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Dept of Urology
Govt Royapettah Hospital and Kilpauk Medical College
Chennai
1
Moderators:
Professors:
 Prof. Dr. G. Sivasankar, M.S., M.Ch.,
 Prof. Dr. A. Senthilvel, M.S., M.Ch.,
Asst Professors:
 Dr. J. Sivabalan, M.S., M.Ch.,
 Dr. R. Bhargavi, M.S., M.Ch.,
 Dr. S. Raju, M.S., M.Ch.,
 Dr. K. Muthurathinam, M.S., M.Ch.,
 Dr. D. Tamilselvan, M.S., M.Ch.,
 Dr. K. Senthilkumar, M.S., M.Ch.
Dept of Urology,GRH and KMC, Chennai. 2
“Man survives earthquakes, experiences the horrors of
illness, and all of the tortures of the soul. But the most
tormenting tragedy of all time is, and will be, the
tragedy of the bedroom.”
Tolstoy
3
Dept of Urology,GRH and KMC, Chennai.
What is ED?
ED is the inability to achieve and maintain erection
adequate for intercourse to the mutual satisfaction of
the man and his partner.
Jardin et al, 2000 .
4
Dept of Urology,GRH and KMC, Chennai.
RISK FACTORS
 Heart disease
 Hypertension
 Diabetes
 Chronic renal failure
 Hepatic failure
 Multiple Sclerosis
 Severe depression
 Other (vascular disease, low HDL, high
cholesterol)
Benet et al. Urol Clinic North Am. 1995; 151:54-61
5
Dept of Urology,GRH and KMC, Chennai.
CLASSIFICATION OF ED
6
Dept of Urology,GRH and KMC, Chennai.
PSYCHOGENIC
 Persistent inability to achieve or maintain erection
satisfactory for sexual performance due predominantly or
exclusively to psychological or interpersonal factors.
 Anxiety
 Self-reported depressive symptoms
 Low degrees of self-esteem
 Negative outlook on life
 Self-reported emotional stress
 H/O sexual coercion.
7
Dept of Urology,GRH and KMC, Chennai.
NEUROGENIC
 10% to 19% of ED is neurogenic , prevalence is much high
if iatrogenic & mixed ED included.
 Parkinson's disease
 Stroke
 Encephalitis
 Temporal lobe epilepsy
 Tumors
 Dementias
 Alzheimer's disease
 Shy-Drager syndrome
 Trauma.
8
Dept of Urology,GRH and KMC, Chennai.
 Iatrogenic impotence :
 Radical prostatectomy 43% to 100%
 Perineal prostatectomy for benign 29%
 APR - 15% to 100%
 External sphincterotomy 2% to 49% .
 Nerve-sparing radical prostatectomy reduced the
incidence 100% to 30%-50%
 Pelvic fracture, ED result of cavernous n’ injury or
vascular insufficiency or both .
9
Dept of Urology,GRH and KMC, Chennai.
NEURO ANATOMY
10
Dept of Urology,GRH and KMC, Chennai.
ENDOCRINOLOGIC
 Testosterone : enhances sexual interest, ↑ frequency of sexual acts, and
↑ frequency of nocturnal erections.
 Men receiving long-term androgen ablation therapy for prostate cancer
reported poor libidoand ED .
 Hyperprolactinemia- pituitaryadenoma or drugs, results in both
reproductiveand sexual dysfunction.
 ED associated with both hyper- and hypothyroidism.
 DM, causes ED through its vascular, neurologic, endothelial, and
psychogenic complications rather than hormone def.
11
Dept of Urology,GRH and KMC, Chennai.
ARTERIOGENIC
 Atherosclerotic or traumatic arterial occlusive disease of hypogastric-
cavernous-helicine arterial tree .
 Risk factors include HT, hyperlipidemia, cigarette smoking, DM,
blunt perineal or pelvic trauma, and pelvic irradiation.
12
Dept of Urology,GRH and KMC, Chennai.
CAVERNOUS (VENOGENIC)
 Tunical changes- degenerative changes (Peyronie's disease, old age, and
DM) or traumatic injury to T.A (penile # )
 Fibroelasticstructural alterations,
 Insufficient trabecular smooth muscle relaxation,
 Venous shunts. (priapism)
13
Dept of Urology,GRH and KMC, Chennai.
14
Dept of Urology,GRH and KMC, Chennai.
MEDICAL HISTORY
The goals of medical history-taking are
(1) to evaluate the potential role of underlying medical
conditions (e.g., atherosclerosis, diabetes) and
comorbidities (e.g., depression)
(2) to differentiate between potential organic and
psychogenic causes
(3) to assess the potential role of medication
(4) Past H/O: Prostatectomy, APR, Pelvic trauma
15
Dept of Urology,GRH and KMC, Chennai.
CHARACTERISTIC ORGANIC PSYCHOGENIC
ONSET GRADUAL ACUTE
CIRCUMSTANCES GLOBAL SITUATIONAL
COURSE CONSTANT VARYING
NON COITAL ERECTION POOR RIGID
PSYCHOSEXUAL
PROBLEM
SECONDARY LONG HISTORY
PARTNER PROBLEM SECONDARY AT ONSET
ANXIETY AND FEAR SECONDARY PRIMARY
16
Dept of Urology,GRH and KMC, Chennai.
A Practical Evaluation of Men with ED
Laboratory Tests
 Fasting glucose, RFT, lipids & testosterone.
 Optional : indicated by history & P/E .( Prolactin, LH, FSH,
Thyroid function.)
 PSA measured >50 yrs age ,F/H ca prostate, if hormonal
replacement planned.
17
Dept of Urology,GRH and KMC, Chennai.
A Practical Evaluation of Men with ED
Physical Examination
 Blood pressure
 Examine penis (R/O Peyronie’s disease)
 Determine size and consistency of testes
 Digital rectal exam
 Focused vascular exam/peripheral pulses
 Focused neurologic exam
18
Dept of Urology,GRH and KMC, Chennai.
Why Use Patient Questionnaires?
 Facilitate dialogue and diagnosis
 Evaluate treatment changes
 Drawback is reliance on self assessment.
 Examples of self-administered, standardized
questionnaires
 Sexual Health Inventory for Men (SHIM)1
 International Index of Erectile
Function (IIEF)2
1. Rosen RC, et al. Int J Impot Res. 1999;11:319-326. 2. Rosen RC, et al. Urology. 1997;49:822-830. 19
Dept of Urology,GRH and KMC, Chennai.
20
Dept of Urology,GRH and KMC, Chennai.
SHIM Score Characterizes
ED Severity
 22-25 Normal erectile function
 17-21 Mild ED
 12-16 Mild to moderate ED
 8-11 Moderate ED
 7 Severe ED
*Total score ranges from 5 to 25 and is based on FIRST 5 questions.
Each rated on a Likert scale of 1 = least functional to 5 = most functional.
Rosen RC, et al. Int J Impot Res. 1999;11:319-326. 21
Dept of Urology,GRH and KMC, Chennai.
EVALUATION OF COMPLEX PATIENT
 Indications for specialized evaluation
 Failure of initial treatment
 Peyronie's disease
 Primary ED
 H/O pelvic/perineal trauma
 Vascular or neurosurgical intervention
 Complicated endocrinopathy
 Complicated psychiatric disorder
 Complex relationship problems
 Medicolegal concerns .
22
Dept of Urology,GRH and KMC, Chennai.
SEXUAL HISTORY
 Interview conducted face-to-face.
 Ensure pt trust, comfort, and openness
 The interviewershould determine whether patient has
cognitive understandingof genital function and penilerigidity.
 Very useful in evaluatingand treating men with deep-seated
psychological problems.
23
Dept of Urology,GRH and KMC, Chennai.
PSYCHOLOGIC
 Diagnostic interview mainstay of evaluation.
 Current sexual problem and its history
 Deeper causes of sexual dysfunction
 Relationship &
 Psychiatric symptoms.
 Immediate causes –
 fear of failure
 performance anxiety
 insufficient sexual stimulation
 loss of attraction
 relationship conflicts.
 “Deeper” causes of psychogenic ED- unresolved parental
attachments, sexual identity, sexual trauma, and cultural-
religious taboos .
24
Dept of Urology,GRH and KMC, Chennai.
EVALUATION
25
Dept of Urology,GRH and KMC, Chennai.
VASCULAR EVALUATION
First-Line Evaluation of Penile Blood Flow
Combined Intracavernous Injection and Stimulation:
 A CIS test consists of intracavernous injection of a vasodilatoror
a combination of two or three vasodilators, genitalor audiovisual
sexual stimulation, and assessmentof the erection by an
observer.
 This screening test is the most commonly performeddiagnostic
procedure for ED.
 It allows the clinician to bypassneurologic and hormonal
influencesand to evaluatethe vascularstatus of the penis
directly and objectively
26
Dept of Urology,GRH and KMC, Chennai.
 alprostadil alone (Caverjector Edex, 10 to 20 μg), a combination
of papaverineand phentolamine(Bimix, 0.3 mL), or a mixture of
all three of these agents (Trimix, 0.3 mL).
 The technique involves injecting the medication through a 5/8-
inch needle (27 to 29 gauge) into the corpus cavernosum.
 The needlesite is compressed manually for 5 minutes to prevent
hematoma formation
 should not leave the office until the penis becomes flaccid
spontaneouslyor by injection of a diluted phenylephrine
solution (500 μg/mL, given 1 mL every 3 to 5 minutes until
detumescence).
27
Dept of Urology,GRH and KMC, Chennai.
Second-Line Evaluation of Penile Blood Flow
Duplex Ultrasonography (Gray Scale or Color-Coded)
 Penile blood flow study, which consists of CIS and blood flow
measurement by duplex ultrasound, is the most reliableand
least invasiveevidence-basedassessmentof ED.
 Duplex ultrasound consists of high-resolution(7 to 10 MHz)
real-time ultrasonographyand color pulsed Doppler
 Visualize the dorsal and cavernousarteries selectivelyand to
perform dynamicblood flow analysis
 best tool availablefor the diagnosisof high-flowpriapismand
localizationof a ruptured artery
28
Dept of Urology,GRH and KMC, Chennai.
Peak Systolic Velocity (PSV) and Arterial Dilation
 In the Mayo Clinic series, PSV less than 25 cm/s had a sensitivity
of 100% and a specificity of 95% in patientswith abnormal
pudendalarteriography ( Lewis and King, 1994 ).
 unilateral cavernousarterial insufficiency results in asymmetry
of PSV greater than 10 cm/s.
29
Dept of Urology,GRH and KMC, Chennai.
Duplex Ultrasound Evaluation in Veno-
occlusive Dysfunction
 High systolic flow (>25 cm/s PSV) and persistent end-
diastolic flow velocity (EDV) (>5 cm/s) accompanied
by quick detumescence after self-stimulation, the
patient is considered to have venogenic impotence.
 Venous leakage on cavernosometry was predicted with
a sensitivity of 90% and specificity of 56% when EDV
was greater than 5 cm/s ( Quam et al, 1989 ; Lewis and
King, 1994 ).
30
Dept of Urology,GRH and KMC, Chennai.
Third-Line Evaluation of Penile Blood Flow
Cavernous Arterial Occlusion Pressure (CASOP)
 It involvesintracavernousinjectionof a vasodilator (usually Trimix
solution) followed by infusion of saline into the corpora cavernosaat
a rate sufficient to raise the intracavernouspressure above the
systolic blood pressure.
 A pencil Doppler transduceris then applied to the side of the penile
base.
 The saline infusion is stopped, and the intracavernouspressure is
allowed to fall.
31
Dept of Urology,GRH and KMC, Chennai.
 The pressure at which the cavernousarterial flow becomes
detectable is defined as the cavernousartery systolic occlusion
pressure (CASOP).
 A gradient betweenthe cavernousand the brachialartery
pressures of less than 35 mm Hg and an equal pressure between
the right and the left cavernous arteries has beendefined as
normal
32
Dept of Urology,GRH and KMC, Chennai.
CAVERNOSAL ARTERY FLOW
BRACHIAL SYSTOLIC AND
DIASTOLIC BP
(CASOP)-108mmHg
INTRACAVERNOSAL HEPARINIZED
SALINE FLOW
33
Dept of Urology,GRH and KMC, Chennai.
RESISTIVE INDEX
 In 1974, Planiol and Pourcelot proposed a resistive index (RI) to
describe vascular resistance from the Dopplerspectrum.
 RI = PSV - EDV/PSV.
 As penile pressure equals or exceedsdiastolic pressure, diastolic flow
in the corpora will approach 0 and the value for RI approaches 1.
 During tumescenceand until full rigidity, diastolic flow is antegrade
(+); the value for RI remains less than 1.0.
 Naroda and associates (1994) found that an RI greaterthan 0.9 was
associated with normal resultsduring DICC in 90% of theirseries and
an RI less than 0.75 was associated withvenous leakage in 95%.
34
Dept of Urology,GRH and KMC, Chennai.
PHARMACOLOGIC ARTERIOGRAPHY
 Best indication is young pt with ED sec to traumatic a’ disruptionor
perineal compression injury.
 Intracavernous inj of vasodil agent followed by selective cannulation of
internal pudendal a’ and inj of contrast.
 Anatomy and radiographic appearance of internal pudendal, and
penile arteries evaluated.
patent commonpenile, dorsal, and cavernous
arteries
nonvisualizationof commonpenile artery
and its branches
35
Dept of Urology,GRH and KMC, Chennai.
DICC
 Dynamic infusion cavernosometry and cavernosography (DICC) is invasive
 Flow rate required to maintain erection at an intracavernous pressure of
more than 100 mm Hg is reported to be less than 3 to 5 mL/min
 Pressure decrease in 30 seconds from 150 mm Hg is less than 45 mm Hg.
 Cavernosography is performed after cavernosometry and should reveal
opacification of the corpora cavernosa but minimal or no visualization of
venous structures or corpus spongiosum
 For young men who might be candidates for penile vascular operations,
specifically those with a history of pelvic trauma or life-long ED (primary
ED).
36
Dept of Urology,GRH and KMC, Chennai.
Pharmacologic cavernosometry
involvessimultaneoussaline infusion and intracavernous pressure
monitoring after intracavernous injectionof a strong vasodilating
solution
 Veno-occlusivedysfunctionis indicated by eitherthe inability to
increase intracavernouspressure to the levelof the mean systolic
blood pressure ora rapid drop of intracavernouspressure after
cessation of infusion
Pharmacologic cavernosography involves
the infusion of radiographic contrast solution into the corpora
cavernosum.
 Leakage sites to the glans, corpus spongiosum, superficial dorsal
veins,and cavernousand crural veinscan then be detected.In the
majority of patients, more than one site is visualized
37
Dept of Urology,GRH and KMC, Chennai.
PHARMACOLOGIC CAVERNOSOGRAPHY
After penile # communication between
CC & CS seen 27-year-old man with primary ED, venous leakage
from crura
38
Dept of Urology,GRH and KMC, Chennai.
Penile Brachial Pressure Index
 The penile brachial pressure index (PBI) represents
the penile systolic blood pressure divided by the
brachial systolic blood pressure.
 The technique involves applying a small pediatric
blood pressure cuff to the base of the flaccid penis
and measuring the systolic blood pressure with a
continuous-wave Doppler probe.
 A PBI of 0.7 or less has been used to indicate
arteriogenic impotence
39
Dept of Urology,GRH and KMC, Chennai.
INVESTIGATIONAL….
 Penile Plethysmography (Penile Pulse Volume
Recording)
 Infrared Spectrophotometry.
 Radioisotopic Penography.
 Magnetic Resonance Angiography (MRA)
 Cavernous Smooth Muscle Content
40
Dept of Urology,GRH and KMC, Chennai.
PSYCHOPHYSIOLOGIC
Nocturnal Penile Tumescence
 Nocturnalpenile tumescence (NPT) monitoringwas first described by
Halverson(1940)
 Karacan and colleagues(1966)were the first to demonstratethat 80% of
NPT occursduringrapid eye movement (REM)sleep
NPT has been measured by a numberof methods:
 stamp test ( Barryet al, 1980 )
 snap gauges ( Diedrichet al, 1992 )
 sleep laboratorynocturnal peniletumescence and rigidity(NPTR)
 RigiScan(Endocare, Inc., Irvine, CA)
 most recently, NPT electrobioimpedance(NEVA, American Medical
Systems, Inc., Minnetonka, MN).
41
Dept of Urology,GRH and KMC, Chennai.
NPT
In its classic form, NPT consists of nocturnal
monitoring devices that measure the
 number of episodes
 tumescence (circumference change by strain gauges)
 maximal penile rigidity
 duration of nocturnal erections
42
Dept of Urology,GRH and KMC, Chennai.
INDICATIONS
 Heaton and Morales (1997) have suggested indications for NPTR
as follows:
(1) suspected sleep disorder
(2) obscure cause of ED
(3) nonresponse to therapy
(4) plannedsurgical treatment
(5) legallysensitivecase
(6) measurementof drug effects in placebo-controlleddrug trials
(7) suspected psychogeniccause
43
Dept of Urology,GRH and KMC, Chennai.
 The patient is awakenedduring maximal tumescence, and the
erection is photographed and axial rigidity measured with a
device applied to the tip of the penis.
 A buckling resistance of 500 g is considered the minimum for
vaginalpenetration; 1.5 kg is considered complete rigidity
according to the original Karacan (1970) criteria.
 Because NPT occurs during REM sleep, tumescence monitoring
repeated over two to three nights to overcome the so-called first-
nighteffect.
44
Dept of Urology,GRH and KMC, Chennai.
RIGISCAN
 In 1985, the RigiScan was introduced
 first device to provide automated, portable NPTR
recording.
 The device combines the monitoring of radial rigidity,
tumescence, number, and duration of erectile events
 It consists of a recording unit that can collect data for
three separate nights for a maximum of 10 hours each
night.
45
Dept of Urology,GRH and KMC, Chennai.
RIGISCAN
 The mechanicsconsist of two
loops: one is placed at the
base of the penisand the
other at the coronal sulcus.
 By constricting the loops, the
device records penile
tumescence (circumference)
and radial rigidity at the
penile base and tip
46
Dept of Urology,GRH and KMC, Chennai.
NPTR CRITERIA
Cilurzo and colleagues (1992) recommend the following as normal
NPTR criteria:
 four to five erectile episodes per night
 mean duration longerthan 30 minutes
 an increase in circumference of more than 3 cm at the base and
more than 2 cm at the tip
 maximal rigidity above 70% at both base and tip
47
Dept of Urology,GRH and KMC, Chennai.
TWO EPISODES OF WELL-SUSTAINED,
COMPLETELY RIGID NOCTURNAL
ERECTIONS
TWO EPISODES OF POORLY
SUSTAINED, POORLY RIGID
NOCTURNAL ERECTIONS
RigiScan
48
Dept of Urology,GRH and KMC, Chennai.
ADVANTAGES:
 relativefreedom from psychologic influencesand its abilityto detect
sleep-related abnormalities.
 Thedocumented presence of a full erection indicatesthat the
neurovascular axis is functionally intact and that the cause of the ED
is most likelypsychogenic.
DISADVANTAGES:
 costly, because it is ideallydonewith a RigiScanin a speciallyequipped
sleep center.
 Not recommendedas a routinepart of ED evaluation
49
Dept of Urology,GRH and KMC, Chennai.
NEVA
 Uses electrobioimpedance to assess volumetricchanges in penis
during nocturnal erections.
 Record number, duration of erectile episodesand penile length and
blood volume changes at night .
 Small recording device is attached to pt's thigh, and three small
electrode pads applied to hip , penile base and glans.
 An undetectable alternating current is sent from glans electrode to
hip ground. The penile base electrode measures impedance and
changes in penile length.
 Relationship to rigidity and volume change needs to be established.
50
Dept of Urology,GRH and KMC, Chennai.
Neurologic Evaluation
Somatic Nervous System
 Biothesiometry
This test is designedto measure the sensory perception threshold
to various amplitudesof vibratory stimulation produced by a
hand-heldelectromagneticdevice (biothesiometer) placed on
the pulp of the index fingers, both sides of the penileshaft, and
the glanspenis.
51
Dept of Urology,GRH and KMC, Chennai.
Sacral Evoked Response—Bulbocavernosus
Reflex Latency
 This test is performed by placing two stimulating ring
electrodes around the penis, one near the corona and the
other 3 cm proximal.
 Concentric needle electrodes are placed in the right and
left bulbocavernous muscles to record the response
 abnormal latency time, defined as a value more than 3
standard deviations above the mean (30 to 40 ms), denotes
a high probability of neuropathology
52
Dept of Urology,GRH and KMC, Chennai.
Dorsal Nerve Conduction Velocity
 averageconduction velocity of 23.5 m/s with a range of 21.4 to 29.1
m/s in normal subjects.
Genitocerebral Evoked Potential
 This test involveselectrical stimulation of the dorsal nerve of the
penisas described for the BCR latency test.
 study records the evoked potential waveformsoverlyingthe
sacral spinal cord and cerebral cortex
53
Dept of Urology,GRH and KMC, Chennai.
Hormonal Evaluation
 Historically, hypogonadismas a cause of ED was thought to be
rare
 recent data support a significantincrease of hypogonadismwith
age.
 The interrelationshipsamong hypogonadism,depression,and
ED are now recognized
 In male sexual dysfunction most endocrinopathiescenter
around testosterone
54
Dept of Urology,GRH and KMC, Chennai.
 morning testosterone values below 350 ng/dL in a young man
with chronicallyelevatedgonadotropins -- hypogonadism.
 blood should be drawn between8:00 AM and 11:00 AM. For
screening, a total testosterone usually adequate.
 If the testosterone level is belowor at the low limit of normal, it
should be confirmed with a second determinationtogetherwith
assessmentof luteinizing hormone (LH) and prolactin.
 One or more of the following serum laboratoryvalues may be
required to diagnose hormone deficiencies:
(1) total/free/bioavailabletestosterone; (2) SHBG; (3) LH; and (4)
follicle-stimulatinghormone (FSH).
55
Dept of Urology,GRH and KMC, Chennai.
56
Dept of Urology,GRH and KMC, Chennai.
Lifestyle Change
 Obesitywas associated with ED (P=.006), with baselineobesity
predicting a higherrisk regardlessof follow-up weight loss.
 Physical activity was also associated with ED (P= .01), with the
highestrisk among men who remained sedentary
 The beneficialeffect of using a statin drug to lowercholesterol in
men in whom the only risk factor for ED is hypercholesterolemia(
Saltzman 2004)
 cigarette smoking significantly increased impotence associated
with cardiovasculardisease, hypertension,and medication use (
Derbyet al, 2000 ).
57
Dept of Urology,GRH and KMC, Chennai.
 Long-distance bicycling is another risk factor -
genital numbness and ED.
58
Dept of Urology,GRH and KMC, Chennai.
ALTERNATE THERAPIES
 Acupuncture
 Androstenedione/DHEA
 Ginkgo biloba
 Korean red ginseng
 L-Arginine -A precursor to nitric oxide.
 Yohimbine
 Zinc
 Avena saliva and other potential cholesterol and blood-pressure
reducers and Tribulus terrestris (precursor to DHEA)
 Antioxidants in combinationwith orally approved FDA
medications
59
Dept of Urology,GRH and KMC, Chennai.
Psychosexual Therapy
 cognitive-behavioral interventionsfocused on challengingor
correcting maladaptivecognitions
 behavioraltechniques such as desensitizationand assertiveness
exercises
 psychodynamicexplorationsexploring the role of past
developmentalexperienceson present behavior
 systemic and couples therapy.
 in mixed psychogenicand organic ED, psychosexual therapy may
help relieveanxiety and remove unrealistic expectations
associated with medical or surgical therapy.
60
Dept of Urology,GRH and KMC, Chennai.
HORMONAL THERAPY
 Testosterone preparations.
Oral
1. Methyl testosterone
2. Testosterone undecanoate
3. Fluoxymesterone
Transdermal patches
1. Testoderm TTS
2. Androderm.
Transdermal gel
1. Androgel 1%
2. Testim 1%
 Intramuscular
1. T. cypionate
2. T. enanthate
 Pellet
1. Testopel.
 Buccal
1. Striant.
61
Dept of Urology,GRH and KMC, Chennai.
62
Dept of Urology,GRH and KMC, Chennai.
PDE 5 INHIBITORS
63
Dept of Urology,GRH and KMC, Chennai.
Mechanism of Action of
PDE5 Inhibitors
Adapted with permission from Lue TF. N Engl J Med. 2000;342:1802-1813. 64
Dept of Urology,GRH and KMC, Chennai.
PDE5 Inhibitors: Pharmacokinetics
Cmax=change in maximum plasma concentration
Tmax=time to maximum plasma concentration
t1/2=plasma half-life
nd=not determined
nr =not reported
*Median
1. Viagra prescribing information, January 2000. 2. Padma-Nathan H, Giuliano F. Urol Clin North Am. 2001;28:321-334.
3. Patterson B, et al. Poster presented at: 4th Congress (Biennial Meeting) of the European Society for Sexual and
Impotence Research; September 30, 2001; Rome. 4. Data on file, Lilly ICOS LLC. 5. Klotz T, et al. World J Urol.
2001;19:32-39. 6. Stark S, et al. Eur Urol. 2001;40:181-190. 7. Sorbera LA, et al. Drugs Future. 2001;26:141-144.
Parameter Sildenafil1,2 Tadalafil3,4 Vardenafil5-7
Bioavailability 40% nd nr
Cmax with food 29% no change nr
Tmax (h) 1* 2* <1
t1/2 (h) 3-5 17.5 ~4
65
Dept of Urology,GRH and KMC, Chennai.
PDE5 Inhibitors:
Onset and Duration of Activity
*RigiScan with visual sexual stimulation; oral dosing, empty stomach.
†Home setting; stopwatch recording.
‡Home setting; journal recording based on time frames.
nr =not reported.
1. Viagra prescribing information, January 2000. 2. Boolell M, et al. Int J Impot Res. 1996;8:47-52. 3. Padma-Nathan H.
J Urol. 2001;165(suppl):224, Abstract 923. 4. Sorbera LA, et al. Drugs Future. 2001;26:141-144.
PDE5 Inhibitor Onset (min) Duration (h)
Sildenafil1,2 30-60* 4*
Tadalafil3 30-45*;16† 24*‡
Vardenafil4 nr nr
66
Dept of Urology,GRH and KMC, Chennai.
PDE5 Inhibitors Meet
Important Patient Needs
 Most patients prefer oral therapy1
 Mechanism of action is physiologically-based
 Newer agent(s) may offer an opportunity to
increase spontaneity/flexibility
 Consideration of partner needs and satisfaction1
 Long-term improvement in quality of life1,2
1. Jarow JP, et al. J Urol. 1996;155:1609-1612. 2. Marwick C. JAMA. 1999;281:2173-2174. 67
Dept of Urology,GRH and KMC, Chennai.
Tadalafil Effect on
Successful Intercourse
*Did your erection last long enough to have successful intercourse?
†All randomized patients. Studies LVBN, LVCE, LVCO, and LVDJ.
Brock GB, et al. J Urol. 2002;168:1332-1336. 68
Dept of Urology,GRH and KMC, Chennai.
Tadalafil Treatment Effect on
Improved Erections
*Has the treatment you have been taking improved your erections?
†All randomized patients. Studies LVBN, LVCE, LVCO, and LVDJ.
Brock GB, et al. J Urol. 2002;168:1332-1336.
Tadalafil: Most Common
Treatment-Related Adverse Events
*Phase II/Ill – Adverse Events 2%.
McMahon CG. Paper presented at: 4th Congress (Biennial Meeting) of the European Society for Sexual and Impotence
Research; September 30-October 3, 2001; Rome.
Adverse Event
% of Patients Reporting Event
Placebo
(n=758)
Tadalafil
(n=1561)
Headache 4 11
Dyspepsia 1 7
Back pain 3 4
Myalgia 1 4
Nasal congestion 2 4
Flushing 1 4
70
Dept of Urology,GRH and KMC, Chennai.
Vardenafil: Tolerability
*Phase IIb – Adverse Events 5%.
Porst H, et al. Int J Impot Res. 2001;13:192-199.
Adverse Event
% of Patients Reporting Event
Placebo
(n=152)
Vardenafil
(n=438)
Headahe 4 10
Flushing 1 11
Dyspepsia 0 3
Rhinitis 3 5
71
Dept of Urology,GRH and KMC, Chennai.
WARNING
 Myocardial infarction within the previous 90 days
▪ Unstable angina or angina occurring during sexual intercourse
▪ New York Heart Association class II or greater heart failure in the previous 6
months
▪ Uncontrolled arrhythmias, hypotension (>90/50 mm Hg), or uncontrolled
hypertension (>170/100 mm Hg)
▪ Stroke within the previous 6 months
▪ Known hereditary degenerative retinal disorders, including retinitis
pigmentosa
▪ Tendency to develop priapism (e.g., sickle cell anemia, leukemia)
 Certain drugs, such as ketoconazole and itraconazole, and protease inhibitors,
such as ritonavir, can impair the metabolic breakdown of PDE-5 inhibitors by
blocking the CYP3A4 pathway.
 Severe kidney or hepatic dysfunction may require dose adjustments or warnings
72
Dept of Urology,GRH and KMC, Chennai.
SILDENAFIL VARDENAFIL TADALAFIL
Cmax ( ng/ml) 450 20.9 378
Tmax ( hr) 0.8 0.7-0.9 2
Onset of action 15 min-1 hr 15 min- 1 hr 15min-2 hr
Half life 3-5 hr 4-5 hr 17.5 hr
Bioavailability 40 % 15 min% Not tested
Fatty food Reduced
absorption
Reduced
absorption
No effect
Dosage 25,50,100 mg 5, 10, 20 mg 5, 10, 20 mg
SIDE EFFECTS
Headache,flushing yes yes Yes
Back ache, Myalgia rare rare Yes
Blurred/blue
vision
yes rare Rare
Precautionwith
antiarrythmics
no yes No
C/I with Nitrates yes yes yes
73
Dept of Urology,GRH and KMC, Chennai.
74
Dept of Urology,GRH and KMC, Chennai.
Intraurethral Therapy
 Alprostadil, the synthetic formulation of PGE1, is the only
pharmacologicagentwith FDA approval for ED managementby
both intracavernousand intraurethral routes.
 When inserted into the urethra, the drug is absorbed from the
urethra by the corpus spongiosum and then transported to the
corpus cavernosum through venous channels.
75
Dept of Urology,GRH and KMC, Chennai.
MUSE
The medicated urethral
system for erection
(MUSE; Vivus, Inc, CA)
consists of a very small
semisolid pellet (3 β1
mm) administered into
the distal urethra (3 cm)
by a proprietary
applicator (MUSE).
76
Dept of Urology,GRH and KMC, Chennai.
 Penile pain is a ubiquitous side effect of alprostadil-
based therapies
 The reported penile pain rate was 33% in MUSE trials.
 Hypotension and syncope have been noted in 1% to
5.8%, mandating the office setting for initial
administration.
77
Dept of Urology,GRH and KMC, Chennai.
INTRACAVERNOUS AGENTS
Drug Dose Range Advantages Disadvantages/Side Effects
Papaverine 7.5-60 mg Low cost; Stableat room
temp
Fibrosis, priapism; Elevation
of liver enzymes
Papaverine + phentolamine 0.1-1 mL More potent than papaverine
alone
Fibrosis, priapism
Alprostadil 1-60 μg Metabolized in penis;
Priapism rare
Painful erection; Requires
refrigeration; Relatively
expensive
Moxisylyte 10-30 mg Priapism rare Less potent
Papaverine + phentolamine+
alprostadil
0.1-1.0 mL Most potent Requires refrigeration
78
Dept of Urology,GRH and KMC, Chennai.
Centrally Acting Drugs
Yohimbine
 α2-adrenergic antagonist obtained from the bark
of the yohim tree
 acts centrally to promote sexual behavior by
blocking presynaptic autoreceptors and
increasing adrenergic receptor activity, which also
alters serotonin and dopamine transmission
 no efficacy of yohimbine over placebo in patients
with organic ED.( AUA 1996)
79
Dept of Urology,GRH and KMC, Chennai.
Trazodone
 commonly prescribed mild antidepressantwith a rare incidence
of priapism.
 positive effecton nocturnal penile erection ( Saenzde Tejada et
al, 1991 ) and sexually stimulated erection ( Lal et al, 1987 ).
Apomorphine
 dopaminergicagonist, activating D1 and D2 receptors.
Dopaminergicstimulation is proerectile
 Sexual arousal is necessary to enhance the effect of apomorphine
80
Dept of Urology,GRH and KMC, Chennai.
Vacuum Constriction Device
 The vacuum constriction device consists of a plastic cylinder
connected directly or by tubing to a vacuum-generatingsource
(manual or battery-operatedpump).
 After the penis is engorged by the negative pressure,a
constricting ring is applied to the base to maintain the erection.
 To avoid injury, the ring should not be left in place for longer
than 30 minutes
81
Dept of Urology,GRH and KMC, Chennai.
Vacuum Constriction Device
82
Dept of Urology,GRH and KMC, Chennai.
 In severe proximal venousleakage or arterial insufficiency, fibrosis
secondaryto priapism, or an infection from a prosthesis- may not
produce adequateerection.
 The devicecan be used successfully by men with a malfunctioning
penile prosthesis in place and after explantationto prevent
shortening.
 In men with severevascular insufficiency, combining intracavernous
injectionwith the vacuum constrictiondevice may enhance the
erection
 Patientstaking aspirin or warfarin should exercise caution when
using thesedevices.
 The patientsatisfaction rate has been reported to range from 68% to
83%
83
Dept of Urology,GRH and KMC, Chennai.
THANK YOUYOU
84
Dept of Urology,GRH and KMC, Chennai.

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Penis ed- evaluation and non surgical management

  • 1. Dept of Urology Govt Royapettah Hospital and Kilpauk Medical College Chennai 1
  • 2. Moderators: Professors:  Prof. Dr. G. Sivasankar, M.S., M.Ch.,  Prof. Dr. A. Senthilvel, M.S., M.Ch., Asst Professors:  Dr. J. Sivabalan, M.S., M.Ch.,  Dr. R. Bhargavi, M.S., M.Ch.,  Dr. S. Raju, M.S., M.Ch.,  Dr. K. Muthurathinam, M.S., M.Ch.,  Dr. D. Tamilselvan, M.S., M.Ch.,  Dr. K. Senthilkumar, M.S., M.Ch. Dept of Urology,GRH and KMC, Chennai. 2
  • 3. “Man survives earthquakes, experiences the horrors of illness, and all of the tortures of the soul. But the most tormenting tragedy of all time is, and will be, the tragedy of the bedroom.” Tolstoy 3 Dept of Urology,GRH and KMC, Chennai.
  • 4. What is ED? ED is the inability to achieve and maintain erection adequate for intercourse to the mutual satisfaction of the man and his partner. Jardin et al, 2000 . 4 Dept of Urology,GRH and KMC, Chennai.
  • 5. RISK FACTORS  Heart disease  Hypertension  Diabetes  Chronic renal failure  Hepatic failure  Multiple Sclerosis  Severe depression  Other (vascular disease, low HDL, high cholesterol) Benet et al. Urol Clinic North Am. 1995; 151:54-61 5 Dept of Urology,GRH and KMC, Chennai.
  • 6. CLASSIFICATION OF ED 6 Dept of Urology,GRH and KMC, Chennai.
  • 7. PSYCHOGENIC  Persistent inability to achieve or maintain erection satisfactory for sexual performance due predominantly or exclusively to psychological or interpersonal factors.  Anxiety  Self-reported depressive symptoms  Low degrees of self-esteem  Negative outlook on life  Self-reported emotional stress  H/O sexual coercion. 7 Dept of Urology,GRH and KMC, Chennai.
  • 8. NEUROGENIC  10% to 19% of ED is neurogenic , prevalence is much high if iatrogenic & mixed ED included.  Parkinson's disease  Stroke  Encephalitis  Temporal lobe epilepsy  Tumors  Dementias  Alzheimer's disease  Shy-Drager syndrome  Trauma. 8 Dept of Urology,GRH and KMC, Chennai.
  • 9.  Iatrogenic impotence :  Radical prostatectomy 43% to 100%  Perineal prostatectomy for benign 29%  APR - 15% to 100%  External sphincterotomy 2% to 49% .  Nerve-sparing radical prostatectomy reduced the incidence 100% to 30%-50%  Pelvic fracture, ED result of cavernous n’ injury or vascular insufficiency or both . 9 Dept of Urology,GRH and KMC, Chennai.
  • 10. NEURO ANATOMY 10 Dept of Urology,GRH and KMC, Chennai.
  • 11. ENDOCRINOLOGIC  Testosterone : enhances sexual interest, ↑ frequency of sexual acts, and ↑ frequency of nocturnal erections.  Men receiving long-term androgen ablation therapy for prostate cancer reported poor libidoand ED .  Hyperprolactinemia- pituitaryadenoma or drugs, results in both reproductiveand sexual dysfunction.  ED associated with both hyper- and hypothyroidism.  DM, causes ED through its vascular, neurologic, endothelial, and psychogenic complications rather than hormone def. 11 Dept of Urology,GRH and KMC, Chennai.
  • 12. ARTERIOGENIC  Atherosclerotic or traumatic arterial occlusive disease of hypogastric- cavernous-helicine arterial tree .  Risk factors include HT, hyperlipidemia, cigarette smoking, DM, blunt perineal or pelvic trauma, and pelvic irradiation. 12 Dept of Urology,GRH and KMC, Chennai.
  • 13. CAVERNOUS (VENOGENIC)  Tunical changes- degenerative changes (Peyronie's disease, old age, and DM) or traumatic injury to T.A (penile # )  Fibroelasticstructural alterations,  Insufficient trabecular smooth muscle relaxation,  Venous shunts. (priapism) 13 Dept of Urology,GRH and KMC, Chennai.
  • 14. 14 Dept of Urology,GRH and KMC, Chennai.
  • 15. MEDICAL HISTORY The goals of medical history-taking are (1) to evaluate the potential role of underlying medical conditions (e.g., atherosclerosis, diabetes) and comorbidities (e.g., depression) (2) to differentiate between potential organic and psychogenic causes (3) to assess the potential role of medication (4) Past H/O: Prostatectomy, APR, Pelvic trauma 15 Dept of Urology,GRH and KMC, Chennai.
  • 16. CHARACTERISTIC ORGANIC PSYCHOGENIC ONSET GRADUAL ACUTE CIRCUMSTANCES GLOBAL SITUATIONAL COURSE CONSTANT VARYING NON COITAL ERECTION POOR RIGID PSYCHOSEXUAL PROBLEM SECONDARY LONG HISTORY PARTNER PROBLEM SECONDARY AT ONSET ANXIETY AND FEAR SECONDARY PRIMARY 16 Dept of Urology,GRH and KMC, Chennai.
  • 17. A Practical Evaluation of Men with ED Laboratory Tests  Fasting glucose, RFT, lipids & testosterone.  Optional : indicated by history & P/E .( Prolactin, LH, FSH, Thyroid function.)  PSA measured >50 yrs age ,F/H ca prostate, if hormonal replacement planned. 17 Dept of Urology,GRH and KMC, Chennai.
  • 18. A Practical Evaluation of Men with ED Physical Examination  Blood pressure  Examine penis (R/O Peyronie’s disease)  Determine size and consistency of testes  Digital rectal exam  Focused vascular exam/peripheral pulses  Focused neurologic exam 18 Dept of Urology,GRH and KMC, Chennai.
  • 19. Why Use Patient Questionnaires?  Facilitate dialogue and diagnosis  Evaluate treatment changes  Drawback is reliance on self assessment.  Examples of self-administered, standardized questionnaires  Sexual Health Inventory for Men (SHIM)1  International Index of Erectile Function (IIEF)2 1. Rosen RC, et al. Int J Impot Res. 1999;11:319-326. 2. Rosen RC, et al. Urology. 1997;49:822-830. 19 Dept of Urology,GRH and KMC, Chennai.
  • 20. 20 Dept of Urology,GRH and KMC, Chennai.
  • 21. SHIM Score Characterizes ED Severity  22-25 Normal erectile function  17-21 Mild ED  12-16 Mild to moderate ED  8-11 Moderate ED  7 Severe ED *Total score ranges from 5 to 25 and is based on FIRST 5 questions. Each rated on a Likert scale of 1 = least functional to 5 = most functional. Rosen RC, et al. Int J Impot Res. 1999;11:319-326. 21 Dept of Urology,GRH and KMC, Chennai.
  • 22. EVALUATION OF COMPLEX PATIENT  Indications for specialized evaluation  Failure of initial treatment  Peyronie's disease  Primary ED  H/O pelvic/perineal trauma  Vascular or neurosurgical intervention  Complicated endocrinopathy  Complicated psychiatric disorder  Complex relationship problems  Medicolegal concerns . 22 Dept of Urology,GRH and KMC, Chennai.
  • 23. SEXUAL HISTORY  Interview conducted face-to-face.  Ensure pt trust, comfort, and openness  The interviewershould determine whether patient has cognitive understandingof genital function and penilerigidity.  Very useful in evaluatingand treating men with deep-seated psychological problems. 23 Dept of Urology,GRH and KMC, Chennai.
  • 24. PSYCHOLOGIC  Diagnostic interview mainstay of evaluation.  Current sexual problem and its history  Deeper causes of sexual dysfunction  Relationship &  Psychiatric symptoms.  Immediate causes –  fear of failure  performance anxiety  insufficient sexual stimulation  loss of attraction  relationship conflicts.  “Deeper” causes of psychogenic ED- unresolved parental attachments, sexual identity, sexual trauma, and cultural- religious taboos . 24 Dept of Urology,GRH and KMC, Chennai.
  • 26. VASCULAR EVALUATION First-Line Evaluation of Penile Blood Flow Combined Intracavernous Injection and Stimulation:  A CIS test consists of intracavernous injection of a vasodilatoror a combination of two or three vasodilators, genitalor audiovisual sexual stimulation, and assessmentof the erection by an observer.  This screening test is the most commonly performeddiagnostic procedure for ED.  It allows the clinician to bypassneurologic and hormonal influencesand to evaluatethe vascularstatus of the penis directly and objectively 26 Dept of Urology,GRH and KMC, Chennai.
  • 27.  alprostadil alone (Caverjector Edex, 10 to 20 μg), a combination of papaverineand phentolamine(Bimix, 0.3 mL), or a mixture of all three of these agents (Trimix, 0.3 mL).  The technique involves injecting the medication through a 5/8- inch needle (27 to 29 gauge) into the corpus cavernosum.  The needlesite is compressed manually for 5 minutes to prevent hematoma formation  should not leave the office until the penis becomes flaccid spontaneouslyor by injection of a diluted phenylephrine solution (500 μg/mL, given 1 mL every 3 to 5 minutes until detumescence). 27 Dept of Urology,GRH and KMC, Chennai.
  • 28. Second-Line Evaluation of Penile Blood Flow Duplex Ultrasonography (Gray Scale or Color-Coded)  Penile blood flow study, which consists of CIS and blood flow measurement by duplex ultrasound, is the most reliableand least invasiveevidence-basedassessmentof ED.  Duplex ultrasound consists of high-resolution(7 to 10 MHz) real-time ultrasonographyand color pulsed Doppler  Visualize the dorsal and cavernousarteries selectivelyand to perform dynamicblood flow analysis  best tool availablefor the diagnosisof high-flowpriapismand localizationof a ruptured artery 28 Dept of Urology,GRH and KMC, Chennai.
  • 29. Peak Systolic Velocity (PSV) and Arterial Dilation  In the Mayo Clinic series, PSV less than 25 cm/s had a sensitivity of 100% and a specificity of 95% in patientswith abnormal pudendalarteriography ( Lewis and King, 1994 ).  unilateral cavernousarterial insufficiency results in asymmetry of PSV greater than 10 cm/s. 29 Dept of Urology,GRH and KMC, Chennai.
  • 30. Duplex Ultrasound Evaluation in Veno- occlusive Dysfunction  High systolic flow (>25 cm/s PSV) and persistent end- diastolic flow velocity (EDV) (>5 cm/s) accompanied by quick detumescence after self-stimulation, the patient is considered to have venogenic impotence.  Venous leakage on cavernosometry was predicted with a sensitivity of 90% and specificity of 56% when EDV was greater than 5 cm/s ( Quam et al, 1989 ; Lewis and King, 1994 ). 30 Dept of Urology,GRH and KMC, Chennai.
  • 31. Third-Line Evaluation of Penile Blood Flow Cavernous Arterial Occlusion Pressure (CASOP)  It involvesintracavernousinjectionof a vasodilator (usually Trimix solution) followed by infusion of saline into the corpora cavernosaat a rate sufficient to raise the intracavernouspressure above the systolic blood pressure.  A pencil Doppler transduceris then applied to the side of the penile base.  The saline infusion is stopped, and the intracavernouspressure is allowed to fall. 31 Dept of Urology,GRH and KMC, Chennai.
  • 32.  The pressure at which the cavernousarterial flow becomes detectable is defined as the cavernousartery systolic occlusion pressure (CASOP).  A gradient betweenthe cavernousand the brachialartery pressures of less than 35 mm Hg and an equal pressure between the right and the left cavernous arteries has beendefined as normal 32 Dept of Urology,GRH and KMC, Chennai.
  • 33. CAVERNOSAL ARTERY FLOW BRACHIAL SYSTOLIC AND DIASTOLIC BP (CASOP)-108mmHg INTRACAVERNOSAL HEPARINIZED SALINE FLOW 33 Dept of Urology,GRH and KMC, Chennai.
  • 34. RESISTIVE INDEX  In 1974, Planiol and Pourcelot proposed a resistive index (RI) to describe vascular resistance from the Dopplerspectrum.  RI = PSV - EDV/PSV.  As penile pressure equals or exceedsdiastolic pressure, diastolic flow in the corpora will approach 0 and the value for RI approaches 1.  During tumescenceand until full rigidity, diastolic flow is antegrade (+); the value for RI remains less than 1.0.  Naroda and associates (1994) found that an RI greaterthan 0.9 was associated with normal resultsduring DICC in 90% of theirseries and an RI less than 0.75 was associated withvenous leakage in 95%. 34 Dept of Urology,GRH and KMC, Chennai.
  • 35. PHARMACOLOGIC ARTERIOGRAPHY  Best indication is young pt with ED sec to traumatic a’ disruptionor perineal compression injury.  Intracavernous inj of vasodil agent followed by selective cannulation of internal pudendal a’ and inj of contrast.  Anatomy and radiographic appearance of internal pudendal, and penile arteries evaluated. patent commonpenile, dorsal, and cavernous arteries nonvisualizationof commonpenile artery and its branches 35 Dept of Urology,GRH and KMC, Chennai.
  • 36. DICC  Dynamic infusion cavernosometry and cavernosography (DICC) is invasive  Flow rate required to maintain erection at an intracavernous pressure of more than 100 mm Hg is reported to be less than 3 to 5 mL/min  Pressure decrease in 30 seconds from 150 mm Hg is less than 45 mm Hg.  Cavernosography is performed after cavernosometry and should reveal opacification of the corpora cavernosa but minimal or no visualization of venous structures or corpus spongiosum  For young men who might be candidates for penile vascular operations, specifically those with a history of pelvic trauma or life-long ED (primary ED). 36 Dept of Urology,GRH and KMC, Chennai.
  • 37. Pharmacologic cavernosometry involvessimultaneoussaline infusion and intracavernous pressure monitoring after intracavernous injectionof a strong vasodilating solution  Veno-occlusivedysfunctionis indicated by eitherthe inability to increase intracavernouspressure to the levelof the mean systolic blood pressure ora rapid drop of intracavernouspressure after cessation of infusion Pharmacologic cavernosography involves the infusion of radiographic contrast solution into the corpora cavernosum.  Leakage sites to the glans, corpus spongiosum, superficial dorsal veins,and cavernousand crural veinscan then be detected.In the majority of patients, more than one site is visualized 37 Dept of Urology,GRH and KMC, Chennai.
  • 38. PHARMACOLOGIC CAVERNOSOGRAPHY After penile # communication between CC & CS seen 27-year-old man with primary ED, venous leakage from crura 38 Dept of Urology,GRH and KMC, Chennai.
  • 39. Penile Brachial Pressure Index  The penile brachial pressure index (PBI) represents the penile systolic blood pressure divided by the brachial systolic blood pressure.  The technique involves applying a small pediatric blood pressure cuff to the base of the flaccid penis and measuring the systolic blood pressure with a continuous-wave Doppler probe.  A PBI of 0.7 or less has been used to indicate arteriogenic impotence 39 Dept of Urology,GRH and KMC, Chennai.
  • 40. INVESTIGATIONAL….  Penile Plethysmography (Penile Pulse Volume Recording)  Infrared Spectrophotometry.  Radioisotopic Penography.  Magnetic Resonance Angiography (MRA)  Cavernous Smooth Muscle Content 40 Dept of Urology,GRH and KMC, Chennai.
  • 41. PSYCHOPHYSIOLOGIC Nocturnal Penile Tumescence  Nocturnalpenile tumescence (NPT) monitoringwas first described by Halverson(1940)  Karacan and colleagues(1966)were the first to demonstratethat 80% of NPT occursduringrapid eye movement (REM)sleep NPT has been measured by a numberof methods:  stamp test ( Barryet al, 1980 )  snap gauges ( Diedrichet al, 1992 )  sleep laboratorynocturnal peniletumescence and rigidity(NPTR)  RigiScan(Endocare, Inc., Irvine, CA)  most recently, NPT electrobioimpedance(NEVA, American Medical Systems, Inc., Minnetonka, MN). 41 Dept of Urology,GRH and KMC, Chennai.
  • 42. NPT In its classic form, NPT consists of nocturnal monitoring devices that measure the  number of episodes  tumescence (circumference change by strain gauges)  maximal penile rigidity  duration of nocturnal erections 42 Dept of Urology,GRH and KMC, Chennai.
  • 43. INDICATIONS  Heaton and Morales (1997) have suggested indications for NPTR as follows: (1) suspected sleep disorder (2) obscure cause of ED (3) nonresponse to therapy (4) plannedsurgical treatment (5) legallysensitivecase (6) measurementof drug effects in placebo-controlleddrug trials (7) suspected psychogeniccause 43 Dept of Urology,GRH and KMC, Chennai.
  • 44.  The patient is awakenedduring maximal tumescence, and the erection is photographed and axial rigidity measured with a device applied to the tip of the penis.  A buckling resistance of 500 g is considered the minimum for vaginalpenetration; 1.5 kg is considered complete rigidity according to the original Karacan (1970) criteria.  Because NPT occurs during REM sleep, tumescence monitoring repeated over two to three nights to overcome the so-called first- nighteffect. 44 Dept of Urology,GRH and KMC, Chennai.
  • 45. RIGISCAN  In 1985, the RigiScan was introduced  first device to provide automated, portable NPTR recording.  The device combines the monitoring of radial rigidity, tumescence, number, and duration of erectile events  It consists of a recording unit that can collect data for three separate nights for a maximum of 10 hours each night. 45 Dept of Urology,GRH and KMC, Chennai.
  • 46. RIGISCAN  The mechanicsconsist of two loops: one is placed at the base of the penisand the other at the coronal sulcus.  By constricting the loops, the device records penile tumescence (circumference) and radial rigidity at the penile base and tip 46 Dept of Urology,GRH and KMC, Chennai.
  • 47. NPTR CRITERIA Cilurzo and colleagues (1992) recommend the following as normal NPTR criteria:  four to five erectile episodes per night  mean duration longerthan 30 minutes  an increase in circumference of more than 3 cm at the base and more than 2 cm at the tip  maximal rigidity above 70% at both base and tip 47 Dept of Urology,GRH and KMC, Chennai.
  • 48. TWO EPISODES OF WELL-SUSTAINED, COMPLETELY RIGID NOCTURNAL ERECTIONS TWO EPISODES OF POORLY SUSTAINED, POORLY RIGID NOCTURNAL ERECTIONS RigiScan 48 Dept of Urology,GRH and KMC, Chennai.
  • 49. ADVANTAGES:  relativefreedom from psychologic influencesand its abilityto detect sleep-related abnormalities.  Thedocumented presence of a full erection indicatesthat the neurovascular axis is functionally intact and that the cause of the ED is most likelypsychogenic. DISADVANTAGES:  costly, because it is ideallydonewith a RigiScanin a speciallyequipped sleep center.  Not recommendedas a routinepart of ED evaluation 49 Dept of Urology,GRH and KMC, Chennai.
  • 50. NEVA  Uses electrobioimpedance to assess volumetricchanges in penis during nocturnal erections.  Record number, duration of erectile episodesand penile length and blood volume changes at night .  Small recording device is attached to pt's thigh, and three small electrode pads applied to hip , penile base and glans.  An undetectable alternating current is sent from glans electrode to hip ground. The penile base electrode measures impedance and changes in penile length.  Relationship to rigidity and volume change needs to be established. 50 Dept of Urology,GRH and KMC, Chennai.
  • 51. Neurologic Evaluation Somatic Nervous System  Biothesiometry This test is designedto measure the sensory perception threshold to various amplitudesof vibratory stimulation produced by a hand-heldelectromagneticdevice (biothesiometer) placed on the pulp of the index fingers, both sides of the penileshaft, and the glanspenis. 51 Dept of Urology,GRH and KMC, Chennai.
  • 52. Sacral Evoked Response—Bulbocavernosus Reflex Latency  This test is performed by placing two stimulating ring electrodes around the penis, one near the corona and the other 3 cm proximal.  Concentric needle electrodes are placed in the right and left bulbocavernous muscles to record the response  abnormal latency time, defined as a value more than 3 standard deviations above the mean (30 to 40 ms), denotes a high probability of neuropathology 52 Dept of Urology,GRH and KMC, Chennai.
  • 53. Dorsal Nerve Conduction Velocity  averageconduction velocity of 23.5 m/s with a range of 21.4 to 29.1 m/s in normal subjects. Genitocerebral Evoked Potential  This test involveselectrical stimulation of the dorsal nerve of the penisas described for the BCR latency test.  study records the evoked potential waveformsoverlyingthe sacral spinal cord and cerebral cortex 53 Dept of Urology,GRH and KMC, Chennai.
  • 54. Hormonal Evaluation  Historically, hypogonadismas a cause of ED was thought to be rare  recent data support a significantincrease of hypogonadismwith age.  The interrelationshipsamong hypogonadism,depression,and ED are now recognized  In male sexual dysfunction most endocrinopathiescenter around testosterone 54 Dept of Urology,GRH and KMC, Chennai.
  • 55.  morning testosterone values below 350 ng/dL in a young man with chronicallyelevatedgonadotropins -- hypogonadism.  blood should be drawn between8:00 AM and 11:00 AM. For screening, a total testosterone usually adequate.  If the testosterone level is belowor at the low limit of normal, it should be confirmed with a second determinationtogetherwith assessmentof luteinizing hormone (LH) and prolactin.  One or more of the following serum laboratoryvalues may be required to diagnose hormone deficiencies: (1) total/free/bioavailabletestosterone; (2) SHBG; (3) LH; and (4) follicle-stimulatinghormone (FSH). 55 Dept of Urology,GRH and KMC, Chennai.
  • 56. 56 Dept of Urology,GRH and KMC, Chennai.
  • 57. Lifestyle Change  Obesitywas associated with ED (P=.006), with baselineobesity predicting a higherrisk regardlessof follow-up weight loss.  Physical activity was also associated with ED (P= .01), with the highestrisk among men who remained sedentary  The beneficialeffect of using a statin drug to lowercholesterol in men in whom the only risk factor for ED is hypercholesterolemia( Saltzman 2004)  cigarette smoking significantly increased impotence associated with cardiovasculardisease, hypertension,and medication use ( Derbyet al, 2000 ). 57 Dept of Urology,GRH and KMC, Chennai.
  • 58.  Long-distance bicycling is another risk factor - genital numbness and ED. 58 Dept of Urology,GRH and KMC, Chennai.
  • 59. ALTERNATE THERAPIES  Acupuncture  Androstenedione/DHEA  Ginkgo biloba  Korean red ginseng  L-Arginine -A precursor to nitric oxide.  Yohimbine  Zinc  Avena saliva and other potential cholesterol and blood-pressure reducers and Tribulus terrestris (precursor to DHEA)  Antioxidants in combinationwith orally approved FDA medications 59 Dept of Urology,GRH and KMC, Chennai.
  • 60. Psychosexual Therapy  cognitive-behavioral interventionsfocused on challengingor correcting maladaptivecognitions  behavioraltechniques such as desensitizationand assertiveness exercises  psychodynamicexplorationsexploring the role of past developmentalexperienceson present behavior  systemic and couples therapy.  in mixed psychogenicand organic ED, psychosexual therapy may help relieveanxiety and remove unrealistic expectations associated with medical or surgical therapy. 60 Dept of Urology,GRH and KMC, Chennai.
  • 61. HORMONAL THERAPY  Testosterone preparations. Oral 1. Methyl testosterone 2. Testosterone undecanoate 3. Fluoxymesterone Transdermal patches 1. Testoderm TTS 2. Androderm. Transdermal gel 1. Androgel 1% 2. Testim 1%  Intramuscular 1. T. cypionate 2. T. enanthate  Pellet 1. Testopel.  Buccal 1. Striant. 61 Dept of Urology,GRH and KMC, Chennai.
  • 62. 62 Dept of Urology,GRH and KMC, Chennai.
  • 63. PDE 5 INHIBITORS 63 Dept of Urology,GRH and KMC, Chennai.
  • 64. Mechanism of Action of PDE5 Inhibitors Adapted with permission from Lue TF. N Engl J Med. 2000;342:1802-1813. 64 Dept of Urology,GRH and KMC, Chennai.
  • 65. PDE5 Inhibitors: Pharmacokinetics Cmax=change in maximum plasma concentration Tmax=time to maximum plasma concentration t1/2=plasma half-life nd=not determined nr =not reported *Median 1. Viagra prescribing information, January 2000. 2. Padma-Nathan H, Giuliano F. Urol Clin North Am. 2001;28:321-334. 3. Patterson B, et al. Poster presented at: 4th Congress (Biennial Meeting) of the European Society for Sexual and Impotence Research; September 30, 2001; Rome. 4. Data on file, Lilly ICOS LLC. 5. Klotz T, et al. World J Urol. 2001;19:32-39. 6. Stark S, et al. Eur Urol. 2001;40:181-190. 7. Sorbera LA, et al. Drugs Future. 2001;26:141-144. Parameter Sildenafil1,2 Tadalafil3,4 Vardenafil5-7 Bioavailability 40% nd nr Cmax with food 29% no change nr Tmax (h) 1* 2* <1 t1/2 (h) 3-5 17.5 ~4 65 Dept of Urology,GRH and KMC, Chennai.
  • 66. PDE5 Inhibitors: Onset and Duration of Activity *RigiScan with visual sexual stimulation; oral dosing, empty stomach. †Home setting; stopwatch recording. ‡Home setting; journal recording based on time frames. nr =not reported. 1. Viagra prescribing information, January 2000. 2. Boolell M, et al. Int J Impot Res. 1996;8:47-52. 3. Padma-Nathan H. J Urol. 2001;165(suppl):224, Abstract 923. 4. Sorbera LA, et al. Drugs Future. 2001;26:141-144. PDE5 Inhibitor Onset (min) Duration (h) Sildenafil1,2 30-60* 4* Tadalafil3 30-45*;16† 24*‡ Vardenafil4 nr nr 66 Dept of Urology,GRH and KMC, Chennai.
  • 67. PDE5 Inhibitors Meet Important Patient Needs  Most patients prefer oral therapy1  Mechanism of action is physiologically-based  Newer agent(s) may offer an opportunity to increase spontaneity/flexibility  Consideration of partner needs and satisfaction1  Long-term improvement in quality of life1,2 1. Jarow JP, et al. J Urol. 1996;155:1609-1612. 2. Marwick C. JAMA. 1999;281:2173-2174. 67 Dept of Urology,GRH and KMC, Chennai.
  • 68. Tadalafil Effect on Successful Intercourse *Did your erection last long enough to have successful intercourse? †All randomized patients. Studies LVBN, LVCE, LVCO, and LVDJ. Brock GB, et al. J Urol. 2002;168:1332-1336. 68 Dept of Urology,GRH and KMC, Chennai.
  • 69. Tadalafil Treatment Effect on Improved Erections *Has the treatment you have been taking improved your erections? †All randomized patients. Studies LVBN, LVCE, LVCO, and LVDJ. Brock GB, et al. J Urol. 2002;168:1332-1336.
  • 70. Tadalafil: Most Common Treatment-Related Adverse Events *Phase II/Ill – Adverse Events 2%. McMahon CG. Paper presented at: 4th Congress (Biennial Meeting) of the European Society for Sexual and Impotence Research; September 30-October 3, 2001; Rome. Adverse Event % of Patients Reporting Event Placebo (n=758) Tadalafil (n=1561) Headache 4 11 Dyspepsia 1 7 Back pain 3 4 Myalgia 1 4 Nasal congestion 2 4 Flushing 1 4 70 Dept of Urology,GRH and KMC, Chennai.
  • 71. Vardenafil: Tolerability *Phase IIb – Adverse Events 5%. Porst H, et al. Int J Impot Res. 2001;13:192-199. Adverse Event % of Patients Reporting Event Placebo (n=152) Vardenafil (n=438) Headahe 4 10 Flushing 1 11 Dyspepsia 0 3 Rhinitis 3 5 71 Dept of Urology,GRH and KMC, Chennai.
  • 72. WARNING  Myocardial infarction within the previous 90 days ▪ Unstable angina or angina occurring during sexual intercourse ▪ New York Heart Association class II or greater heart failure in the previous 6 months ▪ Uncontrolled arrhythmias, hypotension (>90/50 mm Hg), or uncontrolled hypertension (>170/100 mm Hg) ▪ Stroke within the previous 6 months ▪ Known hereditary degenerative retinal disorders, including retinitis pigmentosa ▪ Tendency to develop priapism (e.g., sickle cell anemia, leukemia)  Certain drugs, such as ketoconazole and itraconazole, and protease inhibitors, such as ritonavir, can impair the metabolic breakdown of PDE-5 inhibitors by blocking the CYP3A4 pathway.  Severe kidney or hepatic dysfunction may require dose adjustments or warnings 72 Dept of Urology,GRH and KMC, Chennai.
  • 73. SILDENAFIL VARDENAFIL TADALAFIL Cmax ( ng/ml) 450 20.9 378 Tmax ( hr) 0.8 0.7-0.9 2 Onset of action 15 min-1 hr 15 min- 1 hr 15min-2 hr Half life 3-5 hr 4-5 hr 17.5 hr Bioavailability 40 % 15 min% Not tested Fatty food Reduced absorption Reduced absorption No effect Dosage 25,50,100 mg 5, 10, 20 mg 5, 10, 20 mg SIDE EFFECTS Headache,flushing yes yes Yes Back ache, Myalgia rare rare Yes Blurred/blue vision yes rare Rare Precautionwith antiarrythmics no yes No C/I with Nitrates yes yes yes 73 Dept of Urology,GRH and KMC, Chennai.
  • 74. 74 Dept of Urology,GRH and KMC, Chennai.
  • 75. Intraurethral Therapy  Alprostadil, the synthetic formulation of PGE1, is the only pharmacologicagentwith FDA approval for ED managementby both intracavernousand intraurethral routes.  When inserted into the urethra, the drug is absorbed from the urethra by the corpus spongiosum and then transported to the corpus cavernosum through venous channels. 75 Dept of Urology,GRH and KMC, Chennai.
  • 76. MUSE The medicated urethral system for erection (MUSE; Vivus, Inc, CA) consists of a very small semisolid pellet (3 β1 mm) administered into the distal urethra (3 cm) by a proprietary applicator (MUSE). 76 Dept of Urology,GRH and KMC, Chennai.
  • 77.  Penile pain is a ubiquitous side effect of alprostadil- based therapies  The reported penile pain rate was 33% in MUSE trials.  Hypotension and syncope have been noted in 1% to 5.8%, mandating the office setting for initial administration. 77 Dept of Urology,GRH and KMC, Chennai.
  • 78. INTRACAVERNOUS AGENTS Drug Dose Range Advantages Disadvantages/Side Effects Papaverine 7.5-60 mg Low cost; Stableat room temp Fibrosis, priapism; Elevation of liver enzymes Papaverine + phentolamine 0.1-1 mL More potent than papaverine alone Fibrosis, priapism Alprostadil 1-60 μg Metabolized in penis; Priapism rare Painful erection; Requires refrigeration; Relatively expensive Moxisylyte 10-30 mg Priapism rare Less potent Papaverine + phentolamine+ alprostadil 0.1-1.0 mL Most potent Requires refrigeration 78 Dept of Urology,GRH and KMC, Chennai.
  • 79. Centrally Acting Drugs Yohimbine  α2-adrenergic antagonist obtained from the bark of the yohim tree  acts centrally to promote sexual behavior by blocking presynaptic autoreceptors and increasing adrenergic receptor activity, which also alters serotonin and dopamine transmission  no efficacy of yohimbine over placebo in patients with organic ED.( AUA 1996) 79 Dept of Urology,GRH and KMC, Chennai.
  • 80. Trazodone  commonly prescribed mild antidepressantwith a rare incidence of priapism.  positive effecton nocturnal penile erection ( Saenzde Tejada et al, 1991 ) and sexually stimulated erection ( Lal et al, 1987 ). Apomorphine  dopaminergicagonist, activating D1 and D2 receptors. Dopaminergicstimulation is proerectile  Sexual arousal is necessary to enhance the effect of apomorphine 80 Dept of Urology,GRH and KMC, Chennai.
  • 81. Vacuum Constriction Device  The vacuum constriction device consists of a plastic cylinder connected directly or by tubing to a vacuum-generatingsource (manual or battery-operatedpump).  After the penis is engorged by the negative pressure,a constricting ring is applied to the base to maintain the erection.  To avoid injury, the ring should not be left in place for longer than 30 minutes 81 Dept of Urology,GRH and KMC, Chennai.
  • 82. Vacuum Constriction Device 82 Dept of Urology,GRH and KMC, Chennai.
  • 83.  In severe proximal venousleakage or arterial insufficiency, fibrosis secondaryto priapism, or an infection from a prosthesis- may not produce adequateerection.  The devicecan be used successfully by men with a malfunctioning penile prosthesis in place and after explantationto prevent shortening.  In men with severevascular insufficiency, combining intracavernous injectionwith the vacuum constrictiondevice may enhance the erection  Patientstaking aspirin or warfarin should exercise caution when using thesedevices.  The patientsatisfaction rate has been reported to range from 68% to 83% 83 Dept of Urology,GRH and KMC, Chennai.
  • 84. THANK YOUYOU 84 Dept of Urology,GRH and KMC, Chennai.