What is the initial workup and treatment for erectile dysfunction (ED)?

Erectile Dysfunction Workup

Begin with a detailed medical and sexual history focusing on onset pattern (sudden vs gradual), presence of morning erections, cardiovascular risk factors, medications, and psychosocial stressors, followed by a focused physical examination of blood pressure and genitalia, and obtain morning total testosterone, fasting glucose/HbA1c, and lipid panel as your initial laboratory workup. 1

History Taking

Distinguish ED from other sexual dysfunctions by asking the patient to describe the problem in their own words, specifically excluding premature ejaculation or orgasmic disorders. 2

Key Historical Features to Elicit:

• Onset and pattern: Sudden onset with preserved morning/self-stimulated erections suggests psychogenic etiology, while gradual onset with loss of all erections suggests organic causes. 2, 3
• Severity and duration: Document how long the problem has existed and whether it occurs in all situations or only with specific partners. 2, 1
• Cardiovascular risk factors: ED in men over 30 is a risk marker for underlying cardiovascular disease and typically presents 3 years before coronary symptoms. 1, 4
• Medication review: Antidepressants, antihypertensives (especially beta-blockers and thiazides), and tobacco use are common culprits. 2, 5
• Psychiatric screening: Screen for depression, anxiety, relationship problems, and substance abuse (especially alcohol), as these require treatment before or concurrent with ED therapy. 2, 3
• Comorbid conditions: Diabetes, hypertension, hyperlipidemia, neurological disease, and prior pelvic surgery all increase ED risk. 1, 6

Physical Examination

Perform a focused examination rather than comprehensive assessment in most cases:

• Vital signs: Measure blood pressure to identify uncontrolled hypertension. 2
• Genital examination: Check testicular size (small testes suggest hypogonadism), palpate for Peyronie's plaques in the penile shaft, verify retractable foreskin, and assess urethral meatus placement. 2, 1
• Secondary sexual characteristics: Look for signs of hypogonadism (reduced body hair, gynecomastia). 2
• Cardiovascular and neurological examination: Only perform if history suggests specific abnormalities. 2

Laboratory Testing

Order these three tests for all men with ED:

• Morning total testosterone level: Essential to identify hypogonadism, which commonly contributes to ED and requires specific treatment. 1, 7
• Fasting glucose or HbA1c: Screen for diabetes, a major ED risk factor. 1, 7
• Lipid profile: Assess cardiovascular risk, as ED and cardiovascular disease share common pathophysiology. 1, 7

Additional Testing in Select Cases:

• Prostate-specific antigen (PSA) and digital rectal exam: Required as baseline before initiating testosterone replacement therapy in any patient, and routinely in men over 50 with life expectancy >10 years. 2
• Free testosterone or androgen index: If clinical signs suggest hypogonadism despite normal total testosterone. 2
• Thyroid-stimulating hormone: Only if clinical suspicion for thyroid disease exists. 4

When to Refer for Specialized Testing:

• Young men with lifelong ED (never achieved adequate erections). 2
• History of pelvic or perineal trauma. 2
• Abnormal findings on genital examination (significant Peyronie's disease, testicular abnormalities). 2
• Abnormal screening laboratory results requiring specialist management. 2

Initial Treatment Approach

Initiate phosphodiesterase type 5 inhibitors (PDE5i) as first-line therapy for all men with ED, regardless of whether the etiology appears psychogenic or organic, while simultaneously addressing lifestyle modifications and cardiovascular risk factors. 1, 3

PDE5 Inhibitor Selection and Dosing:

• All four agents (sildenafil, tadalafil, vardenafil, avanafil) have equivalent efficacy (60-65% success rate), so selection is based on patient preference regarding timing and duration of action. 7, 8, 6
• Start at standard dosing and titrate upward: An adequate trial requires at least 5 separate attempts at maximum dose before declaring treatment failure. 3
• Provide explicit instructions: The medication requires sexual stimulation to work; timing varies by agent (sildenafil/vardenafil 30-60 minutes before, tadalafil up to 36-hour window, avanafil 15-30 minutes before). 7

Absolute Contraindications to PDE5 Inhibitors:

• Concurrent nitrate use (can cause fatal hypotension). 7, 9
• Guanylate cyclase stimulators (riociguat). 9
• Severe hepatic impairment (Child-Pugh C for vardenafil). 9

Relative Contraindications and Dose Adjustments:

• Alpha-blocker use: Start PDE5i at lowest dose due to additive hypotensive effects. 9
• Moderate hepatic impairment: Reduce vardenafil starting dose to 5 mg maximum 10 mg. 9
• Congenital or acquired QT prolongation: Avoid vardenafil, especially with Class IA or III antiarrhythmics. 9

Lifestyle Modifications (Initiate Simultaneously):

• Smoking cessation: Tobacco use greatly increases ED risk. 3, 4, 5
• Weight loss if BMI >30 kg/m²: Obesity is a major modifiable risk factor. 3, 4
• Increased physical activity: Regular exercise improves erectile function. 1, 3
• Optimize glycemic control in diabetics. 3
• Optimize blood pressure and lipid management. 3

Etiology-Specific Interventions

For Psychogenic ED:

• Refer to sex therapy or couples counseling concurrently with PDE5i initiation, not sequentially. 3
• Address underlying psychiatric conditions: Treat depression, anxiety, or substance use disorders. 2, 3

For Organic ED with Hypogonadism:

• Testosterone replacement therapy improves ED and libido in men with documented low testosterone. 1, 4
• Combination therapy: Testosterone plus PDE5i may benefit non-responders to PDE5i alone. 7
• Monitoring requirements: Check hemoglobin, liver enzymes, and PSA at intervals due to prostate cancer risk. 4

For Medication-Induced ED:

• Switch antihypertensives to agents with lower ED risk when possible. 3
• Consider alternative antidepressants if SSRIs are contributing. 5

Second-Line Therapies (When PDE5i Fail)

Try a different PDE5i at maximum dose before proceeding to more invasive options, as individual response varies. 7

If two different PDE5i trials fail:

• Intracavernosal injection therapy (alprostadil, papaverine, phentolamine combinations): Highly effective but requires initial supervised test dose. 7, 3
• Intraurethral alprostadil suppositories: Less effective than injections but less invasive. 2, 3
• Vacuum erection devices: Non-invasive mechanical option. 2, 3

Third-Line Therapy

• Penile prosthesis implantation: Reserved for patients who fail all medical therapies; associated with high satisfaction rates. 3, 10

Common Pitfalls to Avoid

• Do not overlook proper PDE5i use education: Many "treatment failures" result from incorrect timing or lack of sexual stimulation. 7
• Do not prescribe PDE5i without screening for nitrate use: This combination is potentially fatal. 7
• Do not ignore testosterone deficiency: Low testosterone requires specific treatment and contributes significantly to ED. 7
• Do not dismiss cardiovascular risk assessment: ED is an independent marker for cardiovascular disease requiring screening and risk factor modification. 1, 4

Follow-Up Strategy

• Schedule 3-month follow-up after initiating PDE5i to assess response and adjust therapy. 7
• Reassess cardiovascular risk factors periodically, as ED and cardiovascular disease share pathophysiology. 1, 7