Benign Prostate

Hyperplasia:
Pathophysiology, Diagnosis &
Treatment

Djoko Rahardjo

Department of Urology,
Cipto Mangunkusumo Hospital/
Faculty of Medicine University of Indonesia
Overview

• Background

• Diagnosis

• Treatment

DR 2009
Overview

• Background

• Diagnosis

• Treatment

DR 2009
 Understanding the prostate

n Walnut-shaped gland that forms part of the male

reproductive system
n Penetrated by the urethra

DR 2009
Understanding the prostate

n Secreting seminal fluid

which carries sperm

n During orgasm, prostate

muscles contract and
help to propel ejaculate
out of the penis

DR 2009
3 Anatomi dasar prostat

1. Bagian anterior (20%) berisi jaringan fibromuskular dan

non glandular dan perannya sedikit dalam fungsi dan
patologi prostat

2. Bagian central (= zona transistional dan periuretra,

10%) tempat terjadinya BPH

3. Zona perifer (70%) tempat tumbuhnya kanker prostat.

What is Benign Prostatic Hyperplasia?

Hyperplasia of the periureteral gland

Peripheral zone

Transition zone

Urethra

DR 2009
Peripheral zone

Transition zone

Urethra

DR 2009
Why Prostate enlarges?
Hipotalamus
Sintesis Protein
LHRH

ACTH

Transkripsi
DNA
Reseptor Inti
+
DHT

T DHT
5-α reductase
Why Prostate enlarges?
Risk factors:
1. Aging
2. Functioning of the testicles (testosteron)

DR 2009

Prostate volume reduced by 20 – 30 % after 3 months of treatment

What is the nature BPH?

BPH is part of the natural aging

process, like getting gray hair or
wearing glasses

BPH cannot be prevented

BPH can be treated

BPH not to develop becoming

Prostate Cancer

DR 2009
 BPH

n Normal Size of the young adult is 15-20 cc.

• Pathological process start at age 40 years

• 50% in men > 60 years*
• 90% in men > 85 years*
• 90% in men 50-80 years**
• Second most frequent in urology in Indonesia

*AUA practice guidelines committee. J.Urol.2003,170 DR 2009

** MSAM-7 Eur Urol. in press 2004
BPH Prevalence

DR 2009
BPH Symptoms
Voiding (obstructive) Storage (irritative or
symptoms filling) symptoms
• Hesitancy • Urgency
• Weak stream • Frequency
• Straining to pass urine • Nocturia
• Prolonged micturition • Urge incontinence
• Feeling of incomplete
bladder emptying
• Urinary retention

DR 2009
BPH Symptoms

DR 2009
Overview

• Background

• Diagnosis

• Treatment

DR 2009
Anamnesa : Apakah anda mengalami
1. keluhan utama kesulitan untuk berkemih
seperti ini?
2. keluhan tambahan …harus mengejan dulu,
tidak lampias dan sering
berkemih pada malam hari

DR 2009
International Prostate Symptom Score (IPSS)

Score / Severity

0-7 Mild
8 - 19 Moderate
20 - 35 Severe

Barry MJ et al. J Urol 1992;148:1549-57. DR 2009

PEMERIKSAAN FISIK
DRE (Digital Rectal Exam)/ pemeriksaan colok dubur

Pemeriksaan fisik :
colok dubur
. Ukuran
. Nodul
. Konsistensi
. Kelembutan

DR 2009
 Pemeriksaan penunjang lain
• Pemeriksaan PSA (Prostate Specific Antigent)
untuk menyingkirkan dugaan menderita kanker
prostat
PSA merupakan suatu protein yang diproduksi
oleh sel prostat dan seringkali pada kanker prostat
levelnya meningkat

• Transrectal Ultrasonografi
jika ada kecenderungan ke arah
keganasan/ kanker prostat
DR 2009
PEMERIKSAAN PENUNJANG LAIN

IVP
Cystoscopy

uroflowmetri DR 2009
TRUS

Hypoechoic lession

DR 2009
Derajat BPH & Komplikasi

ringan sedang berat

DR 2009
Overview

• Background

• Diagnosis

• Treatment

DR 2009
BPH treatment choice
1. Watchful waiting

2. Medical treatment
- Alpha blocker
- Androgen suppression
- Phytotherapy

3. Surgery
DR 2009
Treatment of BPH
• Watchfull Waiting
• IPSS < 8
• Residual urine < 50 cc
• Q max > 15 cc/ sec
• Prostate volume < 20 cc
BPH treatment choice
1. Watchful waiting

2. Medical treatment
- Alpha blocker
- Androgen suppression
- Phytotherapy

3. Surgery
DR 2009
Treatment of BPH
• Indication for medical treatment
• IPSS > 8
• Residual urine > 50 cc
• Q max < 15 cc/ sec
 Mekanisme kerja α-blockers

Nerve ending Menghambat alfa 1a

Causes prostatic
relaxation & 1d pada otot polos
Norepinephrine di uretra & prostat
(Blockade)
Harnal

α1A α1A α1A α1A

α1C α1B α1A
α1A
α1D prostate Relaksasi /
menurunkan tekanan
uretra d bagian
prostat
Nerve ending

Norepinephrine Memperbaiki
α1D α1C α1B α1B α1B α1B α1B Blood Vessel gangguan buang air
Blood Vessel
(causes vascular contraction) = α1B kecil yg disebabkan
oleh BPH DR 2009
 Type of Alpha adrenergic receptor

1 dominant in prostate
2 also in blood vessel
smooth muscle

Lepor E, Saphiro E. J Urol 1984; 132: 1226-9

Non selective adrenergic blocking agent : blocks 1 and 2 receptors

Selective adrenergic blocking agent : blocks only 1 receptor

DR 2009
Types of  adrenergic blocking agent

Type Generic name

Non selective - Phenoxybenzamine
1 short acting - Prazosin
- IR Alfuzosin
1 long acting - Doxazosin
- Terazosin
- SR Alfuzosin
- XL Alfuzosin
1a long acting - Tamsulosin IR : Immediate releas
SR : Sustained release
 Half Life

Substance Half life (hours)

Prazosin (1979 Hedlund) 2–3
Doxazosin (1995) 22
Alfuzosin (1998) 3 – 4 (IR)
Terazosin (1992) 12
Tamsulosin (1998) 10 - 13
Dosage in Indonesia
• Doxazosin 1-2 mg once a day
• Terazosin 1-2 mg once a day
• Tamsulosin 0,2 mg once a day
• Alfuzosin XL 10 mg once a day
 TAMSULOSIN PALING SELEKTIF TERHADAP RESEPTOR  1 a &  1 d
PADA KELAS ALFA BLOKER(1)
25
Alfa 1 a
Alfa 1 b
20
Alfa 1 d
selektivitas reseptor

15

10

Tamsulosin
Harnal Terazosin Alfuzosin Doxazosin

Studi reseptor 1a dilakukan pada manusia, untuk reseptor 1b secara invivo pada
hamster,1d tikus
Foglar R.et.al.,Eur J.Pharmacol Mol Pharmacol Section 288, 201,1995 DR 2009
The lowest switch rate than any other BPH
Drugs

Vallancien G. Eur Urol 2003;38 (suppl 1) DR 2009

BPH treatment choice
1. Watchful waiting

2. Medical treatment
- Alpha blocker
- Androgen suppression
- Phytotherapy

3. Surgery
DR 2009
5  reductase inhibitor

5  reductase
inhibitor

Prostate volume reduced by 20 – 30 % after 3

months of treatment
DR 2009
5  reductase Inhibitor

• Finasteride : Iso enzyme type 2

• Dutasteride : Iso enzyme type 1 and 2

DR 2009
• Proscar world wide efficacy and safety study
(PRO WESS)
• Proscar long-term efficacy and safety study
(PLESS)
Proscar :
• Q max
• reducing prostate volume
• reduce incidence of AUR
• reduce surgical intervention

Mc Connell JD et al Engl J Med.1998; 338

Marberger MJ Urol. 1998; 51
Roehrborn CG Eur Urol. 2000; 37 DR 2009
Dutasteride
Dosage 0,5 mg/day

Symptom Score
Q max
Prostate vol
Incidence of AUR
Better than finasteride

Roehrborn DG et al. Urology 2002; 60(3) DR 2009

O Leary MP et al. BJU Int 2003; 92
Side effect of Finasteride
• Reduces libido
• ED
• Reduced ejaculate
• Lowering PSA  should be doubled to
detect CaP

MC Connel JD et al. Engl J Med. 1998; 338

DR 2009
Kirby RS. Proceeding of AUA 99th Annual Meeting 2004
Placebo effect in medical
treatment is high enough

Madersbacher S et al. Urologe 2008 DR 2009

Combination Therapy

Doxazosin
Finasteride

Terazosin
Finasteride Tamsulosin
Doxazosin
Finasteride Dutasteride

Madersbacher S et al. Urologe 2008 DR 2009

TRIPLE THERAPY
• Since the incidence of overactive bladder in BPH
patients is about 70 %, anti Muscarinic drugs
should be considered as an adjuvant treatment

• Since nocturia may cause worsening of the QOL

Anti Muscarinic drug will improve the condition

• Pressure flow study will give a better indication

for triple therapy

DR 2009
BPH treatment choice
1. Watchful waiting

2. Medical treatment
- Alpha blocker
- Androgen suppression
- Phytotherapy

3. Surgery
DR 2009
Phytotherapy

Species Generic name

• Serenoa repens • Saw palmetto berry
• Hypoxis rooperi • South African star grass
• Pygeum africanum • African plum tree
• Urtica dioica • Stinging nettle
• Secale cereale • Rye pollen
• Cucurbita pepo • Pumpkin seed
• Countia • Cactus flower
• Pinus • Pine flower
• Picea • Spruce

DR 2009
Mechanism of action of Phythotherapy

• Anti inflammation through prostaglandin

metabolism
• 5 reductase inhibitor
• Inhibition of growth factors production
(FGF, EGF)

Lepor H, Leuwe. Campbells Urology, 8th ed 2002 DR 2009

BPH treatment choice
1. Watchful waiting

2. Medical treatment
- Alpha blocker
- Androgen suppression
- Phytotherapy

3. Surgery
DR 2009
ABSOLUTE INDICATION FOR SURGERY
• Chronic urinary retention
• Gross hematuria
• Complicated UTI
• Bladder stone
• Decrease renal function
• Large diverticula
• Failure of medical treatment (Relative)
• Intravesical protrusion of the prostate > 1.5 cc (?)

REFER TO UROLOGIST
DR 2009
Conclusion

• BPH patients should be stratified according to

symptoms score, maximal flow rate, residual
volume and prostate volume
• Medical treatment should be tailored according
to the above stratification
• One should remember that the placebo effect is
there
• Invasive and less invasive treatment should be
with very strict indication

DR 2009
THANK YOU

DR 2009