Erectile dysfunction — the inability to attain or maintain an erection sufficient for satisfactory sex — affects ~40% of men in their 40s and rises ~10% per decade. Most organic ED is vascular, and erection depends on a nitric-oxide → cGMP cascade that PDE5 inhibitors exploit. Management climbs a ladder from PDE5 inhibitors through injection/vacuum/intraurethral therapy to a penile prosthesis.
Erectile Physiology
- Innervation — parasympathetic (S2–S4) drives erection (via the cavernous nerves), sympathetic (T10–L2) drives detumescence, and the somatic pudendal nerve (S2–S4, Onuf's nucleus) carries sensation and powers the ischiocavernosus (rigid-erection phase). Nerve-sparing prostatectomy aims to protect the cavernous nerves.
- Neurochemistry — nitric oxide is the principal pro-erectile transmitter (from NANC nerves and endothelium); nNOS initiates and eNOS maintains the erection. NO → cGMP (via guanylate cyclase) → smooth-muscle relaxation, and PDE5 degrades cGMP (the drug target). Norepinephrine maintains flaccidity.
- Haemodynamics — erection = sinusoidal relaxation + arterial inflow + venous compression against the tunica (intracavernous pressure ~100 mmHg). The corpus spongiosum/glans reaches only ⅓–½ that pressure (it lacks the outer longitudinal tunica layer).
- Erection types — psychogenic (T11–L2), reflexogenic (S2–S4; preserved in 95% of upper-cord but only ~25% of lower-cord injuries), and nocturnal (REM sleep).
Causes
Organic ED is classified "ED VAN" — Endocrine, Drug-induced, Vascular, Anatomic, Neurogenic — plus psychogenic and mixed. Aging is the single most important contributor, and arteriogenic disease is the commonest organic mechanism (ED is a sentinel marker for cardiovascular disease).
- Endocrine — hypogonadism, thyroid disease, diabetes, and hyperprolactinaemia (low libido, ED, galactorrhoea, gynaecomastia, infertility). The testosterone threshold for nocturnal erections is ~200 ng/dL.
- Drugs — associated: thiazides, spironolactone, central α2-agonists (clonidine, methyldopa), and non-selective β-blockers; not associated: ACE inhibitors, ARBs, calcium-channel blockers, α1-blockers (but they cause retrograde ejaculation), and β1-selective blockers. SSRIs cause anorgasmia; bupropion does not cause ED. 5-ARIs and anti-androgens reduce function.
- Vascular (arteriogenic and veno-occlusive), anatomic (pelvic surgery — RP 43–100%; pelvic fracture), neurogenic (spinal-cord injury, neuropathy), and psychogenic (performance anxiety, with nocturnal/situational erections preserved).
Diagnosis
- Work-up — AUA mandates history/exam, a diabetes screen, and morning total testosterone; the CUA mandates history/exam and reserves testosterone for hypogonadal symptoms or PDE5i failure. Repeat a low testosterone with LH and prolactin; image the pituitary if testosterone <150 ng/dL or pituitary disease is suspected.
- Questionnaires — the IIEF (15 items, 5 domains: desire, erectile function, intercourse satisfaction, orgasmic function, overall satisfaction), SHIM, and the Erection Hardness Scale.
- Specialised testing (only if it changes management) — NPTR, the ICI test, and penile duplex ultrasound (the vascular gold standard: peak systolic velocity <25–30 cm/s indicates arterial insufficiency, end-diastolic velocity >5 cm/s indicates veno-occlusive dysfunction).
Treatment
The ladder is PDE5 inhibitors → vacuum / intraurethral / intracavernosal therapy → surgery, alongside psychosexual counselling, medication review, and lifestyle change (aerobic exercise improves IIEF).
PDE5 inhibitors (first-line) raise cGMP and augment but do not induce erection (sexual stimulation is still required); they are metabolised by CYP3A4 and succeed in ~70%. Non-response is usually incorrect use (56–81%).
| Agent | Onset | Duration (T½) | Food effect |
|---|---|---|---|
| Sildenafil | 30–60 min | ~12 h (4 h) | High-fat meal reduces efficacy |
| Vardenafil | 30–60 min | ~10 h (4 h) | High-fat meal reduces efficacy |
| Tadalafil | 60–120 min | ~36 h (17.5 h) | None (the only one licensed for daily dosing) |
| Avanafil | 15–30 min | ~6 h (5 h) | None |
- Contraindications — absolute: nitrates (precipitous hypotension) and hypersensitivity; relative: severe cardiac disease (avoid for 6 months post-MI), non-selective α-blockers, and — for vardenafil — class IA/III antiarrhythmics or congenital long-QT. Adverse effects: headache, dyspepsia, flushing, nasal congestion, myalgia (more with tadalafil), visual disturbance (more with sildenafil/vardenafil, via PDE6 cross-reactivity), and rare NAION.
- Second-line — a vacuum erection device (constriction ring ≤30 min), intraurethral alprostadil (MUSE; inferior to PDE5i/ICI), and intracavernosal injection (alprostadil alone, or trimix = alprostadil + papaverine + phentolamine; inject at 3/9 o'clock, limit to ~10/month to avoid fibrosis). The most serious ICI complication is priapism.
- Surgery (third-line) — the inflatable penile prosthesis (see the Penile Prosthesis tab) is effective and high-satisfaction but irreversible (other therapies rarely work after explant); infection (within 3 months) usually mandates removal, and ~50% of devices still function at 20 years. Penile arterial reconstruction suits young men with focal traumatic arterial occlusion; venous ligation is not recommended.
Low-intensity shockwave, stem-cell, and PRP therapies are investigational. Because ED is a cardiovascular risk marker (as strong as smoking), men who are not clearly low-risk warrant cardiology evaluation before treatment.
Special Scenarios
After radical prostatectomy, erectile recovery occurs over 12–24 months (up to 36), better with bilateral nerve-sparing (~60% vs ~47% unilateral); after radiotherapy, ED is delayed (24–36 months). Evidence for scheduled-PDE5i penile rehabilitation is weak (the CUA recommends against it post-RP). Testosterone monotherapy is not recommended for ED, but PDE5i + testosterone can salvage hypogonadal PDE5i failures.
Self-Test
1. Which nerves mediate erection, detumescence, and penile sensation? Parasympathetic S2–S4 (erection), sympathetic T10–L2 (detumescence), and the somatic pudendal nerve from Onuf's nucleus, S2–S4 (sensation and ischiocavernosus contraction).
2. What is the principal neurotransmitter of erection, and which NOS isoforms initiate vs maintain it? Nitric oxide; nNOS initiates and eNOS maintains the erection (norepinephrine mediates flaccidity).
3. Classify the causes of ED. Organic — Endocrine, Drug-induced, Vascular, Anatomic, Neurogenic ("ED VAN") — plus psychogenic and mixed; arteriogenic disease is the commonest organic cause.
4. Which antihypertensives and which antidepressant are NOT associated with ED? ACE inhibitors, ARBs, calcium-channel blockers, α1-blockers, and β1-selective blockers; bupropion.
5. Compare the PDE5 inhibitors by onset/duration, and give the absolute contraindication. Avanafil is fastest (~15–30 min); tadalafil is longest (~36 h, food-independent, daily-dosing option); sildenafil and vardenafil act in ~30–60 min and are reduced by fatty meals. The absolute contraindication is concomitant nitrates.
6. What is the most serious complication of intracavernosal injection, and the injection limit? Priapism; limit to ~10 injections per month to reduce fibrosis.
7. What is the erectile-recovery rate after bilateral vs unilateral nerve-sparing prostatectomy? ~60% (bilateral) vs ~47% (unilateral), over 12–24 months.