Dr Himali Perera Consultant Venereologist Coordinator Training and Capacity Building, National STD /AIDS Control Programme

1. TREATMENT MODALITIES
IN ERECTILE
DYSFUNCTION
DR HIMALI PERERA
CONSULTANT VENEREOLOGIST
COORDINATOR TRAINING AND CAPACITY
BUILDING
NATIONAL STD /AIDS CONTROL
PROGRAMME

2. ERECTILE
DYSFUNCTION
‘The consistent or recurrent inability
of a man to attain and or maintain a
penile erection sufficient for sexual
performance’

3. EPIDEMIOLOGY OF ERECTILE
DYSFUNCTION
• 50% amongst aged 40y-70y, according to
Massachusetts Male Ageing Study(MMAS)
• 322 million projected cases worldwide by 2025
• Sri Lankan situation unknown

4. RISK FACTORS FOR ED
Advancing age
Drugs
Dyslipidemia
Hypertension
Diabetes mellitus
Atherosclerosis /CAD
Alcohol & Smoking
Trauma
Pelvic surgery
Neurological disorders
Hormonal disorders
Psychological factors
Stress/Sedentary life style

5. STUDY(MMAS)
INCREASING PREVALENCE OF ED WITH
AGE
0 0.5 1.0
70
65
60
55
50
45
40
Age(years)
Probability
None
Minimal
Moderate
Complete
Feldman HA et al. J Urol 1994;151:54-61

6. MASSACHUSETTS MALE AGEING STUDY
(MMAS) PREVALENCE OF ERECTILE
DYSFUNCTION
None 48%
Minimal 17%
Complete
10%
Moderate 25%
Feldman HA et al. J Urol 1994;151:54–61

7. CLASSIFICATION OF ED
Psychogenic Organic (80%)

8. ORGANIC CAUSES
Therapeutic drugs
Endocrinologic
Neurogenic
structural
Peyronie’s dis
Arteriogenic
eg Atherosclerosis
Venogenic
E,venogenicVasculogenic /Arteriogenic
venogenic
Systemic

9. 50% OF DIABETES MELLITUS
PATIENTS HAVE ED
Pathophysiology
•Neurogenic Autonomic NS
Peripheral NS
•Arterial Atherosclerosis
Microangiopathy
•Endothelial Impaired smooth muscle relaxation
•Myogenic Impaired smooth muscle function

10. ED INDICATES A POSSIBLE
CONCOMITANT HEART
PROBLEM
• Men with ED, aged >55 Y have a 25% risk of a
cardiovascular event and ED patients should be promptly
investigated for CV risk. (Tho m pso n IMe t alJAMA
20 0 5; 29 4: 29 9 6 -30 0 2)
• The recognition of ED as a warning sign of silent vascular
disease has led to the concept that a man with ED but no
cardiac symptoms is a cardiac or (vascular) patient until
proven otherwise. (Prince to n II: Jackso n G e t al. 20 0 6 . JSe x
Me d)

11. PHYSIOLOGY OF NORMAL
ERECTION
•Cerebral control -PVN
•Autonomic control-parasympathetic stimulation
• Molecular Mechanisms Endothelial dysfunction

12. ERECTOGENIC & INHIBITORY
STIMULI
Cerebral
cortex
Spinal cord
Erectogenic
stimuli
Inhibitory
stimuli
– anxiety
– fear
– depression
PRO-ERECTILE
neural signalling
PVN
PVN

13. PENILE ERECTION: AN
INTEGRATED RESPONSE
Supraspinal control
and integration
Spinal
reflexes
and integration
Autonomic nervous
system
ERECTION

14. PENILE ANATOMY

15. THE MOLECULAR BIOLOGY OF
ERECTIONS
Ca2+
cGMP
cAMP
Ca2+
Ca2+
Ca2+
K+
Endothelium
Smooth muscle
tonic contraction:
Ca2+
Locking mechanism
PDE-5
PDE-2,3,4

16. ENDOTHELIAL DYSFUNCTION=
ERECTILE DYSFUNCTION
Ca2+
cGMP
cAMP
Ca2+
Ca2+
Ca2+
K+
Na+
Ca2+Ca2+
NO
NO Endothelium
Smooth muscle
relaxation
Role of the endothelium
PDE-5
PDE-2,3,4

17. ENDOTHELIAL DYSFUNCTION=
ERECTILE DYSFUNCTION
NO
cGMP
cAMP
Adr
NA
Ca2+
PDE-5
Ca2+
Ca2+
K+
Na+
NO
Ca2+
PGE
VIP Ca2+
PDE-2,3,4
Endothelium
Smooth muscle
relaxation
Neural mechanisms
Ca2+
ACh

18. CAUSES OF ARTERIOGENIC ED
Causes Examples
Atherosclerosis Smoking
Hypercholesterolaemia
Iatrogenic Aorto-iliac surgery
Renal Transplantation
Radiotherapy
Trauma Pelvic fracture injury
Blunt perineal trauma
Others Post priapism

19. CAUSES OF VENOGENIC ED
Causes Examples
Abn venous channels Surgery forpriapism
Repeated stricture surgery
Veno-occlusive dysfunction Abn smooth muscle
function
Overactive sympathetic
tone
Ischaemia
Hypercholesterolaemia
Loss of smooth muscle Ageing
Ischaemia
Impaired tunica albuginae
function Peyronie’s disease
Ageing
Ischaemia

20. THERAPEUTIC DRUGS
CAUSING ED
• Antidepressants
Tricyclic
MAO inhibitors
SSRI
• Antihypertensives
B-blockers
Ca channel blockers
Diuretics
Central acting drugs
• Anti-cholinergic : Atropine
• Psychotropic : benzodiazepines
• Others: Cimetidine, digoxin, metoclopramide, phenytoin,
carbamazepine, ketoconazole
• HAART

21. NEUROGENIC CAUSES OF ED
SITE CAUSE
CNS Injury, Stroke ,encephalitis
Multiple sclerosis
Parkinson’s disease
Alzheimer’s disease
Temporal lobe epilepsy
Spinal Cord Injury
Multiple sclerosis
Spina bifida
Syringomyelia
Subacute combined degeneration
Spinal cord compression with
tumors

22. NEUROGENIC CAUSES OF ED
SITE CAUSE
Peripheral nervous systemPeripheral neuropathy, &
e.g.alcohol, diabetes,
amyloidosis
Radiation injury
Pelvic fracture injury
Disc Prolapse

23. SURGICAL CAUSES OF ED
SITE SURGERY
Neural Cerebral/Spinal surgery
control of erection
Pelvic Radical cystectomy/prostatectomy
parasympathetic nerves Rectal surgery-Ca Bladder& Rectum
(S2,3.4) Transpubic urethroplasty
TURP
Bladderneckincision
Penile vasculature Aorto-iliac surgery
Renal transplantation
Surgery forpriapism
Urethroplasty
Penis Peyronie’s disease
Penile amputation

24. ENDOCRINE CAUSES
•Diabetes mellitus
•Prolactinaemia
•Hypogonadism
•Hypo & Hyperthyroidism

25. SYSTEMIC DISEASES
• Hyperlipidemia
• Atherosclerosis
• Hypertension
• Chronic renal failure

26. PSYCHOGENIC
• Sudden onset
• Situational
• Relationship problem
• Life event
• Anxiety, fear, depression

27. SPORTS-RELATED ED
SITE SPECIFIC BLUNT
TRAUMA
• Cyclist
• Gymnastics – bars/projections
• Water-ski/water-jet ski
• Football
•
•
•
Munnariz RMe t al. JUro l1 9 9 5; 1 53: 1 8 31 -40

28. HISTORY
• Chronic medical/Psychiatric / Surgical
conditions
• Sexual
• Psychosocial
• Drugs
• Smoking/alcohol/recreational drugs
• Erectile dysfunction
questionnaires(International Index of erectile
function/IIEF)

29. EXAMINATION
• Body habitus -BMI
• 2ry
sexual characteristics
• CVS- Pulses /BP
• CNS –( lower limbs)
• Genitalia

30. INVESTIGATIONS
U/E/LFT,FBC,FBS
HBA1c
Lipid profile
S testosterone
S prolactin
LH/FSH
Urinalysis
Dip-stick
Thyroid function Tests
TSH

31. TREATMENT OPTIONS
Life style changes &
risk factor modification
Phychosexual
counselling
& education
Oral
agents Local
therapies
Surgical
therapy
New treatment modalities
Hormonal

32. ORAL AGENTS
•May act centrally - e.g. dopaminergic agonist
or
•Peripherally - e.g. phosphodiesterase-5
inhibitor

33. AVAILABLE ORAL AGENTS
Phosphodiesterase-5 inhibitor
• Sildenafil citrate (VIAGRA
®
)
• Tadalafil (CIALIS
®
)
• Vardenafil (LEVITRA
®
)

34. MECHANISM OF ACTION OF
PDE5 INHIBITORS

35. PDE5 INHIBITORS
Advantages
• Effective and
inexpensive
• Non invasive
• Require sexual
stimulation to be
effective
• Well tolerated
Disadvantages
• Contraindicated in
patients on nitrate
therapy
• Cytochrome P450 drug
interactions Caution
with protease inhibitors

36. DRUG INTERACTIONS OF PDE5
INHIBITORS
• Nitrates  added hypotensive effect
Recreational ‘Poppers’ (amyl nitrate)
Levels of PDE5 inhibitors Increased by
Protease inhibitors
erythromycin,
itraconazole/ ketoconazole

37. SILDENAFIL (VIAGRA,SELAGRA)
• Take ½ - 1 hour for action
• Action last 4 hours
• Food delays absorption
• Dose 25 mg-100mg
• Side effects: Headache, flushing, blocked nose,
epigastric discomfort, visual disturbance

38. SILDENAFIL & EYE PROBLEM
• Colour discrimination (blue-green)
• Non-anterior ischaemic optic neuropathy (NAION) – Po m e ranz e t
al20 0 2, 20 0 5, Bo shie r e t al20 0 2, Gruhn & Fle de lius 20 0 4
• Anterior ischamic optic neuropathy (AION) – Dhe e r e t al20 0 2
• Central serous chorioretinopathy – Allibhai e t al20 0 4

39. VARDENAFIL
(LEVITRA)
• Rapid onset of action (<30 mins)
• More specific for PDE-5
• Less side effects
• Action lasts 9 -12 hours
• Dose 10,20,40mg

40. TADALAFIL (CIALIS,
MEGAFIL)
• Longer half life
• Active for 24 hours
Dose 2.5mg -20mg
• Side effects- myalgia, back pain
• No visual disturbances

41. LOCAL THERAPIES
Second line
•Intra-urethral therapy
•Intra-cavernosal injection therapy
•Vacuum device therapy

42. INDICATION FOR LOCAL
THERAPIES
• Failure of oral drug therapy (DM)
• Contraindications to oral drugs (Nitrate
uses )
• Adverse events from oral drugs
• Individual preferences

43. TRANSURETHRAL ALPROSTADIL (MUSE/
MEDICATED URETHRAL SYSTEM FOR
ERECTION)

44. TRANSURETHRAL
APPLICATION OF
ALPROSTADIL
Advantages
• No needles
• Effective in about 2/3 of men
• Suitable/acceptable for most
men
Disadvantages
• 30% incidence of penile pain
• Requires dexterity &
insertion post-micturition
• Slower acting than injection
• Patients need to be taught
technique
• Just prior to sex

46. INTRACAVERNOSAL
ALPROSTADIL
•Viridal-duo
•Caverject

47. INTRACAVERNOSAL
INJECTION OF ALPROSTADIL
Advantages
• Rapidly effective
• Good success rates when
well motivated
• Suitable for most men
• Few contraindications &
drug interactions
Disadvantages
• Invasive, not acceptable
to some patients/partners
• Patients need to be
taught technique
• Manual dexterity &
reasonable eye sight
• Local side-effects (e.g.
penile pain, bleeding,
bruising, fibrosis)
• Priapism
• Just prior to sex

48. VACUUM PUMPS

49. VACUUM CONSTRICTION
DEVICES
Advantages
• Suitable for most men with ED
• Less side-effects
• Few contraindications
• Suitable for long term use
• Non invasive
Disadvantages
• Erections can be uncomfortable
• Erections may last > 30 minutes
• Sensation of ejaculation can be
impaired
• Lack of
spontaneity/cumbersome
• Partners may complain the
penis is felt cold
• Pivoting of penis at base
• Just prior to sex

50. SURGICAL THERAPY
• Penile prosthesis – Implant
• Correction of anatomical deformities-Peyronie’s disease
• Vascular surgery-may increase arterial inflow &
decrease venous outflow
young patients with arterial stenosis may be
candidates

51. PENILE
IMPLANT
Highly
invasive
Irreversible

52. HORMONAL REPLACEMENT
INDICATIONS
• Young patients with primary hypogonadisam
• ED with low testosterone level

53. LOW DENSITY EXTRA-
COPORAL SHOCK WAVE
THERAPY(LI-ESWT)
Advantages
No pain
No adverse effects
Not on demand basis
Non invasive
Feasible
Tolerable
Disadvantages
Cost
HCWdependent

54. METHOD OF APPLICATION OFMETHOD OF APPLICATION OF
LI-ESWTLI-ESWT

55. PHYSIOLOGY OF LI-ESWT

56. INTERNATIONAL PROTOCOLINTERNATIONAL PROTOCOL
• 2 sessions per week, for 3 weeks
• 3 weeks off therapy
• Repeat 2 sessions per week for 3 weeks

57. ED - THE FUTURE
• Alprostadil 0.3% topical cream licensing in Canada
and Europe ,Phase iii studies
• Gene therapy - based on vascular endothelial
growth factor and nitric oxide synthase genes-trails

58. TAKE HOME MASSAGE &
CHALLENGES
•In a steady relationship, involve sexual partner/s in
the management. it’s a problem to both partners
•Multidisciplinary approach is needed to manage
ED patients effectively
•Some treatments and investigations are costly and
not available in the SL government sector

59. Thank you