ERECTILE DYSFUNCTION (ED)
Urologická klinika VFN a 1. LF UK
Praha
ED: take the lead
Erectile dysfunction =
consistent inability to
obtain and/or maintain an
erection sufficient for
satisfactory sexual relations
NIH 1992
Mechanism of penile erection
Diagram of penile erection
Incidence of ED
in 40 y. - 22 % pts.
in 70 y. - 49 % pts.
Massachusetts Male Aging Study (1994)
140 mili. men in all world
500 – 800 000 men in ČR
+ 40 000 every year
Prevalence of ED
Major risc factor for ED: aging
Incidence of ED in the Czech R.
35 – 65 y.
54 % of men
(Stem/Mark, Pfizer – 2001)
Risk factors for ED
• Vasculogenic factors
• Age
• Certain medications
• Psychosocial/psychological factors
• Neurogenic factors
• Hormonal factors
Endothelial dysfunction is a risk factor for
CVD and ED
Heart
Heartfailure
failure Atherosclerosis
Atherosclerosis Smoking
Smoking
Hypertension
Hypertension Oxidative stress Diabetes
Diabetes
Endothelial
Endothelialdysfunction
dysfunction
ED
ED
Adapted from Rubanyi GM. J Cardiovasc Pharmacol 1993; 22 (Suppl 4): S1–S4
Causes of ED
1. Organic (80 %)
diabetes mellitus, hypertension,
hyperlipidemie, benign prostate disease,
peripheral vascular disease, cardiac
problems, hormonal problems (pituitary,
testis, thyroid, adrenal), neurogenic
(cerebral, spinal, dorsal nerve,
cavernous nerve)
postsurgical: radical prostatectomy,
abdominoperineal resection
2. Psychogenic, drugs (20 %)
Causes of ED
Neurogenic
Parkinson´s disease – 60%
Multiple sclerosis – 70%
Spinal cord trauma, tumor etc.
Peipheral neuropathy: diabetes,
alcoholism, chronic renal failure
Diagnosis of ED may uncover other
serious treatable disorders
• Hypertension
– 68% of men with hypertension had ED to some
degree
• Dyslipidemia
– 60% of men with ED had dyslipidaemia
• Heart disease
– 56% of men with ED were found to have a positive
stress test
– 40% of men with ED had significant coronary
occlusions
Diagnostic management of ED
Non-invasive:
a) basic: complete medical history, physical
examination (), basic neurological
examinations, DRE, laboratory tests ()
b) Nocturnal Penile Tumescence:
The RigiScan device (1985)
Dupplex ultrasonography, intracavernous
injection of vasoactive substances
The RigiScan device (1985)
The sexual and medical history
Sexual history Medical history
• Erectile function • Rule out comorbid
• Partner’s interest in conditions
patient having ED • Atherosclerotic risk
treatment factors and vascular
disease
• Use of medications/
recreational drugs
• History of surgeries or
pelvic/perineal trauma
• Depressive symptoms
Selected diagnostic tests
• Routine
– random glucose
– serum chemistries, complete blood count, lipid
profile
• If clinically indicated
– fasting glucose
– prostate-specific antigen
– serum prolactin level, luteinizing hormone level
– testosterone assay
Diagnostic management of ED
Invasive
= before surgery only
- cavernosometry, cavernosography
- cavernous tissue biopsy
Discussion with patients
ED therapy
First-line therapy Second-line therapy
Alprostadil (PGE1)
Oral agents intracavernous aplication
Other Alprostadil
intraurethral aplication
• Vacuum constriction
device Third-line therapy
• psychotherapy • penile prostheses
vascular surgery
Oral therapy
• PDE 5 inhibitors (95%)
2-blockers (Yohimbin)
• hormonal therapy (testosteron)
PDE5 inhibitors
O O
O O
H N
N O HN N
HN N O HN
N N
N
N N N
H N N N
2 O
O
0H O S O O S O O
O O N
P N O
O
0H
N
N
cGMP Tadalafil
Sildenafil Vardenafil
O
CH3
H3C
CH3
Caffeine
PDE5: localization
• PDE5 is localized in vascular smooth muscle
cells
• PDE5 is not localized in the following:
– cardiac myocytes
– endothelial cells
– lymphatic cells
– cardiac conduction tissue
PDE5 inhibition with sildenafil
Sexual
stimulation Corpus cavernosum
Erection
NANC
NO Smooth
GTP cGMP muscle
relaxation
of the
GMP cavernosal
PDE5 arteries &
the corpora
NO=nitric oxide; NANC=nonadrenergic-noncholinergic neurons;
PDE5=phosphodiesterase type 5
PDE5 inhibitors – side effects
sildenafil tadalafil
vardenafil
(N = 724/379) (N =
1812/793)
headache 15% 14,5 / 5,5% - placebo 16 / 6%
dyspepsia 6% 12,3 / 1,8% 4 / 1%
backache 0% 6,5 / 4,2% 0%
rhinitis 2% 4,3 / 3,2% 10 / 4%
myalgia 0% 5,7 / 1,8% 0%
flushing 14% 4,1 / 1,6% 12 / 1%
abnormal vision 5% 0% <2 / 0%
PDE5 inhibitors
sildenafil vardenafil tadalafil apomorfin
Effect PDE5, PDE6 PDE5, PDE6 PDE5, PDE11 - central
inhibition inhibition inhibition effect
efficacy 82 % 80 - 86 - 92 % 81 % 45 %
Start time to 12 - 37 min 15 - 30 min 30 min 18 min
efficacy
Time of efficay 3,5 - 5 h. 4 - 5 h. 24 - 36 h. 2 h.
Side effect nausea
contraindication nitrates taking nitrates taking nitrates taking
timing 1x / 24 h. 1x /24 h. No-every 24 h. 1x/ 8 h.
cost 4 x 100 mg 4 x 10 mg 4 x 20 mg 4 x 3 mg
1832,61 Kč 1528,01 Kč 1538,80 Kč 1414,32 Kč
Pharmacotherapy:
Intracavernous injection
Vacuum constriction device
Surgery
• vascular surgery
– dorsal artery revascularization (V. Michal, 1980)
= inferior epigastric artery to dorsal artery of the penis
• penile prostheses
– semirigid
– mechanical
– inflatable devices
