Erectile Dysfunction

Synonym: impotence (no longer used, as implies failure)

Erectile dysfunction (ED) is the inability to attain and maintain an erection sufficient for satisfactory sexual performance. Although a benign disorder, it can have a significant impact on the quality of life of sufferers, partners and families. It is important also to consider the physical and psychosocial health of the sufferer.^1,2 It is important that patients are properly assessed and investigated before embarking on treatment.

• The incidence and prevalence is high worldwide.
• The first large-scale community study showed that 52% of men (aged 40 to 70 years) were affected at some time (mild 17%; moderate 25%; severe 10%).³ About 40% of men at age 40 may suffer some form of erectile dysfunction.⁴
• It is the most prevalent of the male sexual dysfunctions (prevalence age 30 to 80 years) at 19.2% as compared to 31% for all types of male sexual dysfunction.¹
• This study equates to about 26 new cases annually per 1,000 men. Whichever study, country or methodology is used, this is clearly a significant condition likely to present regularly to a GP on average between 1 and 4 times per month.¹ Significant media interest has led more men to seek help for ED.
• There is in all studies a steep age-related increase.¹ The prevalence of complete impotence increases from 5% for men aged 40 years, to 15% for men aged 70 years.³
• Only about 10-20% of patients with erectile dysfunction are believed to have a solely psychogenic cause but psychogenic factors are often present in those who are diagnosed as having a physical cause.

Risk factors for erectile dysfunction

ED shares risk factors with cardiovascular disease (CVD).⁵ The following are all associated with both CVD and ED:

• Lack of exercise
• Obesity
• Smoking
• Hypercholesterolaemia
• Hypertension
• Metabolic syndrome
• Diabetes mellitus (DM)

It is important that underlying diseases and causative conditions do not go undetected. There are many different causes, including many drugs:

• Organic:
  • Vascular factors:
    • CVD
    • Atherosclerosis (approximately 50% of cases)
    • Hypertension
    • DM
    • Hyperlipidaemia
    • Smoking
    • Surgery or radiotherapy to pelvis or retroperitoneum
    • Trauma
  • Neurological:
    • Central causes:
      • Parkinson's disease, stroke
      • Multiple sclerosis (MS)
      • Tumours
      • Traumatic brain injury (causing hypothalamic-pituitary deficiency)
      • Cerebrovascular disease
      • Intervertebral disc disease
      • Spinal cord disease or injury
    • Peripheral causes:
      • Polyneuropathy
      • Peripheral neuropathy
      • DM
      • Alcoholism
      • Uraemia
      • Surgery (for example of pelvis or retroperitoneum)
  • Hormonal:
    • Hypogonadism
    • Hyperprolactinaemia
    • Thyroid disease
    • Cushing's disease
  • Anatomical:
    • Peyronie's disease
    • Micropenis and other penile anomalies
  • Drugs:
    • Antihypertensives
    • Beta blockers
    • Diuretics
    • Antidepressants: both tricyclics and selective serotonin reuptake inhibitors (SSRIs)
    • Antipsychotics: phenothiazines, risperidone
    • Hormonal agents: cyproterone acetate, luteinising hormone-releasing hormone analogues
    • Anticonvulsants: phenytoin, carbamazepine
    • Antihistamines
    • Recreational drugs
    • H₂ antagonists cimetidine and ranitidine
  • Cycling for more than 3 hours per week has been identified as an independent risk factor for erectile dysfunction⁶
• Psychogenic causes include:
  • Psychosexual factors:
    • General (disorders of sexual intimacy, lack of arousability)
    • Situational (partner, performance or stress)
  • Psychiatric illness:
    • Generalised anxiety states
    • Depression
    • Psychosis
    • Alcoholism (the relationship with alcohol is not straightforward. A recent meta-analysis showed a protective effect of alcohol at some levels of consumption)⁷

History

• Sexual history. Validated questionnaires to assess sexual function and the effects of treatment are available. For example, the International Index of Erectile Function (IIEF).⁸ The following should be covered:
  • Current and past sexual relationships
  • Current emotional status
  • Erectile symptoms: onset and duration
  • Previous advice or treatments
  • Quality of erections (erotic and morning erections)
  • Arousal, ejaculation and orgasmic difficulties
• Medical and past medical history:
  • This may include detail of any relevant conditions (see Causes of erectile dysfunction above)
  • Medication should be listed

History suggesting psychogenic causes⁹

• Sudden onset
• Early collapse of erection
• Self-stimulated or waking erections
• Premature ejaculation or inability to ejaculate
• Problems or changes in relationship
• Major life events
• Psychological problems

History suggesting organic causes⁹

• Gradual onset
• Normal ejaculation
• Normal libido (except hypogonadal men)
• Risk factor in medical history (cardiovascular, endocrine or neurological)
• Operations, radiotherapy, or trauma to pelvis or scrotum
• Current drug recognised as associated with erectile dysfunction
• Smoking, high alcohol consumption, use of recreational or body-building drugs

Physical examination¹

The examination should be focused and performed on all patients:

• Genitourinary examination (necessary to detect, for example, Peyronie's disease, gonadal anomalies, retractile foreskin).
• Attention to any endocrine (including testicular size and secondary sexual characteristics), neurological or vascular causes as appropriate, especially if indicated by the history.
• Pulse (including peripheral pulses) and blood pressure if recent readings not available. Because ED shares risk factors with CVD, a full cardiovascular assessment should be performed.⁶
• Rectal examination in patients over age 50 years.

Investigations will be directed by the history and clinical findings.

• The European Association of Urology suggests:¹
  • Fasting glucose and lipid profile for all patients (if not assessed in previous 12 months)
  • Morning sample of total testosterone (free testosterone if available, as more reliable detection of hypogonadism)
  • Further tests (for example PSA) only in selected patients
  • Addition of follicle stimulating hormone (FSH), luteinising hormone (LH) when low testosterone detected
• UK guidelines⁹ from a working party on erectile dysfunction suggest:
  • Blood glucose (DM)
  • Urea and electrolytes (renal impairment)
  • Liver function tests (hepatic disease)
  • Dipstick urinalysis
  • Haemoglobinopathy screen in Afro-Caribbean patients (looking for sickling disorder)
• Several guidelines state that, if the patient has a reduced sex drive or abnormal secondary sexual characteristics, the following investigations may be appropriate:
  • Testosterone - total, serum hormone-binding globulin and free androgen index
  • Serum FSH
  • Serum LH
  • Prolactin - especially for reduced sex drive in a younger man
  • Other tests that may be appropriate are fasting lipids (for hyperlipidaemia) and thyroid function tests
• Other specific investigations may be indicated and are appropriately arranged by urologists. ⁹ Indications for referral for these further tests are given below. Further tests include:
  • Nocturnal penile tumescence and rigidity studies
  • Vascular studies
    • Duplex ultrasound cavernous arteries
    • Intracavernous vasoactive drug injection
    • Dynamic infusion cavernosography
    • Arteriography (internal pudendal)
  • Neurological studies
  • Endocrinology work-up
  • Specialist psychodiagnostic evaluation

The following should be referred for further assessment or specific diagnostic tests:

• Endocrine abnormality.
• Referral for underlying organic disease as appropriate, e.g. cardiovascular or neurological.
• Young patients who have suffered pelvic or perineal trauma.
• Penile disorders or deformities requiring possible surgical correction.
• Complex cases (whether psychiatric, cardiovascular, psychosexual or endocrine).
• If patient of partner requests referral or special tests.

• The main aim of management is to diagnose and treat the cause of ED when possible.
• Associated modifiable or reversible factors (lifestyle, drug-related factors) should be considered as well as specific therapies.
• Most often it cannot be cured but, where appropriate, curative therapies should be offered.¹
• Treatments will be selected therefore according to efficacy, safety, invasiveness, cost and patient preference.
• A flow chart or algorithm can be used to assist treatment plans.¹

Lifestyle

• In one study, men who initiated physical activity had a 70% reduced risk for ED relative to those who remained sedentary.³
• In another randomised study, exercise and weight loss were shown to improve erectile function.¹
• A recent meta-analysis suggested moderate and high levels of exercise were associated with lower incidence of ED.¹⁰
• Well-controlled, long-term studies are needed to show the benefits of lifestyle modification.¹

Treating the cause

The following are regarded as curable causes for ED, which can be treated:

• Hormonal causes:
  • Testicular failure - treat with testosterone.
  • Pituitary or hypothalamic causes - treat underlying causes. For example, pituitary tumours causing hyperprolactinaemia.
• Post-traumatic arteriogenic ED in young patients:
  • Surgery following pelvic or perineal trauma has a 60-70% success rate.¹
  • This requires proper diagnostic work-up (including duplex ultrasound and arteriography).
• Psychosexual causes:
  • Management includes the management of any specific underlying psychological problem.
  • Psychosexual therapy:
    • See separate article Sex Therapy and Counselling.
    • There is evidence that group psychotherapy may improve erectile function.¹¹
    • May be used in conjunction with physical therapies.
    • Successful outcomes in 50-80% of pre-selected patients.⁹
    • However, success depends on the motivation of the patient and is time-consuming.
  • Drug treatments (e.g. the phosphodiesterase type-5 inhibitors sildenafil, tadalafil or vardenafil) may be effective and sometimes need only be used short-term.

First-line therapy for erectile dysfunction

Oral agents

• Phosphodiesterase inhibitors (sildenafil, tadalafil, and vardenafil) improve the relaxation of smooth muscle. Efficacy of the drug is dependent on release of nitric oxide from the nerve terminals of the cavernosal nerve.
• Sildenafil, tadalafil, and vardenafil are contra-indicated in patients receiving nitrates (because of possible severe hypotension, which may lead to acute myocardial infarction (MI), stroke and even death).
• Phosphodiesterase inhibitors are also contraindicated in patients in whom vasodilation or sexual activity are inadvisable, previous history of non-arteritic anterior ischaemic optic neuropathy, hypotension (avoid if systolic blood pressure below 90 mmHg), and recent stroke, unstable angina or MI.
  • Sildenafil:
    • Improves erectile function and is generally well tolerated.
    • Efficacy reduced after fatty meals.
    • 50 mg is the recommended starting dose (change according to response).
    • Adverse events are rare and the drop-out rate similar to placebo.
  • Tadalafil:
    • Has a longer half life - therefore, potentially, a longer action and therefore greater spontaneity (effective after 30 minutes, peak efficacy 2 hours and lasts up to 36 hours).
    • Start at 10 mg (change according to response).
    • Adverse events and drop-outs similar to above.
    • Better results in difficult to treat subgroups.¹
  • Vardenafil:
    • Effective after 30 minutes.
    • More potent than but not necessarily clinically more effective.
    • Useful in difficult to treat subgroups.
    • Effect reduced by fatty meal but has less interaction with food.
• Apomorphine hydrochloride:
  • This works by enhancing centrally-acting erectile signals (it is a dopamine agonist).
  • The speed of action is quicker than with the phosphodiesterase inhibitors.
  • It is taken sublingually 20 minutes before sexual activity.
  • It works best for patients with mild-to-moderate ED.
  • It is less effective than sildenafil.¹
  • It is an effective treatment and does not react with food or other drugs.
• Also used but with less proven efficacy are:
  • Yohimbine:
    • Used for 100 years as an aphrodisiac.
    • Central and peripheral actions.
    • Is claimed to be a safe and effective treatment for ED.
    • Modest effect (equivalent to placebo) on psychogenic but not organic.
    • Not licensed for National Health Service (NHS) treatment in the UK but used as a natural remedy by many patients.
  • Other oral agents with limited data and no place in treatment of ED:¹
    • Delequamine: similar to yohimbine.
    • Trazadone: an SSRI antidepressant associated with prolonged erections and priapism.
    • Red Korean ginseng (unknown mechanism)
    • Limaprost is an alprostadil derivative.
    • Phentolamine derivatives are undergoing trials.

Vacuum devices

• External cylinder fitted over the penis to allow air to be pumped out, resulting in engorgement of penis with blood.
• One study found an overall clinical success rate of about 90%, with more than 80% of patients continuing with the device.
• They work best when there is a motivated, interested and understanding partner. They may be the treatment of choice in well-informed older patients and in those with comorbidities precluding use of drugs or invasive methods.¹
• One study found that only 23% of patients asked for a prescription after a two-week trial and only 53% of these reported complete or reasonable satisfaction.⁹
• Adverse events include pain, petechiae, bruising and numbness.

Second-line therapy for erectile dysfunction

• Intraurethral alprostadil (prostaglandin E1):
  • Is inserted as a pellet into the urethral meatus and produces an erection after about 15 minutes.
  • Barrier contraception must be used if the partner is pregnant.
  • A Cochrane review found prostaglandin E1 to be beneficial for many men with ED of different aetiology.¹²
  • However, it is less effective than intracavernous injections.¹ The most common side-effect is mild penile pain.¹
• Intracavernosal alprostadil (prostaglandin E1):
  • Injections of alprostadil are given into the corpora cavernosa to produce an erection lasting less than one hour.
  • Efficacy rates for intracavernous alprostadil of more than 70% have been reported and it is often effective for those men who don't respond to oral drug treatment.¹
  • Penile pain (50% of patients after 11% of injections) is usually mild but a significant number of men stop using this method because of penile pain.¹
  • If priapism occurs with alprostadil:
    • The patient should be referred urgently to hospital.
    • Patients are advised to seek medical advice if the erection has lasted longer than 4 hours.¹
    • Treatment should not be delayed more than 6 hours. Initial treatment is by aspiration of blood from the corpus cavernosum.
    • If this is unsuccessful, cautious intracavernosal injection of a sympathomimetic, e.g. phenylephrine or adrenaline, may be required.
    • If sympathomimetics are unsuccessful, urgent surgical referral is required (possibly including shunt procedure).

Third-line therapy for erectile dysfunction

• Penile prosthesis:
  • Semi-rigid, malleable or inflatable devices surgically inserted to produce an erect state.
  • Prostheses should be considered in patients whose impotence has an organic cause and who are unwilling to consider, fail to respond to, or are unable to continue with medical treatment or external devices.¹

Topical agents

• Various vasoactive drugs in topical gel formulations are available.
• Local reactions and side-effects in the partner from vaginal absorption have been reported.
• None of these has been approved for use in ED treatment and so cannot be recommended.

Phosphodiesterase inhibitors, apomorphine and alprostadil can only be prescribed by GPs on the NHS for men who:

• Have diabetes, MS, Parkinson's disease, poliomyelitis, prostate cancer, severe pelvic injury, single-gene neurological disease, spina bifida, or spinal cord injury
• Are receiving dialysis for renal failure
• Have had radical pelvic surgery, prostatectomy, or a kidney transplant
• Were receiving Caverject®, Erecnos®, MUSE®, Viagra®, or Viridal® for erectile dysfunction, at the expense of the NHS, on 14 September 1998.
• Treatment should also be available from specialist services (under local agreement) when the condition is causing severe distress. The criteria for severe distress includes:
  • Significant disruption to normal social and occupational activities.
  • A marked effect on mood, behaviour, social and environmental awareness.
  • A marked effect on interpersonal relationships.

If the patient does not fit these criteria, a private prescription can be issued.

1. Guidelines on Male Sexual Dysfunction: Erectile dysfunction and premature ejaculation, European Association of Urology (2009)
2. Litwin MS, Nied RJ, Dhanani N; Health J Gen Intern Med. 1998 Mar;13(3):159 [abstract]
3. Araujo AB, Johannes CB, Feldman HA, et al; Relation between psychosocial risk factors and incident erectile dysfunction: prospective results from the Massachusetts Male Aging Study. Am J Epidemiol. 2000 Sep 15;152(6):533 [abstract]
4. Rajfer J, Magee T, Gonzalez; Future strategies for treating erectile dysfunction. Rev Urol. 2002;4 Suppl 3:S48 [abstract]
5. Miner MM, Kuritzky L; Erectile dysfunction: a sentinel marker for cardiovascular disease in primary care. Cleve Clin J Med. 2007 May;74 Suppl 3:S30 [abstract]
6. Erectile dysfunction, Clinical Knowledge Summaries (October 2008)
7. Cheng JY, Ng EM, Chen RY, et al; Alcohol consumption and erectile dysfunction: meta Int J Impot Res. 2007 May 31;. [abstract]
8. Bandolier; Erectile dysfunction scoring system; IIEF
9. Ralph D, McNicholas T; UK management guidelines for erectile dysfunction. BMJ. 2000 Aug 19-26;321(7259):499-503.
10. Cheng JY, Ng EM, Ko JS, et al; Physical activity and erectile dysfunction: meta Int J Impot Res. 2007 May [abstract]
11. Melnik T, Soares BG, Nasselo AG; Psychosocial interventions for erectile dysfunction. Cochrane Database Syst Rev. 2007 Jul 18;(3):CD004825. [abstract]
12. Urciuoli R, Cantisani TA, CarliniI M, et al; Prostaglandin E1 for treatment of erectile dysfunction. Cochrane Database Syst Rev. 2004;(2):CD001784. [abstract]