Drug-induced Erectile Dysfunction

Drug induced erectile dysfunction is loss of erectile function caused by a prescribed, recreational or other substance. It accounts for about 25% of erectile dysfunction, and is often reversible after the drug is stopped or changed.

The difficulty is that the underlying disease treated (hypertension, depression, diabetes) also causes erectile dysfunction, so the drug is not always the sole cause.

Pathophysiology. Mechanisms include reduced central sympathetic outflow, suppression of nitric oxide mediated relaxation, hypogonadism, hyperprolactinaemia, serotonergic inhibition, anticholinergic effects and reduced penile perfusion.

Major drug classes:

• Antihypertensives: thiazides, spironolactone, beta blockers (less with nebivolol and carvedilol), clonidine, methyldopa.
• Antidepressants: selective serotonin reuptake inhibitors, venlafaxine, tricyclics, monoamine oxidase inhibitors.
• Antipsychotics (especially those raising prolactin: risperidone, haloperidol, amisulpride), and mood stabilisers.
• Antiepileptic enzyme inducers: carbamazepine, phenytoin, phenobarbital.
• 5-alpha-reductase inhibitors (finasteride, dutasteride), GnRH agonists and antagonists, and anti-androgens.
• Opioids and anabolic steroids (hypogonadism), benzodiazepines, cimetidine, metoclopramide, digoxin, ketoconazole.
• Alcohol, nicotine, cannabis, cocaine, amphetamines and heroin.

Onset soon after starting the drug or raising the dose, with improvement on withdrawal. Reduced libido and ejaculatory problems often accompany it, especially with antidepressants, 5-alpha-reductase inhibitors and hypogonadism. Nocturnal erections may be preserved. Review of drug history includes over-the-counter products and supplements.

• Detailed drug and substance history, with time of onset in relation to each drug and dose change.
• International Index of Erectile Function (5-item), blood pressure, genital examination, and cardiovascular and neurological assessment.
• Fasting glucose or HbA1c, lipids, morning total testosterone (under 8 nmol/L, about 230 ng/dL, is low), luteinising hormone, prolactin and thyroid function. Liver and renal function.
• Assess depression and anxiety (PHQ-9, GAD-7), because the illness may be the cause.
• Discussion with the prescriber to confirm that the drug is still needed.

Differential diagnosis.

• Erectile dysfunction from the underlying condition (depression, hypertension, diabetes)
• Psychogenic erectile dysfunction
• Vasculogenic erectile dysfunction
• Hypogonadism of other cause
• Hyperprolactinaemia from a pituitary adenoma
• Neurogenic erectile dysfunction

• Do not stop antihypertensive, antidepressant, antipsychotic or antiepileptic drugs suddenly. Agree changes with the prescriber.
• Antihypertensive related: change from a thiazide or beta blocker to an ACE inhibitor, angiotensin receptor blocker, calcium channel blocker or nebivolol, while keeping blood pressure controlled.
• Antidepressant related: lower the dose if possible, or switch to bupropion 150 to 300 mg daily, or mirtazapine 15 to 45 mg at night, or add sildenafil 50 mg orally 30 to 60 minutes before sex. Do not stop an antidepressant without the prescriber.
• Antipsychotic with high prolactin: switch to aripiprazole or quetiapine under psychiatry. Treat confirmed hyperprolactinaemia with cabergoline 0.25 to 0.5 mg orally twice weekly after an MRI of the pituitary.
• 5-alpha-reductase inhibitor: stop or switch to an alpha blocker or tadalafil 5 mg daily. Erectile function usually improves within weeks to months, with a few men having persistent symptoms.
• Opioid or anabolic steroid hypogonadism: reduce the opioid, stop anabolic steroids, and give testosterone replacement only when low testosterone persists with symptoms. Recovery after anabolic steroids can take months.
• Alcohol, cocaine, cannabis and nicotine: counselling and support to stop, with alcohol limited to 14 units weekly or less.
• Phosphodiesterase type 5 inhibitor as an add on:
  • Sildenafil 50 mg (25 to 100 mg) or tadalafil 10 mg (5 to 20 mg) before sex, or tadalafil 2.5 to 5 mg daily.
  • Contraindicated with any nitrate, nicorandil or riociguat. Caution with alpha blockers and in men over 65, eGFR under 30 and strong CYP3A4 inhibitors, with the lower starting dose on the product label used.
• Second line treatments when drug withdrawal is impossible: intracavernosal alprostadil 2.5 to 5 micrograms titrated to 10 to 20 micrograms, not more than 3 times weekly, or a vacuum device.

Special groups. Men with psychosis or severe depression need psychiatric involvement before any change. Men on chemotherapy or androgen deprivation need oncology review.

Monitoring. Review at 4 to 6 weeks and at 3 months after any change, with repeat International Index of Erectile Function. Repeat testosterone and prolactin when abnormal.

Referral and escalation. Refer to urology or endocrinology for persisting erectile dysfunction, hypogonadism or a raised prolactin. Urgent referral for visual loss on a phosphodiesterase type 5 inhibitor, or an erection over 4 hours.