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Dr Kuku Appiah 21 May 2014 Erectile Dysfunction(ED) February 26, 2014 1
Dr Kuku Appiah
21 May 2014
Erectile Dysfunction(ED)
February 26, 2014
1
Why are we doing this talk?
•ED is very common
•ED is often under-diagnosed
•ED affects quality of life
•ED can be a marker to underlying cardiovascular
diseases
Why is this important to HCP’s?
HCPs :
• May be the first to see a patient with ED
• Prescribe/dispense to the majority of patients with
diabetes, heart disease, and hypertension; key risk
factors for ED
Presentation Layout
1. Definition and Statistics
2. Pathophysiology
3. Risk Factors / Causes
4. Evaluation and Management
5. Mechanism of Action of PDE5 inhibitors
6. Take home messages
Definition and Statistics of ED
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Erectile Dysfunction
What is ED?
• Erectile Dysfunction is defined as the consistent inability to achieve and/or maintain an erection sufficient for satisfactory sexual activity
• ED is the most thoroughly studied sexual dysfunction in men and the most common sexual complaint of men presenting to healthcare providers
• In talking to patients, it is better to refer to their symptoms as ‘erection problems’
‒ ‘Erectile dysfunction’ and ‘erection problems’ are both preferable terms to ‘impotence’, which, when used colloquially, has emotive or derogatory implications
6
Albersen M, Mwamukonda, KB, Shindel AW, et al. Evaluation and treatment of erectile dysfunction. Med Clin N Am. 2011;95:201–212;
NIH Consensus Statement. Impotence. 1992;10(4):1–23.
Erectile Dysfunction (ED)
Man’s sexual chemistry
•At 20 thrice weekly
•At 30 tries weekly
•At 40 tries weakly
•At 50 tries and tries
•At 60 tries and cries
•At 70 tries and dies!
Prevalence
• The reluctance of many men to admit to suffering from erection problems causes difficulties in determining its prevalence
• Worldwide prevalence of ED is between 10% and 20%, and it is strongly correlated with aging
‒ Among younger men, 8% of 20- to 29-year-olds and 11% of men ages 30-39 experience ED
‒ Approximately 52% of men ages 40-70 experience ED
‒ 71% of men over 70 experience ED
• This may be due to:
‒ Increased incidence of diseases that cause ED
‒ Use of treatments that can cause ED
• Estimated prevalence for 2025 = 300M men worldwide
Laumann EO, A Nicolosi, DB Glasser, et al. Sexual problems among women and men aged 40–80 y: prevalence and correlates identified in the global study of
sexual attitudes and behaviors. Int J Impot Res. 2005;17:39–57; Nicolosi A, Laumann EO, Glasser DB, et al. Sexual behavior and sexual dysfunctions after age 40:
the global study of sexual attitudes and behaviors. Urology. 2004;64:991–997; Saigal CS, Wessells H, Pace J, et al. Predictors and prevalence of erectile
dysfunction in a racially diverse population. Arch Intern Med. 2006;166:207-212; Lue TF. Erectile dysfunction. N Engl J Med. 2000;342:1802–1813; Rosen RC,
Fisher WA, Eardley I, et al. The multinational men’s attitudes to life events and sexuality(MALES) study: I. Prevalence of erectile dysfunction and related health
concerns in the general population. Cur Med Res Opin. 2004;20(5):607–617; Feldman HA, Goldstein I, Hatzichristou DG, et al. Impotence and its medical and
psychosocial correlates: results of the Massachusetts male aging study. J Urol. 1994;151(1):54-61; Porst H, Buvat J. Standard Practice in Sexual Medicine. 2006;
Uckert S, Mayer ME, Stief CG et al. The future of the oral pharmacotherapy of male erectile dysfunction: things to come. Expert Opin Emerg Drugs. 2007;12(2):219-
228. 9
ED in men over 55 years
10
Age Prevalence
>55 47%
>75 78%
+ Diabetes 50%
+ Hypertension 34%
Thompson IM, Tangen CM, Goodman PJ, et al. Erectile dysfunction and subsequent cardiovascular disease. JAMA. 2005;294:2996-3002; Saigal CS,
Wessells H, Pace J, et al. Predictors and prevalence of erectile dysfunction in a racially diverse population. Arch Intern Med. 2006;166:207-212.
Pathophysiology of ED
February 26, 2014
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Pathophysiology of ED
Erection is a final common pathway of the integrative synchronized action of:
• Psychological
• Neuronal
• Hormonal
• Vascular and
• cavernous smooth muscle
Mechanism of an Erection
•Erection begins with sensory and mental stimulation
•Impulses from the brain travels down the spinal column
•Impulses from the nerves in the penis relax the smooth muscles in the paired
corpora carvenosa
•When the impulses causes the muscle relaxation , blood flow into the spaces in
the corpus spongiosum and
•The pressure makes the penis to swell out
•The membranes surrounding the corpora carvenosa then trap the blood in the
penis and maintain the erection
•The size of the erect penis is 14-16cm long
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Mechanism of an Erection
•The penis needs blood flow
•Flow goes better through larger vessels
•Vasodilatation turns smaller vessels into larger vessels
•Erections need vasodilatation
Vasodilatation
Erection
•The penis needs erectile tissue and rigidity
•Sexual response is mediated through nerves
•The brain controls and coordinates nerves
CNS
Erection
Mechanism of an Erection
Causes of ED
February 26, 2014
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ED is multifactorial
Erectile Dysfunction
18
Lue TF. Erectile dysfunction. N Engl J Med. 2000;342:1802–1813; Bortolotti A, Parazzini F, Colli E, et al. The epidemiology of erectile dysfunction and its risk
factors. Int J Androl. 1997;20:323–334; Hatzimouratidis K, Amar E, Eardley I, et al. Guidelines on male sexual dysfunction: erectile dysfunction and premature
ejaculation. Eur Urol. 2010;57:804–814; Moreno-Perez O, Escoín C, Serna-Candel C, et al. Risk factors for sexual and erectile dysfunction in HIV-infected men:
the role of protease inhibitors. AIDS. 2010;24:255–264; Saigal CS, Wessells H, Pace J, et al. Predictors and prevalence of erectile dysfunction in a racially
diverse population. Arch Intern Med. 2006;166:207-212; Benet AE, Melman A. The epidemiology of erectile dysfunction. Urol Clin North Am. 1995;22:699-709.
Causes of ED
Psychogenic causes:
•Depression
•Anxiety
•Studies have shown that up to 50% of men diagnosed with 1st episode of
depression at > 40yrs have ED
19
Erectile Dysfunction
Medications associated with ED
20
Cardiovascular drugs Psychotropic drugs Recreational drugs
Thiazide diuretics
Beta blockers
Calcium antagonists
Centrally acting agents
Methyldopa
Clonidine, reserpine
Ganglion blockers
Digoxin
Lipid lowering agents
ACE inhibitors
Major tranquillizers
Anxiolytics and hypnotics
Tricyclic antidepressants
Selective serotonin reuptake
inhibitors
Alcohol
Marijuana
Amphetamines
Cocaine
Anabolic steroids
Heroin
Endocrine drugs
Others Antiandrogens
Oestrogens
LHRH: luteinizing hormone-
releasing hormone analogues
Testosterone
Cimetidine and ranitidine
Metoclopramide
Carbamazepine
Spironolactone blocks testosterone synthesis
and competitively binds to androgen receptors Development of a peripheral autonomic
neuropathy, and behavioral changes
Decreases libido and causes impotence
through elevation of serum prolactin and
blocking of androgen receptors
Foresta C, Caretta N, Corona G, et al. Clinical and metabolic evaluation of subjects with erectile dysfunction: a review with a proposal flowchart. Int J Androl.
2008;32:198-211; Benet AE, Melman A. The epidemiology of erectile dysfunction. Urol Clin North Am. 1995;22:699-709; Krane RJ et al. N Engl J Med.
1989;321:1648-1659.
Risk factors for ED
Age
Smoking (without co-morbidity)
Diabetes
Heart disease
Depression
Hypertension
Obesity
Physical inactivity
HIV
Thompson JAMA 2005;294(23):2996-3002.
Shiri Int J Impot Res 2004;16(5):389-394.
Definition of Metabolic Syndrome
Abdominal obesity
• Women - waist circumference > 80 cm • Men – waist circumference > 94 cm
High triglycerides > 1.7 mmol/L Low HDL cholesterol
• < 1.0 mmol/L in men • < 1.3 mmol/L in women
Elevated BP > 130/85mm Hg or on treatment Fasting glucose > 5.6 mmol/L
The metabolic syndrome is characterized by a constellation of risk factors
in one individual and increases the risk for CVD at any given LDL-C level
Erectile Dysfunction
ED is linked to serious health problems
23
19
7
16
4
13
36
17
29
14
25
64
0
10
20
30
40
50
60
70
High bloodpressure
Heart troubleor angina*
Highcholesterol
Diabetes* Depression* Any of these
Pre
va
len
ce
of co
-mo
rbid
itie
s (
%)
No ED ED
N=23,416
*P<0.0001
Rosen RC, Fisher WA, Eardley I, et al. The multinational men’s attitudes to life events and sexuality (MALES) study: I. Prevalence of erectile dysfunction
and related health concerns in the general population. Cur Med Res Opin. 2004;20(5):607–617
The Link between ED and Cardio vascular disease
Footnotes
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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
1-2 mm
ED
Coronary artery
3-4 mm
Angina/infarction
Carotid artery
5-7 mm
Stroke
Femoral artery
6-8 mm
Claudication
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.
Erectile Dysfunction
Endothelial dysfunction, ED, and CVD
• ED and CVD share aetiologies as well as pathophysiology (endothelial dysfunction), and evidence suggests that the degree of ED correlates with severity of CVD
• ED may be a predictive symptom of CVD in otherwise asymptomatic patients
‒ ED may precede a cardiovascular event by as much as five years in otherwise asymptomatic patients
• A man with ED and no cardiac symptoms is a cardiac (or vascular) patient until proven otherwise
Schwartz BG, Economides C, Mayeda GS, et al. The endothelial cell in health and disease: its function, dysfunction, measurement and therapy. Int J Impot
Res. 2010;22:77–90; Thompson IM, Tangen CM, Goodman PJ, et al. Erectile dysfunction and subsequent cardiovascular disease. JAMA. 2005;294:2996-
3002; Hodges JD, Kirby M, Solanki J, et al. The temporal relationship between erectile dysfunction and cardiovascular disease. Int J Clin Pract.
2007;61(12)2019–2025; Jackson G, Rosen RC, Kloner RA, et al. The Second Princeton Consensus on sexual dysfunction and cardiac risk: new guidelines for
sexual medicine.
J Sex Med. 2006;3:28-36. 25
Erectile Dysfunction
Impact on quality of life
• Men with ED experience low self-esteem, diminished confidence, and relationship problems
• Partners often have feelings of rejection, unattractiveness, and guilt
• Improvements in erection hardness with ED oral treatment have shown to improve satisfaction with sex life, love and romance, and overall health
• An awareness of the impact of ED on quality of life (QoL) can help health care providers:
‒ Empathize and communicate effectively with sufferers
‒ Appreciate the value of appropriate treatment
26
Althof SE. Quality of life and erectile dysfuntion. Urology. 2002;59:803– 810; Cappelleri JC, Bell SS, Althof SE, et al. Comparison between sildenafil-treated
subjects with erectile dysfunction and control subjects on the self-esteem and relationship questionnaire. J Sex Med. 2006;3:274–282; Speckens AEM,
Hengeveld MW, Nijeholt GL, et al. Psychosexual functioning of partners of men with presumed non-organic erectile dysfunction: cause or consequence of the
disorder? Arch Sex Behav. 1995;24(2):157-172; Montorsi F, Padma-Nathan H, Glina S. Erectile function and assessments of erection hardness correlate
positively with measures of emotional well-being, sexual satisfaction, and treatment satisfaction in men with erectile dysfunction treated with sildenafil
citrate(VIAGRA®). Urology. 2006;68(suppl 3A):26–37.
Diagnosis and Treatment of ED
February 26, 2014
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Few men approach a healthcare professional about
their sexual problems
Evaluation and Management of ED
•Early detection – often the pharmacist/primary care clinicians may be a
first point of contact
•Cardiac risk assessment – refer the patient to a physician/doctor
•Directed investigations( e.g. psychiatric, testosterone levels, prostate
check)
•Partner interaction
•Rigorous follow-up
•Specialist referral when necessary
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Physical examination
Diagnosis and Treatment of ED
Assessment of erection problems by validated tools
• Clinical trials use a number of self-assessment methods to quantify ED and treatment response, including:
‒ IIEF: International Index of Erectile Function, 15 items in five domains and the
abbreviated five-item SHIM: Sexual Health Inventory for Men questionnaires
‒ EHS: Erection Hardness Score, four-point scale grading the hardness of the
erection
‒ QEQ: Quality of Erection Questionnaire, six-question, patient-reported outcome
measure for evaluating satisfaction with the quality of erections in terms of
hardness, onset, and duration
‒ SEAR: Self-Esteem and Relationship Questionnaire, the 14-item SEAR
questionnaire is a brief, self-administered, disease-specific scale for assessing the
relevant psychosocial manifestations of ED, specifically patient-reported outcomes
of self-esteem, confidence, and relationships
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Mulhall J, Althof SE, Brock GB, et al. Erectile dysfunction: monitoring response to treatment in clinical practice—recommendations of an international study
panel. J Sex Med. 2007;4:448-464; Goldstein I, Lue TF, Padma-Nathan H, Rosen RC, et al. Oral sildenafil in the treatment of erectile dysfunction. N Engl J
Med. 1998;338:1397-1404; Rosen RC, Althof SE, Giuliano. Research instruments for the diagnosis and treatment of patients with erectile dysfunction.
Urology. 2006;68(Suppl 3A):6-16; Lowy M, Collins S, Bloch M, et al. Quality of erection questionnaire correlates: change in erection quality with erectile
function, hardness, and psychosocial measures in men treated with sildenafil for erectile dysfunction. J Sex Med. 2007;4:83-92; Porst H, Gilbert C, Collins S,
et al. Development and validation of the quality of erection questionnaire. J Sex Med. 2007;4:372-381; Althof SE, Cappelleri JC, Shpilsky A, et al. Treatment
responsiveness of the self-esteem and relationship questionnaire in erectile dysfunction. Urology. 2003;61:888-892; Cappelleri JC, Althof SE, Siegel RL, et al.
Development and validation of the self-esteem and relationship (SEAR) questionnaire in erectile dysfunction. Int J Impot Res. 2004;16:30-38.
Erection Hardness Score
• The EHS is a robust, validated, single-item patient-reported outcome for evaluating erection hardness
‒ Improvements in erection hardness have correlated with a restoration of confidence in the ED patient
• You can educate sufferers to use the EHS to assess the severity of their ED
• An expert panel defined the maximum score 4 as the main goal in the treatment of ED
Diagnosis and Treatment of ED
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EHS 1 EHS 2 EHS 3 EHS 4
Penis is larger but not hard Penis is hard, but not hard enough for penetration
Penis is hard enough for penetration, but not completely hard
Penis is completely hard and fully rigid
Mulhall J, Althof SE, Brock GB, et al. Erectile dysfunction: monitoring response to treatment in clinical practice—recommendations of an international
study panel. J Sex Med. 2007;4:448-464; Mulhall JP, Goldstein I, Bushmakin AG, et al. Validation of the erection hardness score. J Sex Med.
2007;4:1626-1634.
Sources: Goldstein I et al. N Engl J Med. 1998;338:1397-1404; Mulhall JP et al. J Sex Med. 2007;4:1626-1634.
Erection Hardness Score (EHS)
Penis is larger
but not hard
Penis is hard
but not hard
enough for
penetration
Penis is hard
enough for
penetration
but not
completely
hard
Penis is completely hard and fully rigid
Severe ED 6 - 10
Moderate ED 11 - 21
Mild ED 22 - 25
No ED 26 - 30 IIEF
Rigidity is Important to Patients - Mullhall et al.
Optimal Erection Hardness
Confidence/Self-Esteem
Sexual Satisfaction
ED Treatment Success
Source: Mulhall JP et al. J Sex Med. 2007;4:1626-1634.
Patient
Partner Healthcare
Professional
Rigidity is Important to Patients
A shift from EHS Grade 3 at baseline to EHS Grade 4 at the
EOT is accompanied by significant improvements in
intercourse and relationship satisfaction
An international panel of experts convened to evaluate data clinical
trials involving > 10 000 men with ED, concerning the role of
erection hardness in defining the response to treatment with PDE5
therapy
Tools – International Index of Erectile Function (IIEF), Self-Esteem
and Relationship Questionnaire (SEAR) and Erectile Dysfunction
Inventory of Treatment Satisfaction (EDITS Index scores)
Mulhall J, et al. 2007
Studies also show …
Studies show that erection hardness is important to patients
A total of 307 men were randomised to sildenafil or placebo
EHS 3 or 4 had increased by 40% for sildenafil vs. 11% for placebo
(p<0.0001)
Improvement in function, emotional well-being, and satisfaction was
greatest in men with completely hard erections and correlated
positively with other measures of hardness
(Kadioglu A. et al. 2007)
Drug Therapy in ED
Management
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Treatment for ED!
•Main drugs (PDE5 inhibitors) ‒ (Sildenafil)
‒ (Vardenafil)
‒ (Tadalafil)
•Accounts for 95% of all ethical Erectile Dysfunction Rx!
•Combination approach with counseling for psychological factors.
Alternative treatments
Date
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Concerns About Other Therapies in ED Management
What are alternative treatments?
• An alternative treatment is a “health treatment that is not classified as standard Western medical practice”
• Alternative supplements may include:
‒ herbal medicines
‒ nutritional supplements
‒ acupuncture
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Alternative Treatments for ED: Web MD. 23 Feb 2011. Available from: http://www.webmd.com/erectile-dysfunction/guide/alternative-treatments-ed. Accessed
Dec 12, 2012.
Herbal therapy
Date
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Concerns About Other Therapies in ED Management
What are herbal supplements?
• Herbal supplements may be called many things:
‒ herbal medicines
‒ plant preparations
‒ nutritional supplements
‒ alternative medicines
‒ complementary medicines
‒ traditional medicines
What are some herbal supplements for ED?
• Asian ginseng
• Ginkgo biloba
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Alternative Treatments for ED: Web MD. 23 Feb 2011. Available from: http://www.webmd.com/erectile-dysfunction/guide/alternative-treatments-ed. Accessed
Dec 12, 2012.
Concerns About Other Therapies in ED Management
Some herbal products contain PDE5 inhibitors
• Twenty-six herbal products were tested by the US FDA laboratory for the presence of known PDE5 inhibitors or previously identified synthetic analogues
‒ Synthentic analogues include sildenafil citrate, tadalafil, vardenafil hydrochloride trihydrate, methisosildenafil, homosildenafil, piperidenafil, thiosildenafil, and thiomethisosildenafil
• Fifteen of 26 of the “herbal” products actually contained a PDE5 inhibitor or analogue
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Gryniewicz CM, Reepmeyer JC, Kauffman JF, et al. Detection of undeclared erectile dysfunction drugs and analogues in dietary supplements by ion mobility spectrometry. J Pharm Biomed Anal. 2009;49:601-606.
58%
42% Contained ED drugor analogue
Did not containanalogue
Concerns About Other Therapies in ED Management
Some herbal products contain PDE5 inhibitors
• In a separate study, 17 herbal dietary supplements were assessed by a laboratory in France
• Eight of the 17 preparations contained sildenafil or an analogue (including a previously unidentified [and unstudied] propoxyphenyl-thiohydroxyhomosildenafil analogue in two of eight preparations)
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Balayssac S, Trefi S, Gilard V, et al. 2D and 3D DOSY 1H NMR, a useful tool for analysis of complex mixtures: application to herbal drugs or dietary
supplements for erectile dysfunction. J Pharm Biomed Anal. 2012.63-135-150.
78%
22% Contained ED drugor analogue
Did not containanalogue
Concerns About Other Therapies in ED Management
One study shows that the “effectiveness” of the tested herbal treatment may be due to presence of PDE5 inhibitors
• One study comparing an herbal supplement to sildenafil citrate in 32 ED
patients showed:
‒ Similar efficacy between products in the open-label portion
• But in the subsequent double-blind portion comparing the herbal supplement
to placebo:
‒ The herbal product had no effect on ED
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The supplier of the “natural” product confirmed that the product in the first
batch (used for open-label phase) was adulterated with a PDE5 inhibitor.
Cortes-Gonzalez JR, Arratia-Maqueo JA, Gómez-Guerra LS, et al. The use of Butea superba (Roxb.) compared to sildenafil for treating erectile dysfunction.
BJU Int. 2009;105:225–228.
Take Home Messages
•Worldwide, the prevalence of sexual dysfunction is high, but only a small
proportion of individuals complaining seek medical attention1
•By restoring erections, confidence can be restored2
•Patient/couple–centric approach for ED treatment is recommended for
achieving optimal erection hardness and treatment satisfaction
Sources: 1. Nicolosi A et al. World J Urol. 2006;24:423-428. 2. Cappelleri JC et al. J Sex Med. 2006;3:274-282.
3. Heiman JR et al. BJOG. 2007;114:437-447. 4. Chevret M et al. Presented at: 10th Congress of the
European Society for Sexual Medicine; November 26-28, 2007; Lisbon, Portugal. Abstract MP-01-084.
Take Home Messages
•ED, CVD, diabetes, and depression are strongly linked1
•They share a common denominator – endothelial dysfunction2
•Associated risk factors include smoking and obesity2,3
•The psychological impact of ED may result in depression and deterioration in
relationships4,5
1Goldstein I. Am J Cardiol. 2000;86(suppl):41F–45F.2Rubanyi GM. J Cardiovasc Pharmacol. 1993;22(suppl 4):S1–S14. 3Walczak MK, et al. J
Gend Specif Med. 2002;5:19–24.2. 4Cay EL, et al.
J Psychosom Res. 1972;16:425–435. 5Wrześniewski K. Psychother Psychosom. 1977;27:41–46. 6Seidman SN, et al. Am J Psychiatry.
2001;158:1623–1630. 7Paige NM, et al. J Urol. 2001;166:
1774–1778. 8Giuliano F, et al. Qual Life Res. 2001;10:359–369.
Questions???
