Benign Prostatic Hyperplasia
(BPH)
26 Juli 2012
1. Kaplan, S.A. Identification of the patient with
enlarged prostate: diagnosis and guidelines for
management. Osteopathic Medicine and
Primary Care 2007, 1:11.
2. U Chong Lai, Yuk Tsan Wun, Tze Chao Luo & Sai
Meng Pang. In a free healthcare system, why do
men not consult for lower urinary tract
symptoms (LUTS)? Asia Pacific Family Medicine
2011, 10:7.
3. Edwards, J.E., & Moore, R.A. Finasteride in the
treatment of clinical benign prostatic
hyperplasia: A systematic review of
randomised trials. BMC Urology 2002, 2:14
Kaplan, S.A. Identification of the patient with
enlarged prostate: diagnosis and guidelines for
management.
EP (Enlarged Prostate):
• Gejala?  terapi simptomatik BAK dgn α-blocker.
• Perjalanan penyakit yg memburuk menjadi AUR
(Acute Urinary Retention)?  terapi yg
menyusutkan sel epitel prostat dgn 5α-reductase
inhibitor (5ARI)
• Indikator perjalanan penyakit yg memburuk:
LUTS meningkat, ukuran prostat meningkat,
kecepatan aliran urin menurun, komplikasi
kandung kemih, hematuria dan resiko AUR
meningkat.
• Pencegahan AUR lebih baik karena
prostatektomi atau insersi kateter menurunkan
QoL, meningkatkan morbiditas & mortalitas.
Gejala2 yg mengganggu
• Obati gejala (α-blocker/
anti-cholinergik)
•Pemantauan ketat
Tanpa
EP
• Beri nasihat ttg gaya
hidup, periksa
pengobatan, besarkan
hati.
• Rubah perjalan
penyakit (5ARIs,
terapi kombinasi)
•Obati gejala
• Beri nasihat
EP
ttg gaya
hidup, periksa pengobatan,
tenteramkan hati
•Rubah perjalan penyakit
(5ARIs) pd orang ResTi
tertentu
•Pemantauan ketat
Tanpa gejala2 yg mengganggu
Dx BPH:
• LUTS (Lower Urinary Tract Symptoms): freq,
nocturia, weak urinary stream, hesitancy,
intermittence, incomplete emptying &
urgency  Ringan (skor = 1-7), Sedang (skor =
8-19); Berat (skor = 20-35)
• DRE (Digital Rectal Examination): diameter > 2
lebar jari  prostate volume > 30 mL
• PSA (Prostate-specific antigen)  > 1.5ng/mL
• 1 ng = 0.000001 mg = 0.000000001 gr
Peran Dokter Keluarga
•
•
•
•
EP > 50% pada pria antara 50-60 th.
DK memulai diskusi tentang LUTS*.
DK melakukan DRE untuk menentukan EP.
DK meresepkan α-blockers kalau ada gejala yang
mengganggu dan/atau 5α-reductase inhibitors
(5ARIs) kalau ada EP.
*)U Chong Lai, Yuk Tsan Wun, Tze Chao Luo & Sai
Meng Pang. In a free healthcare system, why do
men not consult for lower urinary tract
symptoms (LUTS)? Asia Pacific Family Medicine
2011, 10:7.
Menunda konsultasi LUTS
• Dianggap gejala penuaan biasa
• Malu, takut
• Tidak spesifik EP  DDx
DDx LUTS:
• Urologic and nonurologic : Prostate cancer,
Prostatitis, Bladder cancer, Bladder stones,
Overactive bladder, Interstitial cystitis, DM,
Parkinson's disease, Congestive heart failure,
Lumbosacral disc disease, Multiple sclerosis,
Spinal cord injury, Stroke
• Obat: Tricylic antidepressants, Anticholinergic
agents, Diuretics, Narcotics, First-generation
antihistamines, Decongestants
• Obesitas, merokok, miras, hipertensi.
Peripheral zone (PZ) Up to 70% in young men The sub-capsular portion of the
posterior aspect of the prostate gland that surrounds the distal urethra. It is from
this portion of the gland that ~70–80% of prostatic cancers originate.[16][17]
Central zone (CZ) Approximately 25% normally This zone surrounds the ejaculatory
ducts. The central zone accounts for roughly 2.5% of prostate cancers although
these cancers tend to be more aggressive and more likely to invade the seminal
vesicles.[18
Transition zone (TZ) 5% at puberty ~10–20% of prostate cancers originate in this
zone. The transition zone surrounds the proximal urethra and is the region of the
prostate gland that grows throughout life and is responsible for the disease of
benign prostatic enlargement. (2)[16][17]
Anterior fibro-muscular zone (or stroma) Approximately 5% This zone is usually
devoid of glandular components, and composed only, as its name suggests, of muscle
and fibrous tissue.
Penatalaksanaan BPH
• Obat: α-blocker atau/dan 5ARI
• Prosedur invasif minimal (Rawat Jalan):
TUNA: Transurethral Needle Ablation
TUMT: Transurethral Microwave Thermotherapy
+ Stent prostat sementara
• TURP/TUR (Rawat Inap): Transurethral resection of the
prostate.
Daftar Obat PT Askes
• 5α-reductase inhibitor: Dutasteride (Avodart):
1 dd Caps mg 0.5
• α-blocker:
Terazosin HCl (Hytrin, Hytroz) - 1 dd Tab mg 1-2
Doxasozin Mesylate (Cardura) - 1 dd Tab mg 1-2
Tamsulosine (Harnal)
- 1 dd Tab mg 0.2/04
Edwards, J.E., & Moore, R.A. Finasteride in the
treatment of clinical benign prostatic
hyperplasia: A systematic review of
randomised trials. BMC Urology 2002, 2:14
Contoh Finasteride: 1 dd 1 Tab mg 5
• Finaxal (Sandoz):
• Finpro (Interbat)
• Proscar (Merck Sharp & Dohme)
• Prostacom (Combiphar)
• Reprostom (Fahrenheit)
Finasteride & Dutasteride = 5 α-reductase inhibitor
(5ARI) sintetis
5ARI = suatu inhibitor dari enzyme yg mengkonversi
testosterone ke DHT.
Dihydrotestosterone (DHT), atau
5α-dihydrotestosterone (5α-DHT) = hormon
androgen/sex steroid.
Enzyme 5 α-reductase mensintesis DHT di prostat,
testis, folikel rambut dan kelenjar adrenalis
• Indikasi: pengobatan BPH dan MPB (Male
Pattern Baldness)
Tujuan Penelitian: menentukan eficacy & efek
samping Finasteride melalui telaah pustaka &
meta-analisis.
Pustaka yg dicari: uji-coba finasteride yang
randomised dan double-blind utk BPH
hyperplasia.
• Kata Kunci yg digunakan: 'finasteride', 'proscar',
'clinical trial', & 'benign prostatic hyperplasia'
Dicari di/melalui: PubMed, the Cochrane Library,
dan daftar rujukan laporan dan review.
Randomized & Double Blind Trial:
X = Finasteride
O = symptom score, urinary flow rate, volume
prostat, putus berobat & efek samping
Analisis:
• RR
• NNT atau NNH
• Sensitivity analyses utk menilai pengaruh
kegawatan simptom awal, volume prostat awal,
uji-coba utama dan intervensi sebelumnya.
Hasil: (3 uji-coba dng kontrol aktif dan 19 dgn kontrol placebo).
Uji-coba dgn placebo: 8820 pasien finasteride 5 mg & 5909
pasien placebo selama 3–48 bln.
• Finasteride:
a. Setelah 48 bln - peningkatan lebih besar dlm hal total
symptom score, maximum urinary flow rate, & vol
prostate.
b. Pd 12 bln – lebih banyak disfungsi sexual, impotensi, gg
eyakulasi & penurunan libido. NNH disfungsi sexual pd
12 bln = 14.
c. Pd 24 atau 48 bln: lebih sedikit AUR atau operasi; NNT pd
12 bln = 49 (31-112) utk mencegah 1 AUR dan = 31 (2161) uk mencegah 1 operasi.
d. Analisis sensitivitas menunjukkan manfaat finasteride mg
5 konstan, tidak dipengaruhi volume awal prostat.
Kesimpulan:
• penelitian bermutu dengan N besar
menunjukkan manfaat Finasteride dalam hal
symptoms, flow rate & volume prostate.
• Diperlukan lebih banyak penelitian dengan O
dikotomi.
Kesimpulan Valid?
Penilaian mutu uji-coba:
• Setiap laporan penelitian yg dapat dianggap
sbg randomised controlled trial dibaca
masing2 peneliti dan diberi Jadad Score.
• Ketidak-sepakatan didiskusikan sampai ada
kesepakatan.
• Penelitian yg diikutsertakan jika skor max 5
dan skor min 2
Jadad Score Calculation
Item
1 Was the study described as randomized?
2 Was the study described as double blind?
Score
0/1
3 Was the study described as double blind?
0/1
4 Was the method of double blinding described &
appropriate ?
5 Was there a description of withdrawals and dropouts?
0/1
6 Deduct one point if the method used to generate the
sequence of randomization was inappropriate.
7 Deduct one point if the method of blinding was
inappropriate .
0/-1
0/1
0/1
0/-1
Outcome (O):
Divalidasi dengan 2 urologist & 3 GP dgn minat urologi untuk
menentukan O berdasarkan pendapat peneliti atau pasien.
Informasi yg digali:
1. N finasteride & N placebo
2. symptom score (total, obstructive, mengganggu)
3. volume prostat
4. urinary flow rate (maximum, mean)
5. berhenti (total berhenti, berhenti krn tidak efikasius/efek
samping)
6. efek samping: AUR dan operasi prostat.
7. PSA)
8. Volume sisa
9. Volume total yg dikeluarkan.
• Yang dicatat nilai absolut dan/atau
mean/median (SD) pada titik2 waktu: baseline
dan 3, 6, 12, 18, 24, 36 & 48 bln pengobatan