Autonomic dysfunction - erectile dysfunction

Description

Persistent inability to achieve or maintain an erection adequate for satisfactory sexual performance, for >=3 months
A sentinel cardiovascular event, not merely a quality-of-life issue - this is the physician-exam point

Causes by mechanism

Mechanism	Features
Vascular (commonest organic cause)	Gradual onset, absent nocturnal/morning erections, cardiovascular risk factors present
Neurogenic	Diabetes, spinal cord injury, MS, pelvic surgery, Parkinson disease
Endocrine	Low libido as well as ED -> hypogonadism, hyperprolactinaemia, thyroid disease
Drug-induced	Very common and reversible
Psychogenic	Sudden onset, situational, preserved morning erections, relationship or performance context, younger patient
Structural	Peyronie disease, priapism sequelae, phimosis

Most cases in men over 50 are mixed organic and psychogenic - the psychological component compounds any organic cause

~40% of men at 40, ~70% at 70 - prevalence rises roughly with each decade
Vascular disease (atherosclerosis affecting penile arterial blood flow) is the most prevalent organic cause after age itself, reflecting shared risk factors with cardiovascular disease
~50% of men with diabetes; onset 10-15 years earlier than in non-diabetics
~2/3 of men after radical prostatectomy

Normal erection

Sexual stimulation -> parasympathetic (S2-4, nervi erigentes) and non-adrenergic non-cholinergic nerves
- -> nitric oxide release from endothelium and nerve terminals
- -> inc cGMP in cavernosal smooth muscle
- -> smooth muscle relaxation, arterial inflow, sinusoidal expansion
- -> compression of subtunical venules against the tunica albuginea -> veno-occlusion -> rigidity
Detumescence: phosphodiesterase-5 degrades cGMP -> PDE5 inhibitors prolong the signal
Sympathetic (T11-L2) tone maintains flaccidity -> anxiety and sympathetic overdrive directly cause failure

Why it predicts cardiovascular disease

ED is endothelial dysfunction in a small artery
The cavernosal artery is 1-2 mm; the coronary artery 3-4 mm -> the same degree of endothelial disease becomes symptomatic in the penis first
-> ED precedes a coronary event by a median of 3-5 years - a window for risk factor intervention

Drugs - review before anything else

Thiazides, beta-blockers (nebivolol is NO-mediated and may be neutral or beneficial)
SSRIs, TCAs, antipsychotics, lithium
5-alpha reductase inhibitors (finasteride, dutasteride), antiandrogens, GnRH agonists
Spironolactone, cimetidine, opioids, alcohol, cannabis, anabolic steroids, methamphetamine

History - the discriminators

Points to organic	Points to psychogenic
Gradual onset	Sudden onset
Absent morning/nocturnal erections	Preserved morning erections
Present in all situations	Situational or partner-specific
Cardiovascular risk factors	Life stressor, performance anxiety, relationship difficulty
Older	Younger

Libido: preserved libido with failure of erection -> vascular or neurogenic. Reduced libido -> hypogonadism, depression, drug effect, hyperprolactinaemia
Full drug, alcohol and recreational drug history
Cardiovascular symptoms and exercise tolerance; can he climb two flights of stairs? - the practical threshold for safe sexual activity
Depression, relationship, and psychosocial context

Examination

Cardiovascular: BP, peripheral pulses, waist circumference - the most important part of the examination
Genital: testicular volume and consistency, penile plaques (Peyronie), phimosis
Secondary sexual characteristics, gynaecomastia, visual fields (pituitary)
Peripheral neuropathy, prostate examination if indicated

Investigations

Fasting glucose or HbA1c, fasting lipids, UEC, LFT
Morning (8-10 am) total testosterone on two occasions - a single random level is uninterpretable
- If low: LH, FSH, prolactin, SHBG, ferritin (haemochromatosis), pituitary imaging if central
TSH
Formal absolute cardiovascular risk calculation in every man with ED - this is the point of the consultation
Nocturnal penile tumescence testing and penile duplex are specialist and rarely needed

A. Treat it as a cardiovascular presentation

Calculate absolute cardiovascular risk and treat to target - statin, BP, glycaemia, smoking cessation
Weight loss and exercise improve erectile function directly - among the few interventions that modify the underlying disease
Restrict sexual activity and refer for cardiac assessment if unstable angina, recent MI (<2 weeks), uncontrolled arrhythmia or severe aortic stenosis
Review and substitute causative drugs

B. Lifestyle and psychological

Smoking cessation, alcohol reduction, weight loss, aerobic exercise
Psychosexual counselling - especially for sudden-onset or situational ED, and alongside drug therapy in all cases
Involve the partner where possible

C. PDE5 inhibitors - first-line pharmacotherapy

Drug	Onset	Duration	Note
Sildenafil	30-60 min	4-6 h	Reduced absorption with a fatty meal
Tadalafil	30-120 min	up to 36 h	Also available as a daily low dose (5 mg) - useful with LUTS/BPH
Vardenafil	30-60 min	4-6 h

Require sexual stimulation to work - the commonest cause of apparent failure, along with inadequate dose and too few attempts
- Do not declare failure before 6-8 attempts at maximum tolerated dose
*Absolutely contraindicated with nitrates and nicorandil - profound hypotension. Also caution with alpha-blockers*
- After sildenafil or vardenafil, wait 24 h before nitrates; after tadalafil, 48 h
Adverse effects: headache, flushing, dyspepsia, nasal congestion, visual disturbance (blue tinge), NAION (rare), hearing loss

D. Second-line

Intracavernosal alprostadil injection or intraurethral pellet - effective when PDE5 inhibitors fail, including after prostatectomy
- Warn about priapism: an erection lasting >4 hours is an emergency requiring aspiration
Vacuum erection device - safe, non-pharmacological, useful in penile rehabilitation post-prostatectomy
Penile prosthesis for refractory disease

E. Hypogonadism

Testosterone replacement only for confirmed biochemical hypogonadism on two morning samples with symptoms - not as an empirical ED treatment
- Testosterone alone rarely restores erections if the cause is vascular, but it restores libido and improves PDE5 inhibitor response
- Contraindicated in prostate or breast cancer; monitor PSA, haematocrit, PSA and lipids
Cabergoline for hyperprolactinaemia

Coronary artery disease, peripheral arterial disease, stroke - shared endothelial mechanism
Diabetes, metabolic syndrome, obesity, dyslipidaemia, hypertension
Obstructive sleep apnoea - independently associated, improves with CPAP
CKD, chronic liver disease, COPD
Depression and anxiety (and their treatment)
Prostate cancer treatment - prostatectomy, radiotherapy, androgen deprivation
Parkinson disease, MS, spinal cord injury, pelvic surgery
Hypogonadism, hyperprolactinaemia, haemochromatosis
Peyronie disease

Progressive with age and with vascular risk factor burden
ED precedes symptomatic coronary artery disease by a median of 3-5 years and independently predicts cardiovascular events and all-cause mortality
- Severity of ED correlates with severity of coronary disease
Psychogenic ED often resolves with treatment of the precipitant
Post-prostatectomy: recovery over 12-24 months, better with nerve-sparing surgery and early penile rehabilitation
Substantial impact on mood, self-esteem and relationships; high rates of non-disclosure and treatment discontinuation

Monitor

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