Nathaniel Readal, MD
Trinity J. Bivalacqua, MD, PhD
BASICS
DESCRIPTION
Consistent or recurrent inability to attain and/or maintain an erection sufficient for satisfactory sexual activity
EPIDEMIOLOGY
Incidence
• Crude incidence: 26 cases/1,000 man years
– Incidence increases with each decade above 40
12 cases/1,000 man years: 40–49 yr
30 cases/1,000 man years: 50–59 yr
46 cases/1,000 man years: 60–69 yr
Prevalence
• Increases universally with age and medical comorbidities (cardiovascular disease, hypertension, smoking, inactivity, obesity)
– Prevalence by age
Below age 40: 1–9%
40–59 yr: 20–30%
60–69 yr: 20–40%
>70 yr: 50–75%
RISK FACTORS
• Probability of ED increases with presence of each risk factor
– Diabetes mellitus
Prevalence of ED 3 times higher in diabetic men
ED occurs at earlier age and increases with disease duration
Associated with 14 times increased risk of cardiovascular morbidity and mortality
– Cardiovascular disease (hyperlipidemia, hypertension, peripheral vascular disease)
– Lower urinary tract symptoms/Benign prostatic hyperplasia (BPH)
– Chronic renal failure, chronic liver disease
– Endocrinopathies (hypogonadism, Cushing disease)
– Prior abdominal/pelvic/penile surgery, radiation or trauma
– Priapism, Peyronie disease
– Neurologic disease (Parkinson disease, dementia, prior stroke)
– Depression/Psychological disorders
– Long-distance cycling
– Smoking
– Medications
Antihypertensives (thiazide diuretics, β-blockers, α2-agonists)
ACE inhibitors, angiotensin receptor blockers, and calcium channel blockers cause less ED/may improve erectile function
Psychotropics (monoamine oxidase inhibitors, selective serotonin reuptake inhibitors, lithium)
Antiandrogens
Miscellaneous (digoxin, cimetidine, spirolactone, marijuana)
Tobacco smoking
Genetics
• Several gene polymorphisms linked with ED
• Angiotensin-converting enzyme (ACE) polymorphisms may be risk factors for vasculogenic ED and endothelial nitric oxide synthase (eNOS) polymorphisms alone or in combination with other genetic polymorphisms implicated in ED
PATHOPHYSIOLOGY
• Mechanism of erection
– Relaxation of cavernosal smooth muscle (contracted in flaccid state inhibiting inflow of blood)
Mediated by NO release from pelvic nerves and endothelial cells
Increased cyclic GMP (cGMP) and cyclic AMP (cAMP) trigger signaling pathways leading to decreased intracellular calcium causing smooth muscle relaxation, increased penile blood flow, and tumescence
Smooth muscle relaxation further promoted due to inhibition of Rho-kinase
Veno-occlusive mechanism prevents outflow of blood from penis and maintains erection
cGMP degraded by phosphodiesterase type 5 (PDE5)
• Organic ED
– Vasculogenic
Arteriogenic—atherosclerotic lesions decrease arterial inflow to penis
Venogenic—failure of corporal vasoocclusion
– Neurogenic—Alzheimer disease, Parkinson disease, injury to central nervous system, spinal cord, or peripheral nerves
– Anatomic
– Endocrinologic (hyperprolactinemia, hyper or hypothyroidism, adrenal disorders/Cushing syndrome)
• Psychogenic ED
– Only accounts for 10% of ED
– More common in men <35 yr old
May result from lack of interest in partner, performance-related anxiety, negative mood, life stressors
ASSOCIATED CONDITIONS
• Atherosclerosis
• Diabetes mellitus
• Hypertension, stroke
• Depression
• Parkinson disease, multiple sclerosis
• Priapism
• Peyronie disease
• Prostate cancer
GENERAL PREVENTION
• Avoidance of tobacco use
• Optimal medical management of commonly associated conditions
• Increase exercise/weight loss
• Split bicycle seat for long-distance cycling
DIAGNOSIS
HISTORY
• Medical history—comorbid conditions, medications, alcohol, tobacco, recreational drug use, history of cycling
• Surgical history
• Psychosexual history
– Status of current relationship
– Level of libido/interest in sex
– Quality of erection
– Duration of ED
– Onsent of ED (sudden vs. gradual)
– Presence of nocturnal/early morning erections
– Presence of penile curvature, plaque, pain
– International Index of Erectile Function Questionnaire (IIEF-5)
5 questions scored individually from 0–5 (maximum of 25 points, higher score indicated better function)
Classifies ED into severe (5–7), moderate (8–11), mild to moderate (12–16), mild (17–21), and no ED (22–25)
PHYSICAL EXAM
• Neurologic: Stroke, CNS disease, visual field defects, neuropathy, perineal sensation
• Endocrinologic: Atrophic testes, gynecomastia, loss of secondary sexual characteristics
• Cardiovascular: Blood pressure, femoral/pedal pulses, lower extremity ischemia
• Penile: Curvature, Peyronie disease plaques
• Rectal exam
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• Complete blood count
• Serum chemistries
• Fasting glucose level, hemoglobin A1C
• Lipid profile
• Serum total testosterone
• Thyroid function tests (optional)
• PSA (suspect prostate pathology)
• Urinalysis (glucose as indicator of diabetes)
Imaging
• Duplex penile ultrasound—most reliable and least invasive modality for assessing ED
• Provides imaging evaluation and quantification of penile blood flow
Diagnostic Procedures/Surgery
ALERT
A trial of oral pharmacotherapy is warranted prior to an invasive procedure/test
• Specialized testing indicated for:
– Young men <40 yr old
– Men with previous perineal/pelvic trauma
Combined intracavernosal injection and stimulation (CIS) with duplex ultrasound (US): Intracavernosal injection of vasodilator with genital/audiovisual sexual stimulation and measurement of erection/blood flow—provides objective measurement of vascular parameters
Penile angiography: Reserved for young patient with ED secondary to traumatic arterial disruption/compression to evaluate for revascularization
Nocturnal penile tumescence (RigiScan®): Automated, portable measurement of presence of nocturnal erections—can confirm integrity of neurovascular axis, diagnose psychogenic ED
Pathologic Findings
N/A
DIFFERENTIAL DIAGNOSIS
Psychogenic erectile dysfunction, depression, possible early sign of cardiovascular disease
TREATMENT
GENERAL MEASURES
• Treatment choice should be made among physician, patient, and partner after evaluation of risk/benefits of all treatment choices
• Cardiovascular risk assessment should be performed before initiating therapy
– Low risk: Asymptomatic, <3 risk factors—may proceed with treatment
– Intermediate risk: Asymptomatic, ≥3 risk factors, stable angina, or mild heart failure—requires full cardiovascular assessment to reclassify as high vs. low risk
– High risk: Unstable angina, recent myocardial infarction, uncontrolled hypertension, advanced heart failure or valvular disease—defer until cardiac condition stabilized
MEDICATION
First Line
• PDE5 inhibitors (PDE5i): Inhibit breakdown of smooth muscle cGMP promoting smooth muscle relaxation. >50% of patients will respond
– Drugs:
Sildenafil 50–100 mg : Onset 15–60 min, duration of action 4 hr
Vardenafil 10–20 mg: Onset 15–60 min, duration of action 2–8 hr
Tadalafil 10–20 mg: Onset 15–120 min, duration of action 24–36 hr
Avanafil 100–200 mg
– Contraindications to PDE5i use:
Absolute contraindications: Use of nitrates
Sildenafil: Should be postponed for 4 hr after taking α-adrenergic antagonists
Vardenafil: Should not be taken with type 1A/type 3 antiarrhythmics or with long QT syndrome
– Side effects: All associated with headache, dyspepsia, facial flushing
Tadalafil: Backache, myalgia
Sildenafil: Blurred/blue vision—reacts with PDE6 in retina
Second Line
• Intracavernous injection therapy
– Mechanism: Self-injection of vasoactive agent into corpora cavernosa producing rapid erection
– Drugs:
Alprostadil (PGE1)
Bimix: Papaverine and phentolamine
Trimix: Papaverine, phentolamine, and prostaglandin E1
– Side effects: Fibrosis, priapism, painful erection, hematoma
– Contraindications: Monoamine oxidase medication usage, decreased manual dexterity
– Efficacy: 80–90% effective in wide range of patients
• Intraurethral therapy
– MUSE:Medicated urethral system for erection
– Mechanism: Insertion of alprostadil containing pellet into distal urethral, absorbed into corpora cavernosa production erection within 30 min
– Side effects: Penile/vaginal pain, dysuria
– Contraindications: Priapism risk
– Efficacy: <50% effective
• Vacuum constriction device
– Effective 2nd-line treatment and represents an alternative/adjunct to pharmacotherapy
– Pursued prior to surgical intervention
– Produces negative penile pressure, engorging corpora with blood
– Constrictive ring at the base of penis maintains tumescence
– Side effects: Penile ischemia when duration of use >30 min, pain, abnormal color of penis
SURGERY/OTHER PROCEDURES
• IPP
– Indications: Failed 1st- and 2nd-line pharmacotherapy or vacuum erection device
– Mechanism: Definitive ED treatment with placement of inflatable cylinders into corpora cavernosa
– Complications: Infection (1–3%), erosion (<5%), mechanical malfunction (5–10%)
• Penile revascularization
– Reserved for select young patients with clearly documented arterial occlusion
ADDITIONAL TREATMENT
Radiation Therapy
N/A
Additional Therapies
Psychosexual therapy: Referral for sex therapy in patients with psychogenic ED. Cognitive behavioral intervention identifies sexual stressors and refocus maladaptive thought processes
Complementary & Alternative Therapies
No FDA-approved dietary supplements or herbal medications for ED but gingko biloba, red ginseng, yohimbine reportedly improve ED
ONGOING CARE
PROGNOSIS
Excellent if reduction of cardiovascular risk factors, weight loss, exercise, smoking cessation
COMPLICATIONS
N/A
FOLLOW-UP
Patient Monitoring
• Patients to be reevaluated periodically with following considerations:
– Response to initial therapy
– Need for dose titration
– Patient education on proper medication use (specific PDE5i on empty stomach, use of local injection therapy)
– Need for progression to 2nd-line therapy/surgery based on therapeutic effectiveness and patient satisfaction
Patient Resources
Urology Care Foundation. http://www.urologyhealth.org/urology/index.cfm?article=60
REFERENCES
1. Lue TF. Physiology of penile erection and pathophysiology of erectile dysfunction. In: Wein AJ, Kavoussi LR, Novick AC, et al., eds. Campbell-Walsh Urology. 10th ed. Philadelphia, PA: Saunders-Elsevier; 2012.
2. Carson CC, Lue TF. Phophodiesterase type 5 inhibitors for erectile dysfunction. BJU Int. 2005;96:257–280.
3. Burnett AL. Evaluation and management of erectile dysfunction. In: Wein AJ, Kavoussi LR, Novick AC, et al., eds. Campbell-Walsh Urology. 10th ed. Philadelphia, PA: Saunders-Elsevier; 2012.
ADDITIONAL READING
Montague DK, Jarow JP, Broderick GA, et al. Chapter 1: The management of erectile dysfunction: An AUA update. J Urol. 2005;174(1):230–239.
See Also (Topic, Algorithm, Media)
• Erectile Dysfunction Algorithm 
• Erectile Dysfunction, Following Pelvic Surgery or Radiation
• Erectile Dysfunction/Impotence, General Considerations Image 
• Penile Rehabilitation
CODES
ICD9
• 302.72 Psychosexual dysfunction with inhibited sexual excitement
• 607.84 Impotence of organic origin
ICD10
• F52.21 Male erectile disorder
• N52.9 Male erectile dysfunction, unspecified
• N52.39 Other post-surgical erectile dysfunction
CLINICAL/SURGICAL PEARLS
• ED is a symptom of multiple underlying diseases that affect the following: penile nerve, artery, endothelial or smooth muscle function.
• Cardiac risk assessment should occur prior to initiation of therapy.
• Surgical therapy (penile prosthesis) is an essential therapy when medical treatment has failed or is contraindicated.