Lower Urinary Tract Symptoms in Men for GPs

Lower Urinary Tract Symptoms
Workshop
PETER NG

Lower Urinary Tract Symptoms
(LUTS)

LUTS Are a Constellation of Storage
and Voiding Symptoms
Straining
Urgency
incontinence
IntermittencyNocturia
Sense of
incomplete emptying
Poor flowFrequency
Post-void dribbleHesitancyUrgency
Post-micturitionVoidingStorage
Symptoms Often Relate to Bladder and ProstateSymptoms Often Relate to Bladder and Prostate
Abrams P et al. Neurol Urodyn. 2002;21:167-178.
Terminal dribbleTerminal dribbleOther incontinenceOther incontinence

Overall Prevalence of LUTS in
MenLUTS were experienced by 6 of 10 men in the general population
38.7%38.7%
61.3%61.3%
Men with LUTS
Men without
LUTS
N = 5460
Irwin DE et al. Abstract. EAU 2006.

Prevalence of LUTS in Men
Prevalence,%
Incomplete
emptying
Post-micturitiondribble
Storage Voiding
Post-
micturition
Nocturia
47.2
Terminaldribble
14.8 13.3
Urgency
11.1 Slow
stream
8.9
5.1
Frequency
6.4
Straining
6.4
Incontinence
5.1
Intermittency
2.8
0
5
10
15
20
25
30
35
40
45
50
Nocturia: waking to void ≥1 times per night
Frequency: subject feels he/she urinates too often during the day

Overall Prevalence of LUTS in
Subang Jaya Men
LUTS were experienced by 8 of 10 men in the general population
N =351
Khoo EM ,Tan HM ,Low WY J Sex Med 2008;5:2925–2934.

Prevalence of LUTS in Asians
Homma Y, Kawabe K, Tsukamoto T, et al. Epidemiologic survey of lower urinary
tract symptoms in Asia and Australia using the international prostate symptom
score. Int J Urol 1997;4:40–6[27]

Despite the bother of symptoms, most men with LUTS do
not seek medical help
Garraway et al. Br J Clin Pract 1993;43:318–21
While 48.4% of men reported ‘urgency’, and 28.3% found urgency bothersome,
but only 4.5% consulted a doctor

Prevalence of Nocturia
Men
Women
48.6
20.9
11.9
8.2
5.2
54.5
24.0
13.4
8.9
6.2
0
10
20
30
40
50
60
Prevalence,%
≥1 ≥2 ≥3 ≥4 ≥5
Times Wake per Night to Void, n
EPIC Study. Data on file. Pfizer Inc.

Not Specific to Any Lower Tract
Pathology
BPH

Overactive Bladder
Bladder Cancer
Cystitis
Bladder stones
Neurogenic bladder-DM, Spinal
Urethral stricture
STD
BPO
Prostate cancer
Prostatitis Constipation
Excessive Urine Output
Osmotic diuresis-DM
Diuretics
CCF

BPH – histological process
50% of men aged 50 and
80% of men older than 70

Terminology
BPHBPH BPEBPE
BPOBPO
50%
No obstruction
LUTS
50%
Non enlargement

The lower urinary tract
symptoms in BPH
BPH
Bladder Outlet
Obstruction (BOO)
Bladder Outlet
Obstruction (BOO)
Impaired detrusor
contractility
Impaired detrusor
contractility
Detrusor
Overactivity
Detrusor
Overactivity
• Voiding symptoms
- hesitancy
- weak stream
- prolonged voiding
- post voiding dribbling
- feeling of incomplete emptying
• Decreased flow rates
• Post void residual urine
• Voiding symptoms
- hesitancy
- weak stream
- prolonged voiding
- post voiding dribbling
- feeling of incomplete emptying
• Decreased flow rates
• Post void residual urine
• Storage symptoms
- urge
- frequency
- nocturia
- urge incontinence
• Decreased bladder capacity
• Storage symptoms
- urge
- frequency
- nocturia
- urge incontinence
• Decreased bladder capacity
DHICDHIC
OAB
Sensory
OAB
Sensory

The International Prostate
Symptom Score (IPSS)
 The I-PSS is based on the answers to 7 questions
concerning urinary symptoms.
 Each question is assigned points from 0 to 5
indicating increasing severity.
 The total score can therefore range from 0 to 35
(asymptomatic to very symptomatic).
Mild 0-7
Moderate 8-19
Severe 20-35

Patient name:
Date
1. Incomplete emptying
Over the past month, how often
have you had a sensation of not
emptying your bladder completely
after you finish urinating?
2. Frequency
have you had to urinate again less
than two hours after you finished
urinating?
3. Intermittency
have you found you stopped and
started again several times when
you urinated?
Less than
1 time in 5
Not at all Less than
half in the
time
About
half the
time
More than
half the
time
Almost
always
0 1
0
0
1
1
2
2
2
3
3
3
4
4
4
5
5
5
Symptom Score (1)

Patient name:
Date
4. Urgency
Over the past month, how often have you
found it difficult to postpone urination?
5. Weak stream
Over the pas month, how often have
you had a weak urinary stream?
6. Straining
Over the past month, how often have
you had to push or strain to begin to
urinate?
7. Nocturia
Over the past month, how 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?
Less than
1 time in 5
Not at all Less than
half in the
time
About
half the
time
More than
half the
time
Almost
always
0 1
0
0
1
1
2
2
2
3
3
3
4
4
4
5
5
5
0 1 2 3 4 5
Symptom Score (2)

Patient name:
Date
1. If you were to spend the rest
of your life with your urinary
condition just the way it is now,
how would you feel about that?
PleasedDelighted Mostly
satisfied
Mixed
about
equally
satisfied
and
dissatisfied
Unhappy Terrible
0 1 2 3 4 5
BOTHER SCORE (BS) =
The bother score (IPSS 8th
question)

22
DRE
•Size
•Assymetery
•Nodules
•Tenderness
•Anal Tone

Urinalysis
-Haematuria,
- Proteinuria,
- Pyuria,
Microhematuria = 5rbc/ul
4-5% of men with microscopic
haematuria will be found to have a
cancer or other urological disease
within the first 3 years following
the test.

24
PSA Level
GENERAL PRACTICE
ASSESSMENT
•
Detection of Prostate Cancer
Estimation of Prostate Size

26
Flowmetry Only
This is the
basicbasic
Non-InvasiveNon-Invasive
urodynamic
test
Flow Transducer
Flow Recorder
Flowmeter
Recording Flow

27
Results of Flowmetry
Delay Time s 2.5
Max. Flow Rate ml/s 23.5
Time to Max. Flow s 3.5
Flow Time s 11.3
Voiding Time s 13.5
Voided Volume ml 120
Average Flow Rate ml/s 10.6
Residual Volume ml 90
Flowmeter-Rate ml/s
Time s
10
20

31
Max flow rate % risk of obstruction
<10ml/sec 90
10-14ml/sec 76
>=15ml/sec 30

Indications for urodynamics
• younger person who is about to undergo
surgical intervention
• patient with a large residual volume indicating
a possible hypocontractile bladder as well
• patient where there doubt about the presence
of obstruction
• concomitant neurological disease like
Parkinsons disease which will make the
pathophysiology of the LUTS more
complicated
32

33
VLPP (Cough)
Recording
Vesical & Abdominal
Pressures
and Flowmetry
215
3710 cmH2O
L L L
2 ml / s
Delay 0,8 s
37 cmH2O
Pves
Pump
PabdFlowmeter
My bladder is filled
up to 200 ml before
VLPP testing

Upper urinary tract function assessment
creatinine measurement and/or ultrasonographic
examination
PV determination
the method of choice
is transrectal ultrasonograph
transabdominal ultrasound
is also acceptable

36
 Severe IPSS
 Hematuria
 Elevated PSA
 Elevated Creatinine
 Abnormal DRE
 Recurrent UTI
 Palpable Bladder
 Young Patient <45
 Neurological Disease
 Unresponsive to Mx

37
GENERAL PRACTICE
MANAGEMENT
•
LUTS Bothersome
YES NO
Large Prostate
>30ml
PSA>1.4ng/mlActive Treatment Watchful Waiting

Indications of watchful
waiting
 Uncomplicated BPH
 Symptoms not bothersome (usually
IPSS ≤7)
 Symptoms significantly bothersome
but after being informed of various treatment
options and their consequences, the patient
chooses watchful waiting

Watchful waiting
Fluid restriction
Bowel habit
Care with flu meds
Beverages

 The patient’s symptoms and
clinical course should be
monitored, usually annually.
Definition of watchful waiting

Prostate growth
Rhodes, T, Girman, C. J., Jacobsen, S. J., Roberts, R. O., Guess, H. A.,
Lieber, M. M.: J Urol, 161: 1174, 1999
Average prostatic growth rates were 1.6% yearly in
men between ages 40 and 79 years, faster rate in
larger baseline prostate glands

Placebo cohorts
Variable ALTESS (2yrs) MTOPS (4.5yrs)
Patients 757 735
IPSS worse>=4 127(16.8%) 97(14%)
AUR 14(1.8%) 18 (2%)
BPH surgery 49(6.5%) 37(5%)
Incontinence Not done 6(0.8%)
Sepsis No done 1(0.1%)
Wiygul, Jeremy; Babayan, Richard K Watchful waiting in benign
prostatic hyperplasia. Current Opinion in Urology. 19(1):3-6, January
2009.

Predictive of progression
 IPSS>=8(1)
 Qmax <12ml/sec(1)
 Age >70(1)
 Increasing PVR(2) medical Tx arm MTOPS
 Worsening symptoms(2)
 PSA>1.5ng/ml(2)
 Transitional zone volume >25ml(3)
1.Jacobsen SJ, Jacobsen DJ, Girman CJ, et al. T Urol 1999; 162:1301–1306
2. Emberton M. BJU Int 2006; (97 Suppl 2):12–15 [discussion 21–22].
3. Djavan B, Fong YK, Harik M, et al. Urology 2004; 64:1144–1148.

Indications of medical
treatment
 Uncomplicated BPH
 Symptoms are bothersome (usually
IPSS>7) and after being informed of
various treatment options and their
consequences, the patient chooses
medical treatment
 Progression from watchful waiting

45
GENERAL PRACTICE
MANAGEMENT
•
LUTS Bothersome
YES NO
Large Prostate
>30ml
PSA>1.4ng/ml
Active Treatment Watchful Waiting
OAB BPH obstructionPrimary
Nocturia

There are 3 pharmacological classes
used in BPH
Plant extractsPlant extractsα1-blockersα1-blockers
5α-reductase inhibitors5α-reductase inhibitors

α1-blockers in the Treatment
of BPH

They are sparse in the bladder body
α1-receptors are abundant in the
bladder neck, prostate and urethra

α1-blockers are expected to reduce the sympathetic tone of the prostate and the
urethra.
α1-blockers act on the dynamic
component of BOO
•50% intraurethral
pressure of normal
person
•98% receptors in
prostatic stroma

α1A α1B α1D
α1 α2
α2A α2B α2C
Predominant in
human prostate
α
1995
1974
1948
α-adrenoceptor classification
3.9 :1

Effects of Alpha1 Subtypes
α1B α1D
α1A
Systemic
vasculature
Bladder
Prostate
Older person Alpha 1B upregulated

α1-blockers may have local
but also systemic effects
Prostate
Urethra
Bladder Neck
Prostate
Urethra
Bladder Neck
↓ Outflow
resistance
↓ Outflow
resistance
↑ Flow
Rates
↑ Flow
Rates
↓ Voiding
Symptoms
↓ Voiding
Symptoms
↓ Residual
Urine
↓ Residual
Urine
↓ Filling
Symptoms
↓ Filling
Symptoms
BladderBladder
Blood vesselsBlood vessels
↓ Bladder
Instability
↓ Bladder
Instability
↓ Blood
Pressure
↓ Blood
Pressure
Postural
Hypotension
Dizziness
Postural
Hypotension
Dizziness
URINARY TRACT EFFECT
SYSTEMIC EFFECT
α1A
α1B
α1D

Non Selective Alpha 1 blockers
Terozosin , Doxasosin, Proazosin
α1B α1D
α1A
Systemic
vasculature
Bladder
Prostate
Older person Alpha 1B upregulated

Selective Alpha 1 blockers
Tamsulosin,
α1B α1D
α1A
Systemic
vasculature
Bladder
Prostate
Efficacy the same but far less systemic side effects

Designing the ideal formulation
Michel MC, et al. Eur Urol Suppl 2005;4:15-24.
Eliminate effect of
food on absorption
Control release
– no dose dumping
Consistent release
continues despite
low water content
Absorption of
conventional
tamsulosin and
alfuzosin XL are food-
dependent
Current formulations are
water dependent – this
impedes consistent drug
release in colon
Current controlled-release
α1-A antagonists
Ideal characteristics

OCAS®
: The ideal formulation
• Carries water throughout
the entire GI tract,
including to the colon,
where water content
is lowest
• Consistent drug release
Rapid gelation &
complete hydration
Stevens HNE & Speakman M. Curr Med Res Opin 2006;22:2323-2328.

Tamsulosin Ocas®
:
Improved pharmacokinetic profile
*YM12617.
†617C1302.
Adapted from Djavan B, et al. Eur Urol Suppl 2005;4:61-68.
Steady-state; Tamsulosin Ocas®
vs conventional 0.4 mg capsule

Tamsulosin Ocas®
absorption NOT affected
by food intake
N=24.
Adapted from Michel MC, et al. Eur Urol Suppl 2005;4:15-24.

Tamsulosin Ocas®
:
Superior pharmacokinetic profile
• Delivers consistent drug levels over 24 hours1
• Lower maximum plasma concentration (Cmax)1
• Irrespective of food intake2
Tamsulosin Ocas®
delivers consistent drug levels
for optimal 24-h control of symptoms while minimizing side effects
1. Djavan B, et al. Eur Urol Suppl 2005;4:61-68.
2. Michel MC, et al. Eur Urol Suppl 2005;4:15-24.
Tamsulosin Ocas®
vs conventional tamsulosin

Tamsulosin Ocas®
:
European phase IIIa study design
• Double-blind, randomized, placebo- and active
comparator-controlled, parallel-group study
placebo (N=57)
tamsulosin Ocas®
0.4 mg (N=361)
-2 4 8
Screening Randomization
Final
assessment
Weeks
0
placebo
run-in
conventional tamsulosin 0.4 mg cap (N=710)
tamsulosin Ocas®
0.8 mg (N=724)
12
Adapted from Chapple CR, et al. Eur Urol Suppl 2005;4:33-44.

European phase IIIa: Patient enrolment

European phase IIIa:
Demographic & baseline characteristics
IPSS=International Prostate Symptom Score.
Qmax, prostate volume and PSA data at enrolment instead of baseline visit.

Mean change in total IPSS
-5.8
-7.7*
-8.0* -8.0**
-10
-9
-8
-7
-6
-5
-4
-3
-2
-1
0
placebo (N=350)
tamsulosin Ocas® 0.4 mg
(N=354)
conventional tamsulosin
0.4 mg (N=700)
tamsulosin Ocas® 0.8 mg
(N=707)
MeanchangeintotalIPSS
*P<0.0001 vs placebo; **P=0.9909 vs conventional tamsulosin.

Effect on total IPSS over time
*P<0.0001 vs placebo.

European phase IIIa: Mean change, supine
SBP & DBP
From baseline to week 12
SBP=systolic blood pressure; DBP=diastolic blood pressure.
*P<0.05 vs tamsulosin Ocas 0.4 mg.

European phase IIIa: 0.4 mg Tamsulosin
Ocas®
, lowest incidence of most common AEs
* significant vs placebo.
† significant vs Tamsulosin Ocas®
0.4 mg.

Tamsulosin Ocas®
Conclusions
• Increasing the Tamsulosin Ocas®
dose to 0.8 mg does not
improve IPSS score
• Conventional tamsulosin has a confirmed favourable
efficacy/safety ratio
• Tamsulosin Ocas®
0.4 mg has tolerability comparable
to placebo
• Tamsulosin Ocas®
0.4 mg is the optimal formulation & dose
for treating LUTS/BPH
Chapple CR, et al. Eur Urol Suppl 2005;4:33-44.

Tamsulosin Ocas®
: Less orthostatic stress
*P≤0.05 vs Tamsulosin Ocas®
.
N=40.
OT=orthostatic stress tests.
Adapted from Michel MC, et al. Eur Urol Suppl 2005;4:45-52.
% Patients with positive OT vs conventional tamsulosin

% Positive OTs reduced with
Tamsulosin Ocas®
vs alfuzosin XL 10 mg
*P≤0.05 vs Tamsulosin Ocas®
based on discordant pairs testing.
N=40.
OT=orthostatic stress tests.
Data on file, 2005. Yamanouchi Pharmaceuticals Co.

1
Marks et al. Urology 2003, 62, 888-893
2
Lepor Urology 1998, 51, 892-900
3
AUA Practice Guidelines Committee, J.Urol 2003, 170, 530-547
4.Djavan B et al. Eur Urol 1999;36:1–13; Schulman CC et al. Eur Urol
1996;29:145–54
MTOPS Steering Committee. J Urol 2002; 167:265
Benefits of α1-blockers in BPH
 Rapid onset of action
– From the first dose on peak flow rate for
alfuzosin1
and tamsulosin2
,
– From the first days on LUTS,
– Typically established within 2 weeks
 Majority respond
– Typically 50–70% of patients respond (4)
 Best monotherapy for relief of LUTS3
– Improvement of IPSS of 4 to 6 points
– Improve symptom score by 30-40% (4)
– Improve Qmax by 16-26% (4)

1
Marks et al. Urology 2003, 62, 888-893
2
Lepor Urology 1998, 51, 892-900
3
AUA Practice Guidelines Committee, J.Urol 2003, 170, 530-547
Benefits of α1-blockers in BPH
 Effective irrespective of prostate size
 Improve quality of life and respect
sexual function
– Except tamsulosin which is associated with
ejaculatory dysfunction (EjD)

Popular preparations
• Hypoxis rooperi (South African star grass),
• Serenoa repens/Sabal serrulata (saw palmetto
berry),
• Pygeum africanum (African plum),
• Seceale cereale (rye pollen)
• Cucurbita pep (Pumpkin seeds),
Stephan Madersbacher, Ingrid Berger, Anton Ponholzer and
Martin Marszalek Current Opinion in Urology 2008, 18:16–20

Components Discovered
• Phytosterols,
• [Beta]-sitosterols,
• Fatty acids
• Lectins
More common ones

Possible mechanisms of
Phytotherapy
• 5[alpha]-reductase inhibition,
• Aromatase activity,
• Androgen blockade,
• [Alpha]1-blockade,
• Inhibition of prostaglandin synthesis,
• Anti-inflammatory
• Inhibit growth factors
• Improve detrusor function
• Free radical scavenger
• Alteration cholesterol metabolism
In Vitro activity seen but not confirmed invivo
There is no change in prostate volume or PSA

Trials so far
• In 2006, two clinical trials meeting the
WHO benign prostatic hyperplasia
consensus conference criteria (randomized
against placebo/standard therapy, study
duration 12 months) were published
• Placebo vs saw palmetto – no diff
• Saw Palmetto vs Tamsulosin – improvement identical but
no detailed on Qmax, postvoid residual or prostate
volume

Improvement in symptoms score

AUA BPH
Guidelines
2003
Phytotherapeutic agents
cannot be recommended for
treatment of BPH at this time
… mechanisms of action,
effectiveness, and safety of
these agents have not been
well documented in
multicenter, clinical trials with
independent data monitoring
American
Urological
Association
2003
BPH Guidelines
(1st
Revision Since 1994)
Phytotherapy:
recommendations
AUA Guideline Committee J. Urol 2003, 170, 530-47

EAU BPH
Guidelines
2004
These drugs are not
recommended for the
treatment of elderly men
with LUTS suggestive of
benign prostatic obstruction
benign prostatic
hyperplasia’
Eur. Urol 2004, 46, 547-54
Combination therapy:
recommendations

Case 2

59 yr old Chinese gentleman
presented with acute difficulty in
passing water as well as urinary
incontinence on coughing or
straining. No hematuria nor fever or
pain

He had a history of hypertension and
maturity onset diabetes treated with
oral hypoglycaemics and had a recent
bout of influenza.

DRE
showed a
45g
prostate
smooth

 What is your diagnosis ?
What are the possible triggers for this event?
 What would you do next

 Bladder overdistension
 Imobility, constipation, Long journey,surgery
 Meds like anticholinergics or opiods-decrease
bladder fullness, flu meds -symphaticomimetic
 ETOH symphatetic stimulator
 Diabetic cystopathy
 Prostatic inflammation
 Prostatic infarction
 BPH progression

 Urethral
catheterisation
done with 16f
Foley catheter.


800 ml of urine
was drained
What is
significance of
the urine
volume?
What
investigations?

 UFEME
 UCS
 Serum Creatinine
 US Urinary tract

Upper urinary tract function assessment
creatinine measurement and/or ultrasonographic
examination
PV determination
the method of choice
is transrectal ultrasonography
transabdominal ultrasound
is also acceptable

 Hb 16.0
 Creatinine 110 umol/L
 PSA 15 ng/ml
 Urine 50 rbc/ul wbc 12/ul
 What is your next move?

96
 BPH
 Prostatitis
 Prostatic massage (1.5-2 times the normal
PSA)
 Prostate biopsy (rise by 8ng/ml)
 TURP ( rise by 6ng/ml)
 Urinary retention
 Ejaculation recent within 48-72h
 DRE?

Alpha Blocker
Trial off Catheter in 1-3 days
Refer for Surgery a sudden stimulation of [alpha]1-
adrenergic receptors

 Haematuria
 UTI and urosepsis,
 Urine leak, catheter obstruction
 Double the rate of prolonged hospitalization
than in men catheterized for <= 3 days

McNeill SA, Hargreave TB; members of the ALFAUR study group. Alfuzosin once daily facilitates return to voiding I
n patients in acute urinary retention. J Urol 2004; 171: 2316–20
P=0.012

 What else need to be done? For his PSA?

 Antibiotics for the PSA
 4 weeks of Ciprofloxacin
 Repeat PSA level 3.8ng/ml
 What is the next step?

108
Size is Predictor of progression
Marberger MJ, Andersen JT, Nickel JC et al prostate volume and PSA as predictors of AUR,
Combined experience from 3 large multinational placebo controlled trials Eur Urol 2000; 38:563-8

 The risk of complications increases with
 age (a 70-year old male has a 8x the risk of a 40-year old)
 symptom severity (IPSS > 7 means a 4x risk increase)
 PV (> 30cc means a 3x risk of AUR
1
)
 decreased Qmax (< 12mL/second means a 3x risk)
 antihypertensive (not diuretics) or anti-arrhythmic drug use
1
Jacobsen SJ et al. J Urol 1997;158:481–7

13.7
8.9
4.9 5.4
7.2
5.1
10-yearcumulativerisk(%)
20
15
10
5
0
Risk of AUR versus other diseases
(60 year old male)
AUR Hip fx Hip fx Diabetes Stroke MI
(women) (men)
Jacobsen S. Urology 2001;58(6A):5

Scalp, hair follicle
Sebaceous glands
Liver
Liver
Prostate (mainly in
stroma)
Chest/skin
Beard
Type 1 Type 2
Brain
Brain (low levels in
hypothalamus and
hippocampus)
Skin
Prostate (mainly
in epithelium)
Type 1 and type 2 isoenzyme distribution
Genital tissues
Seminal vesicles

5AR in the prostate
 Two distinct isoforms of 5AR
– type 1 and type 2
 Type 1 is also expressed in the prostate
(mainly epithelium)
 Type 2 is the dominant isoenzyme in the stroma
of normal human prostate

FOR INTERNAL USE ONLY
Inhibitors of 5AR
• Finasteride (ProscarTM
) - MSD
– inhibitor of type 2
• Dutasteride (AvodartTM
) - GSK
– inhibitor of both type 1 and type 2
AvodartTM
is 2.5x more potent against type
2 isoenzyme than finasteride
Increased potency and dual inhibition may
be warranted to enhance suppression of
DHT

FOR INTERNAL USE ONLY
• Finasteride reduces systemic DHT by 65-70%
• Dutasteride reduces systemc DHT by 90%
• Both reduce intraprostatic DHT by 90%
• With Dutasteride the uro-flowrates improving at a
month earlier at 3 months instead of 4 months with
Finasteride and the symptoms score improving two
months earlier at 6 months compared with 8
months with Finasteride.
• No clinical difference demonstrated yet

Rationale for Combination Therapy (2)
5AR2
5AR1
Finasteride Avodart
Reduced PV
5ARIs α-blockers
5AR2
Combination therapy offers rapid onset and durable symptom relief
and long-term reductions in progression
Smooth Muscle
Relaxation

116
Study design (n=3,047 randomised)
Combination Treatments:
MTOPS
MTOPS Steering Committee. J Urol 2002;167:265
Screen
and
placebo
run-in
Placebo
Doxazosin 4 or 8mg once daily
Finasteride
Combination
0 4 weeks 48
months

MTOPS: combination therapy is more
effective in reducing overall progression
Cumulative incidence of overall clinical progression
Years from randomization
0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5
Placebo FinasterideDoxazosin Combination
0
5
10
15
20

118
MTOPS: summary
 Risk of progression reduced by
– 39% for Doxasosin
– 34% Finasteride
– 67% Combination
 Risk Retention reduced by
– 31% doxaosin
– 67% finasteride Monotherapy also significantly reduces the risk of BPH
clinical progression
– 79% combined
 Doxazosin increases the time to progression of AUR and invasive
therapy, but does not reduce the overall risk

AUA BPH
Guidelines
2003
“Appropriate and
effective treatments
for patients with
LUTS and
demonstrable
prostatic
American
Urological
Association
2003
BPH Guidelines
(1st
Revision Since 1994)
Combination ther
recommendat
AUA Guideline Committee J. Urol 2003, 170, 530-47

CombAT study designCombAT study design
Tamsulosin 0.4 mg
Dutasteride 0.5 mg
Combination
Placebo
run-in
Safety
follow-up
Screening
Pre-screen
Screen
Baseline
4 years Follow-up
(+16 weeks)
Single-blind Double-blind
Visits every 3 months, daily dosing
2 years
IPSSPrimary endpoints:
Siami et al. Contemp Clin Trials 2007;28:770–9
AUR / surgery

CombAT main entry criteriaCombAT main entry criteria
 Men agedMen aged ≥≥50 years50 years
 Diagnosis of BPH by history and DREDiagnosis of BPH by history and DRE
 IPIPSSSS ≥≥12 (moderate to severe symptoms)12 (moderate to severe symptoms)
 Two voids at screening with QTwo voids at screening with Qmaxmax >>5 and5 and
≤≤1515 mlml/s (at minimum voided volume of/s (at minimum voided volume of ≥≥125 ml)125 ml)
 Prostate volumeProstate volume ≥≥30 cm30 cm33
byby TRUSTRUS
 Serum PSA 1.5–10.0 ng/mlSerum PSA 1.5–10.0 ng/ml

MeanMean ± S.D.± S.D. CombATCombAT11
(n=4844)(n=4844)
MTOPSMTOPS22
(n=3047)(n=3047)
Age (years)Age (years) 66.166.1 ± 7.01± 7.01 62.662.6 ± 7.3± 7.3
CaucasianCaucasian 4259 (88%)4259 (88%) 2509 (82%)2509 (82%)
Total IPSSTotal IPSS 16.416.4 ± 6.16± 6.16 16.916.9 ± 5.9± 5.9
Prostate volume (cc)Prostate volume (cc)
TotalTotal
Transition zoneTransition zone
55.055.0 ± 23.58± 23.58
29.5 ± 21.97*29.5 ± 21.97*
36.336.3 ± 20.1± 20.1
16.416.433
Serum PSA (ng/mL)Serum PSA (ng/mL) 4.04.0 ± 2.08± 2.08 2.42.4 ± 2.1± 2.1
Qmax (mL/sec)Qmax (mL/sec) 10.710.7 ± 3.62± 3.62 10.510.5 ± 2.6± 2.6
Post-void residual volume (mL)Post-void residual volume (mL) 67.767.7 ± 64.87± 64.87 68.168.1 ± 82.9± 82.9
Baseline characteristics ofBaseline characteristics of
CombAT relative to MTOPSCombAT relative to MTOPS
1. Roehrborn et al. Eur Urol 2008;179:616-21. McConnell et al. NEJM 2003; 349: 2387–98; 3. Roehrborn et al. Unpublished MTOPS data
*Sub-group of 656 men

 PrimaryPrimary
– Time to event/proportion of subjects with AURTime to event/proportion of subjects with AUR
or BPH-related surgeryor BPH-related surgery
 SecondarySecondary
– Time to BPH-related clinical progression –Time to BPH-related clinical progression –
First of:First of:
– Symptom deterioration by IPSS ≥4 pointsSymptom deterioration by IPSS ≥4 points
– Acute urinary retentionAcute urinary retention
– IncontinenceIncontinence
– Recurrent UTI or urosepsisRecurrent UTI or urosepsis
– Renal insufficiency related to BPHRenal insufficiency related to BPH
 All primary and secondary endpoints evaluated at Year 2All primary and secondary endpoints evaluated at Year 2
are secondary endpoints at Year 4are secondary endpoints at Year 4
CombAT 4-year endpointsCombAT 4-year endpoints

CombAT: Time to first AUR or BPH-relatedCombAT: Time to first AUR or BPH-related
surgerysurgery
0 12 24 36 48
Study month
Combination
Dutasteride
Tamsulosin
Risk reduction estimate
combination vs. tamsulosin =
65.8% (95% CI: 54.7, 74.1%)
Risk reduction estimate
combination vs. dutasteride =
19.6% (95% CI: -10.9, 41.7%)
1010
PatientswithAURorBPH-related
surgery(%)
16
14
12
8
6
4
2
0
p<0.001
p = 0.18
Roehrborn et al. In press with Eur Urol
67
84
191
Combination; dutasteride + tamsulosin

IncidenceIncidence
*p<0.001 vs. combination
**
CombAT: Crude incidence of AURCombAT: Crude incidence of AUR
or BPH-related surgery at Year 4or BPH-related surgery at Year 4

CombinationCombination
(n=1610)(n=1610)
DutasterideDutasteride
(n=1623)(n=1623)
TamsulosinTamsulosin
(n=1611)(n=1611)
At Year 4At Year 4 nn %% nn %% nn %%
Clinical progressionClinical progression 203203 12.6%12.6% 289289 17.8%*17.8%* 347347 21.5%*21.5%*
Risk reductionRisk reduction vs.vs. combinationcombination
(95% CI)(95% CI)
31.2%31.2%
(17.7–42.5%)(17.7–42.5%)
44.1%44.1%
(33.6–53.0%)(33.6–53.0%)
Crude rate based on ITT population
*p<0.001 vs. combination
CombAT 4-year BPH clinical progressionCombAT 4-year BPH clinical progression
IPSS incr. ≥4-pointsIPSS incr. ≥4-points 139139 8.6%8.6% 212212 13.1%*13.1%* 229229 14.2%*14.2%*
AURAUR 2626 1.6%1.6% 3737 2.3%2.3% 8282 5.1%*5.1%*
IncontinenceIncontinence 4949 3.0%3.0% 6060 3.7%3.7% 6565 4.0%4.0%
UTIUTI 33 0.2%0.2% 55 0.3%0.3% 55 0.3%0.3%
Renal insufficiencyRenal insufficiency 11 <0.1%<0.1% 22 0.1%0.1% 77 0.4%0.4%

AdjustedmeanIPSSchange
frombaseline
(n = 1610) (n = 1611)
p < 0.001 combination vs. tamsulosin
p < 0.001 combination vs. dutasteride
Study month
(n = 1623)
CombAT IPSSCombAT IPSS
Adjusted mean change from baseline (LOCF)Adjusted mean change from baseline (LOCF)

p<0.001 combination vs. tamsulosin
p≤ .006 combination vs. dutasteride
CombAT QmaxCombAT Qmax
Adjusted mean change from baseline (LOCF)Adjusted mean change from baseline (LOCF)

 A 63 year old gentleman presented with
LUTS for the past 9 months
 His IPSS =6 QL = 2
 There is no hematuria
 He has diabetes
 DRE showed a 30g prostate which was non
tender and smooth

 USKUB showed 12mm cyst left lower pole of
the kidney and enlarged prostate 46g
 PSA 1.04ng/ml
 Cret 69 umol/L
 Uroflowmetery showed
 Max Flow Rate 9 ml/secVol is 183ml and res
74ml and prolonged curve

Your management
 5 alpha reductase inhibitor
 Alpha blocker
 Combination therapy
 Watchful waiting

 A 50 year old gentleman presented with
LUTS for the past 3 years but recently there is
bladder pain and pain at the tip of his penis
whenever he passes water.
 His IPSS =23
 There is obvious hematuria
 He has diabetes as well as HT
 DRE showed a 50g prostate which was tender

 How would you investigate him
 What is your provisional diagnosis?

 RBC nil
 WBC 15 /ul
 Urine culture negative
 PSA 31ng/ml
 US urinary system normal

 Done 6 weeks later on 1.2ng/ml
 He still has IPSS of 15
 How would you treat him?

 90 year old father of a local GP presented
with acute retention of urine after a right
hemicolectomy
 He had denied any antecedant LUTS but his
wife says he does get up out of bed often at
night.
 A CBD was inserted and even after the 7th
post
op day he could not pass water on trial off a
catheter

 Physical examination showed distended
bladder and 45g prostate gland which was
non tender and there is severe pain on doing
DRE and fecal impaction
 What would you do next?

 PSA was 9 ng/ml
 He developed a swinging fever
 What test would you do next?

 Klebsiella 100000 org /ml
 Sens to Ofloxacin and resistance to
Cephalosporins
 How would you treat him?

 Trial off CBD was done after giving alfuzosin
for three days
 He wet his pants in bed so had to use diapper
 Discharged home well after 2 weeks in
hospital
 GP rings up and says he took another urine
culture and this time grew E Coli

 E Coli culture
 Resis to Augmentin and Cefuroxime but sens
to Aminoglycoside and Imepenam
 No fever
 No pain
 Apetite well
 Wet pants- diappers
 What would you do?

Assymptomatic Bacteriuria
• Two consecutive clean voided specimens of
100,000org/ml
Hooton TM. Recurrent urinary tract infection in women [Review]. Int J Antimicrob
Agents 2001; 17:259-268.

ACTIVE Management of
• Pregnant women
• Urological instrumentation
European Urology Association UTI guidelines 2006

Conservative Management of
• pre-menopausal, non-pregnant women
• diabetic women
• older persons living in community
• elderly institutionalized subjects
• persons with spinal cord injury
• catheterized patients while the catheter
remains in situ.
European Urology Association UTI guidelines 2006

 Alpha blocker or 5 alpha reductase inhibitor
or both?

 63 year old Indian gentleman presented with
a 3 year history of LUTS. His IPSS = 27 and QL
= 5.There was recent constipation .
 There was no dysuria nor hematuria nor bone
pain or weight loss
 DRE showed 35g prostate with impacted
stools

 UFEME showed 2 rbc/ul otherwise clear
 Serum creatinine 100umol/L
 USKUB normal kidneys and enlarged
prostate gland
 PSA 2.5ng/ml

 How would you go about treating him?

 He gets on Doxasosin XL 4mg nocte and
Dutasteride 0.5mg daily for 6 months
 His return IPSS = 22 mainly irritative bladder
symptoms
 What would you do next?

Detrusitol®
IR Added to Doxazosin in alpha-Blocker
Non-responders Was More Likely to Improve Symptoms in
Patients with BOO and DO
Doxazosin
+
Detrusitol IR
Doxazosin BOO
ImprovedImproved
n = 60n = 60
79%79%
NOTNOT
ImprovedImproved
n = 16n = 16
21%21%
ImprovedImproved
n = 6n = 6
37.5%37.5%
NOTNOT
improvedimproved
n = 10n = 10
62.5%62.5%
BOO and DO
ImprovedImproved
n = 24n = 24
35%35%
NOTNOT
ImprovedImproved
n = 44n = 44
65%65%
ImprovedImproved
n = 32n = 32
73%73%
NOTNOT
improvedimproved
n = 12n = 12
27%27%
Lee JL et al. BJU Int. 2004;94:817-820.Results of primary end point did not meet statistical significance.
Improvement was defined as at least a 3-point reduction in IPSS

Case 6
• 68 year old gentleman presented with LUTS with
and IPSS of 28
• There was no hematuria
• There was DM
• DRE showed a 45 g prostate smooth non tender
with no nodules
• PSA was 2ng/ml
• Qmax 9ml/sec on a volume of 245ml and residual
of 78ml

• How would you go about treating him?

• He responded to the alpha blocker and
dutasteride
• IPSS = 14
• He has great urinary flow but still has poor
quality of life
• He has to wake up 4 times at night to pass
water and this causes day time sleepiness
• What is your next course of action?

F/V informs about my diuresis
(i.e. bladder capacity)
This is the first urodynamic
screening test.
F/V Frequency Volume Chart
Monday
Thuesday
Wednesday
Thrusday
Friday
Saturday
Date : ……………. Name : ………………………….
FREQUENCY VOLUME CHART
Number Time Volume
3
2
3
4
07:00 250
11:20 200
18:00 420
10:00 600
21:00 700
09:00 450
12:00 320
20:00 600
07:20 400
11:00 350
16:00 410
21:00 350

What causes nocturia?
Nocturnal polyuriaNocturnal polyuria
PRIMARY NOCTURIAPRIMARY NOCTURIA
PsychologicalPsychological
factorsfactors
UntreatedUntreated
diabetesdiabetes
mellitusmellitus
PrimaryPrimary
polydipsiapolydipsia
UnstableUnstable
bladderbladder
UntreatedUntreated
diabetesdiabetes
insipidusinsipidus
UncompensatedUncompensated
heart diseaseheart disease
ReducedReduced
bladderbladder
capacitycapacity
NocturiaNocturia
Fonda 1999; van Kerrebroeck 2002; Wein 2002.

Multifactorial cause of Nocturia
NP
20%
SB
5%
BOO
2%
NP+SB
15%
NP+BOO
20%
SB+BOO
10%
NP+SB+BOO
23%
NP+SB+SA
5%
NP
SB
BOO
NP+SB
NP+BOO
SB+BOO
NP+SB+BOO
NP+SB+SA
Sh
Shyh-Chyi Chang, Alex TL Lin , Kuang Kuo Chen and Luke S Chang ,
Multifactorial Nature of Male Nocturia , Urology 2006: 67: 541-544

• 49 patients 51-78y with BPH in Sultanah
Aminah Hsp JB
• Nocturia 2-5 (3.4 mean)
• Prevalance = 85.4%
Yoong BF, Bala Sundaram M and Aida Z Med J Malaysia Aug 2005, Vol 60:3 p 294-
296
NocturnalNocturnal polyuria with BPHpolyuria with BPH

What causes nocturia?
• Defined as a night-time urine production that
is:
– > 35% of 24-hour urine volume
– > 50% of total 24-hour urine production from 19:00 to
07:00 hours
– in excess of bladder capacity
Weiss 1998; Mattiasson 2002.Weiss 1998; Mattiasson 2002.
NocturnalNocturnal polyuria is a primary cause of nocturiapolyuria is a primary cause of nocturia

What is the role of the kidney?
• Urine production by the kidney follows a
circadian rhythm
• At night, arginine vasopressin (AVP, the
antidiuretic hormone) secretion increases;
urine production therefore falls
• With age:
– nocturnal AVP production falls
– renal response to AVP declines
– renal concentrating capacity reduces
Asplund & Åberg 1991; Miller & Shock 1953; Bauer 1993; Cugini 1992.Asplund & Åberg 1991; Miller & Shock 1953; Bauer 1993; Cugini 1992.

Vilhardt 1990.Vilhardt 1990.
 Selective VSelective V22 receptorreceptor
agonistagonist
 Potent anti-diureticPotent anti-diuretic
effecteffect
 Concentrates the urineConcentrates the urine
Desmopressin
How does desmopressin work?How does desmopressin work?
Desmopressin is a substitutional therapy inDesmopressin is a substitutional therapy in
patients with deficient AVP productionpatients with deficient AVP production
V2

How should MINIRIN tablets be used in
nocturia?
• Single night-time dosing with antidiuretic effect within 30min
• Titrate dose at weekly intervals: 0.1→ 0.2→ 0.4 mg . Higher
dose prolongs duration of action but no greater antidiuretic effect
• Fluid intake must be limited from 1 hour before to 8 hours
after administration as duration of action 6-8h
• Monitor serum sodium level if increased risk of hyponatraemia

Important considerations whenImportant considerations when
using MINIRIN tabletsusing MINIRIN tablets
Measure serum sodium and stop
treatment until the patient has
fully recovered
… patient experiences nausea
and/or headache
Monitor serum sodium… increased risk of
hyponatraemia
Stop treatment until patient has
recovered
… patient has a fever,
gastroenteritis or systemic
infection
Limit fluid intake… patient drinks a lot
RecommendationIf …

MINIRIN shifts nocturnal urine production towardsMINIRIN shifts nocturnal urine production towards
normal circadian rhythmnormal circadian rhythm
• MINIRIN significantly reduced the number of
nocturnal voids
• MINIRIN prolonged the sleep period before first
void – by 2 hours
• 1/3 of the patients had an undisturbed first
period of sleep > 5 hours

Case 7
• 40 year old man who presented with LUTS as
well as suprapubic discomfort, low back pain
for the last 6 months
• There was no hematuria
• UFEME showed 12wbc/ul but UCS was clear
• DRE - 20g normal prostate gland
• What do you think is the diagnosis here?

What is the post probable cause?
A. Prostatitis (Chronic Pelvic Pain Syndrome)
B. Overactive bladder
C. Bladder stone
D. Interstitial Cystitis
E. Recurrent Chronic UTI
Case 14

NIH classification Definition
Cat 1-Acute bacterial prostatitis Acute infection
Cat11-Chronic bacterial prostatitis Recurrent infection
Cat111-Chronic pelvic pain syndrome (CPPS)No demonstrable infection
Cat 111A-Inflammatory CPPS No demonstrable infection;
WBCs in semen EPS/VB3
Cat111B-Noninflammatory CPPS No demonstrable infection;
no WBCs in semen, EPS/VB3
Cat1V-Asymptomatic inflammatory prostatitis No symptoms

Table 2.Screening for prostatitis using the PPMT
Diagnosis Pre-M urine culture Post-M ur cult WBCs post-M
Category11 - + +
Category111A - - +
Category111B - - -
Cystitis (+/- Category 11) + + +
PPMT Premassage and postmassage test
Pre-M Premassage
Post-M Postmassage

Management
• Explanation
• Manage expectations
• Exclude other diagnosis
• Antibiotics
• Alpha blockers- Terozosin
• Prostatic Massage
• Gabapentin

IMPORTANT FEATURE-IN STERILE URINE
• CHRONIC LUTS IN MEN
• PAINFUL BLADDER ON HOLDING ON
CHRONIC PROSTATITIS-Cat 3
INTERSTITIAL CYSTITIS
BLADDER STONE

Case 8
• 35 year old
gentleman
presented with
acute right loin
pain and LUTS a
day prior to seeing
you.
• There was nausea
and vomiting as
well at the time

• Temp 37.2 C
• Comfortable at
rest
• Abdomen showed
some deep
tenderness over
the RIF

UFEME
• Rbc –Nil
• Wbc –nil
• Protein – nil
• Serum Creatinine 135umol/L

Management
• Fluids 2-2.5L /day
• Pain relief

Spontaneous passage rates
• Stones size Passage rates
• <=5mm 68%
• >5<=10mm 47%
European Urology Association Ureteral Stone Guidelines 2007

Medical tx passage rates
• Agent Passage rates
• Nifedipine 75%
• Alpha Blockade 81%
European Urology Association Ureteral Stone Guidelines 2007

Efficacy of [alpha]-Blockers for the Treatment of Ureteral
Stones
• 11 trials and 911 patients
• “Compared to patients who received
conservative management alone, patients who
received [alpha]-blockers were 44% more likely
to expel the stones.”
Parsons, J. Kellogg *,+; Hergan, Lori Ann; Sakamoto, Kyoko; Lakin, Charles Efficacy of
[alpha]-Blockers for the Treatment of Ureteral Stones. Journal of Urology. 177(3):983-
987, March 2007

Comparison of Efficacy of 3 different alpha 1
adrenergic blockers for distal ureteric stones
• 114 patient ages 18-65 yrs
• Followed up for a month
• Weekly Xrays and US
Yilmaz E, Batislam E, Basar MM. J Urol 2005; 173:2010–2012.

Stone Expulsion Rates
P=0.03 P=0.03
Yilmaz E, Batislam E, Basar MM. The comparison and efficacy of 3 different alpha 1 adrenergic blockers for distal ureteral stones. J
Urol 2005; 173:2010–2012.

Pain episodes
P=0.004
P=0.018
Analgesic usage also less
Number of pain episodes
Urol 2005; 173:2010–2012.

Average time to expulsion
P=0.004
P=0.03
Number of pain episodes
Urol 2005; 173:2010–2012.

Criteria
• Distal ureteral stones < 10mm
• Absences of severe colic
• Absence of colic last more than a day
• Absence of infection
• No evidence of renal failure
• Absence of severe hydronephrosis or
hydroureter
• Dual Kidneys

Case 9
• A 56 year old gentleman presented with an
incidentally raised PSA level of 6.7ng/ml
• He has and IPSS = 7
• He has no difficulty with uroflow
• No hematuria
• No medical problems
• DRE showed a normal 45g prostate which was
smooth
• What would you do next?

189
•
What is a raised PSA level?
PSA level Prevalence of
cancer
Sensitivity Specificity
3.1 - 4.0 26.90% 20.50% 93.80%
2.1 - 3.0 23.90% 32.20% 86.70%
1.1 - 2.0 17.00% 52.60% 72.50%
0.6 - 1.0 10.10% 83.40% 38.90%
< 0.5 6.60% Not reported Not reported

190
Raised PSA level
• BPH
• Prostatitis
• Prostatic massage (1.5-2 times the normal
PSA)
• Prostate biopsy (rise by 8ng/ml)
• TURP ( rise by 6ng/ml)
• Urinary retention
• Ejaculation recent within 48-72h
• DRE?

191
TRUS biopsy
• Negative biopsy does not
mean absence of cancer
• Sedation
• Preop antibiotics
• Septicaemia in 3%
• Expect hematuria and
hematospermia
• Anal spasm

Reduce Criteria
 Men 50-75 years old
 PSA 2.5ng-10ng/ml (<60yrs ) or PSA 3-10 in men >=60 yrs
 Single negative biopsy in the last 6 mths
 80 ml prostate gland

Design Control-Placebo
Dutasteride
2 year 10 core biopsy 4 year biopsy
Prn biopsy if clinically indicated 6.4%
Random
7 mths
Biopsy
6726 men
Placebo
run in 1
month
Andriole J Urol 2004; 172:

END POINT
Dutasteride
reduced the risk of
cancer by 23%
p<0.0001
Placebo 857 vs
Dutasteride 659
No increase in high grade cancer

Case 11
• 37 year old gentleman who presented with
premature ejaculation since he has been sexually
active for the last 3-4 years.
• Ejaculates with seconds of penetration.
Sometimes even before penetration.
• No problems with erections.
• Has loss of libido as well.
• Exam : Normal genitalia, Female dist of hair.
• IPSS is 4.

McMahon 2nd
isced ,Committee 9b REPORT
2004
• WJHAT IS NORMAL INTRAVAGINAL
EJACULATION LATENCY TIME?
Normal men IELT 2-10mins
No definite agreement on best PE vs
non PE break point
•Prepenetration (5-7%)
In most large PE groups
• 30-40% <20 sec
• 80% <40 sec
• 90% <60 sec
• 95% <120sec

PREMATURE EJACULATION
3. psychological distress in the patient and/or partne
1. brief ejaculatory latency <1min
2. loss of control
(inability to delay on
vaginal penetration)

Diagnosis of PE
Onset and duration
Degree of distress
Psychosocial hist
Relationship issues
Clinical assessment
PE is due to ED
PDE5 inhibitor
Organic cause
prostatitis
Treat cause
TREAT PE
Richardson, Daniel
BSc; et al
Recommendations for
the management of
premature ejaculation:
BASHH Special Interest
Group for Sexual
Dysfunction
Int J of STD and AIDS
Volume 17(1), January
2006, pp 1-6

COUPLANDETALJCLINPSYCHOPHARMACOL1996:356-362
SSRI WITHDRAWAL SYNDROME
•Diziness
•Parasthesia
•Lethargy
•Vivid
dreams/insomnia
•Irritability
•Lowered mood
Common Symptoms
Men > Women
Occurrence varies amongst SSRI’S
Clomipramine>Paroxetine>Fluvoxa
mine>Setraline>Fluoxetine

USINGTHEPITCHBOOKTEMPLATE
Method
Tramadol 50mg taken 2 hrs before sex
self-administered IIEF, IVELT, mean
weekly coitus episodes, and adverse
drug effects. Patients and their wives
were interviewed separately
Results
•Placebo controlled randomised trial
•Tramadol vs Placebo
•64 potent patient
•mean age, 34 years; range, 20-52 years
•IVELT<2min in 90% of coitus
•Stable relationship 6 mths
•No organic cause of PE
•
Safety and Efficacy of Tramadol in the Treatment of
Premature Ejaculation: A Double-blind, Placebo-Controlled,
Fixed-
Safarinejad, Mohammad Reza MD; Hosseini, Seyyed
Yoosof ,Journal of Clinical Psychopharmacology.
26(1):27-31, February 2006.

MEAN INTRAVAGINAL EJACULATORY LATENCY
TIME
P<0.001
Safarinejad, Mohammad Reza MD; Hosseini, Seyyed Yoosof ,Journal of Clinical
Psychopharmacology. 26(1):27-31, February 2006.

Mean number of intercourse/week
P<0.005

Mean satisfaction domain of IIEF
P<0.005

SATISFACTIONWITHTHEMEDICATION
% of pt or wives * p<0.01
*

TRAMADOL
MECHANISM OF ACTION
•inhibition of neuronal reuptake of
serotonin
•inhibition of neuronal reuptake of
noradrenaline,
•enhancing serotonin efflux,
antinociceptive effect,
•inhibition of spinal somatosensory-
evoked potentials.
Completely absorbed after 30min
Peak plasma concentrations (Cmax) are
attained within 1.6 to 1.9 hours
The mean elimination half-life is
approximately 5 to 6 hours.

ADVERSE EVENTS
No Tramadol
patients (%)
No of Placebo
patients (%)
p
Adverse Events 9(28.1) 5(15.6) <0.05
Nausea 5(15.6) 1(3.1) <0.05
Vomiting 2(6.2) 2(6.2) ns
Dizziness 1(3.1) 2(6.2)
Constipation 1(2.6) 0

Lower Urinary Tract Symptoms in Men for GPs

Empfohlen

Empfohlen

Weitere ähnliche Inhalte

Was ist angesagt?

Was ist angesagt? (20)

Andere mochten auch

Andere mochten auch (20)

Ähnlich wie Lower Urinary Tract Symptoms in Men for GPs

Ähnlich wie Lower Urinary Tract Symptoms in Men for GPs (20)

Mehr von Alan Teh

Mehr von Alan Teh (18)

Kürzlich hochgeladen

Kürzlich hochgeladen (20)

Lower Urinary Tract Symptoms in Men for GPs

Hinweis der Redaktion