Reproductive · PANCE / PANRE

Erectile Dysfunction

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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Question 1ReproductiveMedium
A 52-year-old man reports 6 months of progressively reduced erectile rigidity along with low sexual desire and daytime fatigue. He has not noticed morning erections recently. His history includes well-controlled hypertension. On exam, testes are mildly small and soft and he has scant body hair; cardiovascular and neurologic exams are normal. A fasting lipid panel and hemoglobin A1c are unremarkable. Which of the following is the most appropriate next diagnostic test?
  • ASerum prolactin concentration
  • BNocturnal penile tumescence study
  • CPenile duplex Doppler ultrasound
  • DMorning serum total testosterone
Reveal answer & full explanation
Correct answer: D — Morning serum total testosterone
  • ASerum prolactin concentration
  • BNocturnal penile tumescence study
  • CPenile duplex Doppler ultrasound
  • DMorning serum total testosterone

Why Morning serum total testosterone is correct

  • The combination of ED with low libido, fatigue, loss of morning erections, small soft testes, and reduced body hair points to hypogonadism as the driver, so the next step is an 8-11 AM total testosterone (testosterone peaks in the morning).
  • Endocrine Society and AUA workup: when symptoms suggest low T, measure a morning total testosterone and confirm a low value with a repeat plus free testosterone, LH/FSH, and prolactin before treating.

Why the others are wrong

  • Nocturnal penile tumescence study distinguishes organic from psychogenic ED, but this patient already has clear organic, endocrine features (low libido, fatigue, small testes), so it is not the discriminating next step.
  • Penile duplex Doppler ultrasound assesses arterial inflow versus venous leak and is reserved for refractory ED or pre-procedure vascular evaluation, not the initial workup.
  • Serum prolactin concentration is part of the secondary evaluation of hypogonadism, but it is obtained only after a low morning total testosterone is documented and repeated, so ordering it first inverts the diagnostic sequence.
Question 2ReproductiveMedium
A 62-year-old man reports a 1-year history of gradually worsening difficulty attaining and maintaining erections, including loss of his previous morning erections. He has hypertension, type 2 diabetes, and hyperlipidemia, and he has smoked one pack of cigarettes daily for 35 years. Examination shows diminished dorsalis pedis pulses with an otherwise normal genital and neurologic examination. Morning total testosterone is normal. Which of the following best explains his erectile dysfunction?
  • AEndothelial dysfunction impairing nitric oxide-mediated cavernosal inflow
  • BAutonomic neuropathy disrupting cavernosal parasympathetic nerve signaling
  • CPsychogenic sympathetic outflow blocking cavernosal smooth muscle relaxation
  • DVenous leak preventing adequate blood trapping in the corpora cavernosa
Reveal answer & full explanation
Correct answer: A — Endothelial dysfunction impairing nitric oxide-mediated cavernosal inflow
  • AEndothelial dysfunction impairing nitric oxide-mediated cavernosal inflow
  • BAutonomic neuropathy disrupting cavernosal parasympathetic nerve signaling
  • CPsychogenic sympathetic outflow blocking cavernosal smooth muscle relaxation
  • DVenous leak preventing adequate blood trapping in the corpora cavernosa

Why Endothelial dysfunction impairing nitric oxide-mediated cavernosal inflow is correct

  • Normal erection depends on endothelial and neuronal nitric oxide, which raises cGMP, relaxes cavernosal sinusoidal smooth muscle, and permits arterial inflow with subsequent veno-occlusion.
  • This man carries the full atherosclerotic risk cluster (diabetes, hypertension, hyperlipidemia, heavy smoking) plus a peripheral arterial disease sign (diminished pedal pulses), pointing to vasculogenic ED from endothelial dysfunction.
  • Atherosclerotic endothelial dysfunction impairs NO-mediated vasodilation; the small penile arteries manifest this earlier than coronary vessels, so ED is an independent marker of cardiovascular disease and frequently heralds CAD by 3-5 years.

Why the others are wrong

  • Psychogenic sympathetic outflow blocking cavernosal smooth muscle relaxation — psychogenic ED characteristically begins abruptly, varies by partner or setting, and spares nocturnal and morning erections; his gradual 1-year decline with loss of morning erections and diminished pedal pulses points to an organic vascular cause.
  • Autonomic neuropathy disrupting cavernosal parasympathetic nerve signaling — diabetic autonomic neuropathy can contribute, but his neurologic examination is normal and the dominant clues (PAD, heavy vascular risk burden) favor a vasculogenic rather than neurogenic process.
  • Venous leak preventing adequate blood trapping in the corpora cavernosa — corporal veno-occlusive dysfunction causes ED with rapid detumescence, but it is typically a localized cavernosal or structural problem, not the systemic endothelial process implied by his risk-factor profile and PAD.
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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

ClassDrugsNotes
PDE5 inhibitorSildenafil, tadalafil, vardenafil, avanafilFirst-line; nitrate contraindication; α-blocker caution
Intracavernosal injectionAlprostadil; Trimix (alprostadil + papaverine + phentolamine)High efficacy; priapism risk
Intraurethral suppositoryAlprostadil (MUSE)Less effective than injection
Vacuum erection device(Mechanical)Drug-free; suitable in nitrate users
Testosterone replacementTransdermal gel, IM injection, pelletsOnly if confirmed hypogonadism; monitor PSA, Hct
Penile prosthesisInflatable or malleableRefractory 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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