Approach to Erectile Dysfunction Dr Ho Siew Hong Consultant Urologist S H Ho Urology and Laparoscopy Centre Gleneagles Hospital

Erectile Dysfunction in Family Medicine Definition Diagnosis and Investigations Association with other medical conditions Treatment options – PDE 5 inhibitors Safety Treatment failures

Definition

Diagnosis and Investigations

Association with other medical conditions

Treatment options – PDE 5 inhibitors

Safety

Treatment failures

What is Erectile Dysfunction? Consistent or recurrent inability of a man to attain and/or maintain a penile erection sufficient for sexual activity Independent of sexual desire and the ability to have an orgasm and ejaculate National Institute of Health, USA

Consistent or recurrent inability of a man to attain and/or maintain a penile erection sufficient for sexual activity

Independent of sexual desire and the ability to have an orgasm and ejaculate

Pathophysiology of ED ED by Classification Causes of Organic ED Clinical Manual of Sexual Medicine Sexual Dysfunctions in Men. Based on the Reports of the 2nd International Consultation on Sexual Dysfunctions, 2003.

How is ED diagnosed?

Diagnosis of ED Medical and psychological history from patient and partner Sexual history IIEF Questionaire (International Index of Erectile Function) Focused physical examination, BP Hormones - testosterone Blood glucose Selected patients: - lipid profile - prolactin - PSA

Medical and psychological history from patient and partner

Sexual history

IIEF Questionaire (International Index of Erectile Function)

Focused physical examination, BP

Hormones - testosterone

Blood glucose

Selected patients: - lipid profile - prolactin - PSA

ED as an indicator of other medical conditions

Major Risk Factors for ED: Chronic Diseases 1. Martin-Morales A et al. J Urol . 2001;166:569-575. 2. Braun M et al. Int J Impot Res . 2000;12:305-311. 3. Goldstein I. Am J Cardiol . 2000;86(suppl):41F-45F. 4. Feldman HA et al. J Urol . 1994;151:54-61. Chronic Disease Increased ED Risks* Diabetes 1,2  4.1 Prostate disease 1   2.9 Peripheral vascular disease 1  2.6 Cardiac problems 1  1.8 Hyperlipidemia 1  1.6 Hypertension 1,2  1.6 Depression 3,4  1.8 * Age-adjusted odds ratio.  Prostatic symptoms on the International Prostate Symptom Score (IPSS) questionnaire.

Certain Diseases are Strongly Associated with ED Note: 64% of men with ED reported at least one or more of these conditions Rosen et al. Curr Med Res Opin 2004;20:607-17 ED n=4,422 No ED n=23,416 19 7 16 4 13 36 17 29 14 0 5 10 15 20 25 30 35 40 HTN CHD/ angina High cholesterol Diabetes Depression/ anxiety Men reporting disease (%) 25 p < 0.0001 There is a higher prevalence of co-morbid diseases in men with ED

Current treatment of ED

Current treatment for ED PDE 5 inhibitors Testosterone replacement therapy Intracavernosal injection Vacuum device Surgery

PDE 5 inhibitors

Testosterone replacement therapy

Intracavernosal injection

Vacuum device

Surgery

Oral erectogenic medications Phosphordiesterase inhibitors (PDE5I) Approved for treatment of erectile dysfunction by FDA in 1998 1 st line of treatment for organic ED Levitra, Viagra, Cialis

Phosphordiesterase inhibitors (PDE5I)

Approved for treatment of erectile dysfunction by FDA in 1998

1 st line of treatment for organic ED

Levitra, Viagra, Cialis

Are they effective? Effective in 80% - 84 % Satisfactory erection for penetration In the presence of sexual stimulation Correct dosing, method of administration Less effective in patients with serious diabetes mellitus, hypertension and other long standing medical conditions

Effective in 80% - 84 %

Satisfactory erection for penetration

In the presence of sexual stimulation

Correct dosing, method of administration

Less effective in patients with serious diabetes mellitus, hypertension and other long standing medical conditions

CV Safety Viagra Levitra ® Cialis Myocardial infarction 0.8 % 0.4 % 1.2 % Cardiac death 0.23 % 0.05 % 0.3 % Mittleman et al. Int J Clin Pract 2003;57;597-600; Porst et al. IJIR 2002;14(Suppl 4):S59; Montorsi et al. Eur Urol 2004;45:339-45

What are the side-effects? Headache 15% Flushing 3 – 10% Nose congestion 5 – 10% Indigestion 3 - 10% Visual disturbance (blue vision) 5%

Headache 15%

Flushing 3 – 10%

Nose congestion 5 – 10%

Indigestion 3 - 10%

Visual disturbance (blue vision) 5%

Which is the suitable drug for my patient? Many well conducted RCTs on ‘Preference’ and ‘hardness’ show very little difference between drugs Onset of action is similar Tadalafil has longest half life Choice is entirely up to patient

Many well conducted RCTs on ‘Preference’ and ‘hardness’ show very little difference between drugs

Onset of action is similar

Tadalafil has longest half life

Choice is entirely up to patient

Practical / Reality Patients depend our recommendation for the first drug Allow each drug adequate dosages (up to 4 doses) Water will find it’s level We are not a pharmacy

Patients depend our recommendation for the first drug

Allow each drug adequate dosages (up to 4 doses)

Water will find it’s level

We are not a pharmacy

Effects of PDE 5 inhibitors on the eye Cross reaction with PDE 6 receptors in retina 3% may ‘see blue’, no long term effects PDE 5 inhibitors not recommended for patients with retina disorders

Cross reaction with PDE 6 receptors in retina

3% may ‘see blue’, no long term effects

PDE 5 inhibitors not recommended for patients with retina disorders

PDE 5 inhibitors and... Blindness PDE inhibitors causing blindness – non arteritic anterior ischaemic optic neuropathy (NAION) Small blood vessels in eye not getting enough blood, resulting in a stroke and optic nerve degeneration Can range from loss of a portion to total loss of vision Affects 1 to 10 in 100,000 persons, esp. with diabetes and high blood pressure No definite link between use of PDE5I and NAION

Blindness

PDE inhibitors causing blindness – non arteritic anterior ischaemic optic neuropathy (NAION)

Small blood vessels in eye not getting enough blood, resulting in a stroke and optic nerve degeneration

Can range from loss of a portion to total loss of vision

Affects 1 to 10 in 100,000 persons, esp. with diabetes and high blood pressure

No definite link between use of PDE5I and NAION

PDE 5 inhibitors and... Sudden hearing loss ‘ no causal relationship has been demonstrated, the strong relationship between the use of these drugs and sudden hearing loss in these cases warrants revisions to the product label ’ FDA 2007 Fertility no evidence that Viagra decreases fertility in men

Sudden hearing loss ‘ no causal relationship has been demonstrated, the strong relationship between the use of these drugs and sudden hearing loss in these cases warrants revisions to the product label ’ FDA 2007

Fertility no evidence that Viagra decreases fertility in men

PDE 5 inhibitors and... Alpha blockers (BPH therapy) Individuals who take these alpha-blockers should be on a stable dose of the alpha-blocker before PDE 5 I is started. In such situations, PDE 5 I should be started at the lowest dose . If the patient is already taking PDE 5 I , the alpha-blocker should be started at the lowest dose

Alpha blockers (BPH therapy)

Individuals who take these alpha-blockers should be on a stable dose of the alpha-blocker before PDE 5 I is started.

In such situations, PDE 5 I should be started at the lowest dose .

If the patient is already taking PDE 5 I , the alpha-blocker should be started at the lowest dose

What if PDE5I is not effective?

PDE 5 inhibitors - tablets Vacum device Intra-cavernosal PGE injections Hormone replacement therapy Surgery Others – traditional medicine, supplements

In non-responders to PDE-5 inhibitors Failure rate of 18 – 37% is reported Depending on co-morbidities thereof: Hypogonadism 50% Diabetes mellitus 35% LUTS / BPS 22% Hypertension 23% Yassin et al. IJIR Vol. 14, Suppl. 3, 9/2002

Failure rate of 18 – 37% is reported

Depending on co-morbidities thereof:

Hypogonadism 50%

Diabetes mellitus 35%

LUTS / BPS 22%

Hypertension 23%

Late Onset Hypogonadism ADAM, PADAM, Andropause ‘ clinical and biochemical syndrome associated with advancing age and characterized by typical symptoms and a deficiency in serum testosterone levels. It may result insignificant detriment in the quality of life and adversely affect the function of multiple organ systems ’ ISA, ISSAM, and EAU recommendations SUA recommendations

ADAM, PADAM, Andropause

‘ clinical and biochemical syndrome associated with advancing age and characterized by typical symptoms and a deficiency in serum testosterone levels. It may result insignificant detriment in the quality of life and adversely affect the function of multiple organ systems ’

ISA, ISSAM, and EAU recommendations

SUA recommendations

Clinical manifestation of LOH The easily recognized features of diminished SEXUAL DESIRE ( LIBIDO ) and erectile quality and frequency, particularly nocturnal erections Changes in mood with concomitant decreases in intellectual activity, cognitive functions, spatial orientation ability, fatigue, depressed mood and irritability Sleep disturbances Decrease in lean body mass with associated diminution in muscle volume and strength Increase in visceral fat Decrease in body hair and skin alterations Decreased bone mineral density resulting in osteopenia, osteoporosis and increased risk of bone fractures

The easily recognized features of diminished SEXUAL DESIRE ( LIBIDO ) and erectile quality and frequency, particularly nocturnal erections

Changes in mood with concomitant decreases in intellectual activity, cognitive functions, spatial orientation ability, fatigue, depressed mood and irritability

Sleep disturbances

Decrease in lean body mass with associated diminution in muscle volume and strength

Increase in visceral fat

Decrease in body hair and skin alterations

Decreased bone mineral density resulting in osteopenia, osteoporosis and increased risk of bone fractures

Diagnosing Andropause Symptoms Blood tests: Testosterone Tests usually done in the morning

Symptoms

Blood tests: Testosterone

Tests usually done in the morning

Testosterone replacement therapy Tablets – Andriol Injections - 3 weekly - 3 monthly (Nebido) Skin patch, gel

Tablets – Andriol

Injections - 3 weekly - 3 monthly (Nebido)

Skin patch, gel

Conclusions Initial evaluation and management of ED will shift to the family physician Diagnosis and Investigations Association with other medical conditions Treatment options – PDE 5 inhibitors Safety Treatment failures

Initial evaluation and management of ED will shift to the family physician

Diagnosis and Investigations

Association with other medical conditions

Treatment options – PDE 5 inhibitors

Safety

Treatment failures

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