Vol. 169, No.4, Supplement, Wednesday, April 30, 2003 THE JOURNAL OF UROLOGY® 475

Benign Prostatic Hyperplasia: Medical andHormonal Therapy (II)

Moderated PosterWednesday, April 30, 2003 1:30-3:30 PM

1781DEVELOPMENT OF A NOMOGRAM TO PREDICT BPH PRO­GRESSION WITH OR WITHOUT DUTASTERIDE THERAPYMichael W Kattan, New York, NY; Timothy H Wilson, Research TrianglePark, NC; Claus Roehrbom, Dallas, TX; Kevin Slawin *, Houston, TX

INTRODUCTION AND OBJECTIVE: The purpose of this study was todevelop a prediction model, or nomogram, that would predict the probability thata man with benign prostatic hyperplasia (BPH) would experience acute urinaryretention (AUR) or require surgical intervention (SI) within 2 years, with orwithout dutasteride therapy.

METHODS: We modeled 4294 men treated in the Phase III dutasterideBPH trials. These men were characterized at baseline by a number ofparameters, including AUA symptom index, BII questionnaire, prior use ofblockers, prostate volume, prostate specific antigen (PSA) level, and maximumflow rate (Qmax). Cox proportional hazards regression was used to relate thesebaseline variables to their future probability of AUR/SI within 2 years. Thenomogram was internally validated with bootstrapping to assess itsdiscrimination and calibration. Discrimination was quantified as theconcordance index (CI).

RESULTS: The nomogram appeared to be accurately calibrated anddiscriminating (CI=0.71, P<O.OOl). The table contains the p-values for thepredictors in the multivariable model. The figure contains the nomogram.

CONCLUSIONS: In conclusion, we have constructed a nomogram forpredicting the probability that a man will experience AUR or require SI within 2years. At 24 months follow-up, 7.4% of placebo patients and 3.7% of dutasteridepatients had experienced either AUR and/or SI, representing a 50% relative riskreduction. For the highest risk patient, dutasteride therapy lowers absolute risk by27%.

Table. Coxproportional hazards regression results.

ComboFINDOXSubseale Placebo

1783THE LONG TERM EFFECTS OF DOXAZOSIN, FINASTERIDE,AND THE COMBINATION OF BOTH ON SEXUAL FUNCTIONIN MEN PARTICIPATING IN THE MTOPS STUDY Kevin TMcVary*, Chicago, IL; John Foley, San Antonio, DC; Oliver M Bautista,John Kusek, Rockville, MD

INTRODUCTION AND OBJECTIVE: The impact of long term medicaltherapy for LUTS secondary to BPH on sexual function is not known. A recentlyconcluded clinical trial (MTOPS Study), compared the effects of doxazosin andfinasteride, alone or in combination, with placebo on the clinical progression ofBPH. We examined the effects over time of each of these drugs on sexual function.

METHODS: During the MTOPS a sexual function questionnaire wasadministered at baseline and yearly thereafter. Men were randomized to eitherplacebo(n=705), doxazosin (n=752), finasteride (n=736), or combination therapy(n=746). Average follow-up was 4.5 years; 75% of participants were followed for>4 years. All responses were recorded on a 5-point Likert scale (0-4). Highervalues on the subscales (Sexual Drive(SD), Erectile Function (EF),Ejaculation(EJ), Problem Assessment (PA), and Overall Satisfactiontfrxj)indicated better function/satisfaction.

RESULTS: At baseline, mean age was 63 (+7) years; mean scores for each ofthe 5 subscales were: SD (1.9+0.9), EF (2.1+ 1.2), EJ (2.8+ 1.3),PA(2.5+ 1.3) andOS(2.0+ 1.2). After 4 years of follow-up the subscales were significantly differentbetween the active treatment and the placebo groups. (See Table). Over the entirestudy, the placebo group had decreased OS compared to doxazosin (p<0.05).Finasterde had decreased SD (p<0.05) and PA (p<O.05) when compared toplacebo. Combination therapy had decreased EF (p<O.O I) and PA (p<O.OI) whencompared to placebo. All active therapies had decreased EJ (p<O.Ol).

CONCLUSIONS: In a clinical trial of men with moderate/severe BPH sexualfunction subscales ate consistently and significantly associated with the type ofmedical treatment received.

Sexual Scale Analysis

present study the effect of alpha-blockers on vesical and prostatic blood flow aswell as urodynamic parameters was investigated.

METHODS: 11 patients suffering from lower urinary tract symptoms (LUTS)were treated with long acting alpha-blocker medication for 5 weeks. In all patientscolour Doppler ultrasound of the urinary bladder and the prostate as well ascomparative cystometry were performed before and after treatment. Normal saline(NaCl) was used for the first run, followed by a second run with 0.2 M potassiumchloride (KCI). Additional to standard urodynamic parameters recorded in eachrun, color pixel density was measured in several intramural arteries in the urinarybladdder and the prostate at filling volumes of Oml, 100 ml and maximumcystometric capacity (Cmax) to measure and quantify the perfused vessels and totalperfusion of the lower urinary tract. For these measurements a color Doppler unit(Acuson, USA), an endorectal probe and special software (Scion Image AnalysisSoftware, USA) were used.

RESULTS: Contrary to healthy men all patients showed a strong pathologicresponse to intravesical KCI (mean Cmax 435 ml with NaCI and 333 ml with KCl)before treatment with the long acting alpha-blocker. In presence of NaC!, colorpixel density rose by 26% with distension. Mean color pixel density in the urinarybladder and the prostate rose by only 42% during filling with KCI. After therapymaximum urinary flow and bladder contractility did not change significantly. Cmaxduring filling with NaCl remained unchanged while mean Cmax during filling withKCI was significantly higher after therapy (403 ml). Furthermore, after therapycolor pixel density was siginificantly increased in tbe prostate as well as in theurinary bladder in the presence of KCI (43% in the empty bladder and 104% atCmax with KCI). After alpha-blocker treatment the values of Cmax and color pixeldensity during filling with KCl were comparable to normal values measured inhealthy volunteers in earlier studies.

CONCLUSIONS: Our data strongly suggest that benign prostatic hyperplasiais associated with a dysregulation of normal blood flow in the lower urinary tract.Furthermore, alpha blockers increase blood flow in the lower urinary tract andmaximum bladder capacity. These results may explain the therapeutic effects ofalpha-blockers on lower urinary tract symptoms.

Source of Funding: None.

, I

'2 10 a

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,a 11 1.

0.0.0.07 010.01

o :z .. 6; I 10

all 101 11. '26 .34 151 1$4 HI 189 202 214 227 239 252

GlI...,.50.5MG

Source of Funding: None.

Prob. 2-year AURISI

PSA (ng/mll

1782ALPHA-BLOCKERS INCREASE VESICAL AND PROSTATICBLOOD FLOW AND BLADDER CAPACITY Germar M Pinggera,Anton Schuster, Leo Pallwein, Andrea Klauser, Ferdinand Frauscher,Bernhard Furtmiiller, Gero Hohlbrugger, Georg Bartsch, Hannes Strasser*,lnnsbruck, Austria

INTRODUCTION AND OBJECTIVE: Alpha blockers have been shown torelieve symptoms suggestive of bladder outlet obstruction in patients presentingwith lower urinary tract symptoms but do not treat the obstruction itself. In the

SO@ Baseline 2.0(+0.9)SO~Yr 4 -02(+0.8)EF@Baseline 2.2{+1.2}EF~Yr4 -0.3(+0.9)EJ@Baseline 2.9(+1.2)EJA@Yr4 -0.2(+1.3)PA@Baseline 2.5(+1.3)PA~Yr4 -O.1{+1.2)OS@Baseline 2.1(+1.2}OS~Yr4 -0.1(+1.2)

Source of Funding: NIDDKd.

1,9(+09)-0.2(+0.8)2.1(+1.2}-0.2(+1.0)2.8(+1.3)-0.3(+1.3)2.5(+1.3)-0.1(+1.3)1,9(+12)0.0(+1.3)

1.9(+0.9)-0.3(+08)2,1(+1.2}-0.3(+1.0)2.8(+1.2)-0.5(+1.3)2.5(+1.3)-0.2(+1.3)2.0(+1,2)-0.2(+1.3)

1.9{+O.9)-0.2(+0.8)2.1{+1.2}-0.4{+1.0)2.B(+1.3}-0.7(+1.4)2,5(+1.3)-0.3(+1.3)2.0(+1.2}·0.2(+1.3)

476 THE JOURNAL OF UROLOGY® Vol. 169, No. 4, Supp lement , Wednesday, April 30, 2003

' p<O.050," p<O. 010,·"p<O.OOl forbelween..group comparisons

Source of Funding: Study Funded by Merck & Co., Inc.

1785EFFE CT OF FINASTERIDE ON BLOOD FLOW IN THE PROS­TATE Stuart M Diamond", Chris Garlitz, Scott Hubosky, Pat Shenot,Ethan Halpern, Philadelphia, PA

INTROD UCTION AND OBJE CTI VE: We have previously show n theefficacy of Finasteride in the prevention of hem atur ia and hem atospermiaassociated with prostat e needl e biopsy. We present the first human studyshowi ng tha t Fin asteride decreases prost at ic blood flow, and reducesmicrove sse l density (MVD), using power Doppl er and microsphe re transrectalultr asoun d technology.

METHODS: We prospectively studied 20 new male patients who weredetermined to need transrectal ultrasound (TRUS) guided needle biopsy of theprostate. Patients were evenly double blinded into 2 groups. Group l -placebo,group 2- 2 weeks finasteride prior to biopsy and two weeks after biopsy. Allpatients underwent baseline imaging with Gray scale, Power Doppler, and Grey­scale pulse inversion harmonic imaging of the gland with an imaging agent.Patients were then randomized to the 2 treatment groups and had the same imagingprotocol repea ted at the time of biopsy. For each imaging sequence, the percent ofcolor pixels within the mass was calculated. The fractional moving blood volume(FMBV) values pre and post contrast administration as well as pre and posttreatment was calculated.

RESULTS : Overall finasteride treated patient showed a 63% reduction in bloodflow throughout the gland compared to Placebo. Grey scale analysis did not reveala statis tical significant change in blood flow between the 2 groups. Power Dopplerrevealed an overall reduction in blood flow by 50% in-group 2 compared to group1. Overall there was a 60%, 17%, 45% reduction in blood flow in the transition ,

1784EFFECT OF FINASTERIDE ON SERUM TESTOSTERONE ANDBODY MASS INDEX IN MEN WITH BENIGN PROSTATICHYPERPLASIA Claus G Roehrborn", Dallas, TX; fo r the PLESS StudyGroup, USA

INTRODUCTIO N AND OBJECTI VE: The effects of long-term treatmentwith finasteride on serum testosterone (T) in men with benign prostatic hyperplasia(BPH) have not been well studied. The present analysis from the 4-year Proscar"Long-Term Efficacy and Safety Study (PLESS) evalua ted the effect of finasterideon serum T in men with BPH.

METHODS: PLESS compared the safe ty and efficacy of finasterid e 5 mg toplacebo in 3040 men with moderate to severe symptomatic BPH and enlargedprostates, and included the pro spective measuremen t of serum T in a randomly­selected subset of patients comprisin g approximately 10% of the randomizedpop ulat ion (N = 301). T levels were measured at basel ine and annuallythereafter , and were determined using radioimmunoassay (the normal range forserum T using this assay was 350-1050 ng/dL ). The effects of finasteride onserum T were assessed in the total T subset as well as in patient cohortsorgan ized by baseline T tertiles (:53 30ng/dL , > 330-47 Ing/dL, and >47Ing/dL).

RESULTS: Overall, finasteride treatment led to a mean percent increase frombaseli ne in serum T of 23-24% compared with a mean increase of 1-6% withplacebo (p< O.OOI for between-group compar ison at all time points). The increasein serum T with finasteride was greatest in patients with low baseline T levels.Moreove r, in men in the lower T tertiles, finasteride treatment led to a slight butsignificant decrease in body mass index (BMI). Thus, in the lower T tertiles,finasteride treatment led to a significant mean percent decrease relative to placeboin BMI at Month 48 of -2.0 to -2.9%, which represented a weight loss of 1.8 to 2.7kg. The sexual adverse experience profiles for finasteride and placebo were similaracross the baseline T tertile cohorts .

CONC LUSIONS : Finasteride led to a generally modest but significant increasein serum T, with the greatest increases occurring in men with low baseline T levels.Moreover, finasteride-treated patients with low baseline serum T experienced aslight but significant decrease in BMI and body weight over 4 years. The sexual AEprofile for finasteride was similar in all men, regardless of baseline T level andassociated increase in serum T.

Effectof Anasteride onSerum Testosterone {TI and 8MI

1786EFFECTS OF FINASTERIDE ON PROSTATIC BLOOD FLOWIN PATIENTS WITH BENIGN PROSTATIC HYPERPLASIAFerdinand Frauscher", Andrea Klauser, Bernhard Furthmueller, GudrunFeuchtn er, Germar Pingerra, Wolf gang Horninger , Georg Bartsch,Innsbruck, Austria

INTRODUCTION AND OBJECTIVE: To determine whether finasteride, ablocker of 5-alpha-reductase, has any effects on prostatic blood flow in patientswith benign prostatic hyperplasia (BPH).

METHODS: Fifteen patients with BPH were investigated by transretalcontrast-enhanced color Doppler ultrasound (CDUS) . The CDUS examination wasperformed to assess prostate vascularity using computer-assis ted quantification ofcolor pixel density (CPD). Furthermore the resistive index (RI) was measured inthe gland. Enhanced-CDUS was performed before starting treatmen t withfinasteride (5 mg/da y) and was continued daily for one week. Correlation betweenCPD and RI was assessed.

RESULTS : Finasteride induced a significant decrease in prostatic blood flowafter 5 days of treatment (decrease of CPD from 109 to 23; p< O.OOI ). No furtherdecrease of blood flow was found after one week. The RI decreased from 0.82 to0.74 after 5 days, and to 0.69 after one week. We found an excellent correlationbetween CPD and RI (r= 0.91).

CONCLUSIONS: Finasteride signi ficantly reduces prostatic blood flow andRI. These results may suggest that the effect of alpha-block er for treatingsymptoms of bladder outlet obstruction may be partly related on the changes ofprostatic blood flow.

Source of Funding: None.

central and periph eral zones of the prostate in the finasteride treated patientscompared to placebo . Harmonic imaging with Optison revealed overall reductionof blood flow by 63% with finasteride. Transition, central and peripheral zoneblood flow was decreased by 70%, 40% and 60% in the group 2 patients comparedto group I. FMBV revealed an overall 43% reduction in blood flow in thefinasteride treated patients compared to placebo. FMBV was reduced by 65%,35%, 40% in the transition, central and peripheral zones of the prostate in thefinasteride treated patients.

CONCLUSIONS: Finaster ide appears to dampen the micro vessels of theprostate within 2 weeks, which would ex plain its abili ty to prevent hematuriaand hematospermia related to biopsies, and may explain how it effects bleedingin the prostate . The ability of Finasteride to damp en these microve sse ls, mayenhance the micro vessels produced by neova scularity of prostate cancer andimpro ve the abili ty of cancer detecti on with power Doppler and inte rmittentimagi ng .

Source of Funding: Merck.

1787PERCEIVED SYMPTOM RELIEF IN THE PREDICT TRIAL:IMPROVEMENT IN INTERNATIONAL PROSTATE SYMPTOMSCORE OF AT LEAST 3 POINTS Georg Bartsch on behalf of thePREDICT Steering Committee and Investigators" , Innsbruck, Austria

INTRODUCTION AND OBJECTIVE: We previously reported, based onthe Prospectiv e European Doxazosin and Combi nation Therapy (PREDICT)trial. that after I year doxazosin (DOX) and doxazosin in co mbination withfinasteride (DOXIFIN) were more effective than FIN alone or placebo inimprov ing urina ry symptoms in beni gn prostatic hyperplasia (BPH) patients.FIN did not pro vide any add itional benefit beyond that achie ved with DOXalone. Because 3 poin ts is the minimum change in lPSS that is perce ived bypatients I , we conducted a post-h oc ana lysis of the PREDICT trial data todetermine the proportion of patien ts with at least a 3-point improvement in tota lInterna tional Pro state Symptom Score (IPSS).

METHODS: In the double-b lind , parall el gro up, place bo-contro lle dPREDI CT trial, therapy with DOX, FIN, and DOX/FIN combinatio n therapywas assessed over 52 weeks. The starting dosage for DOX (and match ingplacebo) was I mg/d , and the dosage of FIN (and matching placebo) was 5mg/d . DOX was titrat ed to a maximum of 8 mg/d over the first 10 week s oftrea tment, depending on patients' symptom and flow rate responses. Allstatistica l analyses were conducted on an intent-to-treat (ITT) basis (ie, allpatient s who took at least 1 dose of study medication during the doubl e-bli ndtreatment phase and had at least I post baseline total IPSS). Endpoint data wereanalyzed using Cochran Mantel Haenz sel chi square test for difference inproportions stratified by country.

RESULTS: Presented in the following table is the proportion of patients withat least a 3-point improvement from baseline in total IPSS.

CONCLUSIONS: Treatment with DOX and DOXIFIN resulted in a greaterproportion of patients who had at least a 3-point improvement in total IPSS

Mean1.4

-0.1'1.1

·1.8"1.40.4

N504547484751

%Change from Baseline 8MI,Month 48

N MeanPBO 42 9,2

Finasteride 34 27.0'PBO 36 4.

Finasteride 43 33.1'"PBO 37 .4.5

Finasteride 45 9.6'>471ng/dL

>300-471ngldL

Baseline Serum Treatm I %ChangefromBaseline T,TLevel en Month 48

:S330ng/dL

' Presenting author.

Vol. 169, No.4, Supplement, Wednesday, April 30, 2003 THE JOURNAL OF UROLOGY® 477

Source of Funding: Financial support was provided by Pfizer Inc.

compared with patients treated with FIN or placebo. The addition of FIN to DOXdid not affect the proportion of patients with at least a 3-point improvement in totalIPSS compared with DOX alone.

1. Barry M, Williford W, Chang Y, et al. Benign prostatic hyperplasiaspecific health status measures in clinical research: how much change in theAmerican Urological Association Symptom Index and the Benign ProstaticHyperplasia Impact Index is perceptible to patients? I Urol. 1995;154:1770­1774.

Number (%)ofpatientsPvalue VBpla­cebo

DOX(n=249)

207 (83.1%)

P=0.0014

FIN(n=237)

179 (75.5%)

P=0.3160

DOXlFIN(n=261)

218 (83.5%)

P=0.0009

Placebo(n=252)

180 (71.4%)

1788IDENTIFYING PATIENTS WITH BENIGN PROSTATIC HY­PERPLASIA WITH OVERACTIVE BLADDER AND DETER­MINING THE EFFICACY OF COMBINATION THERAPY WITHALPHA BLOCKER AND TOLTERODINE fi Youl Lee*, ii Hakfung,fun Sung Ko, Pucheon City, Kyounggi-Do, South Korea

INTRODUCTION AND OBJECTIVE: The incidence of the overactivebladder (OAB) in patients with symptomatic benign prostatic hyperplasia (BPH) isevaluated, and the clinical efficacy of combined treatment with alpha blocker andtolterodine is examined.

METHODS: A prospective study of 144 patients with BPH was per­formed between March 2001 and December 2001. The patients weresubdivided into BPH and BPH with OAB based on an initial urodynamic study.All patients were treated with an alpha blocker for 3 months. Patients with nosymptomatic improvement were treated with alpha blocker and tolterodine for2 months.

RESULTS: Of the 144 patients, 76 (53%) had BPH and 68 (47%) had BPHwith OAB. The patients with BPH and OAB were older (p<0.05), but nodifference was seen in serum creatinine, international prostate symptom score,prostate volume, maximum flow rate, or post-void residual urine (PVR) betweenthe groups. After 3 months treatment with alpha blocker, 79% (60/76) with BPHand 35% (24/68) with BPH and OAB had symptomatic improvement. Of thepatients with no improvement, 38% (6/16) with BPH and 73% (32/44) with BPHand OAB had improvement after the addition of tolterodine (Fig.1 conventionaltherapeutic schedule of BPH).

CONCLUSIONS: Combination therapy is more effective than alpha blockeralone in treating patients with coexisting BPH and OAB. We recommendidentifying these patients with an initial urodynamic study. This allows forappropriate management as well as identifying those who may benefit from a moreinvasive treatment sooner (Fig.2. Our suggestion of presumptive therapeuticschedule of BPH).

C BI'H' Io

a-blocker x 3 months(>

~~'-I

C I:lYes N!l

<>

~"'I12 I:l

Yes No

I=: I f?OO'l

Fil;ure 2. Presumptive liJerlopeullc schedule of DPII

Source of Funding: This study was supported by a grant of the Korea Health21 R&D Project, Ministry of Health & Welfare, Republic of Korea (02-PJlO-PG8­ECOl-0033).

1789EARLY USE OF DUTASTERIDE ARRESTS PROSTATE GROWTH,IMPROVES CLINICAL PARAMETERS AND PREVENTSCOMPLICATIONS IN MEN WITH BENIGN PROSTATICHYPERPLASIA Peter Boyle*, Milan, Italy; Claus G Roehrborn,Dallas, TX; Leonard S Marks, Culver City, CA; J Curtis Nickel, Kingston,Canada

INTRODUCTION AND OBJECTIVE: Meta-analyses of data for the 5,,­reductase inhibitor finasteride concluded it was significantly more effective in menwith a prostate volume (PV) 2:40 cc, leading to the recommendation that it shouldbe used in men with enlarged prostates. Given the potential benefits of reducing PVin men with a PV 30-40 cc, who are also at risk of disease progression and acuteurinary retention (AUR), we sought to examine whether dutasteride is effective inmen with slightly enlarged prostates.

METHODS: This prospective analysis was conducted using data from threeidentically designed, randomized, double-blind, placebo-controlled, 2-yearparallel-group studies evaluating the efficacy and tolerability of dutasteride(dut) 0.5 mg/day compared with placebo (PBO). Males 2:50 years of age withBPH, an AUA-SI score 2:12, urinary flow rate <15 mL/sec, serum prostate­specific antigen (PSA) 2:1.5 ng/ml to :510.0 ng/ml and a prostate volume 2:30cc were included. Primary endpoints were symptoms (AUA-SI) and the risk ofacute urinary retention (AUR). Secondary endpoints included PV, Qmax,BPH-related surgical intervention, safety and tolerability, and BPH ImpactIndex score. Analyses were conducted on the intent-to-treat population bycomparing outcomes for the subgroups of patients with a PV <40 cc and2:40 cc.

RESULTS: Of the 4307 patients randomised to treatment with dut or PBO,who had baseline PV recorded, 1223 had a baseline PV 30- <40 cc and 3084had a baseline prostate volume 2:40 cc. Dut significantly reduced PV comparedwith PBO from month 1 to month 24 for patients with PV 30-<40 cc and2:40 cc (p<O.OOl) (-26.1% and -26.9% respectively at month 24). Dutwas significantly more effective than PBO at reducing the risk of AURregardless of baseline PV, reducing the risk of AUR by 85% and 55% forPV 30-<40 cc and 2:40 cc respectively. Dut also reduced the risk of BPH­related surgical intervention by 35% and 52% for patients with PV 30-<40 ccand 2:40 cc respectively. Dut significantly improved Qmax, symptom scoresand BPH Impact Index scores (p<O.OOl) versus PBO within each PV sub­group.

CONCLUSIONS: Dutasteride improves AUA-SI, BII, Qmax, PV andsubstantially reduces the risk of serious complications of BPH in men withprostates 30 cc to <40 cc aswell as 2:40 cc. Therefore, dutasteride may be initiatedearly in the time course of BPH progression to arrest prostate growth, improvesymptoms and flow, and prevents complications of BPH.

Source of Funding: GlaxoSmithKline.

478 THE JOURNAL OF UROLOGY® Vol. 169, No.4, Supplement, Wednesday, April 30, 2003

1790EFFECT OF MAXIMAL DIHYDROTESTOSTERONE SUPPRES­SION WITH DUTASTERIDE ON SEXUAL FUNCTION ANDGYNECOMASTIA Culley Carson", Chapel Hill, NC; RichardHarkaway, Philadelphia; Leonard S Marks, Culver City, CA; Thomas AMcNicholas, Stevenage, UK

INTRODUCTION AND OBJECTIVE: Sexual dysfunction and gynecomastiahave been reported in men with BPH, including those taking 5-alpha reductaseinhibitors (5ARI). Dutasteride is a novel 5ARI which inhibits both type I and typeII 5AR enzymes and has previously been shown to reduce circulatingdihydrotestosterone (DHT) by > 90%. This effect has been studied in three largephase III trials. The objective of this analysis is to define the effects of maximalDHT suppression on sexual function and gynecomastia from these trials.

METHODS: The dutasteride phase III trials randomized 4325 men aged 2:50years with BPH, PSA 2:1.5ng/mL and <lOng/mL, prostate volume 2:30cc,AUA-SI 2:12 (moderate to severe symptoms), and Qmax :515mLlsec. Subjectsreceived dutasteride 0.5mg/day (N=2167) or placebo (N=2158) for 2 years.Adverse events were collected throughout the trial and those events considered bythe investigator to be possibly, probably or most certainly related to the study drug,were considered drug-related.

RESULTS: Drug-related adverse events reported in 2: I % of subjects and morefrequently in the dutasteride group than the placebo groups are reported below.

CONCLUSIONS: The incidence of new drug-related sexual adverse eventsdecreased with duration of treatment. Most new sexual events were reported in thefirst 6 months of therapy. The incidence of drug-related gynecomastia was minimaland remained constant over the 2-year treatment period. Maximal DHTsuppression with the dual 5ARI, dutasteride, does not increase the incidence ofdrug-related sexual adverse events and gynecomastia over that historically reportedfor other 5AR inhibitors.

Study Months

Month 0.6 Month 7-12 Month 13·18 Month 19·24NewOnset Adverse Events

Dutasteride (n)Placebo (n)

Impotence: DutasterldeImpotence: PlaceboDecreased libido: DutasterideDecreased libido: PlaceboEjaculation Disorder: DutasterideEjaculation Disorder: PlaceboGynecomastia': DutasterideGynecomastia': Placebo'Gynecomastia includes breasttenderness andbreast enlarge­ment.

Source of Funding: GSK.

(n=2167)(n=2158)

4.7%1.7%3.0%1.4%1.4%0.5%0.5%0.2%

(n=1901)(n=1922)

1.4%1.5%0.7%0.6%0.5%0.3%0.8%0.3%

(n=1725)(n=1714)

1.0%0.5%0.3%0.2%0.5%0.1%1.1%0.3%

(n=1605)(n=1555)

0.8%0.9%0.3%0.1%0.1%0.0%0.6%0.1%

was objectively noted (P< 0.001). Blood pressure remained unchanged, andadverse events were minimal in all treatment patients. None of the includedpatients discontinued the study because of the adverse events or complications. Nosignificant change in serum level of PSA was noted between before and 12 weeksafter administration of naftopidil.

CONCLUSIONS: Out of 113, 86 cases (76.0 %) showed improvement inLUTS by oral intake with naftopidil. Not only subjective, but also objective dataindicated statistically significant improvement even with short-term medication.Naftopidil appeared to be well tolerated and significantly improved LUTS even inshort-term treatment. The efficacy and safety profiles with naftopidil weresatisfactory for the patients with LUTS related to BPH.

Source of Funding: None.

1792ALFUZOSIN lOMG ONCE DAILY IMPROVES SEXUAL FUNC­TION IN MEN WITH LUTS AND CONCOMITANT SEXUALDYSFUNCTION Rja Van Moorselaar", Utrecht, Netherlands; MarkEmberton, London, UK; Niels Harving, Aalborg, Denmark; Haim Matzkin,Tel-Aviv, Israel; Rudolf Hartung, Miinchen, Germany; Antonio Alcaraz,Barcelona, Spain; M Elhilali, Montreal, Canada; Guy Vallancien, Paris,France; Alf-One Study Group, France

INTRODUCTION AND OBJECTIVE: Recent epidemiological surveys haveshown that sexual dysfunction is highly prevalent and bothersome in men withlower urinary tract symptoms (LUTS) and is strongly related to severity of LUTS.This real-life worldwide study assesses the impact on sexual function of alfuzosinIOmg once daily (OD), a clinically uroselective o l -blocker, given for 12 monthsin patients with LUTS.

METHODS: Sexual function of 838 men with LUTS (age 66.5 years, IPSS15.7, bother 3.7; mean values) from Europe, Russia, Latin America, Asia andMiddle-East was assessed using the DAN-PSSsex questionnaire which evaluates 3sexual symptoms and their related bothersomeness. For each item, a weighted score(rated 0 to 9 by increasing severity) is calculated by multiplying the symptomscore(rated 0-3) by the bother score(0-3). Results are provided at end-point.

RESULTS: Of the 838 patients, 133 (16%) had no sexual activity, 133 (16%)did not wish to answer the questions and 572 (68%) answered properly to at leastone item at baseline and end-point. At inclusion (DO), reduced rigidity of erection,decreased volume of ejaculate and pain/discomfort on ejaculation were reported by66%,65% and 24% of men, respectively. In those patients with sexual dysfunction,alfuzosin IOmg OD administered for 12 months significantly improved eachindividual sexual subscore. Both baseline weighted score and changes versusbaseline were strongly related to baseline severity of LUTS (table).

CONCLUSIONS: This study confirms that sexual dysfunction is highlyprevalent in men with LUTS. Alfuzosin 10 rng OD given for 12 months mayimprove sexual function in these men. The perceived improvement is more markedin patients with severe LUTS at baseline.

Total

1.9(2.1)-06 (2.2)'

2.5 (22)-0.9 (2.0)'

2.1 (1.9)-0.8 (2.2)'

2.8(2.3)-1.1 (21)'

IPSS at 008-19 20·35

1.8 (21)-05 (2.0)'

2.5 (2.1)-0.8 (2.0)'

<7

1.1 (1.7)-0.3 (20)

1.4(2.6)-0.3 (2.0)

Reduced rigidityWeighted score at DO'Change VI DO'Reduced ejaculateWeighted score at00'Change vs DO'Painful ejaculateWeighted scoreat 00' 0.8(0.5) 2.1 (1.7) 2.5 (1.6) 2.2 (1.7)Change VI DO' -0.5 (0.6) -1.3 (1.4)' -1.8 (1.6)' -1.5 (15)''Weighled score ofpatients with the sexual symptom - Mean (sd) values 'p versus base­line<0.001

Source of Funding: None.

1793RISK OF BONE LOSS FOR BENIGN PROSTATIC HYPER­PLASIA (BPH) PATIENTS ON ANTIANDROGEN THERAPYYasuyuki Suzuki", Yukihiko Oishi, Shoichi Onodera, Teturo Onishi, IsaoIkemoto, Hiroshi Kiyota, Teturo Wada, Kouji Asano, Norio Hasegawa,Hodenori Suzuki, Akira Huruta, Akitoshi Takizawa, Takehito Naruoka, Tokyo,Japan

INTRODUCTION AND OBJECTIVE: It is well known that antiandrogentherapy for patients with prostatic carcinoma causes serious bone loss. The aim ofthis study was to determine whether or not antiandrogen therapy for BPH affectsbone metabolism.

METHODS: A total of 440 patients with BPH (44 - 91 years old: average age71.0) were included in this study. Patients with a disease which affects bonemetabolism were excluded. In Japan, two antiandrogen medicines are currently inuse for patients with BPH: allylestrenol (AE) and chlormadinone acetate (CMA).Of the patients, 92 were taking AE at 50 mg/day (AE group), 33 were taking CMAat 50 mg/day (CMA group), and 315 cases (control group) were taking alpha-

1791CLINICAL EVALUATION OF NAFTOPIDIL, A RELATIVELYSPECIFIC ALPHAlD-ADRENORECEPTOR ANTAGONIST, INMALE JAPANESE WITH LOWER URINARY TRACT SYMP­TOMS SUGGESTIVE OF BENIGN PROSTATE HYPERPLASIARyoichi Shiroki*, Kiyohito Ishikawa, Masanobu Izumitani, Harunobu Asano,Aichi, Japan; Ichiroh Nagakubo, Tokyo, Japan; Masanori Yanaoka,Shizuoka. Japan; Kiyotaka Hoshinaga, Aichi, Japan

INTRODUCTION AND OBJECTIVE: There have been many clinicalevidences for an alpha-I adrenoreceptor antagonists to improve lower urinary tractsymptoms (LUTS) associated with benign prostatic hyperplasia (BPH). Naftopidilhas been developed as a second-generation selective alpha I blocker. Althoughsecond-generation agents, tamsulosin and naftopidil, are selective alpha- J blockerswith a moderately higher affinity to alpha-IA and -ID subtype over alpha-IBsubtype, naftopidil showed more selective effect on alpha-IA over -ID subtype.The objective of this open multicenter clinical study was to analyze the efficacy andsafety of naftopidil in the treatment of LUTS related to BPH.

METHODS: The primary variables assessed were international prostatesymptom score (IPSS), quality of life (QOL) index, changes in maximum urinaryflow rate (Qmax), serum level of prostate-specific antigen (PSA) and bloodpressure. Criteria of patient inclusion for this study were I-PSS more than 8 pts,QOL index more than 2, and maximum flow rate less than 15.0 mils. In total, 136patients were enrolled. After baseline evaluation, the study included 113 patientswith symptomatic BPH who received 25 mg of naftopidil twice daily or 50 mgonce a day for the initial 6 weeks.

RESULTS: Six weeks after taking medicine, mean IPSS reduced from 17.8 ptsto 9.4 and mean QOL index from 4.5 to 3.1. Both of these changes werestatistically significant in reduction (P< 0.001). The number of nocturia anddaytime urination was also significantly reduced. In addition, significant increasesin Qmax, from 8.9 at baseline to 11.9 ml/s in 6 weeks and to 12.3 mils in 12 weeks,

*Presenting author.

Vol. 169, No.4, Supplement, Wednesday, April 30, 2003 THE JOURNAL OF UROLOGY® 479

blocker (Tamsulosin or Naftopidil). Metabolic markers of bone formation (bone­specific alkaline phosphatase:BAP), and bone resorption (deoxypyridinium: DPDand N-terminal telopeptide: NTx ) were measured at 4 weeks after medicaltreatment.

RESULTS: Regarding the level of bone formation marker (BAP), there was nosignificant difference between the three groups. However, the bone resorptionmarker (DPD and NTx) levels of CMA group were significantly higher than thoseof the control group (p <0.05 t test). There was no significant difference betweenthe AE group and control group in the levels of bone resorption markers.

CONCLUSIONS: Metabolic markers of bone are useful to predict the risk ofosteoporosis. Early diagnosis and treatment are the key to avoid osteoporosis. Theresults of our study suggest that CMA may cause bone loss. Because bone loss isassociated with an increased risk of bonefracture, bone density measurement isrecommended for patients with BPH receiving long-term CMA.

Source of Funding: None.

1794S-ALPHA REDUCTASE INHIBITORS (SARIS) PROVIDESUPERIOR BENEFITS TO ALPHA BLOCKERS BY PREVENT·ING AUR AND SURGERY Peter Boyle*, Milan, Italy; ClausRoehrborn, Dallas, TX; Richard Harkaway, Philadelphia, PA; J Logie,Greenford, UK; Jean De La Rosette, Nijmegen, Netherlands; Mark Emberton,London, UK

INTRODUCTION AND OBJECTIVE: Benign prostatic hyperplasia (BPH) isa common progressive condition that can lead to acute urinary retention (AUR)and/or BPH-related surgery. This analysis examines the relative effectiveness ofSARIs and a blockers in preventing serious complications, acute urinary retention(AUR) or catheterisation alone or BPH-related surgery alone based on currentclinical practice.

METHODS: This is a retrospective analysis of the General Practice ResearchDatabase (UK). The cohort contains 4500 patients experiencing BPH or lowerurinary tract symptoms suggestive of BPH, aged over 50 years, who wereprescribed their first treatment with a SARI (finasteride) or an a blocker (alfuzosin,doxazosin, indoramin, prazosin, tamsulosin, terazosin) between 1996 and 1999.Cox competing risks analyses, adjusted for age and year of first treatment, followedpatients from the start of first BPH treatment to a failure or censoring (applied ata record of death, de-registration from GPRD, medication switch, or four weeksafter the end of first treatment).

RESULTS: Patients prescribed an a blocker were more likely to experienceAURIcatheterisation (Hazard ratio 2.32, SE 0.27, p=0.OO2)or BPH-related surgery(Hazard ratio 1.78, SE 0.16, p<O.OOI) than patients prescribed a SARI. Thedifference between drug class was most pronounced for AURIcatheterisation.These differences were sustained when only AURIcatheterisation or BPH-relatedsurgery events that occurred during the first treatment or within the following 4weeks were considered.

CONCLUSIONS: In addition to evidence from clinical trials, real world dataalso shows that significantly fewer patients prescribed a SARI experienced seriouscomplications associated with the progression of BPH compared with thoseprescribed an a blocker. The risks of AUR/catheterisation or BPH-related surgerywere significantly reduced for men prescribed SARI therapy. The greatestreduction in risk for the SARI class was for AURIcatheterisation.

Source of Funding: GlaxoSmithKline.

1795THE INCREASED RISK OF SURGERY BY PSA ANDPROSTATE VOLUME: ALPHA-BLOCKER AND WATCHFULWAITING PATIENTS FROM REAL LIFE CLINICALPRACTICE Jean J De La Rosette*, M Pilar Laguna, Chaidir A Mochtar,Lambertus A Kiemeney, Frans M Debruyne, Nijmegen, Netherlands

INTRODUCTION AND OBJECTIVE: The impact of BPH therapies on theprogression of BPH is known to be dependent on baseline factors such as serumprostate specific antigen (PSA) or prostate volume (PV). We investigated theimpact of alpha-blocker and watchful waiting (WW) management on the need forsurgery by baseline serum PSA and PV in real life practice.

METHODS: A retrospective analysis of a database with records of 2222 BPHpatients at our hospital was carried out. The cohort contains 425 patients prescribedalpha-blockers (tamsulosin, alfuzosin or terazosin), 629 who received WW, 45 whoreceived finasteride, and 1121 who immediately went for prostatic surgery. Datawere missing for 2 patients. Patients with a baseline serum PSA < 1.2, 1.2-3.2and > 3.2, PV <40 and > = 40 who were managed with WW or alpha-blockerswere examined for time to BPH-related surgery. These sub groups were comparedusing cox-proportional hazard analyses adjusting for age.

RESULTS: Mean age at baseline was 62.4 yrs, mean length of follow up andtime on alpha-blocker were 4 yrs and 3.2 yrs respectively. The relative risk ofalpha-blocker-treated patients with a PSA 1.2-3.2 or >3.2 for progression tosurgery was 2.02 (1.12 to 3.67) and 4.06 (2.26 to 7.29), respectively, as compared

with patients within the lowest PSA group. The relative risk of patients managedwith WW with a PSA 1.2-3.2 or >3.2 for surgery was 2.31 (1.06 to 5.03) and 3.82(1.74 to 8.38), respectively, as compared with patients within the lowest PSA group« 1.2). The relative risk of alpha-blocker-treated patients with a PV > =40cc forprogression to surgery is 2.94 (1.87 to 4.63) compared with patients with a PV<40cc. The relative risk of WW patients with a PV > =40cc for progression tosurgery is 2.18 (1.26 to 3.79) compared with patients with a PV <40cc. All datawere statistically significant at the 5% level.

CONCLUSIONS: The risk of surgery for patients receiving alpha-blocker orWW management with a baseline PSA >=1.2 is 2.22-4.06 times (respectively)that of patients with a lower PSA. The risk of surgery for patients receiving WWor alpha-blocker management with a baseline PV>=40cc is 2.18-2.94 times(respectively) that of patients with a PV <40cc. The highest risk is associated withPSA> = 1.2. The use of alpha-blockers to treat BPH symptoms does not alter theincreased risk of BPH complications associated with increased PSA levels or PV.The appropriate medical management according to baseline PSA and PV should beused to address the unmet medical need experienced by these patient sub groups.

Source of Funding: unrestricted grant from GlaxoSmithKline (GSK).

1796BONE DENSITY, BONE METABOLISM MARKERS AND LIPIDPROFILES IN HEALTHY MEN ARE UNAFFECTED BY THENOVEL DUAL SA·REDUCTASE INHIBITOR DUTASTERIDERichard V Clark*, North Carolina, NC; Alvin M Matsumoto, Seattle, WA

INTRODUCTION AND OBJECTIVE: Data from three, large-scale, double­blind, randomized trials have demonstrated that the novel dual Sa-reductaseinhibitor dutasteride has significant benefits in the treatment and prevention ofcomplications of benign prostatic hyperplasia (BPH), and is well tolerated.However, as a paucity of testosterone may impact bone density, we furtherinvestigated the safety profile of dutasteride by examining its effects on bonemetabolism markers and lipid profiles.

METHODS: This study was a randomized, double-blind, placebo-controlled,comparative, parallel group, multicenter study in healthy male subjects aged 18-55,with a body mass index of 19-32. Subjects were randomized to receive 0.5 mgdutasteride, 5.0 mg finasteride or placebo for 52 weeks. Subjects were followed-upfor a further 24 weeks following cessation of study medication. Bone density byx-ray absorptiometry was conducted at screening, between weeks 48-52 and againbetween weeks 20-24 of follow-up. Markers for bone resorption and boneformation, serum osteocalcin, serum bone alkaline phosphatase and urinary n­telopeptide, were measured at baseline, week 8, 16, 24, and 52, and follow-upweeks 8, 12 and 24. Lipid levels were recorded at baseline, study weeks 8, 24 and52 and follow-up weeks 4, 8, 12 and 24. Samples were analysed for serumcholesterol, triglycerides, HDL and LDL.

RESULTS: Ninety-nine subjects were randomised and included in the intent­to-treat analysis. There were no clinically significant changes in bone density orbone metabolism markers from baseline, or between treatment groups at weeks48-52 or follow-up weeks 20-24. There were no clinically significant differencesbetween treatment groups in lipid levels during the study. All treatment groups,including placebo, showed an upward trend in mean cholesterol and LDL duringthe study. HDL and triglyceride levels fluctuated in all groups throughout the study,but no consistent trends were observed. By Week 24 of follow-up, all lipid levelswere similar to baseline, with the exception of triglyceride levels in the placebo anddutasteride group, which were increased from baseline (51.4% and 27.8%,respectively). This was not regarded as clinically significant as the increase frombaseline in the placebo group was almost twice that of the dutasteride group, andtriglycerides were the most variable lipid parameter.

CONCLUSIONS: Dutasteride has no clinically significant effect on bonedensity, bone metabolism markers or lipid profiles.

Source of Funding: GlaxoSmithKline.

1797CHANGES IN THE EXPRESSION OF BONE MORPHO­GENETIC PROTEIN RECEPTOR TYPE lA, IB AND II INHUMAN PROSTATE BY THE SUPPRESSION OF DIHYDRO­TESTOSTERONE Soomee Kwon, Hea Young Oh*, Sun II Kim, SungJoan Hong, Seoul, South Korea

INTRODUCTION AND OBJECTIVE: To investigate whether the expressionof bone morphogenetic protein receptors (BMPRs) type lA, IB, and II are affectedby the suppression of dihydrotestosterone in the prostate tissues of patients withbenign prostatic hyperplasia (BPH).

METHODS: Frozen tissue obtained during transurethral resection of theprostate (TURP) in BPH patients 50 years or older and with prostate volume biggerthan 50 ml were used to detect the expression of BMPRs by semiquantitativepolymerase chain reaction (PCR) and immunoblotting. We compared theexpression of BMPRs between patients who had taken Sa-reductase inhibitor(finasteride) for 3 months before TURP and patients who had not.

480 THE JOURNAL OF UROLOGY® Vol. 169, No.4, Supplement, Wednesday, April 30, 2003

%ofpatients with positive mRNA expression or presence of receptors in >2.5% of thecellsfor:

METHODS: In a prospective randomized double-blind study in 21 patientswith severe lower urinary tract symptoms (LUTS) suggestive of BPH, TAM(0.4 mg, 12 patients) or placebo (9 patients) was given once daily for fiveweeks, before performing an indicated transurethral prostatectomy. Epithelialcells were isolated and purified from surgery samples (cytokeratin expressionin > 99% of the cells; vimentin in < 1%). These cells were subjected to flowcytometry assessment of growth factor receptors (GFRs) and to polymerasechain reaction (PCR) studies to identify growth factors (GFs) and p53 mRNAexpression.

RESULTS: Data obtained for other GFs (EGF, PDGF, TGFf32, IGF) and GFRs(IGF-R, PDGF-R) and for c-rnyc, were similar for both treatment groups. For thetabulated GFs and GF-Rs differences were not different using Chi2 statistics.However, the pattern of shifts in combinations with p53 mRNA increases in 58%of samples from TAM treated patients as compared to 22% in the placebo groupis considered to be of biological relevance.

CONCLUSIONS: TAM shows an in vivo modulator effect on the pattern ofexpression of some growth factors and growth factor receptors, and an increasein the expression of apoptosis-inducing factor p53 in epithelial cells fromLUTS/BPH patients. This indicates that blockade of alpha-IA&D­adrenoceptors in vivo with TAM can induce negative signaling for growth andsurvival of epithelial cells in a significant number of patients having LUTS/BPH.

1800FEASIBILITY OF SWITCHING MEN WITH ENLARGEDPROSTATES AND LUTS TO FINASTERIDE AFTER INITIALTREATMENT WITH ALPHA BLOCKADE: DURABILITY DATAStuart M Diamond*, Erica Lambert, Chris Garlitz, Frank Nezu, Philadel­phia, PA

INTRODUCTION AND OBJECTIVE: We previously reported on the abilityof switching from successful alpha blockade to combination therapy withfinasteride and then discontinuation of alpha blockade in men with enlargedprostates and lower urinary tract symptoms. We reevaluated the study patients at 6,12,and 18 months to see whether their symptom scores changed on finasteridemonotherapy.

METHODS: 75 patients with enlarged prostate (>40gm) and AUA symptomscores greater than 15 were involved in our initial study. All 75 patients had takentamsulosin for at least one year, were currently taking tamsulosin at the time ofevaluation and were satisfied with its effectiveness. The 75 patients were placed oncombination therapy with finaster ide, and randomized to tarnsulsiondiscontinuation at 6, 9, and 12 months. 49 patients successfully discontinued alphablockade and remained on finasteride monotherapy. Patients were re-evaluated at6, 12 and 18 months post trial; to determine whether there was any elevation inAUA symptom score. Patient satisfaction was monitored with SF 36questionnaires, which were administered at baseline entry to the trial and onfollow-up visits.

RESULTS; All patients were evaluated for review. 92% 45/49 patients hadeither no change in their symptom score from their one-month post-discontinuationvisit or their symptom scores were lower. 35%% had no change in their overallsymptom scores, and 65% had lowered AUA scores from the end of the initial trial.Overall 90% of the patients had stable or improved voiding with finasteridemonotherapy six months after alpha-blocker discontinuation. Twelve-month datawas available on 45 patients and 40/45 (89%) of them had stable or improvedvoiding at one year. At 18 months 25 patients were available for review and23/25(92%) continued to do well. SF 36 questionnaires revealed improved qualityof life from prior to trial entry and remained stable or improved in over 90% ofpatients during the current study.

CONCLUSIONS: Patients with enlarged prostates and LUTS already undertamsulsion treatment are likely to tolerate discontinuation of alpha blockade aftercombination with finasteride for 9 to 12 months. Overall long term success withfinasteride monotherapy appears to be durable at 6 months (90%), 89% at 12months and 92% at 18 months.

Source of Funding: None.

Source of Funding: Yarnanouchi Europe B.V.

TGF-R10067

FGF-R3317

EGF-R448

Growth factorrecep­tors

TGF~1

o25

TGFa3367

FGF4467

Growth fac­tors

PlaceboTAM

1798EFFECT OF TAMSULOSIN ON BLADDER WALL HYPER·TROPHY IN PATIENTS WITH LOWER URINARY TRACTSYMPTOMS SUGGESTIVE OF BLADDER OUTLET OB­STRUCTION: RESULTS OF A MULTICENTRE, PLACEBO·CONTROLLED TRIAL Andrea Tubaro*, Rome, Italy; Gaby Anthonijs,Mandy W Avis, Robert Snijder, Leiderdorp, Netherlands

INTRODUCTION AND OBJECTIVE: Data in the rabbit model of outletobstruction showed that an a,-adrenoceptor (AR) antagonist (doxazosin)significantly reduces bladder wall hypertrophy (BWH)'- In an open-label pilotstudy it was shown by using ultrasound estimated bladder weight (UEBW) thatl-month treatment with the subtype selective a'A/aID-AR antagonist tamsulosinreduces BWH in patients with lower urinary tract symptoms suggestive of bladderoutlet obstruction (LUTSIBOO). This was maintained during 6 months oftamsulosin treatment". The present study aimed to confirm these findings in adouble-blind, placebo-controlled way.

METHODS: This was a multi-centre, double-blind, randornised, parallel­group, placebo-controlled trial in patients with LUTS/BOO (I-PSS ~ 13,Qmax:oo 12 mLls, UEBW 38-80 g). Patients were randomised to tarnsulosin0.4 mg once daily or placebo for 12 weeks. The primary objective was toevaluate the effect on BWH by using UEBW. Efficacy (l-PSS, I-PSS QoL,Qrnax, PVR) and tolerability were also assessed. To detect a difference in meanchange in UEBW vs. baseline of 5 g (standard deviation (SD) 7.5) with 2-sideda=0.05 and power of 80%, at least 36 evaluable patients/group had to beincluded.

RESULTS: 106 patients were randornised to placebo (n=54) or tarnsulosin(n=52). A total of 72 patients (68%; 36 in each group) were obstructed (Qrnax <10 mLls). In the obstructed patients, 12 weeks of tamsulosin treatment reducedBWH to a greater extent as placebo (see table). The greater reduction was notsignificant because of the large SD (13), which was much larger than anticipated(7.5) for the sample size calculation. Tamsulosin improved total I-PSS significantlymore than placebo, whereas the greater increase in Qmax with tamsulosin overplacebo approached significance (see table).

CONCLUSIONS: These results confirm the good efficacy of tamsulosin.The reduction in BWH with tamsulosin is in line with open-label data". Thelarge SD observed in the study seems to depend upon the large number ofinvestigators and centres that participated in this trial. I. Das AK, et al.Neurourol Urodyn 2002;21:160-6,2. Sironi D, et al. Eur Urol 2000;37(suppl2):103 (abs. 411).

RESULTS: BMP receptors lA, IB and II proteins were expressed in humanbenign prostate tissues in various concentrations. Semiquantitative PCRanalysis showed that mRNA levels of BMPRs were decreased following5a-reductase inhibition and the magnitude of decrease was the greatest forBMPR-IB.

CONCLUSIONS: In human prostate, the action of BMP-BMPR complexseems to be partly regulated by androgen, and the receptor type IB was the mostlyinfluenced. Further studies on the possible role of BMP-BMPR-IB complex in theabnormal proliferation of the prostate under physiologic condition are warranted.

Source of Funding: None.

UEBW results: obstructed patients only; Totall-PSS and Qmax results: allpatients@p=0.281 vs.placebo; 'p=0.OO69 vs. placebo; #p=0.0624 vs. placebo

Source of Funding: Yamanouchi Europe BV.

Parameter Placebo Tamsulosin

1799NEGATIVE SIGNALLING FOR GROWTH AND SURVIVAL INEPITHELIAL PROSTATE CELLS IN VIVO IN BENIGNPROSTATIC HYPERPLASIA (BPH) AFTER TAMSULOSINJoaquin Carballido, Alfredo Prieto, Madrid, Spain; Manuel Sanz,Guadalajara, Spain; Remigio Vela-Navarrete, Madrid, Spain; CeesKorstanje, Leiderdorp, Netherlands; Melchor Alvarez de Mon*, Madrid,Spain

INTRODUCTION AND OBJECTIVE: This study focuses on potential in vivoeffects of the subtype selective alpha-IAIID adrenoceptor blocker tamsulosin(TAM) on the pattern of regulation of the growth of epithelial cells in BPHpatients.

Baseline Change atend- Baseline Change atend·point point

UEBW(g) 48.4(110) -4.1 (13.3) 49.8(10.6) -7.4(12.7)@Totall-PSS 19.4 (3.9) -5.6 (51) 19.6 (47) -8.6 (5.9)'Qmax(mUs) 8.0(2.0) 2.0(41) 7.8(1.8) 3.4(3.9)#

*Presenting author.