Erectile Dysfuntion EPIDEMIOLOGY AND PATHOPHYSIOLOGY

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Erectile 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

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• 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
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• 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
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ED in SA

• 680 patients

AI El-sakka, 2004 International Journal of
Impotence Research
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• ED consistent or recurrent inability to attain
  and/or maintain penile erection sufficient for
  sexual performance.

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Anatomy
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Physiology
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PENILE 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.

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CNS
psych
imagination
auditory
Hypothalamus
tactile
memory
Testosterone
Sexual Ctre
olfactory
visual
Estradiol
Sympathetic parasympathetic
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Nitric 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.

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• 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.

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Phosphodiesterase

• 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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Nitric Oxide-cGMP Mechanism of Corpus
Cavernosal Smooth Muscle Relaxationand Penile
Erection
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• 3

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!!!

• 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

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Etiology
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.
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A functional classification of impotence.

• Note that it is unlikely for an individual
  patients impotence to derive solely from one
  source

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Causes of ED
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Major organic causes of ED
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ED in SA

• 680 patients

• Significant association to severity of ED
• diabetes,
• hypertension,
• dyslipidemia,
• smoking,
• increased BMI,

AI El-sakka, 2004 International Journal of
Impotence Research
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Organic 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
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Psychogenic 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.

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Diabetes 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
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Diabetes 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

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Chronic Renal Failure

• Sexual dysfunction has been reported in 20 to
  50 of men with chronic renal failure

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Cavernous (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

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Anti 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

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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  
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Antipsychotics

• 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.

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Antidepressants

• 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

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Antidepressants

• Monoamine oxidase inhibitors
• associated with higher rates of orgasmic
  dysfunction in controlled trials

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Antidepressants

• 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

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Antidepressants

• 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.

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Antidepressants

• 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.

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Tobacco

• 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.