Erectile dysfunction

• Erectile dysfunction (ED) is the inability to attain or sustain an erection good enough for sexual intercourse. It is common, and its prevalence rises with age: roughly a quarter to a third of men between 45 and 64 years, and half or more of men over 65. ^[1]
• Erection is a neurovascular event: parasympathetic nitric oxide release relaxes penile smooth muscle and raises blood flow, while venous compression traps the blood; nitric oxide falls, phosphodiesterase type 5 (PDE5) breaks down cyclic GMP and sympathetic tone return the penis to flaccidity (detumescence). ^[2]
• Most ED in adult life is "secondary" and mixed: blood vessel disease, nerve injury, hormones (especially low testosterone), and psychological factors combine, and a drug taken for something else is often partly to blame. ^[1]
• ED is not only a sexual problem. New vasculogenic ED can be the first sign of cardiovascular disease, so evaluation should screen the heart, vessels, glucose and lipids. ^[1]
• Most men improve with simple measures plus an oral PDE5 inhibitor; failures move on to devices, intracavernosal injection, a urethral alprostadil pellet, or, last, a penile prosthesis. ^[1][3]

By the end of this page you should be able to:

1. Explain how an erection is produced and what ends it, in terms of blood flow and the nerves that control it.
2. List the organic and psychological causes of ED and match them to the findings on history and examination.
3. Plan the evaluation of a man with ED, including the cardiovascular screen, testosterone testing and penile blood-flow testing.
4. Prescribe and counsel on oral PDE5 inhibitors safely, including the absolute nitrate contraindication and the alpha-blocker caution.
5. Choose the next option when PDE5 inhibitors fail, and know when surgical referral is indicated.
6. Outline priapism.
7. Adapt investigation and treatment to a low-resource setting.

ED is only one part of male sexual function, which also includes libido, emission, ejaculation and orgasm. Low libido from testosterone deficiency can present as ED, so the two are teased apart in the history. ED should be distinguished from premature ejaculation: a man with premature ejaculation may say he has ED because he loses the erection after ejaculating, while a man with ED may rush to ejaculate before the erection is lost. ^[2][3]

The prevalence of ED rises with age, affecting roughly 25 to 33% of men between 45 and 64 years, and half or more of men over 65. ^[1] It significantly impairs mental health and partner relationships. ^[1]

Low testosterone (below 300 ng/dL in a morning sample) is found in roughly 14 to 21% of men between 40 and 80 years, and 20 to 50% of men between 60 and 80. Not all of these men are symptomatic, but when testosterone deficiency is symptomatic it is treatable. ^[2]

ED in adult life is usually secondary and multifactorial: biological, psychological, relational, social and cultural factors overlap rather than operating alone. ^[3]

The major organic causes are vascular, neurological and endocrine. ^[1]

Atherosclerosis of the cavernous arteries of the penis is the most common vascular cause, usually with smoking, endothelial dysfunction and diabetes. ^[1] Atherosclerosis and ageing reduce the capacity of arteries and smooth muscle to dilate, limiting blood flow in; endothelial dysfunction appears to be driven by low nitric oxide and by smoking, diabetes and low testosterone. ^[1] Veno-occlusive dysfunction ("venous leak") allows blood to escape too soon, so an erection cannot be maintained. ^[1]

These include stroke, multiple sclerosis, peripheral and autonomic neuropathies, spinal cord injury, partial complex seizures. Diabetic neuropathy and surgical injury are especially common. ^[1] Pelvic surgery (radical prostatectomy, even nerve-sparing; radical cystectomy; rectal cancer surgery; occasionally transurethral resection of the prostate) is a frequent cause because the cavernous nerves run along the prostate. ^[1] Pelvic radiation, trauma and prolonged perineal pressure (long-distance cycling) can also do it. ^[1]

Testosterone deficiency (hypogonadism) and hyperprolactinaemia. Thyroid disease, Cushing syndrome and severe hypothyroidism or hyperthyroidism also appear among the causes. ^[1]

Peyronie disease (fibrous plaques in the tunica albuginea causing curvature), microphallus, and cavernosal fibrosis from priapism. ^[1]

Psychological factors must be considered in every case. In primary ED they include guilt, fear of intimacy, depression or anxiety. In secondary ED, performance anxiety, stress and depression compound an organic problem. ^[1] Psychogenic ED may be situational (a particular partner, place or time) and is suspected in young healthy men with abrupt onset linked to an emotional event, or when ED occurs only in certain settings. Men with mainly psychogenic ED usually have normal nocturnal and morning erections, whereas men with mainly organic ED often do not. ^[1]

Atherosclerotic risk factors are the main modifiable set: cardiovascular disease, cigarette smoking, hypertension, dyslipidaemia, diabetes mellitus, obesity and metabolic syndrome. ^[3] Other risk factors include substance use (alcohol, illicit drugs), and pelvic surgery, radiation or trauma. ^[3]

Many drugs are culprits. ^[1][3]

Priapism, from trazodone, cocaine, sickle cell disease or intracavernosal injection, can scar the corpora and lead to ED. ^[1]

Erection is a neurovascular reflex to psychological and tactile stimuli. Cortical input and a sacral parasympathetic arc drive the cavernous (nonadrenergic, noncholinergic) nerves, which release nitric oxide in the penile vasculature. Nitric oxide raises cyclic GMP (cGMP), relaxing arterial smooth muscle, increasing inflow into the corpora cavernosa. As the corpora fill, intracavernous pressure rises and compresses surrounding venules, producing veno-occlusion and reduced outflow; further filling and compression produce rigidity. ^[2]

Erection subsides (detumescence) when nitric oxide release falls: PDE5 hydrolyses cGMP, smooth muscle tone returns, inflow falls and venous channels reopen. ^[1][2]

Two types of erection can be distinguished, and they depend on different spinal levels: psychogenic erections (from brain arousal, sight, sound, fantasy) need intact pathways at spinal cord levels T11 to L2, while reflexogenic erections (from direct genital touch) need levels S2 to S4. Spinal cord injury can therefore spare one and abolish the other. ^[2]

Every cause of ED maps onto this chain: the blood must be able to get in (arterial), the blood must be able to stay in (veno-occlusion), the smooth muscle must be able to relax when nitric oxide signals, and the nerves must deliver the signal.

The history must separate a disorder of erection from one of libido or ejaculation. Key questions include whether the problem is intermittent, global or situational; recent or long-standing; whether the erection is curved; and whether there is sexual trauma. ^[3]

• Onset and setting. Abrupt onset in a young healthy man, or a problem only in certain settings, points to psychogenic ED. ^[1]
• Morning and masturbation erections. Healthy early-morning erections suggest that the machinery is intact and the cause is psychogenic. ^[1][3]
• Cardiovascular risk. Smoking, hypertension, dyslipidaemia, diabetes, obesity. New vasculogenic ED can be the first sign of cardiovascular disease. ^[1][3]
• Drugs and surgery. A timeline between starting a drug and the onset of ED is decisive. ^[3]
• Hormonal symptoms. Loss of libido, sleep disturbance, mood change for low testosterone; features of hyperprolactinaemia or thyroid disease. ^[1][2]
• Relationship and mood. Stress, anxiety, depression, partner difficulties, and the response to past treatment. ^[3]
• Degree of ED. The International Index of Erectile Function, abridged (IIEF-5), can support history and examination but should not be used alone to diagnose. ^[3]

Examination focuses on the genitals and on extragenital signs of hormonal, neurological and vascular disease. ^[1]

• Genitals: anomalies, testicular atrophy (hypogonadism), Peyronie's plaques or curvature.
• Neurological: poor rectal tone, decreased perineal sensation, abnormal bulbocavernosus reflex.
• Vascular: diminished peripheral pulses.
• Hormonal: gynaecomastia, changes in body hair and fat distribution.
• General: blood pressure, body mass index and waist circumference. ^[3]

The first question is whether a man has ED, premature ejaculation or low libido, because these are commonly confused. ^[3] Within ED, the differential is organised by cause.

A structural penile problem (Peyronie disease) is usually obvious on inspection and palpation. ^[1]

Laboratory assessment should include a morning testosterone measurement; if it is low or low-normal, measure prolactin and luteinising hormone. Screen for occult diabetes, dyslipidaemia, hyperprolactinaemia, thyroid disease and Cushing syndrome according to clinical suspicion. ^[1]

If investigations are indicated, the minimum is serum lipids, fasting glucose or (preferably) glycated haemoglobin, plus morning testosterone if hypogonadism is suspected. ^[3]

Duplex ultrasound after intracavernosal injection of a vasodilator (such as a mixture of prostaglandin E1, papaverine and phentolamine) is the standard test of penile vasculature. Normal values include a peak systolic flow velocity over 25 cm/sec, an end-diastolic velocity under 5 cm/sec and a resistive index over 0.8 (resistive index = [peak systolic velocity minus end-diastolic velocity] divided by peak systolic velocity). ^[1]

Nocturnal penile tumescence monitoring records the several sleep-entrained erections that a healthy man has each night. It may help distinguish organic from psychogenic ED. ^[1]

Penile arteriography, dynamic infusion cavernosography and cavernosometry are reserved for selected patients in whom revascularisation is being considered after pelvic trauma. ^[1] Screening for depression (Beck Depression Scale, or the Yesavage Geriatric Depression Scale in older men) is recommended in every evaluation. ^[1]

Two physical points help at the bedside: young healthy men with abrupt onset after an emotional event, or ED only in certain settings, point to a psychogenic cause; and a history of spontaneous improvement also suggests psychogenesis. ^[1]

ED itself is diagnosed clinically from history and examination rather than from a single number. Validated questionnaires (IIEF-5) grade severity and track response. ^[3] Severity matters therapeutically: mild ED may be approached first with lifestyle measures and sometimes low-intensity shock wave therapy, while moderate to severe ED is where penile prosthesis surgery becomes realistic. ^[1]

Nocturnal erection testing, penile duplex values and the cardiovascular score together tell you which pathway is failing and whether a medical cardiologist should be involved.

Treat the underlying organic disorder (diabetes, prolactinoma, hypogonadism, Peyronie disease). Stop or replace any drug temporally related to the onset. Treat depression. For every patient, provide reassurance and education, and include the partner whenever possible; use the consultation to discuss behaviour change such as diet and weight loss. ^[1]

Vasculogenic ED can be the first sign of cardiovascular disease, and men with new-onset vasculogenic ED should be referred to a cardiologist for evaluation of previously undiagnosed cardiovascular disease. ^[1]

For psychogenic ED, sex therapy is the mainstay of treatment. Sex therapists should be health professionals with training in human sexuality and counselling; general practitioners, psychologists and sexual health physicians can offer aspects of it, and a fully trained therapist comprehensive care. ^{[3] [1]}

• Lifestyle change: weight loss, exercise, smoking cessation, moderation of alcohol, and good sleep (sleep apnoea is associated with ED).
• Risk-factor treatment of atherosclerosis, hypertension, dyslipidaemia and diabetes, as part of cardiovascular care.
• Vacuum erection devices: an effective, low-cost option, especially in diabetes, spinal cord injury or after prostatectomy; satisfaction is high but use can feel cumbersome. They can be combined with a PDE5 inhibitor. ^{[3] [1]}

In documented testosterone deficiency or hyperprolactinaemia, testosterone replacement (transdermal patch or gel, nasal spray, implant) or medical/surgical treatment of the prolactinoma is warranted. Normalising testosterone, however, may have only a minimal effect on erectile function in men who also have neurovascular disease, which is most men with ED. ^[1] Testosterone is given only when deficiency is documented, and the aim is the physiological range; it is not a general treatment for ED without hypogonadism.

First-line drug treatment is an oral PDE5 inhibitor. ^[1][3] These drugs (sildenafil, vardenafil, avanafil, tadalafil) selectively inhibit PDE5, the predominant phosphodiesterase in the penis; by preserving cGMP they promote the smooth muscle relaxation essential for erection. ^[1] Clinical responses and adverse effects are broadly similar across the class. ^[1]

The choice of dose is individual, but typical starting doses from formularies are: sildenafil 25, 50 or 100 mg; vardenafil 5 or 20 mg; avanafil 50, 100 or 200 mg; tadalafil 5, 10 or 20 mg. ^[3] Take 1 to 2 hours before intercourse; tadalafil taken on demand has a roughly 2-hour lead-in and is often used daily at low dose (5 mg), which may also help benign prostatic hyperplasia symptoms. ^[3] Avoid large meals and alcohol before a dose, though food and alcohol matter less with daily dosing. ^{[3] [1]}

Counsel that these drugs do not create arousal: they only help with erection when there is adequate sexual stimulation. Patients should take the prescribed dose on 5 to 6 occasions before deciding it has failed, because anxiety, alcohol and rushing the onset cause apparent failure. ^[3] Efficacy is similar across the class and dose-response effects are small and non-linear. ^[3] Improved erections occur in roughly 70% with PDE5 inhibitors versus 35% with placebo. ^[1]

Adverse effects include flushing, headache, nasal congestion, dyspepsia, back pain (tadalafil), visual colour disturbance (sildenafil, vardenafil) and myalgia (tadalafil); rarely, non-arteritic ischaemic optic neuropathy or hearing loss. ^[1][3]

Absolute contraindication: nitrates. All PDE5 inhibitors cause coronary vasodilation and potentiate the hypotensive effect of nitrates, including nitrate sprays, tablets and patches for angina and amyl nitrite ("poppers"). Concomitant use can be dangerous and is contraindicated. Even men who only use nitrates occasionally should discuss risks, choice and timing with a cardiologist. ^[1][3]

Cautions: alpha-blockers and hypotension. Use cautiously and at lower initial doses in men taking alpha-blockers (prazosin, terazosin, doxazosin, tamsulosin, silodosin) because of hypotension; a man on an alpha-blocker should wait at least 4 hours before taking a PDE5 inhibitor. ^[1]

When oral therapy fails or is not tolerated, intracavernosal injection is next. Vasoactive drugs (alprostadil, alone or combined with papaverine and phentolamine) produce an erection within 10 to 15 minutes. ^[3] Intracavernosal alprostadil gives erections lasting a mean of 30 to 60 minutes; compounded papaverine/phentolamine mixtures increase efficacy. ^[1] Excessive dosing can cause priapism in 1 to 4% and genital or pelvic pain in about 10%, so teaching and in-clinic dose titration are essential. ^[1]

Drug for penile self-injection is taught in the clinic with a first monitored dose. Priapism is an emergency (see below).

Intraurethral alprostadil (a medicated pellet inserted into the urethra after urination) is an alternative vasoactive option. It is available in 250, 500 and 1000 microgram strengths; onset is 5 to 10 minutes, duration about 30 to 60 minutes, and the maximum is 2 doses in 24 hours. ^[4] Titration starts at 250 micrograms and rises stepwise under medical supervision. ^[4] In studies, about 66% of men who started titration achieved an erection sufficient for intercourse and were randomised; couples on active treatment were more likely (65% versus 19%) to have at least one successful intercourse during home use. ^[4] Contraindications include penile anatomical abnormalities (urethral stricture, balanitis, severe hypospadias or curvature, urethritis), sickle cell disease or trait, thrombocythaemia, polycythaemia, multiple myeloma, and pregnancy of the partner without a condom barrier. ^[4] Hypotension and syncope occurred in 3% and 0.4% of men during in-clinic titration, so the first doses are supervised and the man is warned not to drive afterwards. ^{[4] [1]}

Vacuum erection devices can be combined with a PDE5 inhibitor when either alone is insufficient. ^[1]

Low-intensity extracorporeal shock wave therapy is an emerging treatment for mild vasculogenic ED, theoretically improving vascularisation; evidence quality is still relatively poor and the American Urological Association regards it as investigational. ^[1]

When nonsurgical treatments are ineffective or impractical, surgical penile implantation achieves the highest satisfaction of all ED treatments. ^[1] Implants are semi-rigid silicone rods or inflatable (saline-filled) devices; both give immediate, long-lasting erections on demand. With experienced surgeons, the long-term infection rate in primary cases is well under 5%. ^[1] The irreversibility and the risk of infection, erosion or mechanical failure mean it is a late and considered step. ^[1]

Priapism is a prolonged, often painful erection unrelated to sexual desire. It is a urological emergency because prolonged engorgement can produce ischaemia, fibrosis and permanent ED.

• Ischaemic (low-flow) priapism is the common and dangerous form; it is painful and the corpora are rigid. It can follow sickle cell disease, intracavernosal injection, and some drugs.
• Non-ischaemic (high-flow) priapism is usually less painful and is often post-traumatic, from an arterial fistula; it is not the same emergency but still needs assessment.
• Stuttering (intermittent) priapism recurs in episodes, often in sickle cell disease.
• Any erection rigid for 4 hours or more warrants emergency evaluation and aspiration/irrigation with sympathomimetic injection (for example phenylephrine) under urological care; surgical shunting is reserved for failure. ^[4]
• PDE5 inhibitors rarely cause priapism; intracavernosal alprostadil carries a 1 to 4% risk, and MUSE a much smaller reported rate. ^[1][4]

This is an outline only; full management follows local urology protocols.

• Persistent or progressive ED with loss of sexual function and self-esteem.
• Permanent cavernosal fibrosis from untreated priapism.
• Complications of underlying disease discovered late (coronary heart disease, diabetes, dyslipidaemia).
• Medication adverse effects: PDE5 inhibitor headache, flushing, visual disturbance, NAION; MUSE penile pain, urethral bleeding, syncope.

With treatment of risk factors and appropriate therapy, most men respond: PDE5 inhibitors improve erections in about 70% versus 35% with placebo. ^[1] Men after radical prostatectomy or with severe arterial disease respond less well to pills and more often need injection, device or implant. ^[1][3] Psychogenic ED has a good outlook once the contributing stress, anxiety or depression is addressed.

• Cardiovascular and metabolic risk assessment is central to ED care: treat atherosclerosis, blood pressure, lipids and glucose. ^[1][3]
• Review drug regimens that may contribute; substitute where possible. ^[1]
• Screen for depression at the first visit. ^[1]
• Because ED may precede cardiac symptoms, the ED consultation is an opportunity to detect cardiovascular disease early. ^[1]

Older men. The prevalence of both ED and low testosterone rises with age; PDE5 inhibitors remain effective. Cardiovascular fitness for sexual activity should be considered before starting vasoactive drugs. ^[4]

Diabetes. ED is common and often severe because of combined vascular and neuropathic disease; early referral and multicomponent therapy help. Vacuum devices and injection therapy are comparatively more useful. ^[3]

After prostate surgery. Nerve-sparing and robotic techniques improve recovery but ED remains common; pills are less effective, and injection, device or prosthesis may be needed. ^[1][3]

Sickle cell disease. Ischaemic priapism is a particular risk and can lead to ED; management is urgent.

Young men with abrupt onset. Think psychogenic causes first, and look for relationship and mood problems. ^[1]

The principles do not change, but priorities shift:

• ED can be discussed at all, and many men are too embarrassed to raise it; a brief, direct question in a private setting is often enough to open the conversation.
• A morning testosterone is the most informative single laboratory step when hypogonadism is suspected; if unavailable, clinical judgement and partner-reported symptoms guide.
• Glucose and lipids can be checked with point-of-care tests where possible; refer for cardiovascular evaluation when new vasculogenic ED appears.
• Oral PDE5 inhibitors, where available, are first line; storing and prescribing safely, with the absolute nitrate rule written on the prescription, matters more than brand choice. Where these drugs are not available, vacuum erection devices are cheap, durable and drug-free. ^[3]
• Intracavernosal alprostadil and MUSE require supervised titration and cold storage respectively, so they suit clinic-based programmes. ^[4]
• Penile prosthesis surgery needs an experienced surgeon and a centre; early referral is better than repeated failed attempts.
• Sex therapy and counselling are low-cost and high-value; primary care clinicians can provide basic psychosexual education, with referral where a trained therapist exists.
• Any erection rigid for 4 hours or more is an emergency wherever you are: arrange urgent urological care and aspiration/irrigation.

• Atherosclerosis and cardiovascular disease
• Diabetes mellitus
• Male hypogonadism
• Peyronie disease
• Priapism
• Depression
• Urinary tract obstruction and prostatic disease (separate topic)