Transcript Epidemiology

Medical Management
of BPH
By Dr. Wissam Kh Kamal
KAAUH
Prostatic Zones
1-Anterior fibromuscular stroma
1/3 of prostate mass.
Extends from bladder neck to sphincter.
Replaced by adenoma.
Continuous with capsule.
Collagen, elastin, smooth and straited
muscle.
2-Periphral Zone:
Covers posterior and lateral gland.
70% of cancers arise here.
Most common site of chronic prostatitis.
3- Central Zone:
Ducts arise around opening of ejaculatory ducts.
Glands distinct from rest of prostate.
Expands in cone shape around ejaculatory ducts.
Rare site of cancer arising.
4- Transition Zone
Site of BPH development.
Enlarges with age.
Initial phase of BPH is formation of new glandular
nodules.
Second phase is increase in size of large nodules.
5- Periurethral Zone:
Found proximal to the origin of the transition zone
ducts.
Confined within the preprostatic sphincter and
course parallel to the axis of the urethra.
Cross Section of The Prostate
Vascular Supply
Arterial supply from inferior vesical artery.
Urethral branches are main blood supply to
adenoma.
Blood supply enters at bladder neck at 4 and
8 o’clock positions.
Venous drainage through periprostatic
plexus.
Lymphatic drainage to obturator and
internal iliac nodes.
Nerve Supply
Sympathetic and Parasympathetic innervations from
pelvic plexus through cavernous nerves.
Parasympathetic
promotes glandular secretion.
Sympathetic
contraction of capsular and stromal
smooth muscle.
Location of the prostate
Function of the Prostate
The prostate gland is a male accessory sex
gland.
During ejaculation it produces alkaline
prostatic fluid, which in combination with the
products of the testes, seminal vesicles,
urethral and bulbo-urethral glands, forms
semen.
BPH
ETIOLOGY AND PATHOPHYSIOLOGY
BPH is a common cause of the LUTS in
aging men.
Histopathologically, BPH is
characterized by an increased number of
epithelial and stromal cells in the
periurethral area of the prostate.
The observed increase in cell number
may be due to epithelial and stromal
proliferation or to impaired programmed
cell death leading to cellular
accumulation.
Androgens, estrogens, stromal-epithelial
interactions, growth factors, and
neurotransmitters may play a role, either
singly or in combination, in the etiology
of the hyperplastic process.
Although androgens and growth factors
stimulate cell proliferation in
experimental models, the relative role of
cell proliferation in human BPH is
questioned because there is no clear
evidence of an active proliferative
process.
Although it is possible that the early
phases of BPH are associated with a rapid
proliferation of cells, the established
disease appears to be maintained in the
presence of an equal or reduced rate of
cell replication.
Androgens not only are required for
normal cell proliferation and
differentiation in the prostate but also
actively inhibit cell death.
The Role of Androgen
Although androgens do not cause BPH, the
development of BPH requires the presence of
testicular androgens during prostate
development, puberty, and aging .
Patients castrated prior to puberty or who are
affected by a variety of genetic diseases that
impair androgen action or production do not
develop BPH.
It is also known that prostatic levels of
dihydrotestosterone (DHT) as well as the
androgen receptor (AR) remain high with aging
despite the fact that peripheral levels of
testosterone are decreasing.
In the prostate the nuclear membrane bound
enzyme steroid 5α-reductase converts the
hormone testosterone into DHT, the principal
androgen in this tissue.
Ninety percent of total prostatic androgen is in
the form of DHT, principally derived from
testicular androgens.
Adrenal androgens may constitute 10% of
total prostatic androgen, although the
importance of this stored hormone source in
the etiology of BPH is negligible.
Despite the importance of androgens in
normal prostatic development and
secretory physiology, there is no evidence
that either testosterone or DHT serves as
the direct mitogen for growth of the
prostate in older men.
Androgen Receptors
The prostate, unlike other androgen-dependent
organs, maintains its ability to respond to
androgens throughout life.
In fact, there is evidence to suggest that nuclear
AR levels may be higher in hyperplastic tissue
than in normal controls.
Age-related increases in estrogen, as well as
other factors, may increase AR expression in the
aging prostate, leading to further growth (or to a
decrease in cell death), despite decreasing levels
of androgen in the peripheral circulation and
“normal” levels of DHT in the prostate.
5 Alpha-reductase Enzymes
Two steroid 5α-reductase enzymes have been
discovered, each encoded by a separate gene.
Type 1 5α-reductase, the predominant enzyme in
extraprostatic tissues, such as skin and liver, is
inhibited by dutasteride but not substantially by
finasteride.
Type 2 5α-reductase is the predominant
prostatic 5α-reductase, although it is also
expressed in extraprostatic tissues. It is mainly
sensitive to inhibition by finasteride and
dutasteride.
Tissues in which type I and type II 5reductase are predominant
Type I
Type II
Skin
(sebaceous
glands)
Hair follicles
Liver
Seminal vesicles
Liver
Prostate gland
Adrenal glands
Epididymis
Internal/external
genital tissues
Slide III.4
Clearly, the type 2 enzyme is critical to normal
development of the prostate and hyperplastic
growth later in life.
The role of type 1 5α-reductase in normal and
abnormal prostate growth remains to be
defined.
Given that finasteride produces prostate size
reduction identical to that with dual
type1/type 2 inhibitors and roughly equivalent
to that with castration, it is unlikely that type
1–derived DHT is critical to hyperplastic
growth.
Immunohistochemical studies with type 2
5α-reductase specific antibodies show
primarily stromal cell localization of the
enzyme.
Data demonstrates that the stromal cell
plays a central role in androgendependent prostatic growth and that the
type 2 5α-reductase enzyme within the
stromal cell is the key androgenic
amplification step.
The Role of Estrogen
the role of estrogens in the development of
human BPH is not clear.
Serum estrogen levels increase in men with age.
There is also suggestive evidence that
intraprostatic levels of estrogen are increased in
men with BPH.
Patients with larger volumes of BPH tend to
have higher levels of estradiol in the peripheral
circulation.
Although there are relatively low concentrations
of classical high-affinity estrogen receptors in
human BPH there may be a sufficient amount for
biologic activity.
At present, the role of estrogens in
human BPH is not as firmly
established as the role of
androgens.
Regulation of Programmed Cell Death
Androgens (presumably testosterone and DHT)
appear to suppress programmed cell death
elsewhere in the gland.
Following castration, active cell death is
increased in the luminal epithelial population as
well as in the distal region of each duct.
Abnormal hyperplastic growth patterns, such as
BPH, might be induced by local growth factor or
growth factor receptor abnormalities, leading to
increased proliferation or decreased levels of
programmed cell death.
Growth factors and prostate development
A number of growth factors expressed by
mesenchymal or epithelial components of the
prostate have been identified:
– stimulatory growth factors: epidermal
growth factor (EGF), fibroblast growth
factor (FGF), insulin-like growth factor
(IGF) and transforming growth factor a
(TGF-a)
– inhibitory growth factors including
transforming growth factor b (TGF-b)
Growth factors and prostate development
A number of polypeptide growth factors and
receptors are subject to androgenic influence due to
DHT/RA–DNA interactions
This can alter the balance of cell proliferation and
death to tip the balance in favour of decreased
proliferation and apoptosis
Removal of androgens results in decreased
expression of stimulatory factors and increased
expression of inhibitory factors
The interplay of the growth factors may ultimately
determine the amount of stromal and glandular
hyperplasia in BPH
Other Etiological Factors
Inflammation, common in BPH
specimens, may play a role in the
pathogenesis of the disease through
cytokines that promote cell growth or
lead to smooth muscle contraction.
BPH can have a familial inheritance,
especially if large prostate volumes and
surgical intervention at a young age are
seen in the pedigree.
Epidemiology and natural Hx
There is no globally accepted epidemiologic
definition of BPH, and, thus, prevalence and
incidence rates must be viewed in the context of the
definitions chosen by the investigator reporting the
data.
Despite the significantly different proportion of men
admitting to moderate to severe symptoms, a clear
trend toward an increase in symptom scores with
advancing age is noticeable in all reported studies.
In general, in all cross-sectional studies prostate
volume as assessed by TRUS has been found to
increase slowly but steadily with advancing age.
Analytic epidemiologic data suggest a
limited role of classical determinants of
the disease such as religion,
socioeconomic factors, sexual activity,
alcohol intake, hypertension, dietary
factors, and others.
There is conflicting evidence regarding
smoking and some evidence suggesting
dietary factors, obesity, and increased
BMI as determinants of disease severity.
Pathophysiology
Prostate volume
static
Muscle tonus
Obstruction
dynamic
Pathophysiology of BPH
–
A static component (mechanical compression of the
urethra by the enlarged prostate gland)
–A
dynamic component (increased tone of smooth
muscle fibres in the bladder neck and
prostate gland)
–
Together, the two components can give rise to a
variety of lower urinary tract symptoms (LUTS)
The pathophysiology of BPH is complex .
Prostatic hyperplasia increases urethral
resistance, resulting in compensatory changes in
bladder function.
However, the elevated detrusor pressure
required to maintain urinary flow in the presence
of increased outflow resistance occurs at the
expense of normal bladder storage function.
Obstruction-induced changes in detrusor
function, compounded by age-related changes in
both bladder and nervous system function, lead
to urinary frequency, urgency, and nocturia, the
most bothersome BPH-related complaints.
Definition of BPH:
Histologically: is a microscopic diagnosis
characterized by cellular proliferation of the
stromal and epithelial elements of the prostate.
Radiologically: enlarged prostate either on
ultrasound or with three-dimensional diagnostic
imaging studies of the male pelvis.
Urodynamically: a synchronous observation of
elevated voiding pressure and a low urinary flow
rate in the absence of other disease processes
that cause bladder outlet obstruction.
Clinically:a constellation of signs and lower
urinary tract symptoms (LUTS) that develop in
the male population in association with aging
and prostatic enlargement presumably caused by
BOO.
BPH appearance
A characteristic of the
gross appearance of BPH
is rubbery yellow/grey
nodules of variable size
within the prostate gland.
The nodules are composed
of epithelium, smooth
muscle and fibrous tissue
in varying amounts, which
can be further classified.
BPH
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Kristen G. Barbee, RN, BSN
41
Diagnosis
The complex of symptoms now
commonly referred to as LUTS is not
specific for BPH
Aging men with a variety of lower
urinary tract pathologic processes
may exhibit similar, if not identical,
symptoms.
Voiding and Storage Symptoms
Associated with Clinical BPH
Bladder Outlet
Obstruction
Prostatic
Enlargement
Impaired
Detrusor
Contractility
Involuntary
Bladder
Contractions
Voiding Symptoms:
Storage Symptoms:
•Hesitancy
•Weak Stream
•Intermittency
•Straining
•Prolonged Voiding
•Sense of incomplete emptying
•Decreased flow rates
•Urgency
•Frequency
•Nocturia
•Urge incontinence
•Pain
•Decreased bladder capacity
(Small voided volume)
Post -void symptoms:
•Postvoid dribble or terminal dribble
•Post-void residual urine
Complications of BPH =
Absolute Indications for Surgery
Rec. UTI
Rec. hematuria
Retention of urine
Bladder stones
Bladder diverticulum
Bilateral Hydronephrosis & Renal
insufficiency
VUR
Anatomical hernias
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Kristen G. Barbee, RN, BSN
45
Evaluation
History.
Physical examination.
Investigations.
Symptom assessment.
History
A detailed medical history should be taken to
identify other causes of voiding dysfunction or
cormorbidities that may complicate treatment .
Specific additional areas to discuss when taking
the history of a man with BPH symptoms
include a history of hematuria, UTI, diabetes,
nervous system disease (e.g., Parkinson's
disease or stroke), urethral stricture disease,
urinary retention, and aggravation of
symptoms by cold or sinus medication.
AUA Symptom Score Sheet
Not at all
Less
than 1
time
in 5
Less
than
half the
time
About
half the
time
More
than
half
the
time
Almost
always
0
1
2
3
4
5
0
1
2
3
4
5
0
1
2
3
4
5
0
1
2
3
4
5
0
1
2
3
4
5
0
1
2
3
4
5
None
1 time
2 times
3 times
4 times
5 times
or more
0
1
2
3
4
5
Your
score
Incomplete emptying
Over the past month, how often have you had a sensation of not emptying your
bladder completely after you finish urinating?
Frequency
Over the past month, how often have you had to urinate again less than two hours
after you finished urinating?
Intermittency
Over the past month, how often have you found you stopped and started again several
times when you urinated?
Urgency
Over the last month, how difficult have you found it to postpone urination?
Weak stream
Over the past month, how often have you had a weak urinary stream?
Straining
Over the past month, how often have you had to push or strain to begin urination?
Your
score
Nocturia
Over the past month, many times did you most typically get up to urinate from the
time you went to bed until the time you got up in the morning?
Quality of life due to urinary symptoms
If you were to spend the rest of your life with your
urinary condition the way it is now, how would you
feel about that?
Delighted
Pleased
Mostly satisfied
Mixed – about equally
satisfied and dissatisfied
Mostly
dissatisfied
Unhappy
Terrible
0
1
2
3
4
5
6
Total score: 0-7 Mildly symptomatic; 8-19 moderately symptomatic; 20-35 severely symptomatic.
D.D
Of BPH
BPH
Urethral
Stricture
Neurogenic
Bladder
Prostatitis
CaP
Physical Examination
A DRE and a focused neurologic examination should
usually be performed.
In addition, examination of the external genitalia is
indicated to exclude meatal stenosis or a palpable
urethral mass, and an abdominal examination is
necessary to exclude an overdistended, palpable
bladder.
The DRE and focused neurologic examination are
done to detect prostate or rectal malignancy, to
evaluate anal sphincter tone, and to rule out any
neurologic problems that may cause the presenting
symptoms.
The presence of induration is as
important finding as the presence of a
nodule and should be correlated with a
serum PSA value so that the need for
prostatic biopsy can be assessed.
DRE
DRE establishes the
approximate size of the
prostate gland.
estimation of prostate size is
important to select the most
appropriate pharmacologic or
technical approach.
DRE provides a sufficiently
accurate measurement in most
cases. However, the size of the
prostate is not critical in
deciding whether active
treatment is required.
Investigations
Urinalysis: a urinalysis should be done to rule out UTI
and hematuria.
Serum Creatinine Measurement: the recently
published AUA guidelines on BPH no longer
recommend routine creatinine measurement in the
standard patient.
Serum Prostate-Specific Antigen: Prostate cancer can
lead to LUTS by producing bladder outflow obstruction
similar to BPH. Moreover, prostate cancer commonly
coexists with BPH.
Additional Diagnostic Tests
Additional testing should be considered after the initial
evaluation if there is a significant chance the patient's
LUTS may not be due to BPH.
patients with a normal initial evaluation and only mild
symptomatology on the IPSS (scores 0 to 7) do not need
additional diagnostic evaluation.
Urinary flow rate, postvoid residual (PVR) urine, and
pressure-flow urodynamic studies are appropriate tests
to consider in the evaluation of men with moderate to
severe symptoms (IPSS ≥ 8).
Uroflowmetry
The flowmeter device measures the quantity of fluid
passed per unit time
In addition, several different values can be calculated
– voided volume: the total amount of urine voided
– max flow rate (Qmax): the fastest rate at which
urination occurs
– average flow rate = voided volume/flow time
– time to maximum flow: time between the onset of
micturation and when peak flow occurs
– flow time: the time over which measurable urine
flow occurs
Uroflowmetry
Qmax is the most useful uroflow measure used and
provides a good indication of whether a patient is
obstructed or not
Patients with a value:
– <10 ml/sec are generally considered obstructed
– >15 ml/sec are judged unobstructed
– in the range of 10–15 ml/sec are equivocal
Accuracy is improved if the voided volume exceeds
150 ml
Uroflowmetry
Unobstructed
Detrusor underactivity
Obstructed
Urethral stricture
Post-void residual urine volume (PVRV)
PVRV measurement is performed noninvasively using transabdominal ultrasound
It can be useful in assisting with treatment
decisions but should not be used alone to
diagnose BPH
Patients found to have a large PVRV should
receive active treatment, otherwise they may
be more likely to develop AUR or fail
conservative therapy
Post-void residual urine volume (PVRV)
PVRV measurement can also be useful for
monitoring improvement or worsening of
BPH in non-treated patients
Although an increased PVRV may be
indicative of obstruction, more than one
measurement should be made because
variation has been known to occur between
voids
Urodynamics
These are the only means by which outflow
obstruction can be diagnosed
It is expensive and invasive, involving the
introduction of a small catheter, either urethrally
or suprapublically, to measure detrusor pressure
within the bladder (generated by the contracting
bladder muscle minus rectal pressure)
It can can be used to distinguish outflow
obstruction from impaired detrusor contractility
It has been suggested that this technique should be
confined to patients for whom surgery to relieve
obstruction is being considered
Cystoscopy
Cystoscopy is not recommended to determine the need
for treatment .
The test is recommended for men with LUTS who have
a history of microscopic or gross hematuria, urethral
stricture disease (or risk factors such as history of
urethritis or urethral injury), bladder cancer or suspicion
of carcinoma-in-situ, or prior lower urinary tract surgery
(especially prior TURP).
Cystoscopy may be considered in men with moderate to
severe symptoms who have chosen (or require) surgical
or other invasive therapy to help the surgeon determine
the most appropriate technical approach.




It provides visual documentation of the appearance
of the prostatic urethra and bladder in men with
BPH.
Potential benefits of cystoscopy include :
the ability to demonstrate prostatic enlargement and
visual obstruction of the urethra and the bladder
neck.
identification of specific anatomic abnormalities that
alter clinical decision making.
identification of bladder stones, trabeculation, and
diverticula.
measurement of PVR; and the ruling out of
unrelated bladder and urethral pathologic processes.
Imaging of the Urinary Tract
Upper urinary tract imaging is not recommended in the
routine evaluation of men with LUTS unless they also
have one or more of the following: hematuria, UTI, renal
insufficiency (ultrasound recommended), history of
urolithiasis, or history of urinary tract surgery .
Of all renal imaging studies performed in men with
BPH, 70% to 75% are entirely normal.
Only a small fraction of the 25% to 30% of abnormal
findings mandate changes in the management of the
patient.
Management Of BPH
Management of Patients With Mild Symptoms or Moderate to
Severe Symptoms Without
Bother
Patients with mild symptoms of BPH
(AUA Symptom Score <7) and patients
with moderate or severe symptoms (AUA
Symptom Score > 8) who are not bothered
by their symptoms (i.e., they do not
interfere with the daily activities of living)
should be managed using a strategy of
watchful waiting.
Management of Patients With Bothersome
Moderate to Severe Symptoms
Treatment options for patients with bothersome
moderate to severe symptoms of BPH (AUA
Symptom Score > 8) include watchful waiting
and the medical, minimally invasive, or surgical
therapies.
Information on the benefits and harms of the
BPH treatment options (including watchful
waiting) should be explained to patients with
moderate to severe symptoms (AUA Symptom
Score > 8) who are bothered enough to consider
therapy.
Treatment options for patients
with moderateto severe symptoms of benign
prostatic hyperplasia
Watchful Waiting
Medical Therapies
Alpha-adrenergic blockers
Alfuzosin
Doxazosin
Tamsulosin
Terazosin
5 Alpha-reductase inhibitors
Dutasteride*
Finasteride
Combination therapy (alpha blocker and 5
alphareductaseinhibitor).
Minimally Invasive Therapies
Transurethral microwave heat treatments
CoreTherm™*
Prostatron® (various versions)
Targis®
TherMatrx™*
Transurethral needle ablation
UroLume® stent‡
Surgical Therapies
Transurethral resection of the prostate
Transurethral electrovaporization
Transurethral incision of the prostate
Transurethral holmium laser resection/enucleation
Transurethral laser vaporization
Transurethral laser coagulation (e.g., visual laser ablation)
Open prostatectomy
Watchful Waiting
A significant proportion of men with LUTS will not
elect medical or surgical intervention because the
symptoms are not bothersome.
The complications of treatment are perceived to be
greater than the inconvenience of the symptoms, and
there is a reluctance to take a daily pill owing to
either side effects and the cost of treatment.
Reassured that the symptoms are not caused by
cancer or other serious genitourinary pathology, or
that the delay in treatment will not have irreversible
consequences, watchful waiting is often the patientdriven treatment of choice in the absence of absolute
indications for intervention.
Watchful Waiting
– Periodic monitoring
– Symptoms
– DRE
– Flow-rate
– PSA
– U.S (PVRV)
Medical Therapy
The medical therapies for BPH are alpha-adrenergic
blockers, 5alpha-reductase inhibitors, combination
therapies, and phytotherapy (use of plant extracts).
Medical therapies are not as efficacious as surgical
therapies but may provide adequate symptom relief
with fewer and less serious associated adverse
events.
Alpha-adrenergic blocker therapy
Alfuzosin, doxazosin, tamsulosin and terazosin are
appropriate treatment options for patients with LUTS
secondary to BPH.
Although there are slight differences in the adverseevent profiles of these agents, it’s believed that all four
agents have equal clinical effectiveness.
Four long-acting alpha-1-antagonists, terazosin,
doxazosin, tamsulosin, and alfuzosin have been approved
by the Food and Drug Administration in the United
States for treatment of the symptoms of BPH.
Prazosin,
a short-acting alpha-1-antagonist, is
occasionally used for BPH, but the other
medications are preferred.
Alpha-blocker therapy is based on the
hypothesis that clinical BPH is partly caused
by alpha1-adrenergic-mediated contraction of
prostatic smooth muscle, resulting in bladder
outlet obstruction.
Alpha-adrenergic receptor antagonists
(blockers) such as doxazosin,tamsulosin,
alfuzosin, and terazosin inhibit this process
and thus relieve the bladder outlet
obstruction.
Side effects of Alpha-adrenergic blocking agents
Postural hypotension.
Blurred vision.
Dry mouth.
Nasal Congestion.
Drowsiness.
Ejaculation failure.
Alpha-adrenergic blocking agents
■ Agents requiring dose titration:
Doxazosin ( Cardura)
1 & 4 mg tablets, maintenance dose 2 mg OD
Titrates upwards over several weeks.
Terazosin ( Hytrin)
1mg slowly increase up to 20mg /day
■ Agents not requiring dose titration
Alfuzosin ( Xatral)
10 mg XL OD
Tamsulosin ( Omnic)
0.4mg
main problem abnormal ejaculation
May increased to 0.8 mg after 2-4 wks
These drugs differed in their side-effect profiles.
The frequency of side effects with alfuzosin and
tamsulosin bothersome enough to cause withdrawal
from studies was similar to placebo (4 to 10 percent)
but was 4 to 10 percent higher in men treated with
terazosin and doxazosin.
The most important side effects were orthostatic
hypotension and dizziness. Terazosin and doxazosin
generally need to be initiated at bedtime (to reduce
postural lightheadedness soon after starting the
medication) and the dose should be titrated up over
several weeks.
Tamsulosin and alfuzosin have less effect on blood
pressure than either terazosin or doxazosin, and
tamsulosin may further have slightly less effect on
blood pressure than alfuzosin. These differential
effects on blood pressure by different alpha-1antagonists may be due to their differential blocking
of alpha-1-receptor subtypes.
5-Alpha-reductase inhibitors
There are two 5-alpha-reductase inhibitors,
finasteride and dutasteride.
These drugs act by reducing the size of the prostate
gland.
Treatment for 6 to 12 months is generally needed
before prostate size is sufficiently reduced to
improve symptoms.
Patients with symptomatic prostatic enlargement
but without signs of bother may be offered a 5 alphareductase inhibitor to prevent progression of the
disease.
The efficacy of finasteride appears to persist
with long-term treatment.
As an example, a trial of over 3000 men who
were treated daily with 5 mg of finasteride or
placebo demonstrated that the improvements
in symptom scores, maximal urinary flow
rates, and prostate volume were maintained
for more than four years.
The most important findings were that
finasteride treatment decreased the
probability of surgery and acute urinary
retention.
A 5 alpha-reductase inhibitor is the sole
hormonal therapy, to date, that demonstrates
both efficacy and acceptable safety for
treatment of BPH.
Finasteride can reduce the size of the
prostate, can increase peak urinary flow rate,
and can reduce BPH symptoms.
The Panel's evidence-based review
determined that a 5 alpha-reductase inhibitor
is effective in partially relieving symptoms but
is less effective for this purpose than alphablocker therapy.
It lowers serum and intraprostatic
dihydrotestosterone, but not to castration
levels.
It lowers serum PSA, butdoes not mask the
PSA-based detection of prostate cancer.
In general, patients will perceive this level of
symptom improvement as a meaningful
change.
Finasteride is ineffective in patients who do
not have enlarged prostates.
Reported adverse events are primarily
sexually related and include:
1. decreased libido.
2. ejaculatory dysfunction.
3. erectile dysfunction
and are reversible and uncommon after
the first year of therapy.
Combination
Therapy
The Medical Therapy of Prostatic
Symptoms (MTOPS) trial, a prospective,
randomized, double-blind, multicenter,
placebo-controlled trial, was established to
determine whether medical therapy can
prevent or delay the progression of BPH in
the long term.
In 18 academic centers across the United
States a total of 3047 patients were
recruited and randomized to receive
doxazosin, finasteride, a combination of
both, or placebo.
Disease progression was defined as a worsening
of BPH symptoms according to the AUA
symptom index (AUASI).
Progression was deemed to have occurred in the
case of one of the following:
- A 4-point rise in AUASI, confirmed by a second
visit within 4 weeks;
- A 50% increase in creatinine relative to baseline
levels.
- AUR.
- Two or more UTIs within 1 year or a single
episode of urosepsis due to BOO.
- Socially unacceptable incontinence.
The results of the trial suggest that the combination
of doxazosin and finasteride exerts a clinically
relevant, positive effect on rates of disease
progression (McConnell et al, 2003).
Men who received combination therapy were
significantly less likely to experience BPH
progression than those receiving either monotherapy
or placebo, with risk reduction rates of 39% for
doxazosin, 34% for finasteride, and 67% for
combination therapy compared with placebo.
Invasive therapy and AUR risk were significantly
reduced by finasteride and combination therapy.
AUA symptom score and Qmax improved
significantly more in the combination therapy
group compared with the monotherapy
groups, whereas adverse events were similar
to previously reported studies.
In addition to indicating the potential benefits of
combination therapy, MTOPS provided important
data regarding the natural history of untreated BPH
and the prediction of BPH patients who will respond
most effectively to medical treatment:
Although the patients receiving finasteride alone or
in combination experienced the expected decrease in
prostate volume, patients on placebo or doxazosin
alone experienced an increase in prostate volume
from a baseline of 34.0 mL by 9.3 (30.3%) (placebo)
and from 36.4 mL by 9.9 (31.4%) (doxazosin),
respectively.
Conclusion
The combination of an alpha-adrenergic
receptor blocker and a 5-alpha-reductase
inhibitor (combination therapy) is an
appropriate and effective treatment for
patients with LUTS associated with
demonstrable prostatic enlargement.
Phytotherapy
Herbal therapies for BPH are commonly used in
Europe; these remedies comprised 70 percent of
spending for drug treatment of prostatism in
Germany in 1997.
Saw palmetto is approved by the German
Commission E for stage I and II (mild to moderate)
BPH.
Two herbal extracts have officially been approved
for the treatment of prostatism in France.
No herbal therapies have been approved by the
United States Food and Drug Administration for
this purpose, although many men probably try these
treatments.
Phytotherapy
Most phytotherapeutic preparations are plant
extracts with different components
manufactured by different extraction procedures,
which prevents comparison of the preparations.
Although numerous in-vitro experiments have
been conducted to determine their possible
mechanisms of pharmaceutical action, it is
uncertain which of the actions demonstrated in
vitro might be responsible for clinical responses
in vivo.
Appropriate randomized placebo-controlled
clinical trials monitored by an outside agency are
needed to ascertain and to confirm the efficacy
of these products.
Dr. Wissam Kh. Kamal
R2 Urology KAUH