***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Prostate cancer is a disease associated with and rogens . It has been hypothesized that reducing the conversion of testosterone ( T ) to dihydrotestosterone ( DHT ) in the prostate by the use of the drug finasteride , a 5alpha-reductase inhibitor , will reduce the incidence of prostate cancer . We investigated the chemopreventive potential of finasteride by evaluating its effect on the prostate gl and of men with elevated serum prostate-specific antigen ( PSA ) . Fifty-two men with elevated PSA and prostate sextant biopsies negative for cancer were r and omized to receive finasteride 5 mg day(-1 ) ( 27 patients ) or no medication ( 25 patients ) for 12 months and were rebiopsied at 12 months . The biopsies were evaluated for the presence of cancer , the proportion of gl and ular and hyperplastic tissue , and the presence of high- grade prostatic intraepithelial neoplasia ( PIN ) . Epithelial proliferation was assessed in the pre study and 12-month biopsies by immunohistochemistry using antibody to proliferating cell nuclear antigen ( PCNA ) . Serum blood sample s were drawn at baseline and after 1 , 3 , 6 and 12 months of study . In the control group , serum levels of PSA and T were unchanged throughout the 12 months . In the finasteride group , PSA decreased 48 % ( P < 0.001 ) , DHT decreased 67 % ( P < 0.001 ) and T increased 21 % ( P < 0.001 ) . Histological evaluation of pre study and 12-month biopsy specimens revealed that the finasteride group had a 30 % reduction in the percentage of hyperplastic epithelial tissue ( P = 0.002 ) , although this decrease was not statistically significantly different between the finasteride and control groups ( P = 0.11 ) . In patients with PIN on pre study biopsy , no change occurred in the PIN lesions with finasteride treatment . Finasteride also had no effect on the proliferation index of prostatic epithelial cells . Of the 27 patients treated with  finasteride , eight ( 30 % ) had adenocarcinoma of the prostate detected on the 12-month biopsy , compared with one ( 4 % ) of the control patients ( P = 0.025 ) . In the treatment group , six cancers occurred in the eight patients with PIN on the pre study biopsy ; in the observation group no cancers were detected in the five patients with PIN on the pre study biopsy ( P = 0.021 ) . Two cancers occurred in the 19 men in the treatment group with no evidence of PIN on the pre study biopsy , compared with one cancer in the 20 men in the observation group with no evidence of PIN on the pre study biopsy ( P = 0.60 ) . This study , using a novel model for evaluating short-term efficacy of chemopreventive or therapeutic agents in men at high risk of prostate cancer , provides little evidence that finasteride is an effective chemopreventive agent for prostate cancer in men with elevated PSA In this multicentre , double-blind study , patients with LUTS/BPH were r and omised to 26 weeks with finasteride 5 mg once daily ( n=204 ) or tamsulosin 0.4 mg once daily ( n=199 ) . Double-blind treatment was continued for another 26 weeks ( total treatment duration : 1 y ) . The primary efficacy parameter was the difference in mean change in total Symptom Problem Index ( SPI ) from baseline to end point at week-26 in the intention-to-treat ( ITT ) and per protocol ( PP ) population s. Tamsulosin induced a greater improvement in total SPI ( −5.2 points or −37 % ) compared to finasteride ( −4.5 points or −31 % ) at week-26 ( P=0.055 in ITT and P=0.032 in PP ) . Tamsulosin  improved urinary symptoms ( particularly the more bothersome storage symptoms ) and flow more quickly than finasteride . The difference was statistically significant for the SPI from week-1 ( reduction , respectively , −2.5 vs −1.8 points , P=0.043 ) to week-18 and for Qmax from week-1 ( increase , respectively , 2.3 vs 0.7 ml/s , P=0.0007 ) to week-12 . Both treatments were well tolerated with a comparable incidence of adverse events , including urinary retention 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 BACKGROUND Benign prostatic hyperplasia is commonly treated with alpha-adrenergic-receptor antagonists ( alpha-blockers ) or 5alpha-reductase inhibitors . The long-term effect of these drugs , singly or combined , on the risk of clinical progression is unknown . METHODS We conducted a long-term , double-blind trial ( mean follow-up , 4.5 years ) involving 3047 men to compare the effects of placebo , doxazosin , finasteride , and combination therapy on measures of the clinical progression of benign prostatic hyperplasia . RESULTS The risk of overall clinical progression -- defined as an increase above base line of at least 4 points in the American Urological Association symptom score , acute urinary retention , urinary incontinence , renal insufficiency , or recurrent urinary tract infection -- was significantly reduced by doxazosin ( 39 percent risk reduction , P<0.001 ) and finasteride ( 34 percent risk reduction , P=0.002 ) , as compared with placebo . The reduction in risk associated with combination therapy ( 66 percent for the comparison with placebo , P<0.001 ) was significantly greater than that associated with doxazosin ( P<0.001 ) or finasteride ( P<0.001 ) alone . The risks of acute urinary retention and the need for invasive therapy were significantly reduced by combination therapy ( P<0.001 ) and finasteride ( P<0.001 ) but not by doxazosin . Doxazosin ( P<0.001 ) , finasteride ( P=0.001 ) , and combination therapy ( P<0.001 ) each result ed in significant improvement in symptom scores , with combination therapy being superior to both doxazosin ( P=0.006 ) and finasteride ( P<0.001 ) alone . CONCLUSIONS Long-term combination therapy with doxazosin and finasteride was safe and reduced the risk of overall clinical progression of benign prostatic hyperplasia significantly more than did treatment with either drug alone . Combination therapy and finasteride alone reduced the long-term risk of acute urinary retention and the need for invasive therapy OBJECTIVES To evaluate the efficacy and tolerability of the selective alpha(1)-adrenergic antagonist doxazosin and the 5-alpha-reductase inhibitor finasteride , alone and in combination , for the symptomatic treatment of benign prostatic hyperplasia . METHODS In a prospect i ve , double-blind , placebo-controlled trial , 1095 men aged 50 to 80 years were r and omized to treatment for 52 weeks with doxazosin , finasteride , the combination of doxazosin and finasteride , or placebo . The dose of finasteride ( or its matched placebo ) was 5 mg/day . Doxazosin ( or its matched placebo ) was initiated at 1 mg/day , and titrated up to a maximum of 8 mg/day over approximately 10 weeks according to the response of the maximal urinary flow rate ( Qmax ) and International Prostate Symptom Score ( IPSS ) . The IPSS and Qmax were assessed at baseline and at weeks 10 , 14 , 26 , 39 , and 52 or at the endpoint . RESULTS An intent-to-treat analysis of 1007 men showed doxazosin and doxazosin plus finasteride combination therapy produced statistically significant improvements in total IPSS and Qmax compared with placebo and finasteride alone ( P < 0.05 ) . Finasteride alone was not significantly different statistically from placebo with respect to total IPSS and Qmax . All treatments were generally well tolerated . CONCLUSIONS Doxazosin was effective in improving urinary symptoms and urinary flow rate in men with benign prostatic hyperplasia , and was more effective than finasteride alone or placebo . The addition of finasteride did not provide further benefit to that achieved with doxazosin alone OBJECTIVES To evaluate prostate cancer detection and prostate-specific antigen ( PSA ) among men with benign prostatic hyperplasia treated with finasteride .  METHODS Three thous and forty men 45 to 78 years of age with PSA less than 10 ng/mL and no history of prostate cancer were r and omized in a double-blind , placebo-controlled trial to finasteride ( n = 1524 ) or placebo ( n = 1516 ) for up to 4 years . A prer and omization biopsy negative for prostate cancer was obtained in 98 % of patients with a screening PSA of 4.0 ng/mL or more , and an end-of- study biopsy was requested of all such patients without a recent second negative biopsy or a prostate cancer diagnosis . RESULTS Overall , 644 patients ( 21 % ) underwent biopsy  and 201 ( 6.6 % ) underwent transurethral resection of the prostate .  Prostate cancer was diagnosed in 4.7 % of men on finasteride and 5.1 % on placebo ( P = 0.7 ) . Elevated PSA prompted diagnosis in 35 % of cases on finasteride and 34 % on placebo . The area under the receiver operating characteristic curve for last PSA was 0.84 on finasteride and 0.79 on placebo ( P = 0.07 ) . Use of an upper limit of normal for last PSA of 2.0 ng/mL for finasteride and 4.0 ng/mL for placebo yielded similar sensitivity ( 66 % versus 70 % , P = 0.6 ) , higher specificity ( 82 % versus 74 % , P < 0.0001 ) , and a higher likelihood ratio ( 3.6 versus 2.7 , P < 0.05 ) for finasteride than for placebo . CONCLUSIONS In men treated with finasteride , multiplying PSA by 2 and using normal ranges for untreated men preserves the usefulness of PSA for prostate cancer detection Tamsulosin ( 0.2 mg ) and finasteride ( 5 mg ) once daily for 24 weeks were compared in a single-blind , r and omized study as initial treatments for lower urinary tract symptoms associated with benign prostatic hyperplasia ( BPH ) in 205 Korean patients .  Symptom and quality of life ( QOL ) assessment by the International Prostatic Symptom Score ( I-PSS ) , maximum urinary flow rate ( Q max ) and adverse events were analysed at 4 weeks and 24 weeks . On intention-to-treat analysis , both drugs showed similar efficacy at endpoint ( decreased I-PSS , increased Q max and improved QOL score ; 34.7 % , 23.9 % and 34.1 % for tamsulosin , and 30.5 % , 22.2 % and 23.1 % for finasteride , respectively ) . However , tamsulosin produced significant improvements in I-PSS and Q max at 4 weeks compared with finasteride ( 17.6 % versus 10.0 % and 10.9 % versus 3.1 % , respectively ) , and a superior QOL score improvement during the study . Adverse events were observed significantly more frequently among finasteride than tamsulosin patients ( 23 versus four ) . Both were equally effective in long-term treatment of urinary outflow obstruction symptoms associated with BPH in Korean patients , but tamsulosin was more effective for short-term treatment , with a better safety profile OBJECTIVE To evaluate the efficacy and safety 
    Output:
    
5ARI reduce prostate cancer risk but may increase the risk of high- grade disease in men who are undergoing regular screening for prostate cancer using prostate specific antigen and digital rectal examination .
Effects are consistent across race , family history and age and possibly 5ARI but were limited to men with baseline PSA values < 4.0 ng/mL. The impact of 5ARI on absolute or relative rates of prostate cancer in men who are not being regularly screened is not clear .
Information is inadequate to assess the impact of 5ARI on mortality