Erectile Dysfunction

1
Erectile Dysfunction

• Jhumur Joya Pati FRCS FRCS Urol
• Department of Urology
• Homerton University Hospital
• St Bartholomews Hospital

2
Definition

• The inability of the penis to obey the command
  of its master .
• LEONARDO DA VINCI 1504

3
Penile Vascular Anatomy
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(No Transcript)
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CENTRAL CONTROL
OLFACTORY (rhiencephalon)
VISUAL (occipital)
ERECTION
IMAGINATIVE (limbic systems)
TACTILE (thalamus)
6
Penis
7
(T11-L2)
(S2-S4)
8
NO
NO
NO
9
NA
ET
PGF2a TXA2 AngII
PGE1
VIP
NO
NA
a1
SMOOTH MUSCLE
ETA
EP-R
VIP-R
R
sGC
b2
AC
Intracellular calcium
RELAXATION
CONTRACTION
10
Role of Nitric Oxide in ED
SexualStimulation
nNOS
eNOS
L-Arginine
L-Arginine
NitricOxide
Guanylate Cyclase
Erection
GTP
cGMP
cGK I
GMP
PDE-5
GTP, guanosine triphosphate GMP, guanosine
monophosphate cGMP, cyclic GMP nNOS, neuronal
nitric oxide synthase eNOS endothelial nitric
oxide synthase.
Burnett AL. Int J Impot Res. 200416S15-S19.
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Role of Nitric Oxide in ED DRUG X
SexualStimulation
nNOS
eNOS
L-Arginine
L-Arginine
NitricOxide
Guanylate Cyclase
Erection
GTP
cGMP
cGK I
GMP
PDE-5
DRUG X
GTP, guanosine triphosphate GMP, guanosine
monophosphate cGMP, cyclic GMP nNOS, neuronal
nitric oxide synthase eNOS endothelial nitric
oxide synthase.
Burnett AL. Int J Impot Res. 200416S15-S19.
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Conclusion physiology of penile erection
ERECTION
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Is This A Real Problem ?

• Affects 110 men in UK
• Affects 30 M in USA
• 85 pts wait 1 year to seek medical advice
• 60 ED pts do not continue with treatment

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THE IMPACT OF ED

• Low self esteem
• Negative effect on personal relationships
• Negative impact on psychological and social
  well-being
• Marker for hypertension, cardiovascular disease,
  diabetes and depression

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RISK FACTORS CAUSES

• RISK FACTORS
• Age
• Smoking
• Alcohol

• CAUSES
• ORGANIC
• I
• M
• P
• O
• T
• E
• N
• C
• E
• PSYCHOLOGICAL

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..........he died with a smile on his face !
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EVALUATION

• History Examination
• Sexual
• Medical
• Psychological
• Examination

• Investigations
• Routine
• Blood
• Urine
• Specialised
• NPT
• Nerve Conduction
• PBI/Angiography

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TREATMENT

• Non-Invasive
• Sex Therapy
• Medications
• Vacuum Device
• MUSE
• IC Injections

• Invasive
• Revascularisation
• Venous Plication
• Penile Prosthesis
• Malleable
• Inflatable

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Penile Prosthesis
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THANK YOU
Have You Tried A PDE5 I ?
21
Comparing tadalafil with sildenafil and vardenafil

• Efficacy
• Sexual Encounter Profile (SEP) efficacy
  comparison of Sildenafil and Tadalafil in a open
  label, randomized, cross-over, preference study.
  
• Eardley I et al. BJU International 2005 96
  1323-1332
• Patient Satisfaction
• Patient satisfaction comparisons in a
  non-interventional observational study mimicking
  real life routine clinical practice
• Martin-Morales A et al. Eur Urol 200751541-550
• Erectile Dysfunction Inventory for Treatment
  Satisfaction (EDITS) comparisons in a open label,
  randomized, cross-over, preference study.
• Tolrà J R et al. J Sex Med 20063901-909
• Sexual Self Confidence
• Psychological and Interpersonal Relationship
  Scales (PAIRS) comparisons of sildenafil and
  Cialis in a open label, randomized, cross-over,
  preference study.
• Dean J et al. J Sex Med 20063650-661

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Cialis vs. sildenafil open-label, randomized,
cross-over, preference study in 367 men with ED,
naïve to PDE5 inhibitor therapy
Eardley I et al. BJU International 2005 96
1323-1332 1
STUDY DESIGN
Cialis (10mg 20mg)
Cialis (10mg 20mg)
4-WEEK BASELINE ASSESSMENT
8-WEEK EXTENSION
Sildenafil (25mg 50mg 100mg)
Sildenafil (25mg 50mg 100mg)
7-10 days washout
Preference question
8-week dose optimisation and 4-week assessment
8-week dose optimisation and 4-week assessment

• Sexual Encounter Profile (SEP) was completed
  during baseline and each assessment period
  after every sexual intercourse attempt1
• Psychological And Interpersonal Relationship
  Scales (PAIRS) was assessed at baseline and at
  the end of each 12-week treatment phase2
• At the end of both treatment phases, 7 out of 10
  patients chose to take Cialis for the 8-week
  extension1

• Primary endpoint treatment preference for Cialis
  or sildenafil. Secondary endpoints include
  efficacy comparison on SEP questions 2 and 3 and
  assessment of psychosocial outcomes using PAIRS1
• 2. Dean J et al. J Sex Med 20063650-661

Study limitation open-label design
Prescribing information can be found on the last
slide
23
SEP Efficacy comparison of Cialis Vs sildenafil
in treatment-naïve patients
Eardley I et al. BJU International 2005 96
1323-1332.
2.1 (0.3, 4.0)
STATISTICALLY SIGNIFICANT
SEP 1 SOME ERECTION
2.6 (-0.1, 5.3)
SEP 2 SUCCESSFUL PENETRATION
5.2 (1.8, 8.6)
STATISTICALLY SIGNIFICANT
SEP 3 SUCCESSFUL INTERCOURSE
3.5 (-0.6, 7.6)
SEP 4 SATISFACTION WITH HARDNESS
4.8 (0.8, 8.9)
STATISTICALLY SIGNIFICANT
SEP 5 OVERALL SATISFACTION
-10
0
2
4
6
8
10
-2
-4
-6
-8
Point estimates and 95 confidence intervals
(CIs) for the differences (Cialis minus
sildenafil) in adjusted least-squares mean
changes from baseline on the five SEP diary
questions. CIs did not contain zero, indicating
a greater increase in these SEP scores when men
took Cialis compared with sildenafil
(Plt0.05). For both sildenafil and Cialis,
post-baseline scores were significantly greater
(Plt0.05) than baseline scores for all SEP diary
questions.
Study limitation open-label design
Prescribing information can be found on the last
slide
24
The Erectile Dysfunction Observational Study
(EDOS)
Study design
Martin-Morales A et al. Eur Urol 200751541-5501

• 6 month, pan European, prospective,
  observational study of health outcomes of 8047
  men with ED in routine clinical practice1,2

Primary Objective
To describe the effectiveness and satisfaction of
treatment with Tadalafil and other ED
treatment1,2
Method
Men aged 18 years and older (mean age approx 56)
who visited a physician to initiate or change any
ED treatment as part of their normal course of
care2 ED Therapy effectiveness was assessed using
2 unique, single item questions (SIQ1,2) and 2
Global Assessment Questions (GAQ1,2)1 Patient
satisfaction with an ED therapy was determined
using International Index of Erectile Function
(IIEF 7 14) and Erectile Dysfunction Inventory
of Treatment satisfaction (EDITS) question 11
Patient enrolment
8047 patients enrolled across 9 European
countries1 At baseline 94 (7560) selected
either tadalafil (5315), sildenafil (1252), or
vardenafil (993)1 64 of all patients were ED
treatment naive2 904 investigators1,2 69 GPs
and 31 Specialists2)
2. Haro JM, et al. J Sex Med. 20063530-5401
Prescribing information can be found on the last
slide
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Therapeutic effectiveness comparison of 3 PDE5
inhibitors EDOS Single-item question 1 (SIQ1)
Percentage of patients answering NO to SIQ1 "Has
your erection in the past 4 weeks been
INSUFFICIENT to initiate or complete intercourse?"


STATISTICAL SIGNIFICANCE

• The 99 confidence interval for the adjusted
  odds ratio did not include 1 and is statistically
  significant
• No statistically significant differences were
  found between sildenafil and vardenafil

Adapted from Martin-Morales A
n183
n246
n1710
n223
n301
n1993
Prescribing information can be found on the last
slide
Martin-Morales A et al, Eur Urol 200751541-550
26
Therapeutic effectiveness comparison of 3 PDE5
inhibitors EDOS Single-item question 2 (SIQ2)
Percentage of patients answering YES to SIQ2 "Has
the treatment you have been taking in the last 4
weeks SOLVED your problem?"
STATISTICAL SIGNIFICANCE

• The 99 confidence interval for the adjusted
  odds ratio did not include 1 and is statistically
  significant
• No statistically significant differences were
  found between sildenafil and vardenafil

Adapted from Martin-Morales A
n277
n385
n2372
n302
n418
n2593
Martin-Morales A et al, Eur Urol 200751541-550
Prescribing information can be found on the last
slide
27
PDE5i, is there a difference? Patient
satisfaction
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Patient satisfaction EDOS, IIEF question 7
Patient satisfaction IIEF Q7 "Over the past 4
weeks when you attempted sexual intercourse how
often was it satisfactory for you?"


STATISTICALLY SIGNIFICANT

• The 99 confidence interval for the adjusted
  odds ratio did not include 1 and is statistically
  significant
• No statistically significant differences were
  found between sildenafil and vardenafil

Adapted from Martin-Morales A
n264
n368
n2182
n288
n397
n2438
Martin-Morales A et al, Eur Urol 200751541-550
Prescribing information can be found on the last
slide
29
Patient satisfaction EDOS, IIEF question 14
Patient satisfaction IIEF Q14 "Over the past 4
weeks, how satisfied have you been with your
sexual relationship with your partner?"



STATISTICALLY SIGNIFICANT

• The 99 confidence interval for the adjusted
  odds ratio did not include 1 and is statistically
  significant
• No statistically significant differences were
  found between sildenafil and vardenafil

Adapted from Martin-Morales A
n294
n407
n2439
n312
n422
n2603
Martin-Morales A et al, Eur Urol 200751541-550
Prescribing information can be found on the last
slide
30
Independent, 3 PDE5 inhibitor prospective,
randomized, open-label, fixed-dose, crossover
study in 132 men with ED, naïve to PDE5 inhibitor
therapy
Tolrà J R et al. J Sex Med 20063901909
Main study objective An independently produced
un-sponsored study to evaluate efficacy
(including patient satisfaction as measured by
EDITS) and patient preference with sildenafil
100mg, vardenafil 20mg and tadalafil
20mg. Measuring patient satisfaction
Study participants were required to complete the
Erectile Dysfunction Inventory for Treatment
Satisfaction (EDITS) after taking each of the
drugs
sildenafil 100mg
vardenafil 20mg
tadalafil 20mg
sildenafil 100mg
tadalafil 20mg
vardenafil 20mg
132 ED treatment naïve patients equally randomised
vardenafil 20mg
sildenafil 100mg
tadalafil 100mg
Analysis
vardenafil 20mg
tadalafil 20mg
sildenafil 100mg
tadalafil 20mg
sildenafil 100mg
vardenafil 20mg
tadalafil 20mg
vardenafil 20mg
sildenafil 100mg
Preference question
Adapted from Tolrà J R
Study limitation open-label design, uni-center,
sample size
Prescribing information can be found on the last
slide
31
Erectile Dysfunction Inventory for Treatment
Satisfaction (EDITS)
Althof S E. Urology 199953 793-799

• The EDITS patient questionnaire measures the
  degree of satisfaction with the ED treatment
  received.
• Consisting of an 11- item questionnaire with four
  possible answers for each question.
• Each answer is assigned a value of 04, providing
  final scores that range from 0 to 44.
• 1. Overall, how satisfied are you with this
  treatment?
• 2. During the past four weeks, to what degree has
  the treatment met your expectations?
• 3. How likely are you to continue using this
  treatment?
• 4. During the past four weeks, how easy was it
  for you to use this treatment?
• 5. During the past four weeks, how satisfied have
  you been with how quickly the treatment works?
• 6. During the past four weeks, how satisfied have
  you been with how long the treatment lasts?
• 7. How confident has this treatment made you feel
  about your ability to engage in sexual activity?
• 8. Overall, how satisfied do you believe your
  partner is with the effects of this treatment?
• 9. How does your partner feel about your
  continuing to use this treatment?
• 10. How natural did the process of achieving an
  erection feel when you used this treatment over
  the past four weeks?
• 11. Compared to before you had an erection
  problem how would you rate the naturalness of
  your erection when you used this treatment over
  the past four weeks in terms of hardness?

Althof S E et al, Eur Urol 200751541-550
Prescribing information can be found on the last
slide
32
Patient satisfaction comparison of 3 PDE5
inhibitors in ED treatment-naïve patients
Tolrà J R. J Sex Med 20063901909
The application of the EDITS questionnaire after
taking each drug gave the following results
EDITS scores post ED treatment

STATISTICAL SIGNIFICANCE

• tadalafil vs. vardenafil p0.000075
• tadalafil vs. sildenafil p0.012
• As quantified by EDITS, tadalafil was proven to
  be superior to the other 2 drugs
• No statistical differences were found between
  sildenafil and vardenafil p0.273
• Post-treatment all ED therapies significantly
  improved EDITS scores p lt 0.0001

Adapted from Tolrà J R
Study limitation open-label design, uni-center,
sample size
Median 38
37.5
41 Percentile 10-90 34 43
29 42 33 44
Prescribing information can be found on the last
slide
33
PDE5i, is there a difference? Sexual Self
Confidence
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PAIRS in Dean J et al. J Sex Med 2006

• PAIRS (Psychological And Interpersonal
  Relationship Scales)
• A valid patient-reported measure to assess the
  broader psychosocial and interpersonal outcomes
  of ED treatments
• It consists of 23 statements which fall into 3
  Domain
• The Sexual Self-Confidence domain contains six
  items that describe confidence in ability to
  achieve erection and enjoy fulfilling sexual
  experiences
• The 6 statements that make up the PAIRS Sexual
  self Confidence Domain are
• Patients rate each statement on a 4-point scale
  (1strongly disagree 2disagree 3agree
  4strongly agree). Domain scores are then
  calculated for each patient as the mean of all
  statements

Prescribing information can be found on the last
slide
35
Sexual Self-Confidence comparison in ED
treatment-naïve patients
Dean J et al. J Sex Med 2006 3 650-661.
Cialis provides greater sexual self-confidence
than sildenafil in treatment-naïve patients as
measured by PAIRS in Eardley et als preference
study
0.17 (0.09, 0.25)
STATISTICALLY SIGNIFICANT
SEXUAL SELF-CONFIDENCE
0.15 (0.09, 0.22)
STATISTICALLY SIGNIFICANT
SPONTANEITY
STATISTICALLY SIGNIFICANT
0.39 (0.32, 0.46)
TIME CONCERNS
-1.0
0
0.2
0.4
0.6
0.8
1.0
-0.2
-0.4
-0.6
-0.8
Adapted from Dean J et al
Study limitation open-label design
Point estimates and 95 confidence intervals
(CIs) for the differences in adjusted least
squares mean changes from baseline on PAIRS
Sexual Self-Confidence and Spontaneity Domains
and for the differences in endpoint scores on
PAIRS Time Concerns Domain. CIs did not contain
zero, indicating a greater change in these Domain
scores when patients took Cialis compared with
sildenafil (P lt 0.05). Both Cialis and
sildenafil led to a significant increase in mean
change in sexual self-confidence domain score
from baseline (Cialis from 1.89 to 2.91 (Plt0.001)
and sildenafil from 1.91 to 2.75 (Plt0.001)
Cialis n303 sildenafil n308). The mean
spontaneity domain scores increased from baseline
(Cialis from 3.13 to 3.32 (Plt0.001) and
sildenafil from 3.12 to 3.17 (P0.15) Cialis
n305 sildenafil n306).
Prescribing information can be found on the last
slide
36
CONCLUSIONS

• In both open label, randomised, cross-over
  preference studies and a Observational, real life
  study Cialis has demonstrated
• Efficacy
• Cialis has proven efficacy vs. Sildenafil
• Measured by the Sexual Encounter Profile (SEP)
  diaries in this open label, randomized,
  cross-over, preference study
• Eardley I et al. BJU International 2005 96
  1323-1332
• Cialis has shown statistically significant
  differences in therapeutic effectiveness vs.
  sildenafil and vardenafil using SIQ 1 2
• In this real life observational study of
  routine clinical practice using Single Item
  Questions (SIQ)
• Martin-Morales A et al. Eur Urol 200751541-550
• Patient Satisfaction
• At 6 months Cialis has shown statistically
  significant differences in patient satisfaction
  vs. sildenafil and vardenafil using IIEF Q7 14
• In this real life observational study of
  routine clinical practice using International
  Index of Erectile Function (IIEF Q7 14)
• Martin-Morales A et al. Eur Urol 200751541-550
• AND
• In this controlled clinical trial setting using
  Erectile Dysfunction Inventory for Treatment
  Satisfaction (EDITS)
• Tolrà J R. J Sex Med 20063901-909
• Sexual Self Confidence
• Cialis provided greater Sexual Self confidence
  vs. sildenafil

Prescribing information can be found on the last
slide
37
CONCLUSIONS

• The unmet need of treating ED is high1
• Up to 60 of those who do seek medical care
  discontinue their treatment1
• Patients who become non-responders to a PDE5i
  may have several serious implications2
• All ED patients should receive
• A detailed medical, psychosexual history and a
  focused physical examination3
• Patient and if possible partner education about
  their ED medication1,2
• Patient follow up and adequate exposure to the
  drug therapy2

1. Haro JM et al, JSM 20063530-540 2.
Hatzimouratidis K, j.eururo 20075175-89 3.
Wespes E. EAU Guidelines on Erectile Dysfunction
An Update, j.eururo 200649806-815
Prescribing information can be found on the last
slide