Dutasteride reduces prostate size and prostate specific antigen in older hypogonadal men with benign prostatic hyperplasia undergoing testosterone replacement therapy. Efficacy and safety of dutasteride in Japanese men with benign prostatic hyperplasia. The effects of dutasteride, tamsulosin and combination therapy on lower urinary tract symptoms in men with benign prostatic hyperplasia and prostatic enlargement: 2-year results from the CombAT study. Efficacy and safety of a dual inhibitor of 5-alpha-reductase types 1 and 2 (dutasteride) in men with benign prostatic hyperplasia. Efficacy and Safety of Dutasteride in Chinese Adults with Symptomatic Benign Prostatic Hyperplasia Efficacy and Safety of Dutasteride in Chinese Adults with Symptomatic Benign Prostatic Hyperplasia : A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study with an Open-Label Extension. 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. Effect of Discontinuation of Tamsulosin in Korean Men with Benign Prostatic Hyperplasia Taking Tamsulosin and Dutasteride: An Open-Label, Prospective, Randomized Pilot Study. Effect of dutasteride on the symptoms of benign prostatic hyperplasia, and patient quality of life and discomfort, in clinical practice Effect of dutasteride on the risk of prostate cancer. Long-term sustained improvement in symptoms of benign prostatic hyperplasia with the dual 5alpha-reductase inhibitor dutasteride: results of 4-year studies. The efficacy of terazosin, finasteride, or both in benign prostatic hyperplasia. Veterans Affairs Cooperative Studies Benign Prostatic Hyperplasia Study Group. The influence of baseline parameters on changes in international prostate symptom score with dutasteride, tamsulosin, and combination therapy among men with symptomatic benign prostatic hyperplasia and an enlarged prostate: 2-year data from the CombAT study. Effects of Withdrawing &agr;1‐Blocker from Combination Therapy with &agr;1‐Blocker and 5&agr;‐Reductase Inhibitor in Patients with Lower Urinary Tract Symptoms Suggestive of Benign Prostatic Hyperplasia: A Prospective and Comparative Trial Using Urodynamics Chemoprevention of prostate cancer in men at high risk: rationale and design of the reduction by dutasteride of prostate cancer events (REDUCE) trial. Combination therapy with dutasteride and tamsulosin in men with moderate-to-severe benign prostatic hyperplasia and prostate enlargement: the CombAT (Combination of Avodart and Tamsulosin) trial rationale and study design. Comparison of α-Blocker Monotherapy and α-Blocker plus 5α-Reductase Inhibitor Combination Therapy Based on Prostate Volume for Treatment of Benign Prostatic Hyperplasia [Effect of dutasteride on reduction of intraoperative bleeding related to transurethral resection of the prostate]. Efficacy and safety of dutasteride, tamsulosin and their combination in a subpopulation of the CombAT study: 2-year results in Asian men with moderate-to-severe BPH The effect of dutasteride on the efficacy of photoselective vaporization of the prostate: results of a randomized, placebo-controlled, double-blind study (DOP trial). Effect of dutasteride, tamsulosin and the combination on patient-reported quality of life and treatment satisfaction in men with moderate-to-severe benign prostatic hyperplasia: 4-year data from the CombAT study. Consequences of switching 5alpha-reductase inhibitors on prostate specific antigen velocity. The effects of dutasteride, tamsulosin, and the combination on storage and voiding in men with benign prostatic hyperplasia and prostatic enlargement: 2-year results from the Combination of Avodart and Tamsulosin study
PURPOSE Benign prostatic hyperplasia and hypogonadism are common disorders in aging men . There is concern that and rogen replacement in older men may increase prostate size and symptoms of benign prostatic hyperplasia . We examined whether combining dutasteride , which inhibits testosterone to dihydrotestosterone conversion , with testosterone treatment in older hypogonadal men with benign prostatic hyperplasia reduces and rogenic stimulation of the prostate compared to testosterone alone . MATERIAL S AND METHODS We conducted a double-blind , placebo controlled trial of 53 men 51 to 82 years old with symptomatic benign prostatic hyperplasia , prostate volume 30 cc or greater and serum total testosterone less than 280 ng/dl ( less than 9.7 nmol/l ) . Subjects were r and omized to daily transdermal 1 % T gel plus oral placebo or dutasteride for 6 months . Testosterone dosing was adjusted to a serum testosterone of 500 to 1,000 ng/dl . The primary outcomes were prostate volume measured by magnetic resonance imaging , serum prostate specific antigen and and rogen levels . RESULTS A total of 46 subjects completed all procedures . Serum testosterone increased similarly into the mid-normal range in both groups . Serum dihydrotestosterone increased in the testosterone only but decreased in the testosterone plus dutasteride group . In the testosterone plus dutasteride  group prostate volume and prostate specific antigen ( mean ± SEM ) decreased 12 % ± 2.5 % and 35 % ± 5 % , respectively , compared to the testosterone only group in which prostate volume and prostate specific antigen increased 7.5 % ± 3.3 % and 19 % ± 7 % ( p = 0.03 and p = 0.008 ) , respectively , after 6 months of treatment . Prostate symptom scores improved in both groups . CONCLUSIONS Combined treatment with testosterone plus dutasteride reduces prostate volume and prostate specific antigen compared to testosterone only . Coadministration of a 5α-reductase inhibitor with testosterone appears to spare the prostate from and rogenic stimulation during testosterone replacement in older , hypogonadal men with symptomatic benign prostatic hyperplasia OBJECTIVES To assess the efficacy and safety of dutasteride in Japanese men with benign prostatic hyperplasia ( BPH ) . METHODS This was a r and omized , double-blind , placebo-controlled , parallel-group study . A total of 378 subjects with clinical BPH having an International Prostate Symptom Score ( IPSS ) of 8 points or greater , a prostate volume of 30 mL or greater , and a maximal urinary flow rate ( Qmax ) of 15 mL/s or less were r and omized to receive placebo or dutasteride once daily for 52 weeks . Subjects were stratified according to tamsulosin use at baseline . The numbers of subjects with and without tamsulosin  use were 242 and 136 , respectively . IPSS , Qmax , prostate volume and drug safety were evaluated . RESULTS Continued improvement in IPSS was noted in the dutasteride group , and dutasteride significantly decreased IPSS compared with placebo . At week 52 , dutasteride significantly improved Qmax and prostate volume compared with placebo . Drug-related sexual function events in the dutasteride group were infrequent and generally were not treatment limiting . CONCLUSIONS Dutasteride improves urinary symptoms and flow rate and reduces prostate volume . In Japanese men with BPH , it is effective and generally well tolerated during the one-year treatment period PURPOSE We investigated whether combination therapy with dutasteride and tamsulosin is more effective than either monotherapy alone for improving symptoms and long-term outcomes in men with moderate to severe lower urinary tract symptoms and prostatic enlargement ( 30 cc or greater ) . We report preplanned 2-year analyses . MATERIAL S AND METHODS The CombAT study is an ongoing , multicenter , r and omized , double-blind , parallel group study . Men 50 years or older with a clinical diagnosis of benign prostatic hyperplasia , International Prostate Symptom Score 12 points or greater , prostate volume 30 cc or greater , total serum prostate specific antigen 1.5 ng/ml or greater to 10 ng/ml or less and peak urinary flow greater than 5 to 15 ml per second or less with a minimum voided volume of 125 ml or greater were r and omized to 0.5 mg dutasteride , 0.4 mg tamsulosin or the combination once daily for 4 years . Symptoms were assessed every 3 months and peak urinary flow was assessed every 6 months . The primary end point at 2 years was the change in International Prostate Symptom Score from baseline . RESULTS Combination therapy result ed in significantly greater improvements in symptoms vs dutasteride from month 3 and tamsulosin from month 9 , and in benign prostatic hyperplasia related health status from months 3 and 12 , respectively . There was a significantly greater improvement from baseline in peak urinary flow for combination therapy vs dutasteride and tamsulosin monotherapies from month 6 . There was a significant increase in drug related adverse events with combination therapy vs monotherapies , although most did not result in the cessation of therapy . CONCLUSIONS In men with moderate to severe lower urinary tract symptoms and prostate enlargement ( 30 cc or greater ) combination therapy provides a significantly greater degree of benefit than tamsulosin or dutasteride monotherapy OBJECTIVES To study the efficacy and safety of dutasteride , a dual inhibitor of the 5-alpha-reductase isoenzymes types I and II . METHODS A total of 4325 men ( 2951 completed ) with clinical benign prostatic hyperplasia , moderate to severe symptoms ( American Urological Association-Symptom Index score of 12 points or greater ) , a peak flow rate of 15 mL/s or less , a prostate volume of 30 cm3 or greater ( as measured by transrectal ultrasonography ) , and a serum prostate-specific antigen level of 1.5 to 10.0 ng/mL ( inclusive ) were enrolled into three identical clinical trials and r and omized to 0.5 mg dutasteride daily or placebo . After a 1-month , single-blind , placebo lead-in , patients were followed up for 24 months in a double-blind trial with multiple interval assessment s. RESULTS At 24 months , serum dihydrotestosterone was reduced from baseline by a mean of 90.2 % ( median -93.7 % ; P < 0.001 ) , and the total prostate and transition zone volumes were reduced by a mean of 25.7 % and 20.4 % , respectively ( P < 0.001 ) . The symptom score was improved by as early as 3 months , with pooled significance from 6 months onward ( P < 0.001 ) and a reduction of 4.5 points ( 21.4 % ) at 24 months ( P < 0.001 ) . The maximal flow rate improved significantly from 1 month ( P < 0.01 ) , with an increase of 2.2 mL/s reported at 24 months ( P < 0.001 ) . Hence , the risk reduction of acute urinary retention was 57 % and the risk reduction of benign prostatic hyperplasia-related surgical intervention was 48 % compared with placebo . The drug was well tolerated . CONCLUSIONS Dutasteride is a potent inhibitor of dihydrotestosterone production that is safe and effective in terms of the reduction of prostate volume and symptoms , flow rate improvement , and the reduction of the risk of acute urinary retention and surgery during a 24-month study period Abstract Background : Dutasteride is a dual inhibitor of type I and type II 5α-reductases and provides nearly complete suppression of dihydrotestosterone , which plays a key role in the aetiology and development of benign prostatic hyperplasia ( BPH ) . Most knowledge about the efficacy and safety of dutasteride in BPH derives from three pivotal phase III studies conducted primarily in Caucasian population s. Objective : This study aim ed to evaluate the efficacy and safety of dutasteride in Chinese adults with symptomatic BPH . Methods : This was a r and omized , double-blind , parallel-group , placebo-controlled study conducted over 6 months , followed by an open-label extension of 12 months . A total of 253 BPH subjects with a total prostate volume ( TPV ) of ≥30 cm3 , a maximal urinary flow rate ( Qmax ) between 5 and 15 mL/s , and an American Urology Association Symptom Index ( AUA-SI ) score of ≥12 units were r and omized to dutasteride 0.5 mg/day orally or matching placebo treatment in a 1 : 1 ratio . After 6 months , eligible subjects who volunteered to enter the open-label extension received dutasteride 0.5 mg/day orally . Changes in TPV , Qmax and AUA-SI as well as drug safety were evaluated . Results : Dutasteride significantly reduced mean TPV compared with placebo at 3 and 6 months ( both p<0.05 ) . At 6 months , mean TPV decreased by 17.14 % versus 3.71 % in the dutasteride and placebo groups , respectively . Numerically higher improvements in Qmax and AUA-SI were observed in the dutasteride group at 3 and 6 months , but there was no statistically significant difference between treatment groups . However , ad hoc analysis indicated that , at 6 months , significantly higher proportions of subjects in the dutasteride group experienced a Qmax improvement of ≥3 mL/s , or an AUA-SI improvement of ≥1 unit , compared with the placebo group ( both p<0.05 ) . According to these criteria , the Qmax responder rates were 33.63 % and 19.83 % in the dutasteride- and placebo-treated groups , respectively , and the AUA-SI responder rates were 87.61 % and 76.92 % , respectively . During the open-label extension , continuous improvements in TPV , Qmax and AUA-SI were noted in both groups . Dutasteride was well tolerated with a low incidence of treatment-related adverse events over 18 months . Conclusion : Dutasteride was effective compared with placebo in the treatment of symptomatic BPH among Chinese patients . The efficacy data from trials involving subjects of different ethnic origins showed some similarities . Dutasteride was generally well tolerated during the study period BACKGROUND Dutasteride is a dual inhibitor of type I and type II 5α-reductases and provides nearly complete suppression of dihydrotestosterone , which plays a key role in the aetiology and development of benign prostatic hyperplasia ( BPH ) . Most knowledge about the efficacy and safety of dutasteride in BPH derives from three pivotal phase III studies conducted primarily in Caucasian population s. OBJECTIVE This study aim ed to evaluate the efficacy and safety of dutasteride in Chinese adults with symptomatic BPH . METHODS This was a r and omized , double-blind , parallel-group , placebo-controlled study conducted over 6 months , followed by an open-label extension of 12 months . A total of 253 BPH subjects with a total prostate volume ( TPV ) of ≥30 cm3 , a maximal urinary flow rate ( Qmax ) between 5 and 15 mL/s , and an American Urology Association Symptom Index ( AUA-SI ) score of ≥12 units were r and omized to dutasteride 0.5 mg/day orally or matching placebo treatment in a 1 : 1 ratio . After 6 months , eligible subjects who volunteered to enter the open-label extension received dutasteride 0.5 mg/day orally . Changes in TPV , Qmax and AUA-SI as well as drug safety were evaluated . RESULTS Dutasteride significantly reduced mean TPV compared with placebo at 3 and 6 months ( both p<0.05 ) . At 6 months , mean TPV decreased by 17.14 % versus 3.71 % in the dutasteride and placebo groups , respectively . Numerically higher improvements in Qmax and AUA-SI were observed in the dutasteride group at 3 and 6 months , but there was no statistically significant difference between treatment groups . However , ad hoc analysis indicated that , at 6 months , significantly higher proportions of subjects in the dutasteride group experienced a Qmax improvement of ≥3 mL/s , or an AUA-SI improvement of ≥1 unit , compared with the placebo group ( both p<0.05 ) . According to these criteria , the Qmax responder rates were 33.63 % and 19.83 % in the dutasteride- and placebo-treated groups , respectively , and the AUA-SI responder rates were 87.61 % and 76.92 % , respectively . During the open-label extension , continuous improvements in TPV , Qmax and AUA-SI were noted in both groups . Dutasteride was well tolerated with a low incidence of treatment-related adverse events over 18 months . CONCLUSION Dutasteride was effective compared with placebo in the treatment of symptomatic BPH among Chinese patients . The efficacy data from trials involving subjects of different ethnic origins showed some similarities . Dutasteride was generally well tolerated during the study period 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 ) OBJECTIVE This study was conducted to examine the effect of discontinuing tamsulosin in patients with benign prostatic hyperplasia who had been receiving combination therapy with tamsulosin and dutasteride . METHODS The study sample consisted of 108 men with benign prostatic hyperplasia and lower urinary tract symptoms who visited our urology clinics between April 2008 and December 2010 . All were assessed using the International Prostate Symptom Score ( IPSS ) .  The patients had IPSS of 8 - 19 and prostate volumes ≥25 mL by transrectal ultrasonography . They were put on tamsulosin and dutasteride , and the efficacy of this regimen was assessed every 12 weeks . After 48 weeks , patients were divided at r and om into a group continuing to take the same drug combination ( group 1 ) and a group taking only dutasteride 0.5 mg ( group 2 ) . RESULTS Sixty-nine of the original 108 patients completed the study , 36 ( 52 % ) in group 1 and 33 ( 48 % ) in group 2 . The mean age of all patients was 67.96 ± 7.88 years and mean prostatic volume was 40.45 ± 12.81 mL. Mean prostate-specific antigen was 3.31 ( 0.4 - 9.9 ) ng/mL at the outset . The IPSS scores of the two groups at first visit , 48 and 72 weeks were , respectively , 14.69 versus 15.85 ( P = 0.322 ) , 12.08 versus 12.85 ( P = 0.582 ) and 10.89 versus 11.06 ( P = 0.897 . ) There was a statistically significant difference between the baseline and 72-week IPSS scores in both groups ( group 1 : P < 0.001 , group 2 : P < 0.001 ) . CONCLUSION In patients with moderate IPSS , discontinuing tamsulosin after 48 weeks of combined tamsulosin and dutasteride therapy has no significant effect on outcome To assess the improvements in symptoms , quality of life ( QoL ) , discomfort and satisfaction in patients with symptomatic benign prostatic hyperplasia ( BPH ) treated with dutasteride in clinical practice BACKGROUND We conducted a study to determine whether dutasteride reduces the risk of incident prostate cancer , as detected on biopsy , among men who are at increased risk for the disease . METHODS In this 4-year , multicenter , r and omized , double-blind , placebo-controlled , parallel-group study , we compared dutasteride , at a dose of 0.5 mg daily , with placebo .  Men were eligible for inclusion in the study if they were 50 to 75 years of age , had a prostate-specific antigen ( PSA ) level of 2.5 to 10.0 ng per milliliter , and had had one negative prostate biopsy ( 6 to 12 cores ) within 6 months before enrollment . Subjects underwent a 10-core transrectal ultrasound-guided biopsy at 2 and 4 years . RESULTS Among 6729 men who underwent a biopsy or prostate surgery , cancer was detected in 659 of the 3305 men in the dutasteride group , as compared with 858 of the 3424 men in the placebo group , representing a relative risk reduction with dutasteride of 22.8 % ( 95 % confidence interval , 15.2 to 29.8 ) over the 4-year study period ( P<0.001 ) . Overall , in years 1 through 4 , among the 6706 men who underwent a needle biopsy , there were 220 tumors with a Gleason score of 7 to 10 among 3299 men in the dutasteride group and 233 among 3407 men in the placebo group ( P=0.81 ) . During years 3 and 4 , there were 12 tumors with a Gleason score of 8 to 10 in the dutasteride group , as compared with only 1 in the placebo group ( P=0.003 ) . Dutasteride therapy , as compared with placebo , result ed in a reduction in the rate of acute urinary retention ( 1.6 % vs. 6.7 % , a 77.3 % relative reduction ) . The incidence of adverse events was similar to that in studies of dutasteride therapy for benign prostatic hyperplasia , except that in our study , as compared with previous studies , the relative incidence of the composite category of cardiac failure was higher in the dutasteride group than in the placebo group ( 0.7 % [ 30 men ] vs. 0.4 % [ 16 men ] , P=0.03 ) . CONCLUSIONS Over the course of the 4-year study period , dutasteride reduced the risk of incident prostate cancer detected on biopsy and improved the outcomes related to benign prostatic hyperplasia . ( Clinical Trials.gov number , NCT00056407 . OBJECTIVE To report additional analyses of efficacy over the initial 2 years and during a 2-year open-label extension of the three pivotal phase 3 studies in which dutasteride , a dual inhibitor of type 1 and 2 5alpha-reductase , was shown to be effective and well tolerated . PATIENTS AND METHODS All patients in the placebo and active groups were eligible for entry into the 2-year open-label extension , with all receiving dutasteride 0.5 mg daily . Mean changes from baseline were calculated for the American Urologic Association Symptom Index ( AUA-SI ) score at each scheduled time in the double-blind and open-label phase . The additional analyses included a breakdown of the AUA-SI score , including stratifying patients by symptom severity , assessment by baseline age and prostate volume , and the evaluation of symptoms responders . RESULTS There was a clinical ly meaningful improvement in AUA-SI in patients on dutasteride in the double-blind phase , but not in those on placebo . At 48 months , patients on dutasteride in both study phases had greater improvements in AUA-SI score and individual question scores than those on dutasteride in the open-label phase only . The proportion of patients with severe symptoms declined in both study groups , although these changes were more profound in those receiving dutasteride for the 4-year duration of the study . CONCLUSION In men with symptomatic benign prostatic hyperplasia , long-term ( 4-year ) treatment with the dual isozyme 5alpha-reductase inhibitor dutasteride result ed in sustained and continued improvements in symptoms and flow rate . For 4 vs 2 years , longer dutasteride therapy result ed in greater symptom improvement BACKGROUND Men with benign prostatic hyperplasia can be treated with alpha 1-adrenergic-antagonist drugs that relax prostatic smooth muscle or with drugs that inhibit 5 alpha-reductase and therefore reduce tissue and rogen concentrations . However , the effects of the two types of drugs have not been compared . METHODS We compared the safety and efficacy of placebo , terazosin ( 10 mg daily ) , finasteride ( 5 mg daily ) , and the combination of both drugs in 1229 men with benign prostatic hyperplasia .  American Urological Association symptom scores and peak urinary-flow rates were determined at base line and periodically for one year . RESULTS The mean changes from base line in the symptom scores in the placebo , finasteride , terazosin , and combination-therapy groups at one year were decreases of 2.6 , 3.2 , 6.1 , and 6.2 points , respectively ( P<0.001 for the comparisons of both terazosin and combination therapy with finasteride and with placebo ) . The mean changes at one year in the peak urinary-flow rates were increases of 1.4 , 1.6 , 2.7 , and 3.2 ml per second , respectively ( P<0.001 for the comparisons of both terazosin and combination therapy with finasteride and with placebo ) . Finasteride had no more effect on either measure than placebo . In the placebo group , 1.6 percent of the men discontinued the study because of adverse effects , as did 4.8 to 7.8 percent of the men in the other three groups . CONCLUSIONS In men with benign prostatic hyperplasia , terazosin was effective therapy , whereas finasteride was not , and the combination of terazosin and finasteride was no more effective than terazosin alone BACKGROUND Knowledge of baseline factors that influence outcomes for men with benign prostatic hyperplasia ( BPH ) receiving medical therapy may help to improve outcomes and cost effectiveness . OBJECTIVES To examine the influence of baseline parameters on changes in International Prostate Symptom Score ( IPSS ) and maximum urinary flow rate ( Q(max ) ) in men with BPH receiving dutasteride , tamsulosin , or a combination of the two using 2-yr Combination of Avodart and Tamsulosin ( CombAT ) study data . DESIGN , SETTING , AND PARTICIPANTS CombAT is an ongoing , 4-yr , multicentre , r and omised , double-blind study in 4844 men aged > or=50 yr with clinical diagnosis of BPH , IPSS > or=12 , prostate volume > or=30 cm(3 ) , prostate-specific antigen ( PSA ) 1.5 - 10 ng/ml , and Q(max ) > 5 and < or=15 ml/s with minimum voided volume > or=125 ml . INTERVENTION Daily tamsulosin 0.4 mg , dutasteride 0.5 mg , or the combination . MEASUREMENTS Post hoc analyses of mean IPSS and Q(max ) changes from baseline by treatment group and by baseline prostate volume , PSA , age , body mass index ( BMI ) , IPSS , IPSS quality of life ( QoL ) score , BPH Impact Index score , Q(max ) , and previous BPH medical therapy . RESULTS AND LIMITATIONS Combination therapy was more effective than either monotherapy after 24 mo in improving IPSS in all baseline subgroups , with benefit onset varying by baseline prostate volume . Combination therapy was also more effective in improving Q(max ) versus tamsulosin in all subgroups and versus dutasteride in 10 of 18 subgroups . At 24 mo , dutasteride monotherapy result ed in significantly greater IPSS improvements versus tamsulosin in men with lower age , worse symptoms , worse QoL , less bother , higher BMI , greater Q(max ) , higher prostate volume , and higher PSA at baseline . Post hoc analyses , the lack of placebo control , and the exclusion of men with unsuccessful medical BPH treatment are study limitations . CONCLUSIONS Combination therapy with tamsulosin and dutasteride affords the greatest and the most rapid symptomatic benefit among men with higher baseline prostate volume and is effective regardless of previous BPH medical therapy . Dutasteride monotherapy is more effective than tamsulosin in men with higher baseline prostate volume or PSA and worse symptoms Purpose : We compared the effects on lower urinary tract symptoms and bladder outlet obstruction of combination therapy with & agr;1‐blocker and 5&agr;‐reductase inhibitor or a switch to 5&agr;‐reductase inhibitor monotherapy . We determined the factors influencing changes in lower urinary tract symptoms after & agr;1‐blocker withdrawal . Material s and Methods : A total of 140 out patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia received combination therapy with silodosin 8 mg per day and dutasteride 0.5 mg per day for 12 months . Of the patients 132 were r and omized to continue combination therapy or switched to dutasteride monotherapy through silodosin withdrawal as the monotherapy group . Parameter changes from before r and omization to 12 months after r and omization were assessed based on subjective symptoms and urodynamic findings of voiding and storage function . Results : Efficacy analysis included 57 patients on combination therapy and 60 on monotherapy .  The change in I‐PSS ( International Prostate Symptom Score ) after r and omization was −0.7 and −0.6 in the combination therapy and monotherapy groups , respectively . The bladder outlet obstruction index changed from 46.1 to 41.8 in the combination therapy group and from 42.9 to 39.9 in the monotherapy group . No significant differences in subjective symptoms and bladder outlet obstruction were observed between the 2 groups . However , storage function decreased in the monotherapy group and lower urinary tract symptoms deteriorated significantly after the switch to dutasteride monotherapy in patients with a higher body mass index . Conclusions : We found that & agr;1‐blocker withdrawal from combination therapy was reasonable and tolerable with regard to the effect on lower urinary tract symptoms and bladder outlet obstruction . However , withdrawal must be performed carefully in patients with a high body mass index PURPOSE Chemoprevention may significantly impact the natural history of prostate cancer . The most potent intraprostatic and rogen , dihydrotestosterone , has a significant role in the pathophysiology of prostate cancer . It represents a biologically plausible target for chemoprevention through the inhibition of 5alpha-reductase isoenzymes . MATERIAL S AND METHODS The Reduction by Dutasteride of Prostate Cancer Events clinical trial is an international , multicenter , double-blind , placebo controlled chemoprevention study design ed to determine if dutasteride 0.5 mg daily decreases the risk of biopsy detectable prostate cancer .  A total of 8,000 men will be r and omized to receive dutasteride or placebo for 4 years . Eligible men must be 50 to 75 years old , have a serum prostate specific antigen of 2.5 to 10 ng/ml ( ages 50 to 60 years ) or 3.0 to 10 ng/ml ( older than 60 years ) . Men must have a negative 6 to 12 core biopsy within 6 months prior to enrollment . Repeat biopsies will be taken at 2 and 4 years . The rates of prostate cancer for each treatment group will be compared . Genetic and protein biomarkers of prostate cancer , and the effect of dutasteride on benign prostatic hyperplasia and prostatitis symptomatology and histopathology will also be assessed . RESULTS Results remain to be determined . CONCLUSIONS The study will examine the effects of the dual 5alpha-reductase inhibitor dutasteride on the natural history of prostate cancer in men at increased risk for this malignancy . It affords a unique opportunity to examine biomarkers and genetic linkage for prostate cancer , and assess a range of prostate health outcome measures Benign prostatic hyperplasia ( BPH ) is a highly prevalent condition in aging men , which can be progressive and lead to acute urinary retention ( AUR ) and the need for surgery . It is commonly treated with alpha-blockers and 5alpha-reductase inhibitors ( 5ARIs ) , both of which improve the symptoms of BPH . Long-term treatment with 5ARIs can also reduce the risk of developing AUR and the need for surgery . The l and mark Medical Therapy of Prostatic Symptoms ( MTOPS ) trial demonstrated that over 4 years the combination of the type 2-specific 5ARI , finasteride and the alpha-blocker doxazosin was more effective than either agent alone in reducing overall clinical progression . Since the initiation of MTOPS , it has been shown that patients with larger prostates and higher prostate-specific antigen ( PSA ) levels are at greater risk of BPH progression , and are therefore arguably more likely to benefit from combination therapy . The Combination of Avodart and Tamsulosin ( CombAT ) trial is a 4-year , global , multicenter , r and omized , double-blind , parallel-group study design ed to investigate the benefits of combination therapy with the dual 5ARI dutasteride and the alpha-blocker tamsulosin compared with each monotherapy in improving symptoms and long-term outcomes in men with moderate-to-severe symptoms of BPH and prostate enlargement .  Symptoms and long-term outcomes ( AUR and surgery ) will be assessed as separate primary endpoints at 2 and 4 years , respectively . Eligible patients were at least 50 years old with prostate volume > or = 30 cm(3 ) and PSA level > or = 1.5 ng/mL. A total of 4838 subjects have been enrolled . This paper describes the rationale , design and baseline data of the CombAT study OBJECTIVE : This study compared α-blocker monotherapy with combination therapy involving an α-blocker and a 5-α reductase inhibitor for benign prostatic hyperplasia ( BPH ) , according to baseline prostate volume . METHODS : Korean men diagnosed with BPH were r and omized to 12 months ' treatment with 0.2 mg tamsulosin or 0.2 mg tamsulosin plus 0.5 mg dutasteride . Prostate specific antigen ( PSA ) , prostate volume , transition zone volume ( TZV ) , International Prostate Symptom Score ( IPSS ) , maximal urinary flow rate ( Q max ) , postvoid residual urine volume and sexual function were assessed at baseline and after 12 months ' treatment . Variables were analysed based on baseline prostate volumes of ≤ 35 ml or > 35 ml . RESULTS : In total , 216 men with BPH were included . Combination therapy result ed in significant improvements in prostate volume , TZV , PSA , IPSS and Q max , which were most pronounced in men with a prostate volume > 35 ml . CONCLUSIONS : Tamsulosin monotherapy was sufficient treatment for BPH in Korean men with a prostate volume ≤ 35 ml . Combination tamsulosin and dutasteride therapy provided greater benefits than tamsulosin monotherapy in men with BPH whose prostate volume was > 35 ml OBJECTIVE The pharmacological action of 5-alpha-reductase inhibitors ( 5-ARI ) would reduce angiogenesis associated with benign prostatic hyperplasia ( BPH ) , thereby decreasing peroperative bleeding during transurethral resection of the prostate ( TURP ) . Dutasteride , a double inhibitor of 5-alpha-reductase iso-enzymes types 1 and 2 , was not been previously studied in the context of reduction of peroperative bleeding related to TURP . MATERIAL AND METHODS We conducted a multicentre , r and omized , double-blind , placebo-controlled , parallel group study to evaluate the efficacy of dutasteride 0.5 mg per day , in peroperative bleeding related to TURP for BPH in patients over the age of 50 years with a prostatic volume greater than 30 cm3 . Treatment was administered for 4 weeks before the operation . The primary endpoint was haemoglobin , expressed in grams , and expressed in relation to the weight of prostate resected , also expressed in grams . RESULTS 59 patients were evaluated ( 32 treated with dutasteride and 27 treated with placebo ) . A significant difference in peroperative bleeding was observed between the dutasteride group ( 1.944 + /- 1.816 g of Hb/g of prostate resected ) and the placebo group ( 1.401 + /- 1.021 g of Hb/g of prostate resected ) . Preoperative treatment was well tolerated . CONCLUSION The working hypothesis of the study was not confirmed due to the low bleeding rate in the placebo group and the results suggest that a longer duration of treatment with dutasteride would reduce intraoperative and postoperative bleeding in TURP Although ethnicity-based differences in prostate size and physiology have been reported , results of benign prostatic hyperplasia ( BPH ) treatment trials in predominantly Caucasian patients are assumed to be applicable to non-Caucasian population s. This post hoc analysis investigated whether an Asian sub population of men with moderate-to-severe BPH in the CombAT study achieves treatment responses in line with those of the overall study population . In this double-blind , r and omized , parallel-group trial , 325 Asian men were assigned to treatment with 0.5 mg dutasteride once daily , 0.4 mg tamsulosin once daily or the combination . Decrease in international prostate symptom score ( IPSS ) at month 24 from baseline ( the primary endpoint ) was significantly greater with combination treatment compared with tamsulosin ( P<0.05 ) , and numerically , but not statistically significantly , greater compared with dutasteride .  Mean IPSS was reduced from baseline by 7.5 ( ±0.84 ) in the combination group , by 6.3 ( ±0.86 ) in the dutasteride group and by 4.5 ( ±0.78 ) in the tamsulosin group , result ing in respective mean IPSS at months 24 of 11.4 ( ±0.60 ) , 12.7 ( ±0.70 ) and 14.3 ( ±0.74 ) . The adverse event profile was similar to that observed in the overall CombAT population , and drug-related adverse events were more common with combination therapy ( 26 % ) than with tamsulosin ( 15 % ) or dutasteride ( 9 % ) . No unexpected adverse events emerged . In conclusion , in Asian men with moderate-to-severe lower urinary tract symptoms and an enlarged prostate  , combination therapy achieved significantly greater improvements from baseline BPH symptoms , flow rate , quality of life , reduced prostate volume and improved treatment satisfaction compared with tamsulosin monotherapy OBJECTIVES To study the effect of Dutasteride on the efficacy of GreenLight photoselective vaporization of the prostate ( PV ) . Some investigators have suggested that 5 alpha-reductase inhibitors may interfere with PV by reducing intraprostatic blood flow . Dutasteride offers the most complete blockade of the 5 alpha-reductase inhibitors , with minimal increase in side effects . METHODS This is a prospect i ve , placebo-controlled , r and omized , double-blind study . A total of 59 patients were r and omized to either dutasteride 0.5 mg or placebo  for 3 months before and 12 months after PV .  Surgical time , joules used , estimated blood loss , and ease of the procedure were compared . Other clinical end points investigated include postsurgical catheter time , hematuria , dysuria , urinary flow parameters , American Urological Association symptom score , benign prostatic hyperplasia quality of life score , prostate volume , and prostate-specific antigen level . RESULTS Average surgical time and joules used were 12 % ( P = .24 ) and 16 % ( P = .15 ) less , respectively , for dutasteride patients compared with placebo .  Estimated blood loss was also lower in the treatment group ( P = .14 ) . However , these results were not statistically significant . Surgeon-rated ease of the procedure was comparable between the 2 groups . There were no significant differences in catheter time , dysuria , quality of life scores , or urinary flow parameters . Quality of life and urinary parameters markedly improved after PV . CONCLUSIONS Compared with patients r and omized to placebo , patients r and omized to dutasteride experienced a trend toward decreased time , joules used , and blood loss during surgery . Although we could not convincingly prove an operative benefit of treatment with dutasteride before surgery , we have demonstrated the efficacy of PV in men receiving dutasteride OBJECTIVE To investigate the effect of combination therapy with dutasteride plus tamsulosin compared with each monotherapy on patient-reported health outcomes over 4 years in men with moderate-to-severe lower urinary tract symptoms ( LUTS ) because of benign prostatic hyperplasia ( BPH ) . METHODS CombAT was a 4-year international , double-blind , r and omised , parallel-group trial in men ( n = 4844 ) with moderate-to-severe symptoms of BPH and at increased risk of disease progression [ age > or = 50 years , International Prostate Symptom Score ( IPSS ) > or = 12 , prostate volume > or = 30 cc , serum prostate-specific antigen > or = 1.5 ng/ml to < or = 10 ng/ml and maximum urinary flow rate 5 - 15 ml/s with minimum voided volume > or = 125 ml ] . Subjects were r and omised to receive 0.5 mg dutasteride , 0.4 mg tamsulosin or the combination once daily for 4 years . The primary endpoint at 4 years was the time to event and proportion of subjects with acute urinary retention or undergoing BPH-related prostate surgery . Secondary endpoints included the health- outcomes measures , BPH Impact Index ( BII ) , IPSS question 8 ( IPSS Q8 ) and the Patient Perception of Study Medication ( PPSM ) question naire . RESULTS At 4 years , combination therapy result ed in significantly superior improvements from baseline in BII and IPSS Q8 than either monotherapy ; these benefits were observed from 3 months onwards compared with dutasteride and from 9 months ( BII ) or 12 months ( IPSS Q8 ) onwards compared with tamsulosin . Also at 4 years , the PPSM question naire showed that a significantly higher proportion of patients was satisfied with , and would request treatment with , combination therapy compared with either monotherapy . CONCLUSIONS Combination therapy ( dutasteride plus tamsulosin ) provides significantly superior improvements in patient-reported quality of life and treatment satisfaction than either monotherapy at 4 years in men with moderate-to-severe BPH symptoms PURPOSE The 5alpha-reductase inhibitors improve urinary symptoms related to benign prostatic hyperplasia , deter benign prostatic hyperplasia progression and provide prostate cancer chemoprevention . Currently there are a number of 5alpha-reductase inhibitor formularies , including Proscar , generic finasteride and dutasteride . While all formularies decrease serum prostate specific antigen ( a proxy for prostate volume ) , they may not accomplish this to the same degree , which may have dramatic effects on prostate specific antigen kinetics in men changing 5alpha-reductase inhibitor formularies . We examined prostate specific antigen velocity after changes in 5alpha-reductase inhibitor formularies . MATERIAL S AND METHODS We identified patients treated with 2 or more 5alpha-reductase inhibitor formularies who had sufficient prostate specific antigen values to calculate prostate specific antigen velocity during each 5alpha-reductase inhibitor treatment . Patient data were grouped depending on the formularies received . Statistical analysis was done to compare prostate specific antigen velocity at various time points while on different 5alpha-reductase inhibitors . RESULTS Eight men changed from dutasteride to generic finasteride ( group 1 ) , 21 changed from dutasteride to Proscar ( group 2 ) , 49 changed from Proscar to dutasteride ( group 3 ) and 77 changed from Proscar to generic finasteride ( group 4 ) . We noted a significant increase in prostate specific antigen velocity in groups 1 and 2 ( p < 0.05 ) , and 4 ( p < 0.005 ) . The increase was greater than 0.35 ng/ml per year , the common cutoff for prostate biopsy recommendations , in more than a third of patients . CONCLUSIONS Results confirm that changing 5alpha-reductase inhibitors drugs can be associated with a clinical ly significant change in prostate specific antigen velocity . These prostate specific antigen velocity changes could place patients at risk for unnecessary prostate biopsy . Additional prospect i ve studies are warranted This article reports the results of a post hoc analysis of the multicenter , r and omized , double-blind Combination of Avodart and Tamsulosin ( CombAT ) study , which aim ed to investigate the effects of dutasteride ( 0.5 mg ) , tamsulosin ( 0.4 mg ) , and their combination on storage and voiding symptoms in 4844 men aged ⩾50 years with moderate-to-severe lower urinary tract symptoms ( International Prostate Symptom Score ⩾12 ) , prostate volume ( PV ) ⩾30 cm3 and PSA 1.5–10 ng ml−1 . After 24 months , combination treatment achieved significantly greater mean reductions in both voiding and storage symptoms than either monotherapy , in each of the three baseline PV tertiles ( 30 to < 42 , 42 to < 58 , ⩾58 cm3 ) . Dutasteride was as effective as tamsulosin for control of storage symptoms , but provided significantly greater relief of voiding symptoms than tamsulosin
When comparing dutasteride with finasteride , no significant differences in symptom improvement or the rate of adverse events were observed .
Conclusions Dutasteride can be used to improve urinary symptoms ( IPSS and Qmax ) and reduce TPV but with awareness of its potential adverse events .
Purpose To determine the efficacy and safety of dutasteride , alone or in combination , versus a placebo or control , used for the treatment of benign prostatic hyperplasia .