Vasculogenic Erectile Dysfunction

Vasculogenic erectile dysfunction is failure of erection caused by inadequate arterial inflow, failure of veno occlusion, or both. It is the commonest organic cause of erectile dysfunction in men over 50.

Erectile dysfunction is an early marker of systemic cardiovascular disease, and usually appears 2 to 5 years before a coronary event, because the penile arteries are small and show disease first.

Pathophysiology. Arteriogenic disease: atherosclerosis or traumatic injury of the internal pudendal and cavernosal arteries lowers inflow, so the cavernosal pressure rises too little.

Venogenic disease: endothelial dysfunction and smooth muscle fibrosis prevent compression of the subtunical veins, so blood leaks and the erection cannot be maintained.

Risk factors:

• Diabetes, hypertension, dyslipidaemia, smoking, obesity and metabolic syndrome.
• Chronic kidney disease, pelvic radiotherapy, pelvic or perineal trauma and cycling.
• Ageing and physical inactivity.

Gradual, progressive loss of rigidity or duration, present in all situations, with loss of nocturnal and morning erections. Libido and ejaculation are usually preserved. Associated claudication, angina or a history of peripheral vascular disease. Younger men with sudden onset after perineal or pelvic trauma may have a focal arterial lesion.

• Sexual and medical history, International Index of Erectile Function (5-item), and cardiovascular risk review.
• Examination: blood pressure, body mass index, peripheral pulses, genital examination for plaques and testicular size.
• Fasting glucose or HbA1c, lipids, creatinine and eGFR, morning total testosterone, and ECG. Stratify cardiovascular risk before treatment as low, intermediate or high. High risk men (unstable angina, uncontrolled hypertension, heart failure of class III to IV, recent myocardial infarction, high risk arrhythmia) need cardiology stabilisation before sexual activity or treatment.
• Penile duplex ultrasound after intracavernosal alprostadil 10 to 20 micrograms (or papaverine 30 mg with phentolamine 1 mg): peak systolic velocity under 25 cm/s indicates arterial insufficiency (over 30 cm/s is normal), end diastolic velocity over 5 cm/s indicates venous leak, and a resistance index under 0.8 supports venous leak.
• Cavernosometry, cavernosography, or pelvic arteriography only when vascular surgery is being considered in a young man with a focal arterial lesion.

Differential diagnosis.

• Psychogenic erectile dysfunction
• Neurogenic erectile dysfunction
• Hypogonadism
• Drug induced erectile dysfunction
• Peyronie disease
• Penile fibrosis after priapism
• Diabetic erectile dysfunction with mixed causes

• Risk factor treatment: stop smoking, lose weight, exercise at least 150 minutes weekly, control glucose and blood pressure, treat dyslipidaemia, and limit alcohol. Review antihypertensives and prefer ACE inhibitors, angiotensin receptor blockers, calcium channel blockers or nebivolol over thiazides and non-selective beta blockers.
• Phosphodiesterase type 5 inhibitor as first line:
  • Sildenafil 50 mg orally 30 to 60 minutes before sex (range 25 to 100 mg, no more than once daily).
  • Tadalafil 10 mg orally before sex (range 5 to 20 mg), or 2.5 to 5 mg once daily, which is useful for frequent activity.
  • Vardenafil 10 mg (5 to 20 mg) or avanafil 100 mg (50 to 200 mg) before sex.
  • Contraindicated with any nitrate, nicorandil or riociguat. Caution with alpha blockers and in high cardiovascular risk. Reduce doses in men over 65, eGFR under 30 and with strong CYP3A4 inhibitors, using the lower starting dose on the product label.
  • Response is lower in diabetes, so use the highest tolerated dose, and try each drug 4 to 6 times.
• Treat low testosterone (confirmed on two morning measurements under 8 nmol/L, with symptoms) by testosterone replacement under specialist direction, which improves response to phosphodiesterase type 5 inhibitors.
• Second line:
  • Intracavernosal alprostadil: start 2.5 to 5 micrograms in clinic, titrated in 2.5 to 5 microgram steps to a usual 10 to 20 micrograms (maximum 60 micrograms), no more than 3 times weekly and not within 24 hours of a previous dose. Warn about priapism, and seek emergency care for any erection over 4 hours. Pain, penile fibrosis and bruising are the main adverse effects.
  • Intraurethral alprostadil 250 to 1000 micrograms before sex.
  • Vacuum erection device with a constriction ring left in place for no more than 30 minutes.
• Low intensity shock wave therapy is used in selected men with mild vasculogenic erectile dysfunction, with mixed evidence.
• Third line: inflatable penile prosthesis for refractory erectile dysfunction, with risks of infection (about 1 to 3%) and mechanical failure.
• Arterial reconstruction is considered only in young men with a focal traumatic arterial lesion and no vascular risk factors. Venous ligation is not advised.

Special groups. Men with diabetes and chronic kidney disease respond less well to phosphodiesterase type 5 inhibitors and often need second line therapy.

Monitoring. Review at 4 to 6 weeks for response and adverse effects, then every 6 to 12 months. Cardiovascular risk markers (blood pressure, lipids, glucose) at each review.

Referral and escalation. Refer to urology for failure of oral therapy or consideration of prosthesis, and to cardiology for suspected coronary disease. Urgent referral for chest pain, an erection over 4 hours, or acute loss after trauma.