What is on the differential diagnosis for Erectile Dysfunction?

Key differentials include Hypogonadism, Psychogenic ED, Peyronie's disease, Premature ejaculation, Medication side effect, Pelvic vascular disease (Leriche).

What are the high-yield PANCE pearls for Erectile Dysfunction?

Erectile dysfunction is an independent risk marker for cardiovascular disease — comprehensive cardiac risk assessment is part of ED workup. PDE5 inhibitors are absolutely contraindicated with any nitrate (oral, sublingual, paste, patch) within 24 hours (48 hours for tadalafil) — severe hypotension can be fatal. Confirm low testosterone with TWO morning measurements + symptoms before initiating replacement therapy. Testosterone replacement is contraindicated in active prostate or breast cancer; monitor PSA, hematocrit, lipids during therapy. Daily low-dose tadalafil (2.5-5 mg) also treats lower urinary tract symptoms from BPH — useful when conditions coexist. Sudden hearing loss or vision loss (NAION) on PDE5i requires immediate discontinuation and evaluation. Preserved nocturnal or morning erections argue strongly for psychogenic ED.

Reproductive · PANCE / PANRE

Erectile Dysfunction

Written & clinically reviewed by Ryan Busch, PA-C · Updated July 2026 · Report an error

Persistent inability to achieve or maintain erection adequate for satisfactory sex — vascular disease until proven otherwise.

Also known as: ED, erectile dysfunction, impotence, vasculogenic ED

Overview

Persistent or recurrent inability to attain and/or maintain a penile erection sufficient for sexual satisfaction for at least 3 months. Subtypes are vasculogenic, neurogenic, hormonal, psychogenic, or drug-induced — often multifactorial.

Epidemiology

Affects ~50% of men aged 40-70 to some degree; prevalence rises with age. Strongly associated with cardiovascular disease — ED often heralds CAD by 3-5 years.

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Risk factors

Cardiovascular disease, hypertension, hyperlipidemia
Diabetes mellitus (both vasculogenic and neurogenic mechanisms)
Smoking, obesity, sedentary lifestyle
Hypogonadism (low testosterone)
Pelvic surgery (radical prostatectomy, cystectomy), pelvic radiation
Neurologic disease: multiple sclerosis, spinal cord injury, stroke
Medications: thiazides, beta-blockers, SSRIs, antiandrogens, 5-alpha reductase inhibitors, opioids
Depression, anxiety, relationship issues
Peyronie's disease
Sleep apnea, alcohol/substance use

Pathophysiology

Erection requires intact arterial inflow, venous occlusion (veno-occlusive mechanism), parasympathetic neural signaling (nitric oxide release → cGMP → smooth muscle relaxation in cavernosal sinusoids), and adequate testosterone for libido. Endothelial dysfunction in atherosclerosis impairs NO-mediated vasodilation — the same mechanism affects penile and coronary arteries (penile arteries are smaller, manifest dysfunction earlier).

Clinical presentation

Symptoms

Inability to achieve or maintain erection
Reduced rigidity or duration of erections
Loss of nocturnal/morning erections (organic ED) vs preserved (psychogenic)
Reduced libido (especially with hypogonadism)
Relationship distress, depression

Signs / physical exam

Often normal exam
Cardiovascular: peripheral pulses, blood pressure, signs of PAD
Genitourinary: testicular size, Peyronie's plaque, gynecomastia (hypogonadism)
Neurologic: sensation, anal sphincter tone, bulbocavernosus reflex
Body habitus, secondary sex characteristics

Differential diagnosis

Hypogonadism — Low libido + ED, fatigue; low morning total testosterone (confirm with repeat + free T)
Psychogenic ED — Sudden onset, intermittent, situation-dependent, preserved nocturnal/morning erections; younger men
Peyronie's disease — Penile curvature, palpable plaque, pain with erection; often coexists with ED
Premature ejaculation — Distinct primary complaint; treat with SSRIs (paroxetine, sertraline) or dapoxetine
Medication side effect — Temporal relation; common with SSRIs, beta-blockers, thiazides, finasteride
Pelvic vascular disease (Leriche) — Buttock claudication, ED, absent femoral pulses; aortoiliac disease

Diagnostic workup

Labs

Fasting glucose or A1c, lipid panel
Morning total testosterone (8-11 AM; repeat if low); free testosterone, SHBG, LH, FSH, prolactin if low T
TSH
Consider CBC, BMP, PSA (age-appropriate)
Cardiac risk assessment — ED is a marker for cardiovascular disease

Imaging

Penile Doppler ultrasound — for refractory ED or to differentiate arterial insufficiency from venous leak
Nocturnal penile tumescence testing — distinguishes organic from psychogenic (preserved nocturnal erections favor psychogenic)
Limited routine imaging

Diagnostic algorithm

Class	Drugs	Notes
PDE5 inhibitor	Sildenafil, tadalafil, vardenafil, avanafil	First-line; nitrate contraindication; α-blocker caution
Intracavernosal injection	Alprostadil; Trimix (alprostadil + papaverine + phentolamine)	High efficacy; priapism risk
Intraurethral suppository	Alprostadil (MUSE)	Less effective than injection
Vacuum erection device	(Mechanical)	Drug-free; suitable in nitrate users
Testosterone replacement	Transdermal gel, IM injection, pellets	Only if confirmed hypogonadism; monitor PSA, Hct
Penile prosthesis	Inflatable or malleable	Refractory cases; high satisfaction

ED therapy options by class — PDE5 inhibitors are first-line.

Treatment

First-line

Address modifiable factors: smoking cessation, weight loss, exercise, glycemic and BP control, lipid management, treat depression
Review and modify medications when feasible (e.g., swap thiazide for ARB; selegiline/bupropion if SSRI-induced)
PDE5 inhibitor — sildenafil, tadalafil, vardenafil — first-line pharmacotherapy
• Sildenafil 25-100 mg 30-60 min before sex; effect ~4 h; fatty meals delay onset
• Tadalafil 5-20 mg as needed (effect 24-36 h, 'weekend pill') OR 2.5-5 mg daily for continuous coverage
• Vardenafil 5-20 mg
• Absolute contraindication: nitrate use (severe hypotension)
• Caution: alpha-blockers (separate dosing), severe cardiac disease, retinal disease

ED + cardiovascular disease

Cardiac risk stratification before initiating sexual activity (Princeton Consensus)
Low-risk: PDE5 inhibitors safe
Intermediate-risk: stress testing, defer therapy until stabilized
High-risk: defer until cardiology cleared

Post-prostatectomy ED

Early penile rehabilitation: PDE5 inhibitor (daily low-dose tadalafil) ± vacuum device
Nerve-sparing technique improves outcomes
Recovery may take 12-24 months; intracavernosal injections or prosthesis if persistent

Second-line / adjunct

Testosterone replacement — only if confirmed hypogonadism (low T + symptoms); contraindicated in untreated prostate or breast cancer; monitor PSA and hematocrit
Vacuum erection devices (VED) — mechanical, no pharmacology
Intraurethral alprostadil (MUSE) suppositories
Intracavernosal injections — alprostadil, papaverine, phentolamine (Trimix); high efficacy when PDE5i fails; risk of priapism, fibrosis
Penile prosthesis (inflatable or malleable) — for refractory ED; highest patient satisfaction in selected cases
Psychosexual counseling, couples therapy

Complications

Psychological distress, depression, relationship strain
Untreated cardiovascular disease (ED as harbinger of CAD)
Priapism from intracavernosal therapy or PDE5 inhibitor + sickle cell
Cardiovascular events with concurrent nitrate use
Treatment side effects: headache, flushing, dyspepsia, NAION (rare), hearing loss (rare)

PANCE pearls

Erectile dysfunction is an independent risk marker for cardiovascular disease — comprehensive cardiac risk assessment is part of ED workup.
PDE5 inhibitors are absolutely contraindicated with any nitrate (oral, sublingual, paste, patch) within 24 hours (48 hours for tadalafil) — severe hypotension can be fatal.
Confirm low testosterone with TWO morning measurements + symptoms before initiating replacement therapy.
Testosterone replacement is contraindicated in active prostate or breast cancer; monitor PSA, hematocrit, lipids during therapy.
Daily low-dose tadalafil (2.5-5 mg) also treats lower urinary tract symptoms from BPH — useful when conditions coexist.
Sudden hearing loss or vision loss (NAION) on PDE5i requires immediate discontinuation and evaluation.
Preserved nocturnal or morning erections argue strongly for psychogenic ED.

References

AUA 2018 — Erectile Dysfunction: AUA Guideline (Burnett et al., J Urol 2018; reaffirmed)
Princeton III — The Princeton III Consensus Recommendations for the Management of Erectile Dysfunction and Cardiovascular Disease (Nehra et al., Mayo Clin Proc 2012)
Endocrine Society 2018 — Testosterone Therapy in Men with Hypogonadism: Endocrine Society Clinical Practice Guideline (Bhasin et al., JCEM 2018)

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