1. Canadian Undergraduate Urology Curriculum (CanUUC): Erectile Dysfunction
Last reviewed May 2017

2. Review Notes
? Remove industry images (slide 15)
Slide 36 – include man with partner

3. Objectives
Define erectile dysfunction
Classify the risk factors for erectile dysfunction (ED)
Describe the medical and surgical treatment options available for erectile dysfunction
Describe the contra-indications and patient counselling regarding PDE-5 inhibitors

4. Erectile Dysfunction (ED): Defined
“The consistent or recurrent inability to obtain and/or maintain an erection sufficient for satisfactory sexual activity”

5. Prevalence of ED: Massachusetts Male Aging Study
The Massachusetts Male Aging Study (MMAS), a community-based, multidisciplinary survey of health and aging in more than 1000 men, was conducted from 1987 to
The original data analysis published in 1994 found that 52% of men ages 40 to 70 years reported some degree of ED. In the study, erectile dysfunction was reported as minimal, moderate, or complete. Minimal ED was defined as “usually able to get or keep an erection”; moderate, as “sometimes able”; and complete, as “never able to get and keep an erection.”1
The large percentage of those affected (25% of men surveyed) were classified as having moderate ED, based on their responses to 9 questions about their sexual activity.1
Because of subsequent changes in the operational definition of ED, MMAS investigators recently re-estimated the prevalence of ED in their cohort to be 44%,2 which is slightly lower than the original estimate of 52%.
1. Feldman HA, et al. J Urol. 1994;151:54-61.
2. Kleinman KP, et al. J Clin Epidemiol. 2000;53:71-78.
Men aged 40 to 70 years (N = 1290) *
Feldman HA, et al. J Urol. 1994;151:54-61.

6. Causes of Erectile Dysfunction:
Vascular – arterial (cholesterol, diabetes, hypertension, trauma/surgery), venous
Neurogenic (surgery/trauma, MS, diabetes)
Psychologic (depression, anxiety, substance abuse)
Hormonal (low testosterone, thyroid, prolactin)
Anatomical (Peyronie’s disease, phimosis)
Medications (anti-hypertensives, SSRIs)

7. Pathophysiology of ED
This diagram indicates the relationship between the organic causes of ED and systemic diseased. Also, psychogenic ED can be primary (ie is the main cause of ED), but often arises as a secondary phenomenon in men with organic ED.

8. Major Risk Factors for ED:
CV Risk Factors
Smoking
Obesity
Sedentary
Hypertension
Diabetes
Hyperlipidemia
Cardiovascular Disease
Peripheral VD
Ψ Disease
Chronic Disease
Martin-Morales A et al. J Urol. 2001;166:
Laumann EO et al. JAMA. 1999;281:
Braun M et al. Int J Impot Res. 2000;12:

9. ED: A Canary in a Coal Mine
ED shares many risk factors for heart disease and warrants a cardiac risk assessment in most patients
In men aged 40-50, the first presentation of ED represents and independent risk factor for future cardiac events. Vigorous CV risk factor assessment and stratification should be undertaken in this population.

10. Evaluation & Diagnosis
Organic (90%)
Older adults
Gradual onset
Risk factors
Pervasive problem (nocturnal, intercourse, masturbation)
Psychogenic (10%)
Young
Sudden onset
Absence of risk factors
Situational/intermittent problem
Nocturnal or early morning erections maintained
Psychological history

11. Evaluation & Diagnosis
Medical, Sexual, Psychological History
Validated Questionnaire
Internation Index of Erectile Function (IIEF)
Sexual Health Iventory for Men (SHIM)
Physical Examination
HR, BP, weight/BMI
Penis: size, plaques, foreskin
Testis: size, masses, consistency
Peripheral pulses, sensation
Laboratory Investigations
Hg A1c/fasting glucose
Lipid profile
Testosterone (if signs/symptoms of TDS ex low libido)

12. Evaluation & Diagnosis
Specialized Testing (not routinely used):
Penile Duplex US with injection of vasoactive agent
Arterial inflow, venous outflow (leak) rigidity of erections
Not routinely required
Used in difficult cases, poor treatment response, etc.
Nocturnal Penile Tumescence
Presence, frequency, rigidity of erections
Organic vs. psychlogical cause
Angiography (internal pudendal)
Focal traumatic stenosis

13. Treatment Options for ED
Lifestyle Modification
Medical
Phosphodiesterase Type 5 Inhibitors (PDE5i)
Androgens/testosterone
Vacuum Constriction Device
Intraurethral Rx: MUSE
Intracavernosal Injection: Caverject, Trimix
Penile Prosthesis
Sex Therapy/Counseling

14. Lifestyle Modification
Smoking Cessation
Exercise
Diet
Limit Alcohol intake
Control hypertension/cholesterol
There is evidence that CV risk factor modification can improve sexual function, particularly in men with mild to moderate ED

15. Medical Therapy of ED PDE5i – On-demand
Approved 1998
2003
2003
Oral medical therapy for ED represented a substantial advnace in the treatment of men with ED. However, it is not a cure-all, and typically is most effective in men with vasculogenic ED. In addition, it does not treat isolated cases of low libido, premature ejaculation, or anorgasmia.
Contraindicated in men taking nitroglycerine (nitrates) or known hypersensitivity

16. Medical Therapy of ED PDE5i – Daily
Daily Cialis is an alternative to on-demand dosing. Lower incidence of side effects compared to on-demand treatment (lower peak serum levels) with similar efficacy, allows for more spontaneity, and is particularly useful in men who have difficulty “timing” the on-demand medication ahead of anticipated sexual activity. Relatively higher cost, unless patient is using frequent on-demand treatment (2+ times per week)
Contraindicated in men taking nitroglycerine (nitrates) or known hypersensitivity

17. PDE5 Inhibitors: Pharmacokinetic Comparison
Sildenafil
100 mg (fasted)
Vardenafil
20 mg (fasted)
Tadalafil
20 mg (fasted)
Tmax (min) 70 48
120
T1/2 (h)
4.0
17.5
Tmax significantly longer for tadalafil than for sildenafil, vardenafil
T1/2 significantly longer for tadalafil than for sildenafil, vardenafil
Longer clearance time may interfere with readministration, concurrent meds
Data are shown as means
1. Klotz et al, ACCP 2002
2. Sildenafil product monograph
3. Tadalafil B Pullman, IC351 (Tadalafil) Symposium, Indianapolis, Ind, June 7, 2001.

18. Mechanism of Erections: Vascular Circulation
Smooth muscles contracted > vasoconstriction > low blood flow
Smooth muscles relaxed > vasodilation > high flow
Flaccid Penis
Erect Penis
Patel U, Lees WR. In: Textbook of Erectile Dysfunction. 1st ed. Oxford, UK: Isis Medical
Media Ltd; 1999:

19. Mechanisms of Smooth Muscle Cell Relaxation with PDE5i
For PDE-5i to be effective, mental and physical stimulation, in conjunction with an intact innervation to the penis, are required. Therefore, there is lower efficacy in men with a neurogenic cause of ED (pelvic surgery, peripheral neuropathy from DM). Also, failure may occure if there is severe atherosclerosis, or structural abnormalities of the penis such as Peyronie’s disease

20. Common Side Effects of PDE5i
McMurray: Poster:d
McMurray: Poster: b,d,e
Headache
Dyspepsia
Rhinitis
Flushing of face/skin
Abnormal vision (Viagra)
Dizziness
Myalgias (Cialis)
Slide 34 Incidence of Treatment-Related Adverse Events (AEs) in Sildenafil (sildenafil citrate): Long-term Extension Studies
In the 4-year, open-label, flexible-dose extension study of Sildenafil, involving a total of 979 men aged 27 to 82 years, there were no serious treatment-related AEs. Treatment-related AEs were reported by 3.8% of patients, leading to discontinuation in only 1.2% of the patient population. The most common AEs were headache (1%), followed by dyspepsia (1%), rhinitis (0.6%), flushing (0.5%), abnormal vision (0.4%), and dizziness (0.3%).33
There were no serious treatment-related AEs. During the 4-year study period, 6.3% of patients discontinued because of an insufficient response (2.2% per year).33
Carson CC, et al. Urology. 2002;60:12-27.
McMurray JG, et al. Poster presented at: 10th World Congress of the International Society for Sexual and Impotence Research; September 22-26, 2002; Montreal, Canada.
Please see full prescribing information for Sildenafil 25-mg, 50-mg, 100-mg tablets accompanying this presentation.

21. Contraindications to PDE5i
Absolute:
Use of Nitrate medication
Relative:

22. Contraindications to PDE5i
NOT contraindicated in patients with:
History of stable CV disease/MI (except if absolute or relative contraindications exist)
Patients on alpha-blockers for BPH (historical)
Young patients with psychogenic ED (may help)
Does NOT cause priapism
Still mentioned on product monograph

23. Patient Education – Keys to PDE-5i Success
Patient Education critical to success
Take 30 min in advance of sex (1 hr for Cialis)
Mental and physical stimulation required
Not a “magic” erection pill, best of partner aware
Anxiety can counteract effects of medication
Try medication several times
Efficacy of the 3 drugs varies from patient to patient
Try at least 2 drugs before declaring failure
Warn patient about side-effects, and reassure them that they won’t die by taking PDE-5i

24. Androgens and Testosterone Replacement
May be useful in men with ED and low testosterone (esp if other symptoms of testosterone deficiency exist i.e. low libido)
Consider in men not responding to PDE5i

25. Testosterone Deficiency Syndrome
Bhasin S et al. Testosterone Therapy in Adult Men with Androgen Deficiency Syndromes: An Endocrine Society Clinical Practice Guideline

26. Testosterone Deficiency Syndrome
Initial Evaluation for TDS
Morning serum Total T, FSH, LH, Prolactin
PSA, CBC, DRE if considering therapy
Treatment (indicated for symptoms of TDS + Low T)
Topical Gel – 1st Line (Androgel, Testim, Axiron)
Other agents – 2nd Line (Oral, IM, Patch)
Monitoring (q3-6 months initially)
Symptom assessment and CBC, PSA, DRE

27. MUSE Intraurethral Suppository (PGE-1)
MUSE is a self-adminitered prostaglandin pellet that is introduced into the urethra. The medication is then absorbed locally into the copora cabernosa, where is promoted vasodilation.

28. 1 2 3 4 Problems: Limited efficacy Pain Priapism MUSE *
Pain can occure for the patient and partner (intravaginal deposition of PG). Overall efficacy is relatively low. MUSE must be kept in the fridge 3 4 *

29. Vacuum Erection Device
VEDs are rarely used. There is very limited efficacy data, and mainly is pursued by patients who do not wish to undertake pharmacologic therapy. Often is used in conjunction with a constrictive ring placed at the base od the penis
Cumbersome
Limited efficacy
Non-pharmacologic
Can be used in patients on Ntg

30. Intracavernosal Injection Therapy (ICI)
Caverject
(Alprostadil)
Triple P:
PGE-1
Phentolamine
Papaverine
ICI was the mainstay of treatment for organic ED prior to the introduction of PDE-5i medication. Now it is used as second line treatment, usually for PDE-5i failures. It is particularly useful in patients with neurogenic ED (spinal cord injury, history of pelvic surgery like RP on LAR), where PDE-5i therapy is limited due to the lack of penile innervation. Can also be used in cases of severe vasculogenic ED. Caverject in the only approved injectable Rx, comes in a pre-loaded syringe, and must be kept refrigerated. Cost is realtively high, espicailly for patients who don’t require the full dose provided in the package (single use so unused portion must be discarded). Triple P is compounded in the pharmacy, and is off-label use of the medications (although it represents well-established Rx). There is a risk of priapism with both, and typically these medications are prescribed and monitored by a urologist. Can be used in patients who are on NTG or anticoagulation.

31. Penile Implants/Prosthesis

32. Non-inflatable (malleable) Penile Implant
Cylinder
NON-INFLATABLE PENILE IMPLANT
Advantages
A. Easy for you and your partner to use -- You simply bend it up for an erection. Down when not in use.
B. Good option for men with limited dexterity -- Something to consider if you have arthritis or difficulty using your hands.
C. Totally concealed in body -- All parts of the device are implanted inside the body.
D. The simplest surgical procedure -- Of the three types of implants, the non-inflatable device involves the simplest surgical procedure.
E. Least expensive -- Non-inflatable implants are the least expensive type of penile implant. This may be a consideration for men not covered by insurance.

33. Inflatable 2-Piece Penile Implant
Cylinder
2-PIECE INFLATABLE PENILE IMPLANT
Advantages
A. Simple to use -- Inflating the device is fast and simple, taking just a few seconds to achieve an erection.
B. Excellent comfort -- The device feels natural during intercourse.
C. Fast and simple one-step deflation -- Simply bend the prosthesis down for 12 seconds and then release.
D. Totally concealed in body -- All parts of the device are implanted inside the body.
Pump & reservoir

34. Inflatable 3-Piece Penile Implant
Reservoir
Cylinder
3-PIECE INFLATABLE PENILE IMPLANT
Advantages
The 3-piece Implant offers the same advantages as 2-piece, plus:
A. Acts and feels more like a natural erection -- The 3-Piece Inflatable Penile Implant closely approximates the natural erection process.
B. Expands the girth of the penis -- The cylinders expand more fully, creating an erection that is wider and more full.
C. More firm and full than other implants -- The 3-Piece may provide a more pleasurable experience because it becomes more firm and full than other types of implants.
D. Feels softer and more flaccid when deflated -- Many men forget they have an implant at all because their penis feels so natural when flaccid
Pump

35. Risks of penile implants
Infection: usually requires complete removal
Perforation: in the OR
Malfunction: 5% in 10 years
Urethral injury
Erosion: tip of penis, bladder

36. Psychogenic causes almost always present
Psychogenic ED
Psychogenic causes almost always present
Secondary in men with organic ED (discouragement)
Primary in some men (10%)
Almost all men with ED have a psychogenic component. In men with organic ED, the psychogenic component is secondary to the organic cause, and is usually present due to discouragement/frustration, and may also manifest as low libido. In some men, the primary cause of ED is psychogenic. This should be evaluated on the history and physical.

37. ED is common, and usually has an organic component
Summary
ED is common, and usually has an organic component
Always consider occult CV disease
A variety of treatment options exist
PDE-5i therapy useful in most, pt education key
Urology referral appropriate for PDE-5i failures or contraindications exist
Testosterone therapy useful is select cases