Erectile Dysfunction in T2DM.ppt

(1)

(2)

(3)

(4)

ED More Prevalent Than

Common Chronic Conditions

ED More Prevalent Than

Common Chronic Conditions

1. National Institute of Allergy and Infectious Diseases (NIAID). Focus on Asthma. NIAID Web site.

Available at: http://www.niaid.nih.gov/newsroom/focuson/asthma01/default.htm. Accessed July 18, 2003.

2. National Center for Health Statistics. Fast Stats A to Z: Diabetes. Centers for Disease Control and

Prevention (CDC) Web site. Available at: http://www.cdc.gov/nchs/fastats/diabetes.htm. Accessed July 18, 2003. 3. National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK). Statistics related to

overweight and obesity. NIDDK Web site. Available at: http://www.niddk.nih.gov/health/nutrit/pubs/ statobes.htm. Accessed July 18, 2003. 4. Benet AE, Melman A. Urol Clin North Am. 1995;22:699-709.

Men in the

United States

(millions)

7.8

19.5

30

7.1

0

10

20

30

40

Asthma

Diabetes

Obesity

ED

1 2

4

(5)

(6)

ED May Be a Sign of Endothelial Damage

1. Billups KL. Curr Sexual Health Rep. 2004;1:137-141. 2. Montorsi F et al. Eur Urol. 2003;44:360-365.

3. Kaiser DR et al. J Am Coll Cardiol. 2004;43:179-184. 4. Broadley AJM et al. Heart. 2002;88:521-524.

5. Maas R et al. Vasc Med. 2002;7:213-225. 6. Solomon H et al. Heart. 2003;89:251-254. 7. Hurairah H, Ferro A. Int J Clin Pract. 2004;58:173-183. 8. Matfin G et al. Curr Diabetes Rep. 2005;5:64-69.

9. Bocchio M et al. J Urol. 2004;171:1601-1604. 10. Deedwania PC. J Am Coll Cardiol. 2000;35:67-70.

11. De Angelis L et al. Diabetologia. 2001;44:1155-1160. 12. Jackson G. Int J Clin Pract. 2004;58:431.

ED may occur with early endothelial cell damage before other

serious diseases are manifest

1-3

ED may occur with early endothelial cell damage before other

serious diseases are manifest

1-3

Early endothelial dysfunction may lead to atherosclerosis and

vascular remodeling

10,12

Early endothelial dysfunction may lead to atherosclerosis and

vascular remodeling

10,12

Anxiety/

Depression

4

Dyslipidemia

5-7

ED

3,9

Hypertension

5,7

Diabetes

5,6,11

Atherosclerotic

changes

Endothelial cell:

Early endothelial and

vascular damage

9,10

(7)

Major Risk Factors for ED

•

Aging

1,2

•

Chronic disease

•

Cardiovascular disease, hypertension, diabetes, lower

urinary tract symptoms (LUTS), and depression

2,3

•

Medications, eg, thiazide diuretics, beta-blockers,

selective serotonin-reuptake inhibitors

1

•

Lifestyle

2,4

•

Stress, alcohol and drug abuse, smoking, obesity, and

sedentary lifestyle

1. Feldman HA et al. J Urol. 1994;151:54-61. 2. Lewis RW et al. In: Lue TF et al, eds. Sexual Medicine:

Sexual Dysfunctions in Men and Women. Paris, France: Health Publications; 2004:37-72. 3. Rosen R et al.

(8)

Major Risk Factors for ED:

Antihypertensive Medications

•

Diuretics and



-blockers associated with highest

incidence of ED and



-blockers with lowest incidence in 1

study

1

•

Other findings indicate that thiazide diuretics pose

greater risk than



-blockers

2,3

•

In contrast, use of ACE inhibitors found not to increase

ED risk

4

1. Burchardt M et al. J Urol. 2000;164:1188-1191. 2. Kloner RA. J Clin Hypertens. 2000;2:33-36.

(9)

Causes of ED: Vascular Factors

•

Atherosclerosis

1-3

and associated risk factors

4,5

•

Smoking

4,6

•

Diabetes

5

•

Dyslipidemia

5

•

Hypertension

5

•

Venous leaks

7,8

•

Pelvic or perineal trauma

7

•

Perineal arterial compression from cycling

9

1. Miller TA. Am Fam Physician. 2000;61:95-104, 109-110. 2. NIH Consensus Development Panel on

Impotence. JAMA. 1993;270:83-90. 3. Azadzoi KM et al. J Urol. 1998;160:2216-2222. 4. Kaiser FE et al. J Am Geriatr Soc. 1988;36:511-519. 5. Lue TF. N Engl J Med. 2000;342:1802-1813. 6. McVary KT et al. J Urol. 2001;166:1624-1632. 7. Munarriz RM et al. J Urol. 1995;153:1831-1840. 8. DePalma RG et al. J Vasc Surg.

(10)

Causes of ED: Neurogenic Factors

•

Radical pelvic surgery, including prostatectomy

1,2

•

Pelvic/spinal cord injury

1

•

Multiple sclerosis or demyelinating conditions

3

•

Diabetic neuropathies

1,3

•

Pudendal nerve injury

4-6

•

Stroke, Alzheimer’s disease, Parkinson’s disease

1

1. Lue TF. N Engl J Med. 2000;342:1802-1813. 2. Mirone V et al. Int J Androl. 2003;26:137-140. 3. Romeo JH et al. J Urol. 2000;163:788-791. 4. Seftel A. J Urol. 2002;168:866-867. 5. Lewis RW. Urol Clin North Am.

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1. AACE Male Sexual Dysfunction Task Force. Endocr Pract. 2003;9:77-95. 2. Morales A, Heaton JP. Urol Clin North Am. 2001;28:279-288. 3. Lewis RW et al. In: Lue TF et al, eds. Sexual Medicine: Sexual

Dysfunctions in Men and Women. Paris, France: Health Publications; 2004:37-72. 4. Lue TF. N Engl J Med. 2000;342:1802-1813. 5. Johri AM et al. Int J Impot Res. 2001;13:176-182.

•

Hypogonadism

1-3

•

Hypothyroidism, hyperthyroidism

1-4

•

Pituitary tumor, hyperprolactinemia

1,3-5

(12)

•

Antihypertensives

1-3

•

Diuretics

2

•

Beta-blockers

3

•

Selective serotonin-reuptake inhibitors (SSRIs)

1-4

•

Hormonal agents (eg, antiandrogens)

1-3,5

•

Protease inhibitors

6

•

Cytotoxic agents

5,7,8

•

H

2

antagonists

2,3,5

1. Lue TF. N Engl J Med. 2000;342:1802-1813. 2. Ricci E et al. Int J Impot Res. 2003;15:221-224. 3. Fogari R et al. Curr Hypertens Rep. 2002;4:202-210. 4. Nurnberg HG et al. JAMA. 2003;289:56-64. 5. Lewis RW et al. In: Lue TF et al, eds. Sexual Medicine: Sexual Dysfunctions in Men and Women. Paris, France: Health Publications; 2004:37-72. 6. Schrooten W et al. AIDS. 2001;15:1019-1023. 7.Chatterjee R et al. Bone Marrow Transplant. 2000;25:1185-1189. 8. Lewis RW. Urol Clin North Am. 2001;28:209-216.

Causes of ED: Medications

(13)

Classification of ED:

Psychogenic or Organic?

Psychogenic

Organic

Sudden onset

Gradual onset

Complete immediate loss

Incremental progression

Morning erections present

Lack of

morning

erections

Varies with partner and circumstance

Lack of erections under

most sexually stimulating circumstances

(14)

ED: Initial Clinical Assessment

1-

4

•

Targeted medical, sexual, and

psychosocial history

•

Physical exam of genitalia

•

Secondary sexual characteristics

•

Laboratory tests

1. The Process of Care Consensus Panel. Int J Impot Res. 1999;11:59-74. 2. Kuritzky L. J Am Osteopath Assoc. 2002;102(suppl 4):S7-S11. 3. Rosen R et al. In: Lue TF et al, eds. Sexual Medicine: Sexual

Dysfunctions in Men and Women. Paris, France: Health Publications; 2004:173-220. 4. Lue TF et al. In: Lue TF et al, eds. Sexual Medicine: Sexual Dysfunctions in Men and Women. Paris, France: Health

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Laboratory Tests

•

Testosterone

1,2

•

Morning total testosterone preferred

•

Prostate-specific antigen (when appropriate)

2

•

Plasma glucose

•

Thyroid function

•

Prolactin

•

CVD risk burden profile

1

•

High-density lipoprotein

•

Low-density lipoprotein

(16)

Presenting Complaint:

Successful Management

•

Targeted medical, sexual, and psychosocial history

(typically 4 to 6 minutes)

1

•

Physical exam of genitalia and secondary sexual

characteristics (2 to 4 minutes)

1

•

CV risk assessment

2,3

•

Laboratory tests with explanations

(1 to 2 minutes)

1

Total time=12 minutes.

1. Kuritzky L. J Am Osteopath Assoc. 2002;102(12 suppl 4):S7-S11. 2. Kostis JB et al. Am J Cardiol.

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MALES Study: Increased prevalence of

self-reported ED in men with diabetes

reported ED in men with diabetes

1

0

5

10

15

20

25

30

35

40

45

Total Population

Men with Diabetes

P

re

va

le

n

ce

o

f

E

D

(

%

)

16%

39%

n=27,839

n=1,637

(22)

MALES Study: Increased prevalence of

diabetes in men with self-reported ED

1

0

2

4

6

8

10

12

14

16

Men without ED

Men with ED

P

re

va

le

n

ce

o

f

D

ia

b

et

es

(

%

)

4%

14%

n = 27,839

p < 0.0001

(23)

ED in the man with diabetes

• ED incidence increases with age, duration of diabetes

and deteriorating diabetic control

1

• Compared to men without diabetes, men with diabetes

tend to:

• Suffer ED from an earlier age

2

• Suffer more severe ED

3

• Have worse disease-specific health-related quality

of life

3

• Be less responsive to treatment

4

1. Fedele D et al. Diabetes Care 1998;21:1973-1977. 2. Feldman H et al. J Urol 1994;151:54-61. 3. Penson D et al. Diabetes Care 2003;26:1093-1099. 4. Eardley I et al. Int J Clin Pract 2007;61

(24)

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Conclusions

•

The prevalence of ED is greater in men with diabetes than

the general population

•

Men with diabetes tend to be less responsive to treatment



Testosterone deficiency can be associated with ED and

can give rise to PDE5i failure



Testosterone therapy can restore responsiveness to

PDE5is in hypogonadal men with ED



Measure testosterone in men with ED

(26)

(27)

Sexual Activity and Cardiac

Risk Assessment

Reprinted from Am J Cardiol. Vol. 96. Kostis JB, Jackson G, Rosen R, et al. Sexual dysfunction and cardiac risk (the Second Princeton Consensus Conference). Pages 313-321. Copyright 2005. With permission from Excerpta Medica, Inc.

•

Initiate or resume

sexual activity

or

•

Treatment for

sexual dysfunction

•

Initiate or resume

sexual activity

or

•

Treatment for

sexual dysfunction

•

Sexual activity

deferred until

stabilization of

cardiac condition

•

Sexual activity

deferred until

stabilization of

cardiac condition

CV Assessment

and Restratification

CV Assessment

and Restratification

Indeterminate Risk

Sexual Inquiry

High Risk

Risk factors and coronary heart disease evaluation, treatment,

and follow-up for all patients with ED

Risk factors and coronary heart disease evaluation, treatment,

and follow-up for all patients with ED

(28)

Low-Risk Patient: Princeton Consensus Panel

Recommendations

•

Asymptomatic, <3 CVD risk factors, excluding gender

•

Controlled HTN

•

Mild, stable angina

•

Post-successful coronary revascularization

•

Uncomplicated past MI (>6 to 8 weeks)

•

Mild valvular disease

•

Left ventricular dysfunction (New York Heart Association

[NYHA] class I)

(29)

High-Risk Patient: Princeton Consensus Panel

Recommendations

•

Unstable or refractory angina

•

Uncontrolled HTN

•

Congestive heart failure

(CHF; NYHA class III/IV)

•

Recent MI (<2 wk)

•

High-risk arrhythmias

•

Obstructive hypertrophic cardiomyopathy

•

Moderate/severe valvular disease

(30)

Indeterminate-Risk Patient: Princeton Consensus

Panel Recommendations

•

Asymptomatic,



3 major CAD risk factors, excluding

gender

•

Moderate, stable angina

•

Recent MI (>2wk, <6 wk)

•

LVD and/or CHF (NYHA class II)

•

Noncardiac sequelae of atherosclerotic diseases such as

cerebrovascular accident, peripheral vascular disease

(31)

Management Recommendations Based on Graded

Cardiovascular Risk Assessment

Grade of Risk

Management Recommendations

Low risk

Primary care management

Consider all first-line therapies (eg, PDE5 inhibitors) Reassess at regular intervals (6-12 m)

High risk

Priority referral for specialized CV management

Treatment for sexual dysfunction to be deferred until cardiac condition stabilized; depends on specialist recommendations

Indeterminate risk

Specialized CV testing

(eg, ETT, echocardiography)

Restratification into high risk or low risk based on the results of CV assessment

ETT=exercise tolerance testing.

(32)

Safety of PDE5 Inhibitors in

Cardiac Patients

1-3

•

PDE5 inhibitors

potentiate the hypotensive effects

of organic nitrates and are contraindicated with

concomitant use

•

Avoid use in patients for whom sexual activity is

inadvisable because of underlying cardiac conditions

•

Sildenafil and tadalafil have no clinically relevant

effect on QT interval; vardenafil has precautions for some

patients

•

Not associated with increases in MI or death rates

1. Cialis® (tadalafil) prescribing information. Lilly ICOS LLC: Indianapolis, Ind and Bothell, Wash; 2005.

2. Levitra®_{(vardenafil) prescribing information. Bayer Pharmaceuticals Corp: West Haven, Conn; 2005.}

(33)

Effects of PDE5 Inhibitors on BP

Mean Maximum Decrease in Supine BP

(mm Hg)

Drug

Dose* (mg)

SBP

DBP

Sildenafil

1

100

8.4

5.5

Tadalafil

2

20

1.6

†

0.8

†

Vardenafil

3

20

7

8

BP=blood pressure. DBP=diastolic BP. SBP=systolic BP.

*Single doses, except for tadalafil, which was dosed over a period of 10 days.

†_P_{=not significant.}

1. Viagra®_{(sildenafil) prescribing information. Pfizer Inc: New York, NY; 2005. 2. Cialis}®_(tadalafil)

prescribing information. Lilly ICOS LLC: Indianapolis, Ind and Bothell, Wash; 2005. 3. Levitra®_(vardenafil)

(34)

Emergency Administration of Nitrates Following PDE5

Inhibitor Use

Drug

Time Interval for Nitrate Administration*

During Medical Emergency

Sildenafil

•

Has not been definitively determined

1,2

•

After 24 hours, may be considered based on pharmacokinetic profile

2

Tadalafil

•

At least 48 hours should elapse after the last dose before nitrate

therapy is considered

3,4

Vardenafil

•

Has not been definitively determined, but clinical data show

additional BP and heart rate changes were not detected when drug

dosed 24 hours before nitrate administration

5

*Under close medical

1. Viagra®_{(sildenafil) prescribing information. Pfizer Inc: New York, NY; 2005. 2. Cheitlin MD et al.}_{J Am Coll}

Cardiol. 1999;33:273-282. 3. Cialis®_{(tadalafil) prescribing information. Lilly ICOS LLC: Indianapolis, Ind and}

Bothell, Wash; 2005. 4. Kloner RA et al. J Am Coll Cardiol. 2003;42:1855-1860. 5. Levitra®_(vardenafil)

(35)

Testosterone Deficiency Syndrome (Hypogonadism)

• Testosterone Deficiency Syndrome (TDS) or Male

Hypogonadism is inadequate function of the testes

• Prevalence: 5 men in 1000

1

• 2-4 million men in the US, estimated only 5% treated

2

• Characterised by low serum testosterone (total testosterone

<12nmol/l) + clinical symptoms

4

• Prompt diagnosis and referral are key factors in avoiding

serious long-term consequences for health

1. Handelsman DJ. Androgens. In: Male reproductive endocrinology; Ed. Mclachlan RI. Endotext.com; 2002. 2. Rhoden EL & Morgentaler A.

(36)

(37)

Prevalence of hypogonadism in diabetes (33-44%)

0

10

20

30

40

50

Free T

Total T

Bioavailable T

P

e

rc

e

n

ta

g

e

o

f

p

a

ti

e

n

ts

(38)

Measure serum testosterone (T) levels between 8-10am

T >12nmol/l

Consider alternative

diagnoses

T

≤

12nmol/l

Repeat T level

Measure LH, FSH,

Prolactin, SHBG

Repeat tests

REFERRAL

T >12nmol/L,

normal Prolactin,

SHBG, FSH/LH

T 8-12nmol/L

normal Prolactin,

SHBG, FSH/LH

T 8-12nmol/L, and

Prolactin, SHBG,

abnormal FSH/LH

T <8nmol/L

(39)

Who should receive testosterone treatment?

• Men with clinical symptoms and testosterone <8 nmol/l (overt).

1

(40)

Key Take-Home Messages

•

Initiate first-line therapy including lifestyle modification and oral drugs as a

convenient therapeutic option

•

Consider patient-partner preferences, tolerability, convenience, and/or

concomitant medications and conditions when deciding on treatment

•

Evaluate and classify patients for possible cardiac risk prior to treatment

(majority of patients are at low risk and may be treated)

•

Testosterone augmentation should be prescribed for those with

documented hypogonadism

•

Sexual stimulation is needed

•

Multiple attempts or dosage adjustments may be required