Mohamed Hassanein, FRCP, MPhil. Mohamed Hassanein, FRCP, MPhil.

Consultant Diabetes & EndocrinologyConsultant Diabetes & Endocrinology

Glan Clwyd Hospital. Glan Clwyd Hospital.

ED & CKDED & CKD

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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

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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

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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)

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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

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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)

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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)

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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

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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

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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?

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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?

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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?

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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

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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?

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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?

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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?

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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

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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

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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

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