Clinical BPH and Its ManagementA Comprehensive Slide Kit

Professor Kurt DreikornDirector, Department of Urology

ZentralkrankenhausTeaching Hospital of the University of Gottingen

Bremen, Germany

Mark Speakman, MDConsultant Urologist

Musgrove Park HospitalTaunton, UK

PSC 2001-W-11666-SS

PSC 2001-W-11666-SS

This presentation is provided as a professional service by Merck & Co., Inc. The views expressed herein

represent the independent opinions and experience of the speakers and not necessarily those of Merck & Co., Inc., or its related affiliates.

Any product mentioned in this presentation should be used in accordance with the prescribing information issued by the manufacturer.

Definition, Pathophysiology, and Epidemiology of Clinical BPH

Section I

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Definition of Terms

• LUTS Lower-urinary-tract symptoms

• BPE Benign prostatic enlargement(macroscopic)

• BOO Bladder-outlet obstruction

• BPH Benign prostatic hyperplasia (microscopic/histologic)

• BPO Benign prostatic obstruction (BOO caused by BPE)

• Clinical BPH LUTS + BPE + BOO

Slide I.1

PSC 2001-W-11666-SS

Adapted from Nordling J et al. In Benign Prostatic Hyperplasia. Plymouth, United Kingdom: Health Publication, 2001:107-166.

Pathophysiology of Clinical BPH:Overlapping but Independent Features

Slide I.2

LUTSEnlargedprostate

BOO

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Adapted from Nordling J et al. In Benign Prostatic Hyperplasia. Plymouth, United Kingdom: Health Publication, 2001:107-166.

Pathophysiology of Clinical BPH:Conditions Potentially Leading to LUTS

Slide I.3

Aging

Anoxia

Obstruc-tion

Highnocturnaldiuresis

Age-relateddiseases

Neuro-logic

diseases

Localdisease

Bladder

LUTS

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Pathophysiology of Clinical BPH:Predictive Risk Factors

Slide I.4

• Increasing age

• Prostatic enlargement

• Elevated prostate-specific antigen (PSA)

• Lower-urinary-tract symptoms (LUTS)

• Decreased urinary flow rate

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Natural History of BPH: Relationship Between Symptoms and Prostate Volume

Adapted from Girman CJ et al J Urol 1995;153:1510-1515.

Slide I.5

40–49 50–59 60–69 70–79

Age (years)

30

20

10

0

Mild symptoms

Moderate/severe symptoms

% o

f m

en w

ith

pro

stat

e vo

lum

e >

50 m

l (N=2115)

PSC 2001-W-11666-SS

Natural History of BPH: Relationship Between Symptoms and Peak Urinary Flow

Adapted from Girman CJ et al J Urol 1995;153:1510-1515.

Slide I.6

% o

f m

en w

ith

pea

k f

low

rat

e <

10 m

l/se

c

40–49 50–59 60–69 70–79

Age (years)

30

20

10

0

Mild symptoms

Moderate/severe symptoms

(N=2115)

PSC 2001-W-11666-SS

Natural History of BPH:PSA Is a Powerful Risk Factor for Clinical BPH

p<0.00001 for trend across odds ratiosFree PSA values adjusted for age and total PSA

Adapted from Meigs JB et al J Clin Epidemiol 2001;54(9):935-944.

Slide I.7

Od

ds

rati

o

5

4

3

2

1

0

1

1.91.8

4.4

0.0–0.07 0.08–0.10 0.11–0.17 0.18–2.43

Free PSA value

(N=1709)

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3.5

3

2.5

2

1.5

1

0.5

0

Pathophysiology of Clinical BPH:The Risk of AUR Increases with Increasing

Prostate Volume (community-based data)

Adapted from Jacobsen SJ et al J Urol 1997;158:481-487.

Slide I.8

1

3

30 >30

Baseline prostate volume (ml)

Rel

ativ

e ri

sk o

f A

UR

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10

8

6

4

2

0

Baseline prostate volume (ml)Adapted from Jacobsen SJ et al J Urol 1999;162:1301-1306.

Slide I.9

Pathophysiology of Clinical BPH:The Risk of TURP Increases with Increasing

Prostate Volume (community-based data)

1

9.2

30 >30

Rel

ativ

e ri

sk o

f T

UR

P

(N=2115)

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Definition, Pathophysiology, and Epidemiology of Clinical BPH: Summary

Slide I.10

• Clinical BPH is a multifactorial disease composed mainly of prostatic enlargement, LUTS, and BOO

• Age, prostatic enlargement, elevated PSA, LUTS, and decreased urinary flow rate are major independent predictive risk factors – Elevated PSA levels powerfully predict clinical BPH and

subsequent outcomes

• Prostate volume correlates with BOO, severity of symptoms, and risk of serious outcomes

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Consequences of BPH

Section II

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Complications of UntreatedClinical BPH

Slide II.1

• Acute urinary retention

• Urinary tract infection

• Bladder calculi

• Bladder damage

• Renal impairment

• Hematuria

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Incidence of Serious Clinical Outcomes in Untreated Patients with BPH vs. Other Diseases

Slide II.2

Condition Clinical Outcome Incidence (%)*

Osteoporosis Vertebral fracture 1.5Hip fracture 18

Atherosclerosis Fatal/nonfatal MI 2.1

Superficial bladder cancer Recurrence 30–88

Kidney stones Recurrence 2–47

BPH AUR 7Surgery 10

*Annual incidence or rate per person-years

Adapted from Roehrborn CG et al Urology 2000;56:9-18. McConnell JD et al N Engl J Med 1998; 338(9):557-563.

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10

8

6

4

2

0

Impact of Clinical BPH on the Patient’s Quality of Life

Higher scores reflect worse status.

Adapted from Girman CJ et al Eur Urol 1999;35(4):277-284.

Slide II.3

6.1

9.0

3.6

5.6

2.3

Prostate 40 ml

Prostate >40 ml

Symptom score(p<0.0001)

Bother score(p<0.005)

Activity score(NS)

Hea

lth

-rel

ated

qu

alit

y-of

-lif

e sc

ore

3.1

(n=458)

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Impact of Clinical BPH on the Spouse’s Quality of Life

Adapted from Sells H et al Br J Urol Int 2000;85:440-445.

Slide II.4

80

70

60

50

40

30

20

10

0

47

6671

66

Adverse effects on social life

Adverse impact on

sex life

Worry aboutprostate cancer

Worry aboutpartner’s need

for surgery

% o

f sp

ouse

s

(n=90)

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Consequences of Untreated Clinical BPH:Summary

Slide II.5

• Serious clinical outcomes– AUR– BPH-related surgery

• Adverse impact on quality of life– For patients – For spouses

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Regulation of Prostate Growth

Section III

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Regulation of Prostate Growth:Intrinsic and Extrinsic Factors

Adapted from Lee C et al. In Benign Prostatic Hyperplasia. Plymouth, United Kingdom: Health Publication, 2001:79-106.

Slide III.1

Extrinsic factors Testicular• Androgens• Estrogens• Nonandrogenic

Nontesticular• Endocrine organs• Neurotransmitters• Immunologic

Epithelium• Luminal• Basal• Neuroendocrine

Genetic• Homeobox genes• Hereditary

diseases

Stroma• Fibroblast• Smooth muscle• Extracellular matrix

Environmental• Dietary• Micro-organisms

(immune response)

Urethra• Urine• Testis-epididymal fluid

Extrinsic factors

Intrinsic factors(prostate)

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• DHT is the principal androgen responsible for prostatic growth and BPH

• 5-reductase mediates the conversion of testosterone to DHT

Regulation of Prostate Growth:Role of Androgens

Slide III.2

Testosterone Dihydrotestosterone

O

OH

O

OH

H

5-reductase

Adapted from Bartsch G et al Eur Urol 2000;37(4):367-380.

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• Inherited 5-reductase deficiency results in male pseudohermaphroditism, characterized by

– Markedly reduced DHT and normal testosterone levels– Lack of prostatic development and/or enlargement (BPH)

• 5-reductase plays a key role in both normal and abnormal prostate growth

Regulation of Prostate Growth:Role of 5-Reductase

Slide III.3

In the 1980s, inhibitors that selectively blocked the action of 5-reductase were synthesized for the treatment of symptomatic BPH.

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Tissues in which type I and type II 5-reductase are predominant

Relative Roles of Type I and Type II 5-reductase

Slide III.4

Type I Type II

Skin (sebaceous glands)

Liver

Adrenal glands

Hair follicles

Liver

Seminal vesicles

Prostate gland

Epididymis

Internal/externalgenital tissues

PSC 2001-W-11666-SS

Regulation of Prostate Growth:Summary

• DHT is a key to the regulation of prostatic growth and BPH

• 5-reductase mediates the conversion of testosterone to DHT

• 5-reductase plays a key role in normal and abnormal prostate growth

• 5-reductase has two isoenzymes, type I and type II– Type II predominates in the prostate and other genital

tissues

• Agents that selectively block the action of 5-reductase have been synthesized for the treatment of symptomatic BPH – Finasteride is a selective inhibitor of type II 5-reductase

Slide III.5

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Management of BPH

Section IV

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Diagnosis of Clinical BPH: International Recommendations

Slide IV.1

Assessment ICBPH Guidelines

Quantification of symptoms–IPSS RecommendedQuantification of symptoms—bother score RecommendedDigital rectal examination RecommendedUrinalysis RecommendedPSA measurement RecommendedVoiding diary (frequency-volume charts) RecommendedUrinary flow-rate recording OptionalPostvoid residual urine volume studies OptionalPressure-flow studies OptionalProstate imaging (TRUS) OptionalUpper-urinary-tract imaging (US or IVU) OptionalLower-urinary-tract endoscopy OptionalSerum creatinine measurement Not recommendedAdapted from Fifth International Consultation 2001 on BPH. In Benign Prostatic Hyperplasia. Plymouth, United Kingdom: Health Publication, 2001:519-535.

PSC 2001-W-11666-SS

*Absolute indications for surgery include urinary retention; significant gross hematuria refractory to finasteride treatment; renal failure, bladder stones, or recurrent urinary tract infections due to BOO; or large bladder diverticulum.

Adapted from Fifth International Consultation 2001 on BPH. In Benign Prostatic Hyperplasia. Plymouth, United Kingdom: Health Publication, 2001:519-535; De la Rosette JJMCH et al Eur Urol 2001;40:256-263.

Treatment of Clinical BPH: International Recommendations

Slide IV.2

Findings RecommendationMinimal/not bothersome LUTS Watchful waitingNo absolute indication for surgery*

Bothersome LUTS Watchful waitingEnlarged prostate Medical treatmentNo absolute indication for surgery* • Finasteride

• Alpha blockerInterventional treatment

Bothersome LUTS Watchful waiting Normal prostate Medical treatmentNo absolute indication for surgery* • Alpha blocker

Interventional treatment

Bothersome LUTS SurgeryNormal or enlarged prostateAbsolute indication for surgery*

PSC 2001-W-11666-SS

ICBPH guidelines• Short term

– Improve symptoms

• Long term – Slow disease progression– Minimize adverse effects of treatment– Preserve quality of life

Treatment of Clinical BPH:Objectives

Adapted from Fifth International Consultation 2001 on BPH. In Benign Prostatic Hyperplasia. Plymouth, United Kingdom: Health Publication, 2001:519-535.

Slide IV.3

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Alpha Blockers:Mechanism of Action

• Improve urinary flow and reduce BOO and LUTS

• Do not affect prostate enlargement

• Established mechanisms– Blockade of sympathetic activity– Relaxation of prostatic and bladder-neck smooth

muscle– No effect on disease progression

Slide IV.4

PSC 2001-W-11666-SS

Type II 5-reductase

Type II 5-reductase

5-Reductase Enzyme Inhibitors: Mechanism of Action of PROSCAR™

• Significantly reduces serum and intraprostatic DHT• Treats the underlying cause of BPH

Slide IV.5

PROSCAR (finasteride) is a trademark of Merck & Co., Inc., Whitehouse Station, NJ, USA.

Testosterone

Conversion of Testosterone to Dihydrotestosterone

Testosterone

PROSCAR

Enzyme Inhibition

DHT

DHT

PSC 2001-W-11666-SS

Management of Clinical BPH:Summary

• International guidelines for the management of clinical BPH recommend– Diagnostic tests to characterize disease severity and rule

out other disorders– Treatment to relieve symptoms and prevent complications

• Alpha blockers relieve BPH symptoms primarily by relaxing smooth muscle

• PROSCAR™ relieves BPH symptoms primarily by reducing prostate volume

• PROSCAR slows the progression of BPH

Slide IV.6

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Time-Tested Clinical Benefitsof PROSCAR™

Section V

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Evidence-Based Medicine:Proven Treatment for Clinical BPH

• Evidence-based medicine is based on results of clinical research.

• Drugs in the same therapeutic class may exert different pharmacologic effects.

• Independent clinical studies must establish each drug’s efficacy, safety, and effect on outcomes.

• Outcome studies with drugs for clinical BPH should evaluate the effects of therapy on AUR and BPH-related surgery.

Slide V.1

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Acute Urinary Retention in Clinical BPH Treatment Trials

Slide V.2

Trials with Trials withPROSCAR™ Alpha Blockers

Patient population (no.) 3000–4222 518–2084Study duration 2–4 years 6 months–1 yearAverage prostate size 41–55 ml 41 mlFollow-up of discontinued Yes No patientsNo. of AUR events during trial 72–81 4–24Predicted no. of AUR events for 5–8 1–10 patients after discontinuationTotal no. of AUR events 80–86 4–34 (actual and predicted)

Adapted from Roehrborn CG Urology 2002;59:811-815.

• PLESS was the only study to provide spontaneous AUR data for the active treatment versus post-treatment follow-up.

PSC 2001-W-11666-SS

PROSCAR™:Treatment Goals

• Improves symptoms

• Reduces risk of AUR

• Reduces risk of BPH-related surgery

• Slows disease progression

Slide V.3

PROSCAR has been proved effective in the treatment of clinical BPH in men with an enlarged prostate.

PSC 2001-W-11666-SS

PROSCAR™:Durable Efficacy in Long-Term Trials

Duration Long-Term ImprovementStudy (years) Symptoms Prostate Volume Urinary Flow

North American 1 SCARP 2 PROSPECT 2 PROWESS 2 PLESS 4 North American Extension* Maintained Maintained MaintainedScandinavian Open Extension* Maintained Maintained Maintained

Slide V.4

= significant improvement from baseline vs. placebo (p0.05); SCARP = Scandinavian Study of Reduction of the Prostate; PROSPECT = Proscar Safety Plus Efficacy Canadian Two-Year Study; PROWESS = Proscar Worldwide Efficacy and Safety Study; PLESS = Proscar Long-term Efficacy and Safety Study

*Benefits achieved during double-blind therapy were maintained in extensions.

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Effects of PROSCAR™ on the Natural History of Clinical BPH: Reduced Risk of AUR

Slide V.5

Placebo

PROSCAR

57%risk

reductionp<0.001

15

10

5

0

41 2 30

Pro

bab

ilit

y of

AU

R

Years No. of AURs 36 25 20 18 No. at risk 1503 1454 1398 1347

No. of AURs 14 11 7 10 No. at risk 1513 1487 1449 1421

Placebo

PROSCAR

p<0.001 at 4 years PROSCAR vs. placebo

Adapted from McConnell JD et al N Engl J Med 1998;338(9):557-563.

PSC 2001-W-11666-SS

Effects of PROSCAR™ on the Natural History of Clinical BPH: Reduced Risk of Surgery

Slide V.6

55%risk

reductionp<0.001

15

10

5

01 2 30

Pro

bab

ilit

y of

su

rger

y

No. of surgeries 37 52 32 31No. at risk 1503 1454 1374 1314

No. of surgeries 18 22 9 20No. at risk 1513 1483 1438 1410

Years4

Placebo

PROSCAR

Placebo

PROSCAR

p<0.001 at 4 years, PROSCAR vs. placebo

Adapted from McConnell JD et al N Engl J Med 1998;338(9):557-563.

PSC 2001-W-11666-SS

Effect of PROSCAR™ on the Natural History of BPH: Relative Risk Reductions

vs. Interventions in Other Diseases

RiskCondition Outcome Intervention Reduction (%)

Osteoporosis Vertebral fracture Alendronate 44–47Hip fracture Alendronate 21–51

Atherosclerosis PTCA or CABG Statins 17–37 Fatal/nonfatal MI Statins 25–40

Epilepsy Seizures Anticonvulsants 38–87

Superficial bladder cancer Recurrence BCG + surgery 31–80

Kidney stones Recurrence Pharmacotherapy 63–80

BPH AUR PROSCAR 57Surgery PROSCAR 55

Slide V.7

PTCA = percutaneous transluminal coronary angioplasty; CABG = coronary artery bypass graft; BCG = bacillus Calmette-Guérin

Adapted from Roehrborn CG et al Urology 2000;56:9-18. McConnell et al N Eng J Med 1998;338(9):557-563.

PSC 2001-W-11666-SS

PSA and PROSCAR™

• Predictably reduces PSA by 50% in men with BPH

• Multiplication of PSA values by 2 in men treated for 6 months preserves predictive value of PSA measurements

Slide V.8

In PLESS, PROSCAR did not mask prostate cancer detected by PSA

PSC 2001-W-11666-SS

Time-Tested Clinical Benefits of PROSCAR™: Summary

• Evidence-based medicine calls for clinical studies of individual drugs that investigate efficacy and disease outcomes.

• Outcomes studies with drugs for clinical BPH should evaluate effects on AUR and BPH-related surgery.

• Multicenter, double-blind, placebo-controlled trials of up to 6 years’ duration have established the effects of PROSCAR:– Durable improvements in symptoms, prostate volume,

and maximum urinary flow (p0.05) over 1 to 4 years vs. placebo

– Significant reductions in the risk of AUR and BPH-related surgery (p<0.001) at 4 years vs. placebo in PLESS

• No other therapy—including alpha blockers—proven to reduce AUR

Slide V.9

PSC 2001-W-11666-SS

New Data on the Long-Term Efficacy and Tolerability of PROSCAR™

Section VI

PSC 2001-W-11666-SS

Long-Term Experiencewith PROSCAR™

• Sustained improvements over 7 years of therapy– Reductions in symptom scores– Sustained reductions in prostate volume

25% reduction at year 7– Sustained increases in urinary flow

2.5 ml/sec increase at year 7

• Consistent safety and tolerability profile over 8 years of therapy

Slide VI.1

Data on file, MSD.

PSC 2001-W-11666-SS

Efficacy of PROSCAR™ in Younger vs. Older Men with Clinical BPH (PLESS Subanalysis)

Slide VI.2

Adapted from Kaplan SA et al Urology 2001;57(6):1073-1077.

Younger men(<65 years)

Placebo(n=774)

PROSCAR(n=786)

201816141210

86420F

our-

year

pro

bab

ilit

y of

AU

Ran

d/o

r n

eed

ing

surg

ery

0 1 2 3 4

Year

51% riskreduction(p<0.001)51% risk

reduction(p<0.001)

• PROSCAR significantly reduced the incidence of AUR and BPH-related surgery in younger and older patients at 4 years (p<0.001).

Older men(65 years)

Placebo(n=742)

PROSCAR(n=738)

Fou

r-ye

ar p

rob

abil

ity

of A

UR

and

/or

nee

din

g su

rger

y

201816141210

86420

0 1 2 3 4

Year

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Rapid and Sustained Reduction in the Risk of Long-Term Outcomes with PROSCAR™

Double-blind study Open-label extension

Slide VI.3

n values indicate number of patients completing each trial phase

Adapted from Roehrborn CG et al. Poster 419.

Placebo (n=1503)PROSCAR 5 mg (n=1513)

Placebo PROSCAR 5 mg (n=858)PROSCAR 5 mg PROSCAR 5 mg (n=979)

5

4

3

2

1

0

Yea

rly

% o

f A

UR

an

d/o

r B

PH

-rel

ated

su

rger

y

1 2 3 4 5 6

Study year

3.7

1.9

4.4

2.1

3.3

1.0

3.0

2.0

1.00.7

1.4 1.3

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PROSCAR™ Significantly Reduced Bother Over Long-Term Therapy (4 Years) (PLESS Substudy)

Slide VI.4

*p<0.05 PROSCAR vs. placebo at every time point after 4 months to 1 year and p<0.001 PROSCAR vs. placebo every 4 months, years 1 to 4**Significant improvement vs. baseline with PROSCAR and placebo at 4 years, p<0.001

PSA = prostate-specific antigen

Adapted from Bruskewitz R et al Urology 1999;54:670-678.

Overallbother score*,** By baseline PSA tertile (ng/ml)

Placebo(n=1503)

PROSCAR

5 mg(n=1513)

PSA: 0–12 PSA: 0–1.3 PSA: 1.4–3.2 PSA: 3.3–12

1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4

Year of follow-up

0

–1

–2

–3

–4

Mea

n (

±SE

) ch

ange

inb

oth

er s

core

fro

m b

asel

ine

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PROSCAR™ Had No Effect on Bone Mineral Density (BMD) (PLESS Substudy)

Slide VI.5

p = NS between treatments

Adapted from Matsumoto AM et al J Urol 2002;167:2105-2108.

1.12

1.10

1.14

1.13

1.15

1.14

1.13

1.12

1.11

1.10

1.09

1.08 Baseline End of study

BM

D (

g/cm

2 )

PROSCAR (n=63)

Placebo (n=54)

PSC 2001-W-11666-SS

New Data on the Long-Term Efficacy and Tolerability of PROSCAR™: Summary

• PROSCAR maintains clinical improvements over long-term therapy– Sustained reductions in symptom scores and prostate volume

and increases in urinary flow over 7 years – Durable effects up to 10 years – Similar effects in older vs. younger men– Reductions in risk of outcomes maintained over 6 years– Significant reductions in bother due to BPH symptoms at 4 years

(p<0.001 vs. placebo)

• PROSCAR is well tolerated over long-term therapy– Consistent safety/tolerability profile through year 7 – No effect on BMD

Slide VI.6

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The Patient-Physician Connection

Section VII

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Patient Satisfaction Is Important in the Treatment of Clinical BPH

• Treatment selection in BPH should take into account– Patient’s perception of the impact of BPH on

quality of life– Patient’s ability to deal with bother caused

by symptoms– Patient’s attitudes toward risk of possible

complications

Slide VII.1

PSC 2001-W-11666-SS

The Physician’s Rolein Patient Education

• Physicians should involve patients with BPH in the choice of therapy

• Patient education should include discussions of– The natural history of BPH (including potential

for serious complications)– Benefits, risks, and costs of alternative approaches

Slide VII.2

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Combination Therapyfor Clinical BPH

Section VIII

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Combined Therapy with PROSCAR™ and an Alpha Blocker (terazosin) for Clinical BPH

Slide VIII.1

p<0.05 PROSCAR + terazosin vs. either agent used alone at 12 months

Adapted from Savage SJ et al Can J Urol 1998;5(3):578-584.

20

18

16

14

12

10

8

0 2 4 6 8 10 12

Time (months)

Mea

n I

PS

S

PROSCAR 5 mg/day

Terazosin titrated to 5 mg

Combination

PSC 2001-W-11666-SS Slide VIII.2

Discontinuation of Alpha Blockade After Combined Therapy with PROSCAR™ and

an Alpha Blocker (doxazosin) for BPH

Adapted from Baldwin KC et al Urology 2001;58(2):203-209.

Su

cces

s ra

tes

afte

r d

isco

nti

nu

atio

n

(% o

f p

atie

nts

)

100

80

60

40

20

0 3 months 6 months 9 months 12 months

Doxazosin 2 mg (n=25)

Doxazosin 4 mg (n=20)

Doxazosin 8 mg (n=15)

2015 13

4845

40

8480

73

84 85 87

Time after discontinuation

PSC 2001-W-11666-SS

Combined Therapy with PROSCAR™ and an Alpha Blocker for Clinical BPH: Summary

Slide VIII.3

• Enhanced relief of symptoms

• After withdrawal of alpha blocker– Satisfaction (success) rates maintained

87% after 12 months in one study

PSC 2001-W-11666-SS

Other Emerging Usesof PROSCAR™

Section IX

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63

PROSCAR™ Decreases the Risk of Hematuria

Slide IX.1

*p<0.05 between groupsPROSCAR is not indicated for treatment of BPH-related hematuria.

Adapted from Foley SJ et al J Urol 2000;163:496-498.

Control (n=27)

PROSCAR (n=28)

70

60

50

40

30

20

10

0

% o

f m

en

Hematuria*at 1 year

Hematuria requiring surgery

at 1 year

14

0

26

PSC 2001-W-11666-SS

Pretreatment with PROSCAR™ Decreases Perioperative Bleeding Associated with TURP*

Slide IX.2

*PROSCAR was given 2–4 months before TURP.PROSCAR is not indicated for pretreatment before prostate surgery.

Adapted from Hagerty JA et al Urology 2000;55:684-689.

Total group <30 g resected 30 g resected

40

35

30

25

20

15

10

5

0

% o

f p

atie

nts

wit

h b

leed

ing

Placebo

PROSCAR

(n=25) (n=12)

8.3

0

4

(n=13)(n=50) (n=19)

14

36.8

0

(n=31)

PSC 2001-W-11666-SS

Other Emerging Usesof PROSCAR™: Summary

• Extended benefits of PROSCAR in men with BPH – Reduced risk of hematuria and hematuria-related

surgery– Improved outcomes when used prior to BPH-related

surgery

• PROSCAR is not currently indicated for these uses.

Slide IX.3

PROSCAR is not currently indicated for these uses.

PSC 2001-W-11666-SS

Summary

Section X

PSC 2001-W-11666-SS

Overall Summary and Conclusions

• BPH, a multifactorial disorder characterized by an enlarged prostate, LUTS, and BOO, can lead to serious clinical outcomes (AUR and BPH-related surgery).

• PROSCAR™ is a competitive and specific inhibitor of type II 5-reductase, which mediates the conversion of testosterone to DHT.

• PROSCAR reduces BPH symptoms and prostate size, improves urinary flow, and decreases the risk of AUR and BPH-related surgery.

• PROSCAR slows the progression of BPH.

• The clinical effects of PROSCAR have been established in clinical trials of up to 7 years’ duration.

Slide X.1

PSC 2001-W-11666-SS

Bibliography

• See Notes page

PSC 2001-W-11666-SS

Bibliography (cont’d)

• See Notes page

PSC 2001-W-11666-SS

Before prescribing any of the products mentioned

in this slide presentation, please consult the manufacturer’s

prescribing information.

Copyright © 2002 Merck & Co., Inc., Whitehouse Station, NJ, USA.

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Clinical BPH and Its ManagementA Comprehensive Slide Kit