Title: Erectile Dysfuntion EPIDEMIOLOGY AND PATHOPHYSIOLOGY
1Erectile Dysfuntion EPIDEMIOLOGY AND
PATHOPHYSIOLOGY
- Dr. Anmar Nassir, FRCS(C)
- Canadian board in General Urology
- Fellowship in Andrology (U of Ottawa)
- Fellowship in EndoUrology and Laparoscopy
(McMaster Univ) - Assisstent Prof Umm Al-Qura
- Consultant Urology King Faisal Specialist
Hospital
2- Before age 40 ? 1- 9
- from 40 to 59 ? 5-30
- from 60 to 69 ? 20- 40
- men in their 70s and 80s?50-75
24 international studies between 1993 and 2003
3- Males 40 and 70 years
- 52 reported some degree of ED.
- 40 ? 70 the probability of
- complete impotence tripled from 5.1 ? 15
- moderate impotence doubled from 17 ? 34
- minimal impotence remained constant at 17.
- By the age of 70 years 68 have ED.
1709 noninstitutionalized men The Massachusetts
Male Aging Study 1994
4ED in SA
AI El-sakka, 2004 International Journal of
Impotence Research
5- ED consistent or recurrent inability to attain
and/or maintain penile erection sufficient for
sexual performance.
6Anatomy
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8Physiology
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10PENILE SMOOTH MUSCLE RELAXATION CAUSES ERECTION
Sexual stimulation Sympathetic
parasymp Smooth muscle relaxation Arterial
dilation venous occlusion
- Relaxation of the cavernous smooth muscle is the
key to penile erection.
11CNS
psych
imagination
auditory
Hypothalamus
tactile
memory
Testosterone
Sexual Ctre
olfactory
visual
Estradiol
Sympathetic parasympathetic
12Nitric oxide
- Synthesis of NO is catalyzed by NOS,
- converts l-arginine and oxygen ? l-citrulline and
NO. - NOS exists as three isoforms in mammals
- nNOS - in neurons cells
- eNOS - in endothelial cells,
- iNOS in virtually all cell types.
- In the corpus cavernosum
- nNOS ?initiating erection
- eNOS ? sustaining erection.
-
- Future
- Gene transfer of nNOS or eNOS to the penis has
been shown to augment erectile responses in
animal studies.
13- Nitric oxide
- Upon entering the smooth muscle cells, stimulates
the production of cGMP. - Cyclic GMP
- activates protein kinase G,
- opens potassium channels and closes calcium
channels. - Low cytosolic calcium favors smooth muscle
relaxation. - The smooth muscle regains its tone when cGMP is
degraded by phosphodiesterase.
14Phosphodiesterase
- All PDEs have been identified in the corpus
cavernosum - With the exception of PDE6, which is specifically
expressed in photoreceptor cells. - PDE5 is the principal PDE for the termination of
cavernous cGMP signaling. - Inhibition of the cGMP-catalytic activity of PDE5
by specific inhibitors has been shown to be
highly effective in treating ED .
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16 Nitric Oxide-cGMP Mechanism of Corpus
Cavernosal Smooth Muscle Relaxationand Penile
Erection
1
2
17!!!
- Other substrates relevant to vascular or
cavernous smooth muscle functions are as follows
- Inositol 1,4,5-trisphosphate (IP3) receptor
- IP3 receptor-associated PKG substrate (IRAG)
- Phospholamban (PLB)
- Heat shock-related protein (HSP20)
- Myosin phosphatase (MP)
- Phosphatase inhibitor-1 (PPI-1)
- GTPase RhoA
18Etiology
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.
19A functional classification of impotence.
- Note that it is unlikely for an individual
patients impotence to derive solely from one
source
20Causes of ED
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22Major organic causes of ED
23ED in SA
- Significant association to severity of ED
- diabetes,
- hypertension,
- dyslipidemia,
- smoking,
- increased BMI,
AI El-sakka, 2004 International Journal of
Impotence Research
24Organic vs. psychogenic causes for ED
Characteristic Organic Psychogenic
Onset Gradual Acute
Circumstances Global Situational
Course Constant Varying
Noncoital erection Poor Rigid
Psychosexual problem Secondary Long history
Partner problem Secondary At onset
Anxiety and fear Secondary Primary
25Psychogenic dysfunction
- Two possible mechanisms to explain the inhibition
of erection - Direct inhibition of the spinal erection center
by the brain - exaggeration of the normal suprasacral inhibition
- Excessive sympathetic outflow or elevated
peripheral catecholamine levels, - increase penile smooth muscle tone to prevent its
necessary relaxation.
26Diabetes Mellitus
Organic dysfunction
- Diabetes mellitus is a common chronic disease
- Affecting 0.5 to 2 worldwide.
- The overall prevalence of DM in KSA is 23.7.
- males ? 26.2
- females ? 21.5.
Saudi Med J. 2004 Al-Nozha et al
27Diabetes Mellitus
Organic dysfunction
-
- The prevalence of ED is three times higher in
diabetic men (28 versus 9.6) - occurs at an earlier age,
- increases with disease duration, being
approximately 15 at age 30 and rising to 55 at
60 years
28Chronic Renal Failure
- Sexual dysfunction has been reported in 20 to
50 of men with chronic renal failure
29Cavernous (Venogenic)
- Failure of adequate venous occlusion is the most
common causes of vasculogenic impotence. - It may result from
- degenerative tunical changes
- Peyronie's disease, old age, and diabetes
- fibroelastic structural alterations,
- traumatic injury to the tunica albuginea
- penile fracture
- insufficient trabecular smooth muscle relaxation
- anxious individuals with excessive adrenergic
tone - patients with inadequate neurotransmitter release
- venous shunts
30Anti HTN and ED
- The underlying disorder may be more relevant for
ED than the medication. - Thiazide diuretic
- Associated with higher rates of ED,
- This may be reduced by combination therapy and
weight loss. - The a1 blockers and Angiotensin II receptor
blocker - Tend to improve sexual functioning
- Calcium Channel Blockers
- No adverse effect on erection
31 Effect of Antihypertensive
Agent Effect Mechanism
Diuretics ED (twice as placebo) Unknown
ß blocker (nonselective) ED Prejunctional a2-receptor inhibition
ß1 blocker (selective) None
a1 blocker Decreases ED rate but may cause retrograde ejaculation Relaxation of internal urinary sphincter
a2 blocker ED Inhibition of central a2 receptor
ACE inhibitor None
Angiotensin II receptor blocker Decreases ED rate
Calcium channel blocker None
32Antipsychotics
- The prevalence of sexual dysfunction ranged from
40 to 70. - Newer agents such as clozapine showed a lower
reduction in sexual desire. - The group taking risperidone had the greatest
decrease in erectile frequency.
33Antidepressants
- Tricyclics
- Antagonize 5-HT receptors.
- Controlled clinical studies suggest that orgasmic
disorders in both sexes are frequent, explaining
the use of these drugs as inhibitors of
ejaculation
34Antidepressants
- Monoamine oxidase inhibitors
- associated with higher rates of orgasmic
dysfunction in controlled trials
35Antidepressants
- Selective serotonin reuptake inhibitors (SSRIs)
- Commonly used to treat depression.
- They inhibit the reuptake of 5-HT into CNS
neurons ?produce stimulatory effects on 5-HT
receptors. - 50 of patients experience a change in sexual
function - mainly anorgasmia,
- adverse effects can be modified by co-treatment
with sildenafil
36Antidepressants
- SSRIs differ in their ability to cause ED.
- A high incidence has been observed in patients
treated with paroxetine - A lesser impact has been reported with
citalopram. - Thus, the ability to produce ED and the mechanism
by which SSRIs cause ED may differ with the
specific SSRI compound.
37Antidepressants
- Recently developed antidepressants such as
mirtazapine and nefazodone tend to have
beneficial effects on sexual function, - Possibly by activating the 5-HT1 C receptor,
- augments sexual response,
- But still antagonize the 5-HT2 C receptor.
38Tobacco
- Tobacco induce vasoconstriction and penile venous
leakage. - Smokers reported an inverse correlation between
nocturnal erection (both rigidity and duration)
and the number of cigarettes smoked per day - men who smoked more than 40 had the weakest and
shortest nocturnal erections.