Contributed by Mr Rowland Rees, consultant urological surgeon, Royal Hampshire County Hospital, Winchester.
Section 1: Epidemiology and aetiology
Erectile dysfunction (ED) is defined as the ‘consistent or recurrent inability to attain and/or maintain a penile erection sufficient for sexual intercourse’.1
It affects 150 million men worldwide, and can have a significant impact on quality of life.
The decline of sexual function with age was first documented in 1948,2 but the largest contemporary study looking at the prevalence of ED is the Massachusetts Male Ageing study.3
Of 1,290 non-institutionalised men between 40 and 70, 52 per cent had some degree of ED, with 10 per cent having complete ED and a further 25 per cent describing moderate dysfunction. There was a linear increase in incidence with age.
Traditionally, ED was thought of as being of either organic or psychogenic origin, but it has become clear that there is often a combination of factors at play.
Penile erection is a complex function of neurovascular, endocrine and psychological function, impairment of any of these systems may cause ED.
Nitric oxide (NO) is synthesised inside the nitrergic (nitric oxide-containing) neurons from L-arginine by nitric oxide synthase (NOS), and then diffuses into the smooth muscle cell where it activates soluble guanylate cyclase (sGC).
This causes a rise in cyclic GMP (cGMP) which in turn causes smooth muscle relaxation, allowing greater inflow of blood and therefore tumescence (see figure).
Any factor impacting on the cardiovascular, neurological or endocrine systems can have an impact. The cardiovascular risk factors of obesity, smoking, diabetes, dyslipidaemia, low fruit/vegetable intake, physical inactivity and psychosocial stress are also risk factors for ED.
Possibly due to the smaller diameter of penile arteries compared to the coronaries (1-2mm versus 3-4mm), ED can herald the onset of cardiovascular disease by many years, and confers a 1.46 increased risk overall.4
Studies have found 20 per cent of new ED patients to have diabetes5 and 42 per cent to have dyslipidaemia.6
Section 2: Patient assessment
An attentive history is essential, as a number of other problems can be labelled as ED.
These include premature ejaculation, atrophic vaginitis in the partner, deficient suspensory ligament (causing a hard but low-hanging erection) or relationship problems.
The quality and duration of erection, when there is a problem (with a partner versus masturbation), spontaneous erections, relevant medical, psychological and drug history, as well as an assessment of risk factors are important.
The response to any previous therapy should be recorded, as well as any ejaculatory and orgasmic dysfunction.
Genital examination and a cardiovascular examination are recommended. In patients with urinary or ejaculatory symptoms, a digital rectal examination should also be carried out.
The British Society for Sexual Medicine guidelines recommend checking fasting glucose, lipid levels and a morning testosterone level in newly presenting patients. PSA levels should be tested where indicated by clinical assessment.7
Thyroid function should only be tested if indicated by clinical assessment.
Patients presenting with primary/lifelong ED, abnormalities on examination, a history of trauma, failed non-surgical therapies, or those simply wanting to understand the exact aetiology of their condition may require referral.
Modern Doppler ultrasound can accurately assess the penile vasculature and cavernosal architecture, and if there is suspicion of arterial injury then an arteriogram can delineate the problem more accurately.
A cavernosogram can demonstrate veno-occulsive dysfunction (‘venous leak’), but the false-positive rate is high, leading to anxiety and requests for venous surgery among patients who may not benefit.
Where there is a need to distinguish organic from psychogenic aetiology (eg prior to considering surgery), or in medico-legal cases, assessment of nocturnal penile tumescence either as an inpatient or at home is reliable and useful.
The presence of three or four strong erections during REM sleep confirms the adequate functioning of the erectile mechanism.
Assessing cardiac risk
The Princeton consensus8 suggests that a man with ED is a cardiac patient until proven otherwise, and proactive management of ED can aid cardiovascular treatment outcome.
However, the consensus found no increased risk for cardiac events in those taking PDE5 inhibitors compared with placebo, and indeed some studies report fewer cardiac events.
The metabolic equivalent and risk of developing symptoms during ‘normal’ sexual intercourse is that of light housework. Therefore sex and ED treatment is safe in the majority of cardiovascular patients, provided they are counselled appropriately.
Patients can be stratified into three risk groups according to clinical evaluation, and essentially those in the third category (‘high risk’ – unstable disease or recent events) should not be offered treatment.
ED in patients in the ‘low risk’ group (such as those with controlled hypertension or minimal angina) can be managed in primary care, and ‘intermediate risk’ patients require further specialised evaluation.8
Common pathophysiological causes of ED
- Diabetes: vascular, neurogenic and endothelial dysfunction
- Arterial disease: hypertension, congestive heart failure, dyslipidaemia, arteriosclerosis
- Venous: veno-occlusive disease
- Neurological: MS, spinal cord injury, Parkinson’s
- Pelvic pathology: surgery, radiotherapy or trauma
- Endocrine disease: hypogonadism, thyroid disease
- Drugs: antihypertensives, psychotropic medications, anti-androgenics, cytotoxics
- Poor past sexual experiences, previous sexual abuse
- New relationship or relationship difficulties
- Partner factors eg pregnancy, menopause, atrophic vaginitis, low desire
- Major life events
- Family or social pressures
- Restrictive upbringing
Section 3: Pharmacotherapy
A holistic approach to the problem will improve the results of prescribed treatment.
Regular exercise, weight loss and lowering lipid levels have all been shown to improve erectile function. Normalisation of testosterone levels in hypogonadal men can improve responsiveness to PDE5 inhibitor therapy as well as enhance sexual interest and weight loss.
Review the patient’s medication prior to starting treatment. The most common problem is hypertension, and there is evidence to suggest that thiazides and non-cardio-selective beta-blockers are associated with ED,9 whereas angiotensin II inhibitors may actually improve erectile function.10
PDE5 inhibitors act to increase penile smooth muscle relaxation by increasing cGMP levels. As cGMP levels are NO-dependent, PDE5 inhibitors are ineffective in the absence of nitrergic nerves or sexual stimulation.
The three PDE5 inhibitors licensed for use in the UK have broadly similar efficacy, with approximately 75 per cent of sexual attempts resulting in successful intercourse.
Tadalafil has a longer half-life (17.5 hours), whereas sildenafil and vardenafil have half lives of approximately four hours.
The side-effect profiles of the PDE5 inhibitors are similar and generally attributable to the vasoactivity of this class and their varying effects on other PDEs around the body (see box).
Due to potential dramatic hypotension, the use of organic nitrates is absolutely contraindicated with PDE5 inhibitors. Consideration may be given to alternative anti-anginals if appropriate, or to removing a nitrate spray if not being used.
Another important interaction is with alpha-blockers, a common problem as there is a significant association between benign prostatic hyperplasia (BPH) and ED. The use of tadalafil is not recommended, but shorter-acting PDE5 inhibitors can be used safely provided the two drugs are separated by a six-hour gap.
The PDE5 inhibitor should be started at the lower dose in patients well established on alpha-blocker therapy. On-demand PDE5 inhibitors themselves have been shown to improve lower urinary tract symptoms secondary to BPH.11
Patients should not be considered to have failed on PDE5 inhibitors until they have made at least four attempts to have intercourse at the maximum dosage in the correct circumstances (with sexual stimulation), ideally within a six-week period.
Intracavernous injection therapy is highly efficacious (up to 80 per cent) as it does not require intact nerves to have effect (for example following pelvic surgery, spinal cord injury or diabetic neuropathy).
The preparation most commonly in use in the UK is alprostadil, a synthetic prostaglandin E1, which acts to increase cGMP within corporal smooth muscle.
Medicated urethral system for erection (MUSE) is a synthetic PGE1 pellet administered into the urethra via a specialised applicator. The drug is absorbed by the urethral mucosa, and with gentle penile massage, reaches the corporal smooth muscle.
It has a 30-60 per cent efficacy, and the main adverse event is penile pain, experienced in up to 40 per cent.12
|Most common adverse events of PDE5 inhibitors (%)|
|Source: Urol Clin N Am 2007; 34: 507-15|
Section 4: Devices and prostheses
Vacuum erection devices
The vacuum device involves a cylinder and pump to induce erection, after which a ring is placed at the base of the penis to maintain tumescence. It is a cost-effective and successful treatment in patients and partners who find it acceptable and are motivated to use it.
It is less practical for those not in a long-term relationship. Problems encountered include pain, failure to ejaculate and a cold penis. It should not be prescribed for those with a bleeding diathesis.
The use of penile prostheses has increased since the advent of PDE5 inhibitors, presumably due to increased awareness of the disease and treatment options, but also due to recent technical advances improving the reliability of devices.
They are a highly effective form of treatment for the motivated patient (and partner) who has failed, or is not suitable for other forms of therapy, and are particularly suitable for younger patients with end-stage ED (eg patients with diabetes, post-radical prostatectomy) and those with associated Peyronie’s disease.
The results of surgery at high-volume centres are excellent (93 per cent five-year survival of devices), and satisfaction rates high among patients (up to 89 per cent).13
Erections are reliably rigid, consistent and last for as long as the couple want. Despite this, PCO funding for this procedure varies considerably in the UK, and currently only 350 or so patients undergo this procedure on the NHS. Men in North America are significantly more likely to receive such treatment and patients in the UK with refractory ED should at least be made aware of this treatment option, and offered care delivered to a high standard by appropriately trained, experienced surgeons.