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Subject: Erectile Dysfunction
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Erectile dysfunction (ED): the consistent or recurrent inability to acquire or sustain an erection of sufficient rigidity and duration for sexual intercourse
In the past, ED was assumed to be a symptom of the aging process in men, but it is more often the result of concurrent medical conditions of the patient or from medications that patients may be taking to treat those conditions.
Sexual problems are frequent among older men and have a detrimental effect on their quality of life but are infrequently discussed with their physicians.
Synonym(s): impotence
52% in men age 40 to 70 years
Age-related increase ranging from 12.4% in men age 40 to 49 years up to 46.6% in men age 50 to 69 years
ED is a neurovascular event.
With stimulation, there is release of nitrous oxide, which increases production of cyclic guanosine 3′,5′-monophosphate (cGMP).
This leads to relaxation of cavernous smooth muscle, leading to increased blood flow to penis.
As cavernosal sinusoids distend with blood, there is passive compression of subtunical veins, which decreases venous outflow, and this leads to an erection.
Alterations in any of these events lead to ED.
ED may result from problems with systems required for normal penile erection.
Vascular: diseases that compromise blood flow
Peripheral vascular disease, arteriosclerosis, essential hypertension
Neurologic: diseases that impair nerve conduction to brain or penile vasculature
Spinal cord injury, stroke, diabetes
Endocrine: diseases associated with changes in testosterone, luteinizing hormone, prolactin levels
Structural: phimosis, lichen sclerosis, congenital curvature
Psychological: patients suffering from malaise, depression, performance anxiety
Social habits such as smoking or excessive alcohol intake
Medications may cause ED.
Prostate cancer treatment
Structural injury or trauma (bicycling accident)
Advancing age
Cardiovascular disease
Diabetes mellitus
Metabolic syndrome
Sedentary lifestyle
Cigarette smoking
Urologic surgery, radiation, trauma/injury to pelvic area or spinal cord
Medications that induce ED
SSRIs, β-blockers, clonidine, digoxin, spironolactone, antiandrogens, corticosteroids, H2 blockers, anticonvulsants
Central neurologic and endocrinologic conditions
Substance abuse (alcohol, cocaine, opioids, marijuana)
Psychological conditions: stress, anxiety, or depression; sexual abuse; relationship problems
Making healthy lifestyle choices by exercising regularly, eating well-balanced meals, limiting alcohol, and avoiding smoking
Treating existing health problems and working with your patients to manage diabetes, heart disease, and other chronic problems
Aging alone is not a cause.
Cardiovascular disease:
Men with ED have a greater likelihood of having angina, myocardial infarction, stroke, transient ischemic attack, congestive heart failure, or cardiac arrhythmia compared to men without ED (1).
Diabetes
Neurologic conditions
Psychiatric disorders
Identify concurrent medical illnesses or surgical procedures, history of trauma, and a list of current medications (e.g., antihypertensive meds).
Psychosocial history: smoking, ethanol intake, recreational drug use, anxiety and depression, satisfaction with current relationship
Presence or absence of morning erections
Speed of onset and duration of symptoms
Relationship of symptoms to libido
Detailed sexual history important to rule out premature ejaculation, as this is frequently confused with ED
International Index of Erectile Function (IIEF) patient questionnaire is a useful tool in the clinical assessment and measurement of effectiveness of ED treatments (1). (http://files.sld.cu/urologia/files/2011/08/iief.pdf)
Signs and symptoms of hypogonadism: gynecomastia, small testicles, decreased body hair
Penile plaques (Peyronie disease)
Detailed examination of the cardiovascular, neurologic, and genitourinary systems
Blood pressure, waist circumference, BMI
Check femoral and lower extremity pulses to assess vascular supply to genitals.
Check anal sphincter tone and genital reflexes, including cremasterics and bulbocavernosus.
Premature ejaculation
Decreased libido
Anorgasmia
Sudden versus chronic ED
Hgb A1c, lipid panel, CBC, BMP, TSH, morning total and free testosterone level (1)[C]
Doppler, angiogram, and cavernosogram are available radiologic modalities but not recommended in routine practice for the diagnosis of ED (2)[C].
Lifestyle modifications and managing medications contributing to ED is first-line therapy for ED (3)[C]. Use least invasive therapy first; reserve more invasive therapies for nonresponders.
Cardiovascular risk stratification and risk-factor management is recommended in all men with vasculogenic ED (4).
Current smoking is significantly associated with ED, and smoking cessation has a beneficial effect on the restoration of erectile function (1)[A].
Phosphodiesterase type 5 (PDE-5) inhibitors are the first-line treatment for ED (1)[A].
Psychosexual therapy alone or in combination with psychoactive drugs may be helpful in men whose ED is related to depression or anxiety (5).
Weight loss and increased physical activity for obese men with ED. Men with metabolic syndrome should be counseled to make lifestyle modifications to reduce the risk of cardiovascular events and ED (1)[B].
Sildenafil (Viagra): usual daily dose: 50 to 100 mg within at least 60 minutes of sexual intercourse
Vardenafil (Levitra): usual daily dose 5 to 20 mg within at least 60 minutes of sexual intercourse
Vardenafil (Staxyn): ODT: usual dose 10 mg within 60 minutes of sexual intercourse
Tadalafil (Cialis): usual daily dose 5 to 20 mg within at least 30 minutes of sexual intercourse or 2.5 mg once daily without regard to sexual activity
Avanafil (Stendra): usual daily dose: 50 to 200 mg within at least 15 to 30 minutes of sexual intercourse
Adverse effects of PDE-5 inhibitors: headache, facial flushing, dyspepsia, nasal congestion, dizziness, hypotension, increased sensitivity to light (sildenafil and vardenafil), vision changes, lower back pain (tadalafil), and priapism (with excessive doses)
Sildenafil and vardenafil should be taken on an empty stomach for maximum effectiveness.
Use doses at the lower end of the dosing range for elderly patients and evaluate exercise tolerance before prescribing.
Sildenafil 25 mg daily
Vardenafil 5 mg daily
Intraurethral alprostadil (Muse):
Intraurethral suppository: 125-, 250-, 500-, and 1,000-μg pellets. Administer 5 to 50 minutes before intercourse. No >2 doses in 24 hours are recommended.
Intracavernosal alprostadil (available in two formulations):
Alprostadil (Caverject): usual dose: 10 to 20 μg, with max dose of 60 μg. Injection should be made at right angles into one of the lateral surfaces of the proximal 3rd of the penis using a 0.5-inch, 27- or 30-gauge needle. Do not use >3 times a week or more than once in 24 hours.
Alprostadil may also be combined with papaverine (Bimix) plus phentolamine (Trimix), plus atropine (Quadmix).
Vacuum Erection Device (VED): non-invasive option, available over the counter.
Penile Prosthesis (7)
Initial trial dose of second-line agents should be administered under supervision of a specialist or primary care physician with expertise in these therapies.
Patient should notify physician if erection lasts >4 hours for immediate attention.
Do not use vacuum devices in men with sickle cell anemia or blood dyscrasias.
Testosterone supplementation in men with hypogonadism improves ED and libido (6)[B]. Available formulations include injectable depots, transdermal patches and gels, SC pellets, and oral therapy.
Best practices in urology recommendation: Do not prescribe testosterone to men with ED who have normal testosterone levels (1).
Contraindications:
Nitroglycerin (or other nitrates) and phosphodiesterase inhibitors: potential for severe, fatal hypotension
Precautions/side effects:
Testosterone: precautions: Exogenous testosterone reduces sperm count and thus do not use in patients wishing to keep fertility; side effects: acne, sodium retention
Intraurethral suppository: local penile pain, urethral bleeding, dizziness, and dysuria
Intracavernosal injection: penile pain, edema and hematoma, palpable nodules or plaques, and priapism
Sildenafil: hypotension (caution for patients on nitrates)
PDE-5 inhibitors: Use caution with congenital prolonged QT syndrome, class Ia or II antiarrhythmics, nitroglycerin, α-blockers (e.g., terazosin, tamsulosin), retinal disease, unstable cardiac disease, liver and renal failure.
Significant possible interactions
PDE-5 inhibitor concentration is affected by CYP3A4 inhibitors (e.g., erythromycin, indinavir, ketoconazole, ritonavir, amiodarone, cimetidine, clarithromycin, delavirdine, diltiazem, fluoxetine, fluvoxamine, grapefruit juice, itraconazole, nefazodone, nevirapine, saquinavir, and verapamil). Serum concentrations and/or toxicity may be increased. Lower starting doses should be used in these patients.
PDE-5 inhibitor concentration may be reduced by rifampin and phenytoin.
All commercially available PDE-5 inhibitors are equally effective. In the presence of sexual stimulation, they are 55–80% effective.
Lower success rates with diabetes mellitus and radical prostatectomy patients who suffer from ED
Overall effectiveness is 70–90% for intracavernosal alprostadil and 43–60% for intraurethral alprostadil (2)[B].
Penile prostheses are associated with an 85–90% patient satisfaction rate (2)[C].
N52.9 Male erectile dysfunction, unspecified
N52.1 Erectile dysfunction due to diseases classified elsewhere
F52.21 Male erectile disorder
N52.2 Drug-induced erectile dysfunction
N52.02 Corporo-venous occlusive erectile dysfunction
N52.0 Vasculogenic erectile dysfunction
N52.32 Erectile dysfunction following radical cystectomy
N52.34 Erectile dysfunction following simple prostatectomy
N52.33 Erectile dysfunction following urethral surgery
N52.31 Erectile dysfunction following radical prostatectomy
N52.39 Other post-surgical erectile dysfunction
N52.01 Erectile dysfunction due to arterial insufficiency
N52.03 Comb artrl insuff & corporo-venous occlusv erectile dysfnct
N52.8 Other male erectile dysfunction
607.84 Impotence of organic origin
302.72 Psychosexual dysfunction with inhibited sexual excitement
473020005 primary erectile dysfunction (disorder)
198036002 Impotence of organic origin
73491007 psychogenic impotence (disorder)
236751006 Drug-induced impotence (disorder)
Nitrates should be withheld for 24 hours after sildenafil or vardenafil administration and for 48 hours after use of tadalafil. PDE-5 inhibitors are contraindicated in patients taking concurrent nitrates of any form (regular or intermittent nitrate therapy), as it can lead to severe hypotension and syncope.
Reserve surgical treatment for patients who do not respond to drug treatment.
The use of PDE-5 inhibitors with α-adrenergic antagonists may increase the risk of hypotension. Tamsulosin is the least likely to cause orthostatic hypotension.
Avanafil should not be used with strong CYP3A4 inhibitors and max dose should be 50 mg with moderate CYP3A4 inhibitors.
ED may be a marker for subclinical cardiovascular disease. Thoroughly assess patients with nonpsychogenic ED for CV risks.