Transcript Errectile Dysfunction: Management Update

PAMELA YOUDE N ETHERSOLE EASTERN H OSPITAL
Evolving Strategy in Erectile
Dysfunction Management
TY Chu
Urology Division
Department of Surgery
PYNEH
Don’t Be Shy !!!
Prevalence of Erectile Dysfunction
Massachusetts Male Aging Study (N=1,290)
Men aged 40 to 70 years
No erectile dysfunction
(48%)
Complete
(10%)
Erectile dysfunction
(52%)
Moderate
(25%)
Mild
(17%)
Feldman et al, 1994
Age and Prevalence
Massachusetts Male Aging Study (N=1,290)
80
Prevalence (%)
67%
57%
60
48%
40
39%
Complete ED
Moderate ED
Mild ED
20
0
40
50
60
Age (yr)
Feldman et al, 1994
70
Pump it Up !
In the past ……
Inject it Up !
Put in Rods !
Definition
• Erectile dysfunction (ED) is defined as
the consistent inability to attain and
maintain a penile erection adequate
for satisfactory sexual activity.
In the past: … … penile erection
adequate for vaginal penetration
NIH Consensus Development Panel on Impotence, 1993
Etiology of Erectile Dysfunction
For simplicity, erectile dysfunction can be
classified as:
 Organic - due to vasculogenic, neurologic,
hormonal, or cavernosal abnormalities or
lesions
 Psychogenic - due to central inhibition of the
erectile mechanism without a physical insult
*However, in most patients with erectile dysfunction, a
combination of organic and psychogenic components is involved.
NIH Consensus Development Panel on Impotence, 1993
Benet and Melman, 1995
Physiology of penile erection
Central Control of Penile Erection
Proerectile stimuli:
imagination, audiovisual, tactile
Inhibitory stimuli:
depression, anxiety, fear
Cortex
+ PVN –
Dopamine
Dopamine receptors
NO
Neural erectile signalling
Penile erection
Cavernosal
smooth
muscle cells
Penile Erection
PDE-5 Inhibitors
• Because these drugs do not stimulate the
cascade of events, but rather prevent a catabolic
step, they have no inherent ability to produce an
erection.
• Therefore, sexual stimulation is required for the
medications to be effective, leading some to
characterize PDE5 inhibitors as facilitators rather
than instigators of tumescence.
Krenzelok EP. Sildenafil: clinical toxicology profile. Clin Toxicol. 2000;38:645-51.
PDE5 – inhibitors
• Sildenafil (Viagra) – initially under trial for cardiac
conditions such as angina found to increased blood
flow to the penis & increased erections in 1994
• 1998 – sildenafil the first oral anti-impotence drug
approved by the FDA
• Various newer oral anti-impotence drugs emerged
within the last few years (introduction of Tadalafil and
Vardenafil to HK in the years 2003 and 2004
respectively)
• The treatment of ED was revolutionized because of
their effectiveness and convenience
Sildenafil is effective in all types of ED
% of patients with improved
erections (95% CI)
Placebo
100
80
Sildenafil
†
†
60
40
20
0
n=755 n=766
Organic
n=145 n=166
Psychogenic
†p=0.0001
†
n=295 n=312
Mixed
sildenafil vs placebo
Results of a combined, retrospective analysis of the intent-to-treat population from 11 randomized, placebocontrolled, flexible-dose, clinical trial at week 12
Percentage patients with
improvement in erections by age
% of patients reporting
improvement in erections
Placebo
Sildenafil
100
80
60
40
20
0
n=1567 n=1968 n=143n=222
All patients
Age <40
n=603 n=753
n=470 n=586
Age 40–55
Age 56–64
n=351 n=407
Age ≥65
+p=0.0001 sildenafil vs placebo
Results of a combined, retrospective analysis of the intent-to-treat population from 11 randomized, double-blind,
placebo-controlled, flexible-dose, clinical trials at week 12 on the Global Efficacy Assessment measure of
improvement in erections
Current PDE-5 Inhibitors
O
Cyclic GMP
O
N
HN
H2N
N
Vardenafil
N
O
HC
3
N
O O
S
N
HN
N
O
Sildenafil
H3C
N
O O
S
N
P
H
O
N
CH
N
N
H H
N
O
Tadalafil
O
CH 3
O
N
N
HN
CH3
CH3
O
OH
N
CH3
N
O
OH
O
CH3
O
O
CH
3
PDE5 – Inhibitors
Efficacy
Sidenafil (Viagra) Vardenafil (Levitra)
Tadalafil (Cialis)
Potency
IC50 (nM)
3.5
0.1
6.7
Dosage
50 / 100 mg
10 / 20 mg
10 / 20 mg
Response Rate
82 % (100mg)
80 % (20mg)
70 % (20mg)
*IC50: inhibitory concentration – concentration of chemical agent to inhibit 50% of
receptors
PDE5 – Inhibitors
Therapeutic window
Sidenafil (Viagra) Vardenafil (Levitra)
Tadalafil (Cialis)
Peak plasma
concentration
(hours)
0.5 – 2
Median: 1
0.5 – 2
Median: 1
0.5 – 6
Median: 2
To Be taken
~1 hour before
sexual activity
~1hour before
sexual activity
Prior to
anticipated
sexual activity
Duration (hours)
4
5
36
Half-life
(hours)
4
4-5
17.5
Side Effects of the 3 PDE-5 Inhibitors
Sildenafil
Vardenafil
Tadalafil
Headache
20%
17%
12%
Flush
16%
10%
7%
Rhinitis
7%
6%
4%
Dyspepsia
6%
6%
5%
Myalgia / back
pain
Visual
disturbance
<1%
<1%
3%
3%
<2%
<0.1%
In the Past … …
What’s New … …
• The current availability of these high efficacy oral drugs,
have changed our strategy in ED management
• Any men who wishes to have erectile function can do so
regardless of the etiology of the problem, and the task of
the physician is to help the patient seek the best solution
- Goal Directed Approach – the single most important
concept in managing ED
• Men with ED could be treated with PDE5 inhibitors (no
cause-specific treatment option) with little or no
evaluation, in view of its efficacy, safety, invasivess and
cost, as well as patient preference
Lue TF. Erectile dysfunction. N Engl J Med 2000
Take Home Messages
 Erectile dysfunction is a common condition.
 Advances in understanding the physiology of
penile erection make a great deal of progress in the
pharmacological treatment of ED.
 Modern treatment of ED has been revolutionized
by the worldwide availability of the oral PDE5
inhibitors, which are associated with high efficacy
and safety rates, regardless of the causes.