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Erectile Dysfunction
Michael C. Barros, PharmD, BCPS, BCACP
Neela Bhajandas, PharmD
Paul N. Williams, MD, FACP
image BASICS
DESCRIPTION
  • 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 can result from 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 (1).
  • Synonym(s): impotence
EPIDEMIOLOGY
Incidence
It is estimated that >600,000 new cases of ED will be diagnosed annually in the United States, although this may be an underestimation of the true incidence, as ED is vastly underreported.
Prevalence
Overall prevalence for ED:
  • 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
ETIOLOGY AND PATHOPHYSIOLOGY
  • ED is a neurovascular event.
    • With stimulation, there is release of nitrous oxide, which increases production of guanosine 3′,5′-cyclic 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 leads 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.
  • Structural injury or trauma (bicycling accident)
Genetics
Rarely related to chromosomal disorders
RISK FACTORS
  • 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, &bgr;-blockers, clonidine, digoxin, spironolactone, antiandrogens, corticosteroids, H2 blockers
  • Central neurologic and endocrinologic conditions
  • Substance abuse
  • Psychological conditions: stress, anxiety, or depression
GENERAL PREVENTION
The two best ways to prevent ED are by the following:
  • 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
COMMONLY ASSOCIATED CONDITIONS
  • 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 (3).
  • Diabetes
  • Psychiatric disorders
image DIAGNOSIS
Inability to achieve or maintain erection satisfactory for intercourse
PHYSICAL EXAM
  • 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
    • Check femoral and lower extremity pulses to assess vascular supply to genitals.
    • Check anal sphincter tone and genital reflexes, including cremasterics and bulbocavernosus.
DIFFERENTIAL DIAGNOSIS
  • Premature ejaculation
  • Decreased libido
  • Anorgasmia
  • Sudden versus chronic ED
DIAGNOSTIC TESTS & INTERPRETATION
Vascular and/or neurologic assessment, and monitoring of nocturnal erections may be indicated in selected patients but not for routine workup (4)[C].
Initial Tests (lab, imaging)
  • Hgb A1c, lipid panel, TSH, and morning total testosterone level (3)[C]
  • Doppler, angiogram, and cavernosogram are available radiologic modalities but not recommended in routine practice for the diagnosis of ED (4)[C].
Follow-Up Tests & Special Considerations
Other hormonal tests, such as prolactin, should only be ordered when there is suspicion for a specific endocrinopathy.
Diagnostic Procedures/Other
Questionnaires can be offered to assess the severity of ED, including the International Index of Erectile Function (IEFF) and its validated and more easily administered abridged version, the Sexual Health Inventory for Men (SHIM) (4)[C].
image TREATMENT
  • Lifestyle modifications and managing medications contributing to ED is first-line therapy for ED (5)[C]. Use least invasive therapy first; reserve more invasive therapies for nonresponders.
  • Phosphodiesterase type 5 (PDE-5) inhibitor choice should be based on patient's preference (cost, ease of use, and adverse effects).
GENERAL MEASURES
  • Psychotherapy alone or in combination with psychoactive drugs may be helpful in men whose ED is related to depression or anxiety.
  • Weight loss and increased physical activity for obese men with ED
MEDICATION
First Line
PDE-5 inhibitors are effective in the treatment of ED in many men, including those with diabetes mellitus and spinal cord injury and sexual dysfunction associated with antidepressants (3)[A]. There is insufficient evidence to support the superiority of one agent over the others (5)[A]:
  • 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
  • P.357

  • 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.
Geriatric Considerations
Use doses at the lower end of the dosing range for elderly patients.
  • Sildenafil 25 mg daily
  • Vardenafil 5 mg daily
Second Line
Intraurethral and intracavernosal injectables are second-line therapies shown to be effective and should be administered based on patient preference (3)[B]. Intraurethral suppositories are a less invasive treatment option than intracavernosal injections; however, they are not as effective (5)[C]. Alprostadil, also known as prostaglandin E1, causes smooth muscle relaxation of the arterial blood vessels and sinusoidal tissues in the corpora:
  • Intraurethral alprostadil (Muse):
    • Urethral suppository: 125-, 250-, 500-, and 1,000-&mgr;g pellets. Administer 5 to 50 minutes before intercourse. No more than 2 doses in 24 hours are recommended.
  • Intracavernosal alprostadil (available in 2 formulations):
    • Alprostadil (Caverject): usual dose: 10 to 20 &mgr;g, with max dose of 60 &mgr;g. Injection should be made at right angles into one of the lateral surfaces of the proximal third 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 (Tri-Mix).
ADDITIONAL THERAPIES
Behavioral therapy: Couples therapy aimed at improving relationship difficulties found that men who received this therapy plus sildenafil had more successful intercourse than those who received only sildenafil (6)[A].
SURGERY/OTHER PROCEDURES
Penile prosthesis should be reserved for patients who have failed or are ineligible first- or second-line therapies.
COMPLEMENTARY & ALTERNATIVE MEDICINE
Trazodone, yohimbine, and herbal therapies are not recommended for the treatment of ED, as they have not proven to be efficacious.
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
Treatment should be assessed at baseline and after the patient has completed at least 1 to 3 weeks of a specific treatment: Monitor the quality and quantity of penile erections, and monitor the level of satisfaction patient achieves.
DIET
Diet and exercise recommended to achieve a normal body mass index; limit alcohol
PROGNOSIS
  • 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 (4)[B].
  • Penile prostheses are associated with an 85-90% patient satisfaction rate (4)[C].
REFERENCES
1. Lindau ST, Schumm LP, Laumann EO, et al. A study of sexuality and health among older adults in the United States. N Engl J Med. 2007;357(8): 762-774.
2. Inman BA, Sauver JL, Jacobson DJ, et al. A population-based, longitudinal study of erectile dysfunction and future coronary artery disease. Mayo Clin Proc. 2009;84(2):108-113.
3. Heidelbaugh JJ. Management of erectile dysfunction. Am Fam Physician. 2010;81(3):305-312.
4. McVary KT. Clinical practice. Erectile dysfunction. N Engl J Med. 2007;357(24):2472-2481.
5. The American Urological Association. Guideline on the management of erectile dysfunction: diagnosis and treatment recommendations. Reviewed and Validity Confirmed in 2011. http://www.auanet.org/education/guidelines/erectile-dysfunction.cfm. Accessed 2015.
6. Melnik T, Soares BG, Nasselo AG. Psychosocial interventions for erectile dysfunction. Cochrane Database Syst Rev. 2007;(3):CD004825.
Codes
&NA;
ICD10
  • N52.9 Male erectile dysfunction, unspecified
  • N52.1 Erectile dysfunction due to diseases classified elsewhere
  • F52.21 Male erectile disorder
Clinical Pearls
&NA;
  • 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 &agr;-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 serves as a predictor for future cardiovascular events; thus, these patients should be followed vigilantly.