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Erectile Dysfunction

James G. Nee, MD, FAAFP Reviewed 06/2020
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Subject: Erectile Dysfunction

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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 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

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 some degree of 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 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)

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

  • Central neurologic and endocrinologic conditions

  • Substance abuse (alcohol, cocaine, opioids, marijuana)

  • Psychological conditions: stress, anxiety, or depression; sexual abuse; relationship problems

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

ALERT

Aging alone is not a cause.

 

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 (1).

  • Diabetes

  • Neurologic conditions

  • Metabolic syndrome

  • Psychiatric disorders

DIAGNOSIS

Inability to achieve or maintain erection satisfactory for intercourse 

HISTORY

  • 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)

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, 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.

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 (2)[C]. 

Initial Tests (lab, imaging)

  • 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].

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 IIEF and its validated and more easily administered abridged version, the Sexual Health Inventory for Men (SHIM) (2)[C]. 

TREATMENT

  • 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].

GENERAL MEASURES

  • 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].

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 (6). Choice should be based on patient’s preference (cost, ease of use, and adverse effects). There is insufficient evidence to support the superiority of one agent over the others (3)[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

  • 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 and evaluate exercise tolerance before prescribing.

 

Second Line

Intraurethral and intracavernosal injectables are second-line therapies shown to be effective and should be administered based on patient preference (1)[B]. Intraurethral suppositories are a less invasive treatment option than intracavernosal injections; however, they are not as effective (3)[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):

    • 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)

ALERT

  • 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:

 

ADDITIONAL THERAPIES

Men with relationship difficulties who received therapy plus sildenafil had more successful intercourse than those who received only sildenafil (8)[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. Low intensity shock wave treatment is not FDA approved, but some studies have shown improvement particularly in younger, non-diabetic patients with milder cases of ED. Further research is needed (9). 

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 (2)[B].

  • Penile prostheses are associated with an 85–90% patient satisfaction rate (2)[C].

REFERENCES

1
Rew KT, Heidelbaugh JJ. Erectile dysfunction. Am Fam Physician.  2016;94(10):820–827. [View Abstract on OvidMedline]
2
McVary KT. Clinical practice. Erectile dysfunction. N Engl J Med.  2007;357(24):2472–2481. [View Abstract on OvidMedline]
3
American Urological Association. Guideline on the management of erectile dysfunction: diagnosis and treatment recommendations. http://www.auanet.org/education/guidelines/erectile-dysfunction.cfm. Accessed January 13, 2017. [View Abstract on OvidMedline]
4
Miner M, Nehra A, Jackson Get al. All men with vasculogenic erectile dysfunction require a cardiovascular workup. Am J Med.  2014;127(3):174–182. [View Abstract on OvidMedline]
5
Wiggins A, Tsambarlis PN, Abdelsayed Get al. A treatment algorithm for healthy young men with erectile dysfunction. BJU Int.  2019;123(1):173–179. [View Abstract on OvidMedline]
6
Heidelbaugh JJ. Management of erectile dysfunction. Am Fam Physician.  2010;81(3):305–312. [View Abstract on OvidMedline]
7
Le TV, Tsambarlis P, Hellstrom WJG. Pharmacodynamics of the agents used for the treatment of erectile dysfunction. Expert Opin Drug Metab Toxicol.  2019;15(2):121–131. [View Abstract on OvidMedline]
8
Melnik T, Soares BG, Nasselo AG. Psychosocial interventions for erectile dysfunction. Cochrane Database Syst Rev.  2007;(3):CD004825. [View Abstract on OvidMedline]
9
Kitrey ND, Vardi Y, Appel Bet al. Low intensity shock wave treatment for erectile dysfunction-how long does the effect last? J Urol.  2018;200(1):167–170. [View Abstract on OvidMedline]

CODES

ICD10

  • 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

ICD9

  • 607.84 Impotence of organic origin

  • 302.72 Psychosexual dysfunction with inhibited sexual excitement

SNOMED

  • 473020005 primary erectile dysfunction (disorder)

  • 198036002 Impotence of organic origin

  • 73491007 psychogenic impotence (disorder)

  • 236751006 Drug-induced impotence (disorder)

CLINICAL PEARLS

  • 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.

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