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Mohamed Hassanein, FRCP, MPhil. Mohamed Hassanein, FRCP, MPhil.
Consultant Diabetes & EndocrinologyConsultant Diabetes & Endocrinology
Glan Clwyd Hospital. Glan Clwyd Hospital.
ED & CKDED & CKD
Apr 21, 2023Apr 21, 2023 MHMH
1st International Consultation on Erectile Dysfunction, Paris, July 1999.
ED: DefinitionED: Definition
The consistent or recurrent The consistent or recurrent inability of a man to inability of a man to attainattain and/or and/or maintainmaintain a penile a penile
erection sufficient for erection sufficient for sexual intercoursesexual intercourse
Apr 21, 2023Apr 21, 2023 MHMH
EpidemiologyEpidemiology
ED affects ED affects at leastat least 1 in every 10 men 1 in every 10 men11
It is estimated that the prevalence of ED will double over the next It is estimated that the prevalence of ED will double over the next 20 years20 years22
ED affects an estimated 2.3 million men in the UK aloneED affects an estimated 2.3 million men in the UK alone11
Affects ~30 million men in USAAffects ~30 million men in USA33
1. Impotence Explained. A couple’s guide to Erectile Dysfunction. The Impotence Association.2. Aytac LA et al. BJU International 1999; 84: 50-56. 3. Benet AE, Melman A. Urol Clin North Am. 1995;22:699-709
Apr 21, 2023Apr 21, 2023 MHMH
Prevalence of ED: Sampling of Worldwide ResultsPrevalence of ED: Sampling of Worldwide Results
1. Braun M, et al. Int J Impot Res. 2000;12:305-311. 2. Martin-Morales A, et al. J Urol. 2001;166:569-575. 3. Chew KK, et al. Int J Impot Res. 2000;12:41-45. 4. Blanker MH, et al. J Am Geriatr Soc. 2001;49:436-442. 5. Goldmeier D, et al. Int J STD AIDS. 1997;8:303-306, 6. Nicolosi et al 2003, Urology, 61 (1); 201-205. 7. Laumann et al, 2003 GSSAB, Progres en Urologie, Abstract, Vol.13,S,No.2 No 3.
Age Age % %
Japan,Japan,66 40-7040-70 34.0 34.0AustraliaAustralia33 40-69 40-69 33.9 33.9Malaysia,Malaysia,66 40-7040-70 22.0 22.0Cologne,GermanyCologne,Germany11 30-80 30-80 19.2 19.2 London, UKLondon, UK55 16-78 16-78 19.0 19.0 Iberian Peninsula, SpainIberian Peninsula, Spain22 25-70 25-70 18.9 18.9Italy,Italy,66 40-70 17.0 40-70 17.0Brazil,Brazil,66 40-70 40-70 15.0 15.0Krimpen, NetherlandsKrimpen, Netherlands44 50-78 50-78 11.0 11.0Middle EastMiddle East7 (Algeria, Egypt, 7 (Algeria, Egypt, 40-80 10.140-80 10.1 Morocco, Turkey. n.= Morocco, Turkey. n.= 1,349)1,349)
Apr 21, 2023Apr 21, 2023 MHMH
1. Lewis RW. Urol Clin North Am. 2001;28:209–216.2. Nicolosi A, Glasser DB, Brock G, et al. Br J Diabetes Vasc Dis. 2002;2:336–339. 3. M Hassanein, et al Diabetic Medicine, Suppl 1 Diabetes UK, March 2005
ED and diabetesED and diabetes
The prevalence of ED in men with diabetes is estimated The prevalence of ED in men with diabetes is estimated as 35-75%as 35-75%11. .
ED occurs in at least 50% of male patients with ED occurs in at least 50% of male patients with diabetes within 10 years of the diagnosisdiabetes within 10 years of the diagnosis11
The frequency of ED in diabetic men aged 45–49 years The frequency of ED in diabetic men aged 45–49 years was similar to non-diabetic men aged 70+ yearswas similar to non-diabetic men aged 70+ years22
In a UK study of 1362 men with ED, 21% had DMIn a UK study of 1362 men with ED, 21% had DM33
Apr 21, 2023Apr 21, 2023 MHMH
CVD & EDCVD & ED1,21,2
•The risk of developing ED is increased in the presence of diabetes, heart disease, and hypertension. @2005 American Urological Association Education and Research, Inc.® Appendix 1-10
•CV Risk factors in 1152 ED patients :
-40.7% Hypertension
-- 19.3% Diabetes
- 22.6% Dyslipidaemia
-- 34.1% Smoking
- 13.7% Obesity-Partrico M et al, J Sex Med, 2005 (ESSM)
Apr 21, 2023Apr 21, 2023 MHMH
Prevalence of Co-morbidity in ED: M.A.L.E.S StudyPrevalence of Co-morbidity in ED: M.A.L.E.S Study
26
35
21
30
43
48
2629
44
51
0
10
20
30
40
50
60
Depression Diabetes High TC CVD Hypertension
2001 2004
Eardley, I et al, J Sexual Med, Suppl 1 2005 (ESSM)
Apr 21, 2023Apr 21, 2023 MHMH
Aetiology of Erectile DysfunctionAetiology of Erectile Dysfunction
80% Organic80% Organic
– Cardiovascular DiseaseCardiovascular Disease– DiabetesDiabetes– Post SurgeryPost Surgery– Spinal Cord InjurySpinal Cord Injury– Multiple SclerosisMultiple Sclerosis– EndocrineEndocrine
20% Psychogenic20% Psychogenic
• The risk of developing ED is increased in the presence of diabetes, heart disease, and hypertension. @2005 American Urological Association Education and Research, Inc.® Appendix 1-10
Apr 21, 2023Apr 21, 2023 MHMH
Why we don’t Treat ED?Why we don’t Treat ED?
Lack of timeLack of time
Lack of knowledgeLack of knowledge
Not convinced of the medical relevance Not convinced of the medical relevance of treating EDof treating ED
Embarrassed?Embarrassed?
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Why Treat ED in DM?Why Treat ED in DM?
Diabetes NSF :Standard 12 - Rationale- point 7Diabetes NSF :Standard 12 - Rationale- point 7
Regular surveillance for, and effective Regular surveillance for, and effective management of depression and ED, management of depression and ED,
can reduce the impact of these conditions on can reduce the impact of these conditions on the quality of lifethe quality of life of people with DM of people with DM
Apr 21, 2023Apr 21, 2023 MHMH
How does ED affect lives?How does ED affect lives?
1. Men, Sex and Erectile Dysfunction: Through the Looking Glass, Survey 2002, Wirthlin, Europe.
PRESSURE WITHIN
THE MAN
+
PRESSURE WITHIN
THE RELATIONSHIP
=
PRESSURE WITHIN LIFE?
“I would feel more masculine if I were able to obtain an erection”1
“I feel I am letting my partner down”1
“If I didn’t have ED I would enjoymy life more”1
“We’re not so close anymore”
“Something’s missing”
“Whose fault is it?”
“I can’t satisfy my partner anymore”
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Organic Causes of EDOrganic Causes of ED1,21,2
40
30
15
3
5
6
1
0 10 20 30 40 50
Other
Surgical
Neurological
Endocrine
Medications
Diabetes
Vascular
88%
1.1. Lue TF. Lue TF. N Engl J MedN Engl J Med. 2000;342:1802-1813. . 2000;342:1802-1813. 2.2. Miller TA. Miller TA. Am Fam Physician Am Fam Physician. 2001;61:95-104, 109-110. . 2001;61:95-104, 109-110.
Why Treat ED?Why Treat ED?
Apr 21, 2023Apr 21, 2023 MHMH
Long-term Glycaemic Control:Long-term Glycaemic Control:Proportion of patients attaining treatment goalProportion of patients attaining treatment goal
Turner R, et al. JAMA 1999;281:20052012
HBA1C <7%
Group
3 years
6 years
9 years
Diet
25%
12%
9%
Sulphonylureas
47%
37%
28%
Metformin
50%
34%
24%
Insulin
44%
34%
13%
Why Treat ED?Why Treat ED?
Patients (%) with Controlled BP WorldwidePatients (%) with Controlled BP Worldwide
USA 1
27%
England 3
6%
<140/90 mmHgCanada 2
16%Australia 5
France 4
24%India 5Scotland 5
17.5%
Spain 5
20%Finland 5
20.5%
Germany 5
22.5%
>65 yr only
<160/95 mmHg
19%
9%
1. JNC VI. Arch Intern Med.1997; 157: 2413-2446. 2. Joffres MR et al. Am J Hypertens 1997; 10: 1097-
1102.
3. Colhoun HM et al. J Hypertens.1998; 16: 747-752.4. Chamontin B et al. Am J Hypertens.1998;11: 759-762.
5. Marques-Vidal P et al. J Hum Hypertens.1997; 11:213-220.
Why Treat ED?Why Treat ED?
Apr 21, 2023Apr 21, 2023 MHMH
Prevalence of CV Risk factors in DM Prevalence of CV Risk factors in DM
-5
10
25
40
55
70
85
100
%
1 + 2+ 3+ 4+ 5+ 6+
Number of Added Risk Factors
MDGH COCH RBH
M Hassanein et al, IDF Mexico 2000
Why Treat ED in DM?Why Treat ED in DM?
Apr 21, 2023Apr 21, 2023 MHMH
Why Treat ED?Why Treat ED?
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STATINACE - I
Why Treat ED?Why Treat ED?
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Should ED be considered as a sign of occult CAD?Should ED be considered as a sign of occult CAD? Vlachopoulos C, Vlachopoulos C, et al, et al, J Sex Med vol 1, 2005J Sex Med vol 1, 2005
26 ED patients with no CAD symptoms aged 40-70:26 ED patients with no CAD symptoms aged 40-70:– HistoryHistory– ETTETT– Stress EchocardiogramStress Echocardiogram– If 1-2 non-invasive tests were +ve: Coronary angiogramIf 1-2 non-invasive tests were +ve: Coronary angiogram
Results:Results:– 73% had 73% had 2 CVD risk factors2 CVD risk factors– 32% had 1 or 2 +ve non-invasive tests32% had 1 or 2 +ve non-invasive tests– 23% had CAD on angiography23% had CAD on angiography
Apr 21, 2023Apr 21, 2023 MHMH
Erectile Dysfunction and No Previous CV Event
Time to Any CV Event
At risk, n = 2495;
JAMA, Volume 294(23).December 21, 2005.2996–3002
Why Treat ED in DM?Why Treat ED in DM?
Apr 21, 2023Apr 21, 2023 MHMH
Thompson: JAMA, Volume 294(23).December 21, 2005.2996–3002
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Erectile Dysfunction and No Previous CV Event
Time to Any CV Event
At risk, n = 2495; number of cardiovascular events, 255; 5-year estimate of cardiovascular events, 11%.
JAMA, Volume 294(23).December 21, 2005.2996–3002
Why Treat ED in DM?Why Treat ED in DM?
Apr 21, 2023Apr 21, 2023 MHMH
Endothelial dysfunction is a risk factor for CVD and EDEndothelial dysfunction is a risk factor for CVD and ED
Heart failureHeart failure AtherosclerosisAtherosclerosis SmokingSmoking
HypertensionHypertension Oxidative stress DiabetesDiabetes
Endothelial dysfunctionEndothelial dysfunction
EDED
Rubanyi GM. J Cardiovasc Pharmacol 1993; 22 (Suppl 4): S1–S4
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Treat EarlyTreat Early
When to treat?
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In a study of >8000 men with ED, 65% of UKIn a study of >8000 men with ED, 65% of UK1 1 men men & 75% of European& 75% of European22 men initiated ED discussion men initiated ED discussion themselves.themselves.
From 500 men with ED visiting a urologistFrom 500 men with ED visiting a urologist– Only 22% reported discussing the problem with Only 22% reported discussing the problem with
their primary care physiciantheir primary care physician– 8 of 10 said they would have liked their physician 8 of 10 said they would have liked their physician
to initiate a discussion on ED during routine to initiate a discussion on ED during routine visitsvisits33
1. M Hassanein, et al Diabetic Medicine (suppl1), (oral presentation) Diabetes UK, March 2005.
2. Martin-Morales et al, JSM 2005, 2 (suppl1), P-041 ESSM 3.4. Baldwin KC. J Urol 2000; 163 (Suppl): 243 Abstract 1080
When to treat?
Apr 21, 2023Apr 21, 2023 MHMH
A holistic:A holistic:
management of ED & DMmanagement of ED & DM
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1. Physical Fitness1. Physical Fitness
MET equivalents (MET equivalents (metabolicmetabolic equivalent of the task) equivalent of the task)
Daily Activity MET Score rating
Sexual activity with established partner
Lower range (‘normal’) 2-3
Upper range (vigorous activity) 5-6
Lifting and carrying objects (9-20kg) 4-5
Walking one mile in 20 minutes on the level 3-4
Golf 4-5
Gardening (digging) 3-5
DIY, wallpapering, etc 4-5
Light housework, e.g. ironing, polishing 2-4
Heavy housework, e.g. making beds, scrubbing floors 3-6
Reference:A systematic approach to erectile dysfunction in the cardiovascular patient; A Consensus Statement. The International Journal of Clinical Practice, Sep 1999, vol. 53 (6)
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Psychogenic FactorsPsychogenic Factors
Partners rolePartners role
Holistic approachHolistic approach
Type of PDE5IType of PDE5I
QoLQoL
0
20
40
60
80
100
Organic Psychogenic Mixed
% of
patie
nts w
ith im
prove
d ere
ction
s
Placebo Sildenafil
Treat the CauseTreat the Cause
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Sildenafil (Viagra)
Vardenafil (Levitra)
Tadalafil (Cialis)
Apomorphine (Uprima) sublingual
Alprostadil (MUSE) intra-urethral
Intra-cavernosal injections
Vacuum devices
Surgical
Oral (PDE5 inhibitors)
The patient and, when possible his The patient and, when possible his partner, partner,
should be informed should be informed of the relevant treatment optionsof the relevant treatment options
and their associated risks and and their associated risks and benefits. benefits.
AUA, 2005AUA, 2005
Which Drug?Which Drug?
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PDE5 inhibitors increase the physiological response to PDE5 inhibitors increase the physiological response to sexual stimulationsexual stimulation
Apr 21, 2023Apr 21, 2023 MHMH
PDE5 inhibitorsPDE5 inhibitors
cGMPSildenafil
Tadalafil Vardenafil
NNO
N
O
OO
ONH2 N
NH
N
NH
O
OP O
O 0H
0H
N
NH NNO
S
O
O ON
N
N
NH NO
S
O
O ON
N
N
Caffeine
OCH3
CH3
H3C
O
Sildenafil, tadalafil, and vardenafilare ALL potent, reversible, competitive PDE5I.
AUA 2005
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Differences in pharmacokinetic and adverse event
profiles do exist.
SildenafilSildenafil VardenafilVardenafil TadalafilTadalafil
T maxT max 1 hour1 hour 1 hour1 hour 2 hours2 hours
Half-lifeHalf-life 4 hours4 hours 4 hours4 hours 18 hours18 hours
PDE5I are contraindicated in patients who are taking organic nitrates
Safe time interval between the use of nitrates and PDE5I during a
medical emergency in patients who have received:
• sildenafil & vardenafil is 24 hours
• tadalafil is 48 hours.
AUA 2005
Apr 21, 2023Apr 21, 2023 MHMH
ConclusionConclusion
ED is a widely prevalent distressing problem ED is a widely prevalent distressing problem
among men with CVD risk factorsamong men with CVD risk factors
Men with ED should be assessed regarding:Men with ED should be assessed regarding:1.1. Physical FitnessPhysical Fitness
2.2. History (sexual, medical & psychosocial) History (sexual, medical & psychosocial)
3.3. Holistic approach to Co-morbid conditions Holistic approach to Co-morbid conditions
4.4. Early treatmentEarly treatment
5. ED is probably a MVD risk factor
Apr 21, 2023Apr 21, 2023 MHMH