BENIGN PROSTATIC

HYPERPLASIA
Dr. Akhtar Nawaz Orakzai
FCPS Urology

Institute of Kidney Diseases

Hayatabad

What is BPH?
Benign

prostatic hyperplasia (BPH) is defined as

a benign enlargement of the prostate gland
caused by the growth of new cells
One of the most common conditions affecting
older men which can lead to LUTS
Advancing age and testicular androgens play a
central role
Age related enlargement of the prostate seen in
men with BPH may be caused by increased
cellular proliferation combined with a decreased
rate of apoptosis

Cause of BPH
The

primary androgenic stimulator of

prostate growth is dihydrotestosterone
(DHT)
DHT is produced from testosterone via the
5alpha-reductase (5AR) isoenzymes type I
and II

Testosterone synthesis
Hypothalamus
LHRH

Pituitary
LH

ACTH

Testes
~90%

Adrenal gland

Testosterone

~10%

DHT
LHRH = luteinising hormone releasing hormone
ACTH = adrenocorticotrophic hormone
Walsh P (ed). Campbells Urology. WB Saunders, 2002
LH = luteinising hormone

Regulation of cell growth

Serum DHT

Serum testosterone (T)

T
5AR (I and II)
Growth
factors

DHT

Prostate
cell

DHT-androgen
receptor complex
Cell death

Increased Unbalanced
Cell growth
Adapted from Kirby RS, McConnell. Benign Prostatic Hyperplasia. Health Press Ltd, 1999

Type I and type II isoenzyme

Type I distribution Type II
Scalp
Brain

Liver
Sebaceous glands
Seminal vesicles
Liver
Prostate

Prostate
Skin

Genital tissues
(genital skin and
epididymis)
Anderson JB et al. Eur Urol 2001; 39: 390399
Bartsch G et al. Eur Urol 2000; 37: 367380
Thigpen AE et al. J Clin Invest 1993; 92: 903910

5AR in the prostate

5AR
type I

Testosterone

DHT

5AR
type II

Andriole G et al. J Urol 2004; 172: 13991403

DHT, The Cause of BPH

Intra-prostatic

DHT remains high in ageing

men
A 5AR deficient state can be induced by
5AR inhibitors which have been shown to
shrink the enlarged prostate

Andriole G et al. J Urol 2004; 172: 13991403

Anatomy of BPH
Normal
BPH

Bladder

Prostate

Hypertrophied
detrusor muscle

Urethra

Adapted from Kirby RS et al. Benign Prostatic

Hyperplasia. Health Press, Oxford, 1999

Obstructed
urinary flow

Zonal origin of BPH

Normal
BPH
Urethra

Peripheral
zone

Transition
zone

Central
zone

BPH: symptoms
Symptoms

associated with BPH include the

voiding and storage symptoms

LUTS

is not specific to BPH not all men

with LUTS have BPH and not all men with
BPH have LUTS

Cunningham GR et al. Epidemiology and pathogenesis of benign

prostatic hyperplasia. Up To Date Literature Review, Apr 29; 1998
EAU BPH guidelines. Madersbacher S et al. Eur Urol 2004; 46: 547554

Symptom type

Symptom

Obstructive (voiding)

Weak urinary stream

Prolonged voiding
Abdominal straining
Hesitancy
Intermittency
Incomplete bladder emptying
Terminal and post-void dribbling

Irritative

Frequency
Nocturia
Urgency
Incontinence
Associated symptoms Dysuria
Haematuria
Haematospermia

EAU 2004 recommendations

regarding initial assessment of BPH
Medical history

Recommended

Symptom score

Recommended

Physical
examination
including digital
rectal
examination
(DRE)

Recommended

Prostate specific
antigen (PSA)

Recommended

Creatinine
measurement
Urinalysis
Flow rates
Post-void residual
volume
Pressure flow
studies
Imaging of the
upper urinary
tract
Imaging of the
prostate
Voiding charts

Recommended
Recommended
Recommended

Recommended
Optional

Optional

Optional
Optional

Recommended investigations
(EAU guidelines)
Medical history
Symptom scores
Physical examination
PSA
Flow rates
Creatinine measurement
Post-void residual volume

EAU BPH guidelines. Madersbacher S et al. Eur Urol 2004; 46: 547554

Total IPSS* score indicates

symptom severity
IPSS
Score

Symptom
severity

Symptom description

07

Mild

819

Moderate

Little bother, reasonable

urine flow and low
residual volume
Bothersome, reduced
residual volume but no
evidence of
complications

20

Severe

Complications of
obstruction

PSA
PSA

is a protein produced almost exclusively

in the epithelial cells of the prostate
Elevated levels of PSA signify change in the
prostate typically caused by:

BPH
Prostate cancer
Prostatitis
? Ageing
Instrumentation

Guideline recommendations
A

PSA-test should be offered to those with

at least a 10-year life expectancy and for
whom knowledge of the presence of
prostate cancer would change management

PSA

can be used to evaluate the risks of

either requiring surgery or developing AUR

Transrectal ultrasound: early

stage BPH

Arrows indicate the

moderately enlarged
transition zone

Prostate volume: 29 mL

Conclusion from studies:

risk factors of progression
The

most valid factors for progression

were:
Prostate volume (Combined 2-year placebo
analysis)
PSA level (PLESS)
Age (Olmsted County)
LUTS

BPH

can be considered as a progressive

disease

Predictors of BPH progression:

overview
Primary

predictor

Prostate volume
PSA
Age
Secondary

predictors

flow
Symptom score

Emberton M et al. Urology 2003; 61: 267273

Management of BPH

Aims of treatment: EAU

guidelines
The

aim of therapy is to improve lower

urinary tract symptoms (LUTS) and
quality of life, and to prevent BPE/BPOrelated complications such as urinary
retention or upper urinary tract dilatation

EAU BPH guidelines. Madersbacher S et al. Eur Urol 2004; 46: 547554

Treatment
The

identification of specific risk

factors for disease progression
provides a basis for a risk profile
oriented therapy
Patients at increased risk of
progression should be offered early
preventive treatment

Treatment
Management

of men with LUTS suggestive

of BPH can be categorized into:
Watchful waiting
Medical therapy
Surgical management

EAU BPH guidelines. Madersbacher S et al. Eur Urol 2004; 46: 547554

Current treatments
Recommended?
Watchful waiting

Alpha-blockers

5-alpha-reductase inhibitors (5ARIs)

Combination therapy

Phytotherapy

Minimally invasive techniques

Surgery

EAU BPH guidelines. Madersbacher S et al. Eur Urol 2004; 46: 547554

Watchful waiting
Watchful Waiting (WW) is a viable option to many

men as the risk of progression is small

Regular monitoring allows physicians and patients to

assess whether symptoms improve or deteriorate

WW is often more suitable for those with symptom

scores which are less bothersome and who have a

low risk of progression
Small prostates <30 mL
Lower PSA <1.5 ng/mL
EAU BPH guidelines. Madersbacher S et al. Eur Urol 2004; 46: 547554
Roehrborn CG. In: Lepor H (ed). Prostatic Diseases. WB Saunders, 2000: 143159.

Watchful Waiting
The following are important components of WW:
Education
Reassurance
Periodic monitoring
Lifestyle modifications

Brown C et al. Curr Opin Urol 2004; 14: 712

Lifestyle modifications
Various lifestyle modifications can be used with WW

to reduce the impact of symptoms:

Reduction in fluid intake
Avoidance/moderation of alcohol and caffeine
intake
Bladder retraining
Use of timed voiding schedules

Discontinuation of drugs that may aggravate

bladder outlet obstruction

Assistance when there is impairment of dexterity,

mobility, mental state and treatment of constipation

EAU BPH guidelines. Madersbacher S et al. Eur Urol 2004; 46: 547554
Brown C et al. Curr Opin Urol 2004; 14: 712

Medical therapy
The following medical treatments are
currently available for BPH:
Alpha-blockers
5ARIs
Combination therapy
Phytotherapy

Goals of pharmacotherapy in
BPH
Prevent progression of BPH
Impact on the
disease process
by reducing prostate
volume

Improve LUTS and

reduce bother in
the long-term

Improve and maintain

flow in the long-term

Reduce serious
complications

Alpha-blockers
4

currently available alpha-blockers:

Tamsulosin
Terazosin
Alfuzosin
Doxazosin

EAU BPH guidelines. Madersbacher S et al. Eur Urol 2004; 46: 547554

Mode of action
Alpha-blockers

relieve symptoms of BPH by

causing smooth muscle relaxation through
blockade of alpha-1 adrenoceptors in the
prostate

Alpha1A

is the predominant subtype

localised in the prostate

EAU BPH guidelines. Madersbacher S et al. Eur Urol 2004; 46: 547554

Alpha-blocker tolerability
Common alpha-blocker adverse events include:

Dizziness
Erectile dysfunction
Asthenia
Postural hypotension

McConnell JD et al. N Engl J Med 2003; 349: 23872398

Guideline recommendations
for alpha-blockers
Alpha-blockers

are an acceptable medical

therapy for men with moderate-to-severe
LUTS

EAU BPH guidelines. Madersbacher S et al. Eur Urol 2004; 46: 547554

Alpha-blockers: Summary
Alpha-blockers

rapidly improve symptoms

and urinary flow but do not reduce
prostate volume

Generally

tolerability is good

Alpha-blockers

do not reduce the overall

long-term risk of AUR or surgery

An

acceptable treatment for patients with

moderate/severe LUTS and prostate
volume <40 mL

5ARIs
Two

5ARIs:

Finasteride inhibits 5AR Type II

Dutasteride inhibits 5AR Type I and II

Dutasteride

is 2.5x more potent against

Type II isoenzyme than finasteride

Suppression

of DHT

5ARIs for BPH

5AR
Type I

Testosterone

DHT

5AR
Type II

Anderson JB et al. Eur Urol 2001; 39: 390-399.

5ARI tolerability
Common

include:

5ARI adverse events

Impotence
Gynaecomastia
Ejaculation disorders

McConnell JD et al. N Engl J Med 1998; 338: 557563

Roehrborn CG et al. Urology 2002; 60: 434441
Marberger M et al. Eur Urol 2004; 45: 411419
Gormley GJ et al. N Engl J Med 1992; 327: 11851191

Guideline recommendations
for 5ARIs
5ARIs

are an acceptable treatment option

for patients with moderate/severe LUTS
and an enlarged prostate (>3040 mL)

5ARIs

should be offered to patients for the

prevention of progression of BPH
EAU BPH guidelines. Madersbacher S et al. Eur Urol 2004; 46: 547554

5ARI therapy: summary

Data

from extensive, robust, controlled

studies have confirmed that in men with
enlarged prostates, both dutasteride and
finasteride have a significant effect
compared with placebo on:

Reducing symptoms and impact of BPH

Reducing prostate volume
Improving Qmax
Reducing risk of AUR and surgery

Combination therapy?
5ARI
Long-term

symptom
benefits
Reduction in
prostate volume
Decrease in risks of
AUR/Surgery

Alpha-blocker

Rapid

symptom

relief
Increased urinary
flow

Combination therapy:
guideline recommendations
5ARI DHT suppression and decrease in prostate

volume provides the foundation for long-term

pharmacotherapy in men with enlarged prostates
Adding an alpha-blocker can provide a more rapid

onset of symptomatic relief in appropriate patients

5ARIs are well-tolerated and can be continued long-

term to provide symptom relief and reduce risk of

complications
EAU BPH guidelines. Madersbacher S et al. Eur Urol 2004; 46: 547554