quality of life , symptom bother , and treatment satisfaction were assessed , including OAB-q Symptom Bother score , health-related quality of life ( HRQOL ) Total score , treatment satisfaction-visual analogue scale ( TS-VAS ) , and patient perception of bladder condition ( PPBC ) question naires . RESULTS Overall , 3527 patients were r and omized into the study , with 3494 receiving double-blind treatment . At end of treatment ( EoT ) , both combination groups showed greater improvements in OAB-q Symptom Bother score compared with the monotherapy groups ( nominal P < 0.001 ) . Statistically significant improvements in HRQOL Total scores were observed in the combination groups versus monotherapy groups ( P ≤ 0.002 ) . For both combination groups , the OAB-q Symptom Bother score responder rates at EoT were statistically significantly higher versus mirabegron monotherapy ( P < 0.05 ) . The mean adjusted changes from baseline to EoT for PPBC were greater in the combination groups compared with monotherapy groups . CONCLUSIONS PROs showed that combination therapy provided clear improvements and an additive effect for many HRQOL parameters , including OAB-q Symptom Bother score , HRQOL Total score , and PPBC Abstract Purpose To evaluate the efficacy and safety of imidafenacin ( IM ) , a novel short half-life anticholinergic , as add-on therapy for male LUTS with nocturia and nocturnal polyuria . Material s and methods This multicenter , prospect i ve , r and omized , open-labelled study was conducted and involved men who had frequency , urgency , and nocturia despite receiving a stable dose of α1-blocker for ≥1 month . Subjects were r and omised to control ( α1-blocker alone ) , IM twice/day ( α1-blocker + 0.1 mg imidafenacin twice daily ) , or IM nightly ( α1-blocker plus 0.1 mg imidafenacin nightly ) group ; the treatment period was 8 weeks . Primary endpoints included improvements in night-time frequency and Nocturia Quality of Life Question naire ( N-QOL ) scores . Secondary endpoints included changes from the baseline in frequency volume chart variables , and post-void residual volume . Results and limitations Compared with the controls , IM twice/day and IM nightly patients had a significantly lower night-time frequency ( changes from baseline : 0.1 ± 0.8 in control , −0.6 ± 0.9 in IM twice/day , and −0.4 ± 1.0 in IM nightly , p = 0.5227 , 0.0006 and 0.0143 , respectively ) . The hours of undisturbed sleep and N-QOL score were significantly improved in IM twice/day group , though not IM nightly group . Nocturnal urine volume was significantly reduced in IM nightly group , although total urine volume remained unchanged . Conclusions A short half-life anticholinergic is suggested to be safe and effective as an add-on therapy for residual nocturia in patients with male LUTS receiving α1-blocker treatment .  Anticholinergic administration nightly could reduce the nocturnal urine volume PURPOSE To evaluate the long term efficacy and safety of the use of propiverine and terazosine combination in patients with LUTS and DO by a placebo controlled study . MATERIAL S AND METHODS One hundred patients were enrolled in the study . They were r and omized into two groups ( each group consisted of 50 patients ) . Terazosine and placebo were administered to the patients in Group 1 and terazosine plus propiverine HCL was administered to Group 2 . The patients were evaluated by international prostate symptom score ( IPSS ) , the first four questions of IPSS ( IPSS4 ) , the 8th question of IPSS ( quality of life-QoL ) , overactive bladder symptom score question naire ( OAB-q V8 ) , PSA test , urodynamic studies , post voiding residue ( PVR ) . All patients were followed for one year and were reassessed for comparison . RESULTS IPSS , IPSS4 , OAB symptoms , QoL score , PVR , and Qmax scores of the groups did not differ . After one year treatment , there was significant improvement in IPSS , IPSS4 , OAB symptoms , QoL and Qmax values in Group 2 . No significant improvement was noted for the same parameters in Group 1 . CONCLUSION This is the first study to show long term safety and efficacy of anticholinergic therapy for patients with LUTS . In patients with OAB or DO , long term anticholinergic treatment may be regarded as a treatment option PURPOSE To revise the 2003 version of the American Urological Association 's ( AUA ) Guideline on the management of benign prostatic hyperplasia ( BPH ) . MATERIAL S AND METHODS From MEDLINE ® search es of English language publications ( January 1999 through February 2008 ) using relevant MeSH terms , articles concerning the management of the index patient , a male ≥45 years of age who is consulting a healthcare provider for lower urinary tract symptoms ( LUTS ) were identified . Qualitative analysis of the evidence was performed . Selected studies were stratified by design , comparator , follow-up interval , and intensity of intervention , and meta-analyses ( quantitative synthesis ) of outcomes of r and omized controlled trials were planned . Guideline statements were drafted by an appointed expert Panel based on the evidence . RESULTS The studies varied as to patient selection ; r and omization ; blinding mechanism ; run-in periods ; patient demographics , comorbidities , prostate characteristics and symptoms ; drug doses ; other intervention characteristics ; comparators ; rigor and intervals of follow-up ; trial duration and timing ; suspected lack of applicability to current US practice ; and techniques of outcomes measurement . These variations affected the quality of the evidence review ed making formal meta- analysis impractical or futile . Instead , the Panel and extractors review ed the data in a systematic fashion and without statistical rigor . Diagnosis and treatment algorithms were adopted from the 2005 International Consultation of Urologic Diseases . Guideline statements concerning pharmacotherapies , watchful waiting , surgical options and minimally invasive procedures were either up date d or newly drafted , peer review ed and approved by AUA Board of Directors . CONCLUSIONS New pharmacotherapies and technologies have emerged which have impacted treatment algorithms . The management of LUTS/BPH continues to evolve Thirty-six postmenopausal women with objective ly verified stress incontinence were treated with oral estriol ( Triovex , 2 mg x 1 ) and phenylpropanolamine ( Kontexin , 50 mg x 2 ) alone and in combination . After an initial four-week single-blind period with phenylpropanolamine ( PPA ) , either estriol or estriol and PPA were given r and omly in four-week periods , in a crossover design . PPA and estriol in combination as well as PPA alone , raised the intraurethral pressure and significantly reduced the urinary loss by 35 per cent in a st and ardized physical strain test . In women with an initial low urethral pressure estriol also induced pressure increase . The leakage episodes and the assessed leakage amounts were significantly reduced by both estriol and PPA given separately as single treatment ( 28 % ) or when given as combined therapy ( 40 % ) . Most of the women preferred the combined treatment to either drug alone . Additive but no synergistic effects are indicated PURPOSE We evaluated the efficacy and safety of add-on treatment with a β3-adrenoceptor agonist ( mirabegron ) for overactive bladder symptoms remaining after α1-blocker ( tamsulosin ) treatment in men with benign prostatic obstruction . MATERIAL S AND METHODS Patients with benign prostatic obstruction with urinary urgency at least once per week and a total OABSS of 3 or more points after 8 or more weeks of treatment with tamsulosin were enrolled in the study . They were r and omly allocated to receive 0.2 mg tamsulosin daily or 0.2 mg tamsulosin and 50 mg mirabegron daily for 8 weeks . The primary end point was change in total OABSS . Safety assessment s included change in post-void residual urine volume and adverse events . RESULTS From January 2012 through September 2013 a total of 94 patients were r and omized . Of these patients 76 completed the protocol treatment . In the full analysis set the change in total OABSS during the treatment period was significantly greater in the combination group than in the monotherapy group ( -2.21 vs -0.87 , p=0.012 ) . The changes in scores for urinary urgency , daytime frequency , International Prostate Symptom Score storage symptom subscore and quality of life index at 8 weeks were significantly greater in the combination group . The change in post-void residual urine volume was significantly greater in the combination group . Although 6 patients experienced adverse events in the combination group , urinary retention was observed in only 1 patient . CONCLUSIONS Combined tamsulosin and mirabegron treatment is effective and safe for patients with benign prostatic obstruction who have overactive bladder symptoms  after tamsulosin monotherapy Purpose A cost minimisation analysis compares the costs of different interventions ’ to ascertain the least expensive over time . We compared different prostate targeted drug treatments with TURP to identify the optimal cost saving duration of a medical therapy for symptomatic benign prostatic enlargement ( BPE ) . Methods The Evolution registry is a prospect i ve , multicentre registry , conducted by the European Association of Urology Research Foundation ( EAUrf ) for 24 months in 5 European countries . Evolution was design ed to register the management of symptomatic BPE in clinical practice setting s in 5 European countries .  Direct cost evaluation associated with prostate targeted medical therapies and TURP was also recorded and analysed . Results In total , 1838 men were enrolled with 1246 evaluable at 24 months .  Medical therapies were more cost saving than TURP for treatment duration s ranging from 2.9 to 70.4 years . Cost saving depended on both medication class and individual country assessed . Daily tamsulosin monotherapy was more cost saving than TURP for ≤ 13.9 years in Germany compared to ≤ 32.7 years in Italy . Daily finasteride monotherapy  was more cost saving for ≤ 5.9 years in France compared to ≤ 36.9 years in Spain . Combination therapy was more cost saving for ≤ 5.9 years for Italian patients versus ≤ 13.8 years in Germany . Conclusions BPE medical management was more cost saving than TURP for different specific treatment duration s. Information from this study will allow clinicians to convey medical and surgical costs over time , to both patients and payors alike , when considering BPE treatment OBJECTIVE To investigate the treatment outcome of discontinuing 1 medication from 2-year combination therapy for male benign prostatic hyperplasia/lower urinary tract symptoms . MATERIAL S AND METHODS Patients with International Prostate Symptom Score ≥ 8 , total prostatic volume ( TPV ) > 30 mL , and maximum flow rate ( Qmax ) < 15 mL/s were r and omly assigned to the 5α-reductase inhibitor ( 5ARI ) discontinue ( DC-5ARI ) or α-blocker discontinue ( DC-α-blocker ) group . All patients received combination therapy with dutasteride ( 0.5 mg QD ) and doxazosin ( 4 mg QD ) for 2 years and then discontinued either one drug for 12 months . The primary endpoint was the occurrence of resuming medication . The secondary endpoints were the net parameters changed or the need of transurethral resection of the prostate ( TURP ) . RESULTS A total of 117 patients in DC-5ARI and 113 in DC-α-blocker group completed the study .  The baseline TPV and Qmax were similar between groups before combination therapy . Resumption of combination therapy was significantly more in DC-5ARI than DC-α-blocker group ( 51.3 % vs 31.0 % ; P = .005 ) . The mean duration from discontinuing to resuming medication was 5.0 ± 4.4 months in DC-α-blocker and 7.8 ± 3.8 months in DC-5ARI group ( P < .05 ) . The TPV progression ( 29.1 % vs 8.0 % ; P < .001 ) and the need for TURP ( 14.5 % vs 7.1 % ; P = .043 ) were significantly higher in DC-5ARI than DC-α-blocker group . Patients with larger TPV ( 45.8 ± 18.1 mL ) had significantly greater need for resuming 5ARI than smaller TPV ( 36.3 ± 16.9 mL ; P = .007 ) , and a lower Qmax might predict resuming α-blocker . CONCLUSION After a 2-year combination therapy , discontinuation of either one drug induced benign prostatic hyperplasia progression in either group . Greater risk of resuming medication and needing TURP were noted in patients who discontinued 5ARI OBJECTIVE To evaluate the clinical response and adverse events ( AEs ) of solifenacin ( SOL ) or mirabegron ( MIR ) in benign prostatic hyperplasia patients with persistent overactive bladder ( OAB ) symptoms after dutasteride ( DUT ) treatment . METHODS Fifty cases with residual OAB symptom score ( OABSS ) ≥ 5 and OABSS Q3 ≥ 2 after at least 6 months treatment of DUT were included in this study . Patients were administered 5 mg/d of SOL ( N = 25 ) or 50 mg/d of MIR ( N = 25 ) , and International Prostate Symptom Score ( IPSS ) and OABSS were prospect ively collected at 4 and 12 weeks . The safety was evaluated by changes in postvoided residual urine volume and the incidence of AEs . RESULTS After DUT administration , the mean prostate volume , IPSS , and OABSS were 39.0 mL , 17.6 , and 8.1 , respectively . SOL 5 mg significantly reduced the IPSS , OABSS , and OABSS Q3 at 4 and at 12 weeks ( -3.1 , -2.7 , -1.3 ; P < .05 ) ; however , 4 patients could not continue the SOL treatment owing to AEs . All patients could continue the 12 weeks of MIR treatment , and MIR 50 mg reduced IPSS and OABSS at 4 weeks and reduced IPSS , OABSS , and the OABSS Q3 ( -3.0 , -2.5 , -0.9 ; P < .05 ) at 12 weeks . Postvoided residual urine volume increased by ≥ 100 mL after treatment in 2 cases in the SOL group but not in any patient in the MIR group . CONCLUSION Additional SOL or MIR might result in amelioration of the persistent OAB symptom after DUT treatment in patients with an enlarged prostate INTRODUCTION Safety and efficacy of tamsulosin and vardenafil are well established : however , there is no report regarding combined therapy with these drugs for  lower urinary tract symptoms ( LUTSs ) secondary to benign prostatic hyperplasia ( BPH ) . AIM To compare the safety and efficacy of tamsulosin 0.4 mg/day vs. tamsulosin 0.4 mg/day plus vardenafil 10 mg/day in patients with LUTS/BPH in a r and omized trial with 12-week follow-up . METHODS We conducted a r and omized , double-blind , placebo-controlled study on 60 men with persistent storage LUTS after 2-week run-in with tamsulosin .  MAIN OUTCOME MEASURES International Prostate Symptom Score ( IPSS ) , IPSS-bother , International Index of Erectile Function , Version 5 ( IIEF-5 ) and Over Active Bladder question naire ( OAB-q ) scores , uroflowmetry data ( Qmax , Qave ) , and postvoiding residual urine were recorded after run-in ( baseline ) , and 2 and 12 weeks after treatment . Differences between vardenafil and placebo at different times were calculated with unpaired sample s t-test . Between-group differences in change from baseline to 2 and 12 weeks were evaluated with analysis of variance . RESULTS We found a between-group significant difference from baseline to 12 weeks in the following : ( i ) Qmax ( placebo : + 0.07 , vardenafil : + 2.56 , P = 0.034 ) ; ( ii ) Qave  ( placebo : -0.15 , vardenafil : + 1.02 , P = 0.031 ) ; ( iii ) irritative-IPSS subscores ( placebo : -1.67 , vardenafil : -3.11 , P = 0.039 ) ; and ( iv ) IIEF ( placebo : + 0.06 , vardenafil : + 2.61 , P = 0.030 ) . No patient reported any serious ( grade ≥ 2 ) adverse event ( AE ) . There were no differences in the incidence of common , treatment-related AEs between men undergoing combined therapy or tamsulosin alone . CONCLUSIONS The combination of tamsulosin and vardenafil for 12 weeks was well tolerated and more effective to improve both LUTS and erectile function , as compared with tamsulosin alone . Further studies are needed to assess the role of combined therapy of phosphodiesterase type 5 inhibitors and alpha blockers in treating LUTS/BPH PURPOSE Medical treatment for men with lower urinary tract symptoms and prostatic enlargement secondary to benign prostatic hyperplasia is 5α-reductase inhibitor monotherapy or coadministration with an α-blocker . We assessed the effects of tadalafil 5 mg coadministered with finasteride 5 mg during 26 weeks on lower urinary tract symptoms and sexual symptoms . MATERIAL S AND METHODS In an international , r and omized , double-blind , parallel study of men 45 years old or older who were 5α-reductase inhibitor naïve and had an I-PSS ( International Prostate Symptom Score ) of 13 or greater and prostate volume 30 ml or greater , 350 were treated with placebo/finasteride  and 345 received tadalafil/finasteride for 26 weeks . Changes in lower urinary tract symptoms secondary to benign prostatic hyperplasia were assessed with the I-PSS , erectile dysfunction improvements were assessed with the IIEF-EF ( International Index of Erectile Function-Erectile Function ) in sexually active men and safety was assessed by evaluating adverse events . RESULTS Least squares mean changes from baseline in I-PSS after 4 , 12 and 26 weeks of tadalafil/finasteride coadministration were -4.0 , -5.2 and -5.5 , respectively . Corresponding values for placebo/finasteride coadministration were -2.3 , -3.8 and -4.5 ( p ≤ 0.022 at all visits favoring tadalafil/finasteride  coadministration ) . I-PSS subscores ( storage and voiding ) and quality of life index were also numerically improved with tadalafil/finasteride coadministration . Least squares mean changes from baseline in IIEF-EF  with tadalafil/finasteride coadministration were 3.7 after 4 weeks , and 4.7 after 12 and 26 weeks . Corresponding values for placebo/finasteride coadministration were -1.1 , 0.6 and -0.0 ( p < 0.001 at all visits favoring tadalafil/finasteride coadministration ) . Tadalafil/finasteride coadministration was well tolerated and most adverse events were mild/moderate . CONCLUSIONS The coadministration of tadalafil/finasteride provides early improvement in lower urinary tract symptoms in men with benign prostatic hyperplasia and prostatic enlargement . Tadalafil/finasteride coadministration also improves erectile function in men who have comorbid erectile dysfunction BACKGROUND Short-term trials have demonstrated the efficacy and safety of combination therapy using antimuscarinics and α-blockers in men with lower urinary tract symptoms ( LUTS ) . The Study of Solifenacin Succinate and Tamsulosin Hydrochloride OCAS ( oral controlled absorption system ) in Males with Lower Urinary Tract Symptoms ( NEPTUNE ) II is the first long-term study using solifenacin ( Soli ) and the oral controlled absorption system formulation of tamsulosin ( TOCAS ) . OBJECTIVE To evaluate long-term ( up to 52 wk ) safety and efficacy of flexible dosing of two fixed-dose combinations ( FDC ) of Soli plus TOCAS in men with moderate to severe storage symptoms and voiding symptoms . DESIGN , SETTING , AND PARTICIPANTS Patients with both storage and voiding LUTS , maximum urinary flow rate of 4.0 - 12.0 ml/s , prostate size < 75 ml , and postvoid residuals ≤ 150 ml , who completed the 12-wk , double-blind NEPTUNE study could continue in the 40-wk , open-label NEPTUNE II study . INTERVENTION FDC of Soli 6 mg plus TOCAS 0.4 mg , or Soli 9 mg plus TOCAS 0.4 mg ; patients could switch between doses in NEPTUNE II . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Safety and efficacy data from NEPTUNE and NEPTUNE II were combined to cover a 52-wk period . Primary efficacy end points were total International Prostate Symptom Score ( IPSS ) and total urgency and frequency score ( TUFS ) ; secondary end points included IPSS storage and voiding subscores , micturition diary variables , and quality of life parameters . RESULTS In all , 1066 men completed NEPTUNE and received one dose or more of study medication in NEPTUNE II . Treatment-emergent adverse events were reported in 499 ( 46.8 % ) patients who participated in NEPTUNE II ; most were mild or moderate . Urinary retention occurred in 13 of 1208 ( 1.1 % ) patients receiving one or more FDCs in NEPTUNE and /or NEPTUNE II ; 8 ( 0.7 % ) required catheterisation ( acute urinary retention [ AUR ] ) . Reductions in total IPSS and TUFS during NEPTUNE were maintained for up to 52 wk of FDC treatment , with mean reductions of 9.0 ( st and ard deviation [ SD ] : 5.7 ) and 10.1 ( SD : 9.2 ) , respectively , from baseline to end of treatment . Clinical ly relevant improvements were also observed for secondary efficacy end points . CONCLUSIONS Long-term treatment with FDC Soli plus TOCAS was well tolerated and efficacious in men with storage and voiding LUTS , with a low incidence of AUR . PATIENT SUMMARY Treatment with solifenacin plus tamsulosin in a fixed-dose combination tablet was well tolerated by men with lower urinary tract symptoms . Improvements in symptoms were achieved after 4 wk of treatment , with further improvements at week 16 maintained for up to 52 wk throughout the study
target: EVIDENCE SYNTHESIS The most studied combination therapy for the treatment of male LUTS is the α1-adrenoceptor antagonist/5α-reductase inhibitor combination .
  This combination seems to be more efficacious in terms of several outcome variables , in particular in men who have moderate-to-severe LUTS and are at risk of disease progression .
  Also in terms of nocturia improvements , this combination is significantly more effective than the monotherapy .
  The other often studied combination treatment , in both male and female patients with LUTS , was the combination of antimuscarinics ( in particular solifenacin ) and mirabegron .
  This combination seems to be more effective in comparison with the monotherapies with respect to urinary incontinence and urgency urinary incontinence episodes and several other objective and subjective parameters , without relevant increase of adverse events .
  The combination of hormone therapy and antimuscarinics in women with LUTS does not seem to be useful .
  For the treatment of LUTS in men and women , combination therapy appears to be a promising option to optimize the efficacy of the available drugs for those who do not experience sufficient benefit with monotherapy .
  This add-on scenario offers the possibility to have a more tailored approach to the management of LUTS , always seeking the optimal balance between efficacy and tolerability for a given patient .
  PATIENT SUMMARY Some combination of drugs may offer advantages over monotherapies for the treatment of voiding and storage complaints in men and women
background: CONTEXT Several drugs are approved and available for the treatment of lower urinary tract symptoms ( LUTS ) in men and women .
  However , the vast majority of available data , upon which the approval and recommendation in guidelines are based , considered only the role of the monotherapies and did not evaluate possible combination therapies .
  OBJECTIVE This systematic review analyzes the efficacy and adverse events of combination therapies for male and female LUTS .