Etiology &

Pathophysiolog
y of

Benign
Prostatic

Chaidir A Mochtar
Department of Urology, FKUI-
RSCM

Hyperpla

Epidemiology
of BPH

Etiology of
BPH

Pathophysiol
ogy of
BPH

Key Points

EPIDEMIOLOGY OF BPH
Uncommon before age 40
50% of men develop BPH-related symptoms at 50 years of age
Incidence of BPH increases by 10% per decade and reaches
80% at 80 years of age
75% men >50 yr have symptoms arising from BPH
20-30% of men reaching 80 year old require surgical
management for BPH

Briganti A, et.al. Benign prostatic hyperplasia and its aetiologies.

J.eursup.2009

Prevalence of Anatomical BPH

Kirby RS, An atlas of prostatic disease, 3rd edition, 2003,

Parthenon publishing

Prevalence of Symptomatic BPH

Kirby RS, An atlas of prostatic disease, 3rd edition, 2003,

Baseline Prostate Volume

against the Annual
Percentage Increase

Kirby RS, An atlas of prostatic disease, 3rd edition, 2003,

PSA Values as the predictor of the need

BPH-related Surgery/Acute urinary
retention

Kirby RS, An atlas of prostatic disease, 3rd edition, 2003,

Parthenon publishing

etiology
benign prostatic
hyperplasia

ETIOLOGY OF BPH
Multiple theories have been proposed,
but the etiology still remains uncertain in
some aspects.

Androgens, estrogens, stromal-epithelial

interactions, growth factors, and
neurotransmitters may play role in the
hyperplastic process.
Briganti A, et.al. Benign prostatic hyperplasia and its aetiologies. J.eursup.2009
Benign prostatic hyperplasia:etiology,pathophysiology, epidemiology, and natural history.Campbell-Walsh
Urology, 10th ed. 2012

ETIOLOGY

Briganti A, et.al. Benign prostatic hyperplasia and its aetiologies.

J.eursup.2009

ETIOLOGY: Tissue Remodelling

Ageing is the most signicant risk factor for the development
of BPH and the occurence of LUTS1
Moderate to severe urinary symptoms in 13% of men 40-49
years old VS 28% in men >70 years old1
Prostatic volume change of 0,6ml/year growth rate of
2,5%/year1

1. Briganti A, et.al. Benign prostatic hyperplasia and its aetiologies. J.eursup.2009

2. Benign prostatic hyperplasia:etiology,pathophysiology, epidemiology, and natural
history.Campbell-
Walsh Urology, 10th ed. 2012

ETIOLOGY: Tissue Remodelling (ctd)

Expression of antiapoptotic proteins growth imbalance in
favour of cell proliferation1

Aging
process

Blockade
of
maturati
on
process

Progression
to
terminally
dierentiate
d cells is
reduced

Reducing
the overall
rate of cell
death2

1. Briganti A, et.al. Benign prostatic hyperplasia and its aetiologies. J.eursup.2009

2. Benign prostatic hyperplasia:etiology,pathophysiology, epidemiology, and natural
history.Campbell-
Walsh Urology, 10th ed. 2012

Tissue Remodelling Theory

ETIOLOGY: Hormonal Alteration

Estrogen

Androgen

Estrogenic stimulation in the aging man

epithelial and stromal cell
proliferation1 reactivation of prostatic
growth1
Estrogen may increase androgen
receptors (AR) expression in the
aging prostate
ER induces proliferation, ER induces
proliferation and induction of apoptosis

Androgens do not cause BPH, altough

BPH requires the presence of testicular
androgens1
DHT is generated by the 5-reductase that
present in broblasts of the stroma and in
basal epithelial cells1
Androgen signalling is signicantly
elevated in hyperplastic tissue
relative to the adjacent normal prostate1

1.Briganti A, et.al. Benign prostatic hyperplasia and its aetiologies. J.eursup.2009

2.Benign prostatic hyperplasia:etiology,pathophysiology, epidemiology, and natural
history.Campbell-Walsh
Urology, 10th ed. 2012

Lumen

STROMAL
C ELLS

E PITHEUA L
CELLS
.
L u m in a
um

e p i t h e l-

A p o p t o s is

Tes o s t e r o n e

DHT

Basal ep -

e l iu m

-H---is

Basement
membrane
Stroma

D H T p ro d u c e d peripherally b y type 1 a n d type 2 Sa-reductase

1.
2.

Benign prostatic hyperplasia :etiology,pathophysiology, epidemiology, and natural history.Campbeii-Walsh Urology, 1oth ed. 2012
Ho CKM. Estrogen and androgen signaling in the pathogenesis of BPH. Nat. Rev. Urol,2011. 8, 29-41.

Apoptos

ETIOLOGY: Metabolic Syndrome

Risk factors for

BPH
NIDDM
Diabetes is associated with LUTS,
reduced maximum ow rate and
increased postvoid residual volume

Hypertension
Hypertension occurs in about 25% of
patients with BPH

Obesity
Obesity is related to the increase of
estrogen- androgen ratio and
activation of sympathetic nervous
system

Median annual total prostate

growth rate and median
annual TZ were signicantly
higher in the group with risk
factors (1 and 1,25ml/yr VS
0,64 and 0,93/yr)
Previously hypothesised that
the sympathetic nervous
system might have an eect
on prostate growth by slowing
down the apoptotic
process, commonly found in
hyperinsulinemia

Low A,
HDLC Benign prostatic hyperplasia and its aetiologies.
Briganti
et.al.
J.eursup.2009

Metabolic Syndrome and BPH

Nunzio CD, Aronson W, Freedland SJ, Giovannucci E, Parsons JK. The correlation
between metabolic syndrome and prostatic diseases. Eur Urol. 2012;61:560-70.

ETIOLOGY: Inammation
Chronic inammation is believed to support the process of
bromuscular growth in BPH1
The inammation may contribute to tissue injury and cytokines
produced by inammatory cells local growth factor production and
angiogenesis in the tissues as a wound healing response1
Inltrating cells
(T cells and
macrophages) are
responsible for the
production of
cytokines (IL-2 and
IFN-)2

Local
hypoxia as a
Inammati
result of
on- based
increased
tissue
oxygen
remodelling
Induces the
demands of
production of IL-15
as the main
proliferating
interleukin
1.Briganti A, et.al. Benign prostatic hyperplasia and
its aetiologies.
cells

Induced low
levels of ROS
Neovascularisati
on
Fibroblast to
myobroblast
transdierentiati
on1

J.eursup.2009
2.Nickel JC. Inammation and benign prostatic hyperplasia. Urol Clin N Am

Pro-Inflammatory

Muscle cells
Fibroblast

CD4+ helper T cells

CD4+ cytotoxi c T
c ells
Dendritic cells

..
. c..
I t
)

::

Basal

cells
Pro-lnnamrnatory

Fibroblast
s

First
signal
In DC
activation

:::1
Gl

"t:

Gl

Induction of
Pro3-beta ( hormone
HSD Honnone
synthesis

Figure 91-4. A, Tissue effect of T ceiHJer i ved proinflammatory

cytokines on the pathogenes i s and progress ion of immune
i nflammation and stromal growth in the aging prostate {T cells
i nd icated i n red). B, Role of smooth muscle cells (indicated in
red )
i n maintenance and propagat i on of immune inf i ltrat ion in the
aging prostate . PSA, prostate-specif ic ant igen ; PAP, prostat ic acid
phosphatase ; TLR, toll-l i ke receptor. (From Kramer G, Mitteregger
D,
et al. Is benign prostatic hyperplasia [BPH ] an immune
inflammatory disease? Eur Urol2007;51[5]:1202-16.)

Benign prostatic hyperplasia:etiology,pathophysiology, epidemiology, and natural history.Campbell-Walsh

Urele etRee. e - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Benign prostatic hyperplasia:etiology,pathophysiology, epidemiology, and natural

history.Campbell-Walsh Urology, 10th ed. 2012

Relationship between Chronic

Inammation and BPH

Kramer G, Mitteregger D, Marberger M. Is benign prostatic hyperplasia (BPH) an

immune inammatory disease?. Eur Urol. 2007;51:1202-16.

pathophysiol
ogy
benign prostatic hyperplasia

PATHOPHYSIOLO
GY

BPH rst
develops in
the

periurethr
al
transition
zone of the
prostate

All BPH nodules

develop either in the
transition zone or
in the periurethral
region
The transition zone
also enlarges with
age
The earliest transition
zone nodules
represent proliferation
of glandular tissue
Periurethral nodules
are purely stromal in
character

Prostatic
capsule has
important role
in the
development of
LUTS
transmits the
pressure

The relative
proportion of
stromal and
epithelial
hyperplasia is
related to the
development
of
symptomatic
BPH
The size of the
prostate does not
correlate with the
degree of
obstruction

Benign prostatic hyperplasia:etiology,pathophysiology, epidemiology, and natural

history.Campbell-Walsh Urology, 10th ed. 2012

SYMPTOMS OF
BPH
Obstructive
Component of
Prostate
Mechanical Obstruction
Prostatic enlargement intrusion
into the urethral lumen bladder
outlet resistance

Dynamic Obstruction
Prostatic stroma,composed of
smooth muscle and collagen, rich in
adrenergic nerve supply
autonomic stimulation sets a tone
to the prostatic urethra

Secondary Response of
the Bladder to the outlet
resistance
Irritative voiding
complaints secondary
response from detrusor
instability or decrease
compliance

Urinary obstruction & stasis.Smith & Tanaghos General urology, 18th edition,
2013.McGrawHill

Obstruction-
induced changes
in detrusor function
and age related
changes in
bladder and
nervous system
function lead to:
Urinary
frequency
Urgency
Nocturia
Benign prostatic hyperplasia:etiology,pathophysiology, epidemiology, and natural history.Campbell-Walsh
Urology, 10th ed. 2012

Pathophysiology of BPH

Kirby RS, An atlas of prostatic disease, 3rd edition, 2003,

Parthenon publishing

Bladders Response to Obstruction

One third of men continue to have signicant voiding
dysfunction and mostly storage symptoms after surgical relief
of obstruction
The major endoscopic detrusor change (trabeculation) is due
to an increase in
detrusor collagen
Obstruction-induced changes in the bladder are of two basic
types:
1.

Detrusor instability or decreased compliance (frequency and

urgency)

2.

Decreased detrusor contractility (further deterioration in the

force of the urinary stream, hesitancy, intermittency, increased
residual urine)

Benign prostatic hyperplasia:etiology,pathophysiology, epidemiology, and natural history.Campbell-Walsh

Urology, 10th ed. 2012

Phase of Bladders Response

Compensatory
Decompensation
phase
phase
Muscle wall
Progressive
becomes
outlet
hypertrophied
obstruction
and thickened
Decompensation
Trabeculation,
of the detrusor,
resulting in the
cellules,
presence of large
diverticula
amount of
In the presence
residual urine
of acute
after voiding
infection, the
mucosa may be
Urinary obstruction
reddened
and& stasis.Smith & Tanaghos General urology, 18th edition,
2013.McGrawHill
edematous

Response
to
Obstructi
on

Kirby RS, An atlas of prostatic disease, 3rd edition, 2003,

Parthenon publishing

A Model of The Natural Process of BPH

McConnell JD. The pathophysiology of benign prostatic hyperplasia. J Androl

THANK
YOU.