Erectile Dysfunction: A Window

To Men’s Health
Prof Dato Dr. Zulkifli Md Zainuddin
Consultant Urologist
 Over the last 20 years …

Google has transformed the internet1

1. https://www.livescience.com/20727-internet-history.html Accessed on 16th February 2019

 Over the last 20 years …
The published literature has grown.

434
publications
in 1998 w
increased to
1,035 in
2013.

1. https://www.ncbi.nlm.nih.gov/pubmed/ Accessed on 16th February 2019

 History
It’s 25 years since the first PDE-5i was lauched1

19981 20031 2022 SPEDRA

Sildenafil Vardenafil,
Tadalafil
And now,
a new PDE-5i
arrives2

1. Huang SA, Lie JD. Phosphodiesterase-5 (PDE5) Inhibitors In the Management of Erectile Dysfunction. P T. 2013 Jul;38(7):407-19.
2. SPEDRA Malaysia Approved Product Information, August 2021
 Over the last 20 years …
Men’s health has stayed the same1
Compared to women, men are:
§ Fatter
§ Smoke more
§ Exercise less
§ Higher blood pressure
§ Higher cholesterol
§ More diabetes
§ Abuse alcohol more
§ More cancer
§ More heart disease
§ More depression, violence & suicide
1. Crimmins B 2010. Blokes’ Health. The doctors guide that comes with a good laugh. Wilkinson Publishing Pty Ltd, Melbourne. 2010
 Predicted Increase in Prevalence
of ED by 2025

North America Europe Asia

21.1 42.8 199.9
30.1
11.9 86.9

1995 2025 1995 2025 1995 2025

South & Central Africa

America and the 30.8
Caribbean
26.1
11.5 Oceania
10.5
1.0 1.9

1995 2025 1995 2025

1995 2025

Worldwide prevalence will increase from

152 million men in 1995 to 322 million men in 2025

Aytac IA et al. BJU Int 1999; 84: 50-56

§ The overall prevalence of self-reported ED was
81.5%
 Many men with ED still aren’t
talking to their physician
Recent survey conducted in men with ED aged ≥45 years

- 38% of men had never talked to a

physician about their ED
- Of those men who had spoken to
their physician, 86% initiated the
conversation themselves

§ Average time from first development of

symptoms to presentation = 2 years

Ipsos Survey 2008. http://www.menshealthnetwork.org/library/EDsurvey2008.pdf

 Alarm Bells

“ED should not be

regarded only as a QoL
issue, but also as a
potential warning sign of
cardiovascular disease.”1

1. Hatzimouratidis K et al EAU Guidelines on Erectile Dysfunction, Premature Ejaculation, Penile Curvature and Priapism. European Association of Urology 2016.
2. Crimmins B 2010. Blokes’ Health. The doctors guide that comes with a good laugh. Wilkinson Publishing Pty Ltd, Melbourne. 2010
 Erectile Dysfunction
• ED often occurs before other vascular diseases
The artery size theory
–ED manifests earlier than cardiovascular disease because the smaller
penile arteries reach critical narrowing, with insufficient blood flow, earlier
than larger vessels
(Threshold for symptom development is 50% lumen.)

Early

Late

Penile artery Coronary artery Carotid artery Femoral artery

1-2 mm 3-4 mm 5-7 mm 6-8 mm
ED Angina/infarction Stroke Claudication

18
Montorsi P, Ravagnani PM, Galli S, et al. The artery size hypothesis: a macrovascular link between erectile dysfunction and coronary artery disease. Am J
Cardiol. 2005;96(suppl):19M–23M.
19
Penis is the dipstick to men’s health.
 Management of
Erectile Dysfunction
 World Health Organization
Guidelines
ED Unresolved
Oral Agents (unless contraindicated),
Sexual Counseling,
and Education
Local
Therapies
• Intracavernosal injections
ED resolved. • Intraurethral PGE1
Patient satisfied. • Vacuum device
ED Unresolved
ED Unresolved
Alter
Modifiable
Risk Factors Surgical
and Causes Treatments
Recommendations of the 1st International Consultation on Erectile Dysfunction. In: Jardin A et al, eds. Erectile
Dysfunction. Plymouth, UK: Health Publication, Ltd; 2000:711-726.
IIEF Scale: A multidimensional
scale
• International index of erectile function (IIEF)
• Developed in 1996
• First multidimensional scale developed to assess erectile function
• 15-item self-administered questionnaire

Five domains:
• Erectile function
• Orgasmic function
• Sexual desire
• Intercourse satisfaction
• Overall satisfaction
Addresses erection hardness with Q2: “Erection firmness”

• Addresses all aspects of ED as defined by NIH Consensus Panel

– Ability to achieve (Q3) and maintain (Q4) an erection sufficient for
satisfactory sexual performance (Q7)
ED, erectile dysfunction; NIH, US National Institute of Health Rosen RC et al. Urology 1997;49:822-830 9
 The Erection Hardness Scale (EHS)
IIEF-EF Severe ED Moderate ED Mild ED No ED
6–10 11–21 22–25 26–30
Optimal
Suboptimal Erection
Moderate Erectile Erection
Dysfunction
Severe Erectile
Dysfunction

Penis is hard Penis is hard Penis is

Penis is larger
but not hard enough for completely
but not hard
enough for penetration hard and
penetration but not fully rigid
completely
hard

Goldstein I, et al. N Engl J Med 1998;338:1397-1404; Mulhall JP, et al. J Sex Med 2007;4:1626-1634.
 Diagnosis and Treatment of ED
• First-line treatment: Oral treatment – PDE5 inhibitors
– PDE5 inhibitors are recommended as the preferred
pharmacotherapy for ED
– PDE5i is a class of vasodilators that work on the nitric oxide-
cGMP mechanism to help restore natural erectile function in
the presence of sexual stimulation
– Efficacy is defined by rigidity sufficient for vaginal penetration

Wespes E, Amar E, Hatzichristou D, et al. EAU Guidelines on erectile dysfunction: an update. Eur Urol. 2006;49:806-815; Wright PJ. Comparison of
phosphodiesterase type 5 (PDE5) inhibitors. Int J Clin Pract. 2006;60:967–975; Mulhall J, Althof SE, Brock GB, et al. Erectile dysfunction: monitoring
response to treatment in clinical practice—recommendations of an international
25 study panel. J Sex Med. 2007;4:448-464; Rosen RC, Kostis JB. Overview
of phosphodiesterase 5 inhibition in erectile dysfunction. Am J Cardiol. 2003;92(suppl):9M-18M; Wespes E, Amar E, Eardley I, et al. Erectile dysfunction
and premature ejaculation. Guidelines on Male Sexual Dysfunction. 2010.
Not all PDE 5 Inhibitors are the same
 Summary of the key pharmacokinetic data for the four
PDE5Is currently EMA-approved to treat ED*1

1. Hatzimouratidis K, et al.. EAU Guidelines on erectile dysfunction, premature ejaculation, penile Curvature and Priapism. Edn. presented at the EAU
Annual Congress Barcelona 2019. ISBN 978-94-92671-04-2
 Efficacy of Tadalafil for LUTS BPH
Effect on IPSS

*Please note, Tadalafil 2.5mg OD is not a licensed dose for the signs and symptoms of BPH.
† IPSS = International Prostate Symptom Score.

Egerdie et al. J Sex Med 2011;9: 271 - 281

 IPSS Total: Mean Change from
Baseline
12-week
0
Baseline
Endpoint Placebo
LS Mean Tadalafil 5 mg
Treatment Mean
Change -1
(SD)
(ANCOVA,
Tamsulosin 0.4 mg
-2

LS Mean Change from Baseline

LOCF)

Placebo 17.4 (6.0) -4.2

-3

IPSS Total
**
-4
**
Tadalafil 5 mg 17.2 (4.9) -6.3***
-5 ***
*
-6 ***
***
Tamsulosin 0.4
16.8 (5.3) -5.7*
-7
mg Baseline Week 1 Week 4 Week 12

*p<.05,***p≤.001 compared to
placebo

Oelke et al. Eur Urol 2012;doi:10.1016/j.eururo.2012.01.013.

 Uroflowmetry

Placebo Tadalafil 5 mg Tamsulosin 0.4 mg

(N = 172) (N = 171) (N = 168)

Mean Mean Mean

Baseline Change ± Baseline Change Baseline Change
Measure n Mean ± SD SD n Mean ± SD ± SD n Mean ± SD ± SD

Qmax, mL/s 147 10.5 ± 4.1 1.2 ± 4.8 156 9.9 ± 3.6 2.4 ± 5.5** 144 9.4 ± 3.3 2.2 ± 4.1*

*p<.05, **p<.01
Qave, mL/s 147 6.1 ± 2.4 0.7 ± 2.7 156 5.9 ± 2.1 1.6 ± 3.2** 145 5.8 ± 2.3 1.3 ± 3.0*

Oelke et al. Eur Urol 2012;doi:10.1016/j.eururo.2012.01.013.

 Efficacy of Tadalafil for LUTS BPH
Effect on IIEF

*Please note, Tadalafil 2.5mg OD is not a licensed dose for the signs and symptoms of BPH.
**IIEF-EF = International Index of Erectile Function, Erectile Function domains.

Egerdie et al. J Sex Med 2011;9: 271 - 281

Study n Δ IPSS Δ IIEF

Porst et al 325 -5.6 6.7 Significant

Egerdie et 606 -6.1 6.5 Significant

al
Oelke et al 511 -6.3 4.0 Significant

Donatucci 428 -5.0 5.9 Significant

et al
You need to know your patient’s
sexual ecology
Side Effects
 Similar Side effects of all three
PDE5i……

• facial flushing
• nasal congestion
• headache
• dyspepsia
 Common adverse events of the four PDE5Is
currently EMA-approved to treat ED*1

1. Hatzimouratidis K, et al.. EAU Guidelines on erectile dysfunction, premature ejaculation, penile Curvature and Priapism. Edn. presented at the EAU
Annual Congress Barcelona 2019. ISBN 978-94-92671-04-2
 Selectivity profiles of PDE-5i1

Superior selectivity for PDE5 over

PDE1, PDE3, PDE6 and PDE11 may be
responsible for Avanafil’s low adverse
1. Wang R et al. Selectivity of avanafil, a PDE5 inhibitor for the treatment of erectile dysfunction: Implications for clinical safety and improved tolerability. J Sex Med 2012;9:2122-2129

event profile
 All PDE 5 Inhibitors are
contraindicated with Nitrates
 Fatty meal
• Sildenafil:
• Cmax reduced by
29%

• Avanafil unchanged

• Tadalafil -unchanged
Most Important Educational Points
• Need sexual stimulation
• Proper time to take the
medication
• Need patience
• Avoid sexual attempts
when fatigued, drinking or
smoking
• Be optimistic!
 With increasing age:
- Men need longer time to get
erection
- Men need direct genital
stimulation to get erection
- Orgasm and ejaculation are
less intense
- Refractory period increase
Vacuum Devices
Vacuum erection device

52
Vacuum erection device

53
Penile Injections ( ICI)
Semi-Rigid Penile Implants

57
Penile prosthesis

58
Inflatable Penile Prosthesis

60
 Summary
– Erectile dysfunction can be treated.
– Proper history and physical examination crucial
– Need to screen cardiovascular as ED preceed coronary artery
disease 3-5 years
– First line treatment is PDE 5 inhibitor
• Proper advice on pharmacokinetics
– Other treatment options
• Intracavernosal prostaglandin injection
• Vacuum pump
• Penile prosthesis

61
Thank You