2. “The penis does not obey the order of its master,
who tries to erect or shrink it at will.
Instead, the penis erects freely while its master
is asleep.
The penis must be said to have its own mind, by
any stretch of the imagination.”
- Leonardo da Vinci
3. Definition
• Consistent inability to attain or maintain an
erection sufficient to permit satisfactory sexual
intercourse. (NIH,1992)
• Symptoms for at least 3 months , except post-
traumatic or surgically induced ED (Lewis,
1994)
5. • Corpus spongiosum : single circular layer of
tunica
• Low pressure during erection
• Emissary veins : run obliquely between the
layers
• Tunica absent in the glans
13. Mechanism of erection
• Flaccid state : smooth muscle are tonically
contracted – only small amount of arterial
flow to corpora
• Flaccid penis – moderate state of contraction
• Erection : sinusoidal relaxation, arterial
dilation and venous compression
15. • Sexual stimulation : neurotransmitter release
from cavernous nerve terminals
• Smooth muscle relaxation
• Following events :
16. • 1) dilation of arteries and arterioles by
increased blood flow in diastolic & systolic
phases
• 2) trapping of incoming blood by expanding
sinusoids
17. • 3) compression of subtunical venous plexuses,
between peripheral sinusoids &tunica
albuginea- reducing venous outflow
• 4) stretching of tunica to capacity occludes
emissary veins
18. • 5) increase in PO2 to 90mmHg and
intracavernous pressure to 100mmHg (full
erection phase)
• 6) further pressure increase due to reflex
contractions of ischiocavernosus (rigid
erection phase)
24. Neurotransmitters
• Flaccidity : norepinephrine , AT2, PGF2a, ET1
• Detumscence : cessation of NO release,
breakdown of cGMP by PDEs, sympathetic
discharge during ejaculation
25. Erection
• NO principal neurotransmitter mediating
erection
• Noradrenergic/norcholinergic
neurotransmission and endothelium
• NO increase cGMP production, which relaxes
cavernous smooth muscle
26. • NO from nNOS in nitrergic nerves : initiation
• NO from eNOS : maintenance of smooth
muscle relaxation and erection
27. Smooth muscle physiology
• Relaxation of cavernous smooth muscle is the
key to penile erection
• NO enters smooth muscle cells and stimulates
cGMP production
• cGMP activates protein kinase G (PKG)
• PKG open potassium and closes calcium
channels
28. • Low cytosolic calcium favors smooth muscle
relaxation
• Erectile process
• cGMP degraded by phosphodiesterases (PDE)
• Regained smooth muscle tone and
detumescence
29. International Society of Impotence
Research Classification of ED
• ORGANIC
• i)vasculogenic – arteriogenic,cavernosal,mixed
• ii)neurogenic
• iii)anatomic
• iv)endocrinologic
30. • PSYCHOGENIC
• i)generalized (generalized unresponsiveness –
primary lack of sexual arousability or aging
related decline in sexual arousability OR
generalized inhibition – chronic disorder of
sexual intimacy)
31. • Situational
• i)partner related (lack of arousability in
specific relationship OR owing to sexual object
preference OR high central inhibition owing to
partner conflict/threat)
32. • ii)performance related (associated with other
sexual dysfunction such as rapid ejaculation
OR situational performance anxiety such as
fear of failure
34. Broad classification – MIXED type is
commonest
PSYCHOGENIC ORGANIC
Sudden onset Gradual onset
Complete immediate loss Incremental progression
Situational dysfunction Global dysfunction
Waking erections present Waking erections poor/absent
35. Psychogenic
• Masters and Johnson (1965) : 90% of
impotent men - psychogenic
• ED is a MIXED CONDITION – may be
predominantly functional or physical
36. Neurogenic
• 10-19% of ED
• Any disease affecting brain, spinal cord, and
cavernous or pudendal nerves can induce
dysfunction
• Stroke, Parkinson disease, encephalitis,
temporal lobe epilepsy, tumors, dementias,
Alzheimer disease, multiple system atrophy,
trauma
37. • Spinal diseases
• Surgery of cancer of rectum, bladder and
prostate
• Pelvic fracture, posterior urethral injury
• Diabetics – impaired neorogenic and
endothelium dependent relaxation
• Decreased penile tactile sensitivity with age –
sensory evaluation is mandatory in ALL
patients
38. Endocrinologic
• Testosterone enhances sexual interest,
increases frequency of sexual acts and
increases frequency of nocturnal erections
• Hypogonadism
• Hyperprolactinemia
• Hyper or hypothyroidism
39. Arteriogenic
• Atherosclerotic or traumatic occlusive disease
of hypogastric-cavernous-helicine arterial tree
• Increasing time to maximal erection
• Decreasing rigidity of the erect penis
• Hypertension, hyperlipidemia, cigarette
smoking, DM, blunt perineal or pelvic trauma,
pelvic irradiation
40. • Long-distance cycling : perineal compression -
vascular, endothelial and neurogenic
dysfunction
• Cardiovascular disease and ED
• Hyperlipidemia and ED
• Obesity and ED
• Hypertension and ED
44. Other causes
• Aging ( progressive decline in sexual function,
decreased frequency & duration of nocturnal
erection, loss of penile tactile sensitivity,
vascular endothelial dysfunction)
45. • Diabetes mellitus : 3 times higher prevalence
of ED, occurs earlier and increases with
disease duration. >75% prevalence of penile
arterial insufficiency
46. • Metabolic syndrome (glucose intolerance,
insulin tolerance,obesity,dyslipidemia,
hypertension)
• 26.7% prevalence of ED
• CKD, angina, MI, HIV infection, severe
pulmonary disease
47. Primary erectile dysfunction
• Lifelong inability to initiate/maintain erections
beginning with the first sexual encounter.
• Most cases due to psychological factors
• Maldevelopment of penis or blood & nerve
supply.
48. Public health significance
• Worldwide prevalence: closer to 20% of males
• 1-10% younger than 40
• 15% for 40-49 years
• 30% for 50-59 years
• 40% for 60-69 years
• 50-100% men in their 70s and 80s
51. Predictors for ED development
• Increasing age
• Lower education
• DM
• CV disease
• HTN
• Cigarette smoking and passive exposure to it
• Overweight condition
52. ED and subsequent morbidity &
mortality
• Men with ED 45% more likely to experience a
CV event in next 5 years (Thompson,2005)
• 80% higher risk of CAD at 10 years
(Inman,2009)
• ED is a clinical barometer of overall male
health status
56. • International Index of Erectile Function - IIEF
• Brief Male Sexual Function Inventory – BMSFI
• Erectile Dysfunction Inventory of Treatment
Satisfaction (EDITS)
57. IIEF – most widely used
• Five domains : erectile function, orgasmic
function, sexual desire, intercourse
satisfaction, and overall satisfaction
• Five categories of severity : severe (5-7),
moderate (8-11), mild to moderate(12-16),
mild(17-21) and no ED(22-25)
58.
59. Routine lab tests for men with sexual
problems
• Serum chemistries
• Fasting glucose
• CBC
• Lipid profile
• Serum total testosterone
60. Specialized evaluation for organic ED
• ED treatment planning does not routinely require
extensive evaluation
• Diagnostic precision applied by specialists
• Setting of complex clinical presentations
• Arterial impairment OR veno-occlusive
dysfunction
66. Duplex ultrasonography
• Second-line evaluation of penile blood flow
• Most reliable and least invasive
• Follows CIS or pharmacostimulation
• High resolution USG and color-pulsed Doppler
• Flow velocities in dorsal penile and cavernous
arteries
67. • Flow velocities at baseline and every 5minutes
upto 20 minutes
• Diameter of cavernous arteries
• Erection quality
• Standard pattern of doppler waveforms
68. • Filling phase : waveform increases, high
forward flow in systole and diastole
• As intracavernous pressure increases, diastolic
velocity decreases
• Full erection : systolic waveforms sharply peak
• Maximum rigidity : diastolic flow zero
69. • Peak systolic velocity (PSV) less than 25cm/s
after vasodilator inj suggests cavernous
arterial insufficiency
• Cavernous artery diameter normally more
than 0.7mm
• Resistive Index greater than 0.9 normal and
less than 0.75 consistent with veno-occlusive
dysfunction
70. Dynamic Infusion Cavernosometry &
Cavernosography
• Third-line evaluation of vascular integrity,
generally before corrective penile vascular
surgery
• Suspected site-specific vasculogenic leak
• Pelvic/perineal trauma
• Lifelong (primary) ED
71. • Heparinized saline infusion and cavernous
pressure monitoring after vasodilator injection
• Evaluates penile venous outflow system
• Failure to increase intracavernous pressure to
level of mean SBP or
• Rapid drop of intracavernous pressure after
cessation of saline infusion
72. • Cavernosography follows to show the venous
leakage
• Normally, opacification of corpora cavernosa
• No visualisation of venous structures or
corpus spongiosum
• Leakage : glans, spongiosum,superficial dorsal
veins, cavernous veins, crural veins
73. Penile Angiography
• Third-line
• Young patients
• Traumatic arterial disruption
• Penile compression injury
• Considered for revascularization surgery
• Selective cannulation of internal pudendal
artery
80. Criteria for normal NPTR
• 4 to 5 episodes of nocturnal erections /night
• Mean duration > 30 minutes
• Increase in circumference > 3 cm at base and >
2cm at the tip
• Maximal rigidity > 70% at both base and tip
81. • Objective evaluation of somatic basis of
erectile ability
• Devoid of psychological interference
• Does not indicate cause & severity of ED
• Poorly reproducible results
• When cause of ED is obscure and noninvasive
testing is desirable
82. Audiovisual & Vibratory Stimulation
• Time and cost-effective alternative to NPTR
• More physiologic
• With or without pharmacologic or vascular
testing
83. Psychological evaluation
• Must not underestimate psychological and
interpersonal factors
• ED associated with anxiety, depression, low
self-esteem, negative outlook on life,
emotional stress, fear of failure, performace
anxiety, loss of attraction for the sexual
partner, adjustment to chronic illness or
surgery and relationship conflicts
86. Serum testosterone
• Low testosterone in 2% - 33% men with ED
• Aging - primary cause of declining androgens
(ADAM, PADAM, SLOH, andropause or
hypoandrogenism)
87. • Free (0.55 to 3%)
• SHBG bound (30%)
• Albumin and other serum protein bound
(67%)
• Bioavailable testosterone = free + albumin-
bound
88. • Commercial assays for free testosterone
inconsistent
• Best indicator of androgen status is
CALCULATED bioavailable testosterone
• Screening purposes – total testosterone
• Total : 280-1000 ng/dL
• 7am to 11am
• Low normal or low - repeat
89. Serum gonadotropins
• Before second total testosterone - LH, FSH
and prolactin
• Localizes the source of hypogonadism
• Primary hypogonadism (testicular failure): low
testosterone, increased LH & FSH
• Secondary hypogonadism (central cause) :
normal or low LH & FSH with low testosterone
90. Serum prolactin
• Hyperprolactinemia causes hypogonadism by
suppression of GnRH
• Also interferes with conversion of testosterone to
DHT
• Suspected when low testosterone with low or
inappropriately normal LH
• Hyperprolactinemaia : antipsychotics, TCAs,
opiates, prolactinoma, HYPOthyroidism,
hypothalamic lesions, renal insufficiency,
cirrhosis, chest wall lesions
91. MRI pituitary indications
• Severe central ( hypogonadotropic)
hypogonadism : testosterone < 150ng/dL
• Suspicion of pituitary disease
(panhypopituitarism, persistent
hyperprolactinemia, tumor mass effect
symptoms)
92. Serum thyroid function tests
• HYPERthyroidism causes ED by increasing
aromatization of testosterone into estrogen or
by increasing adrenergic tone
• HYPOthyroidism : low testosterone secretion,
elevated prolactin contribute to ED
94. Lifestyle modification improves
erectile function
• Discontinuation of smoking
• Increasing exercise and weight control
• Mediterranean diets and calorie restriction
• No-nose saddle for occupational bicycle riders
95. Medication change
• Thiazide diuretics and beta blockers changed
to CCBs, ARBs and ACEIs
• SSRI drug holidays, substitution and PDE5
inhibitors
99. Hyperprolactinemia
• Drugs such as estrogens, morphine, sedatives
and neuroleptics discontinued
• Prolactinomas treated by Bromocriptine
(lowers prolactin and restores testosterone)
• Surgical ablation if visual effects appear
101. Pharmacologic therapies of ED
• Oral therapy
• Intracavernosal injection
• Intraurethral suppositories
• Topical / transdermal pharmacotherapy
102. PDE5 inhibitors
• Sildenafil citrate (Viagra, Pfizer) in 1998
• Vardenafil hydrochloride (Levitra, Bayer) in
2003
• Tadalafil (Cialis, Lilly) in 2003
• Avanafil (Stendra, Vivus) in 2012
103. • Block PDE5, which degrades cGMP, the
downstream effector of nitric oxide
• NO causes corporal smooth muscle relaxation
required for erection
• These medications augment but do not
induce the erectile response
• Sexual stimulation is required for NO release
from penile nerve endings and vascular
endothelium
104. • Sildenafil and vardenafil – cross-react with
PDE6 in retina – visual distrubances
• Tadalafil : longer half-life, longer therapeutic
window and more convenience
• All have equivalent efficacy and tolerability
• Successful intercourse rates of 70%
105. property Sildenafil vardenafil tadalafil avanafil
Tmax(hr) 0.8 0.7-0.9 2 0.3-0.5
Onset of action
(min)
15-60 15-60 15-120 15-60
Half-life (hr) 3-5 4-5 17.5 3-5
Bioavailability 40% 15% Not tested 30%
Fatty food Reduced
absorption
Reduced
absorption
No effect Reduced
absorption
Dosage 25,50,100mg 5,10,20mg 5,10,20mg 50,100,200mg
Headache,dyspe
psia,facial
flushing
yes yes yes Yes
Backache,myalgi
a
rare rare yes Rare
Blurred/blue
vision
yes rare rare No
Precaution with
antiarrythmics
no yes no No
C/I with nitrates yes yes yes yes
106. • Instructed to take on-demand 30-60 minutes
before intended sexual activity
• Daily dosing regimen approved for tadalafil
107. Optimization of effect
• Applying sexual stimulation properly
• Reducing food intake
• Escalating drug dosing as needed
• Correcting health conditions (glycemic control,
hyperlipidemic control, androgen
replacement)
108. Warnings & drug interactions
• Severe CV diseases & left ventricular outflow
obstruction (AS)
• Severely impaired autonomic BP control
• MI, stroke, arrhythmias within last 6 months
• NYHA class II or greater heart failure
• CAD causing unstable angina
• Resting hypotension (<90/50) or
hypertension(>170/100)
• Known hereditary retinal disorders e.g. RP
• Severe hepatic impairment or ESRD requiring dialysise
109. Precautions
• Cardiovascular risk assessment and
stabilization before PDE5 inhibitor therapy
• Nitrate use in any form within past 2 weeks -
absolute contraindication – if angina develops,
seek emergency care instead of taking nitrate
• Refractory hypotension
110. Side effects
• Headache (7-16%)
• Dyspepsia(4-10%)
• Flushing(4-10%)
• Myalgia/back pain(0-3%)
• Nasal congestion(3-4%)
• Visual disturbances ( photophobia, blurring of
vision, blue vision)(0-3%)
• NAION (nonarteritic anterior optic neuropathy)-
sudden blindness – case reports in HTN,DM and
dyslipidemic patients
111. Intracavernosal injection
Trade name drug dosage Intercourse efficacy
Caverject alprostadil 5-40mcg/ml 70%
Viradal/Edex alprostadil 5-40mcg/ml 70%
Bimix alprostadil+phentol
amine
20mcg/ml+0.5mg/
ml
90%
Bimix Androskat Papaverine+phentol
amine
30mg/ml+0.5mg/m
l
90%
Trimix Alprostadil+papveri
ne+phentolamine
10mcg/ml+30mg/m
l+1mg/ml
90%
Invicorp VIP+phentolamine 80%
112. Contraindications of ICI
• Psychological instability
• History/risk of priapism
• Severe coagulopathy
• Unstable CV disease
• Reduced manual dexterity
• Use of MAO inhibitors
113. Intraurethral suppositories
• Medication absorbed into spongiosum from
urethra, later passes into cavernosa
• Synthetic PGE1 (MUSE – Medicated Urethral
system for Erection)
• Suppository dispenses semisolid pellet of
alprostadil (125,250,500,1000 mcg dosages)
into distal urethra
114.
115. • Combined with adjustable penile constriction
band (ACTIS)
• Transurethral bimix (ALIBRA)
alprostadil+prazosin
• PDE5I>ICI>suppository
• Main indications : nonresponsive to PDE5I due
to RP,RC,trauma ; combination with PDE5I:
soft (cold) glans syndrome after penile
prosthesis
116. • Side effects; urogenital pain (one third),
minor urethral bleeding (5%), hypotension
(3%), dizziness(4%), priapism (0.4%)
• 5.8% incidence of vaginal burning or itching in
the partner
• Contraindications : known hypersensitivity to
alprostadil, abnormal penile anatomy,
conditions that increase risk of priapism
118. Medical device
• Vacuum erection device for those who decline
or do not respond to oral/local vasoactive
medications
• Suction cylinder, vacuum-generating source
and elastic constriction ring
• efficacy 90%, satisfaction 30-70%
• Penile pain, numbness, difficult ejaculation,
petechiae, ecchymosis, skin necrosis, Fournier
gangrene
122. Arterial revascularization
• Inferior epigastric to cavernosum directly or
dorsal artery (revascularization) or deep dorsal
vein (arterialization) or deep dorsal vein with
venous ligation ( arterialization with venous
reconstruction)
123. • Careful patient selection
• Penile arteriography
• Age less than 55 years
• Nonsmoker
• Nondiabetic
• Absence of venous leakage
• Radiographic confirmation of internal
pudendal artery stenosis
124. Venous reconstruction
• To prevent pathologic blood egress from penis
(venoocclusive ED)
• Ligating or embolizing penile veins (superficial
dorsal vein, crural vein)
• Surgically compressing penile crura (crural
plication/ligation, pericavernoplasty)
• Currently considered investigational
125. Alternative therapies
• Zotarolimus-eluting peripheral stents in
atherosclerotic lesions of internal pudendal
artery
• Low-intensity extracorporeal shockwave
therapy applied to the penis
127. Penile prosthesis surgery
• NA Borgoraz (1936) : rib cartilage to fashion a
rigid implant
• Dr Brantley Scott (1973) : 3 piece inflatable
device
• Dr. Hernan Carrion , Dr. Michael Small (1974) :
semi-rigid prostheses
128. Penile prosthesis implantation –
indications
• Failure/rejection of more conservative therapies
• Peyronie disease in which ED coexists with penile
deformity
• Irreversible organic etiology of ED
• Penile fibrosis
• Post priapism ED unresponsive to other therapies
• Phalloplasty after radical penile surgery for
cancer/gender change surgery
• Psychological impotence after failure of all other
treatment
133. Advantages of semirigid devices
• Relatively inexpensive
• Easy to implant
• Relatively low mechanical failure rate
• Easy to use
134. Drawbacks of semirigid devices
• Simulate a constant erection (do not permit
flaccidity)
• May be difficult to conceal
• Do not increase penile girth
• Quality of erection decreases over time
• Distal tip of device more likely to
atrophy/migrate toward distal glans and to
erode through meatus
138. Inflatable prostheses - advantages
• Permit girth as well as length expansion
• Penile flaccidity when not in use
• Act and feel more like a natural erection :
three-piece device is more rigid when inflated,
more flaccid when deflated
139. Potential contraindications
• Situational ED
• ED resulting from relationship conflict
• Potentially reversible ED
• Inability to follow instructions
• Hygiene issues and skin cleanliness
• Noncompliance with concurrent medications
• Spinal cord injury
• Uncontrolled DM