Erectile Dysfunction

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 (age 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 per1000 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, to 15% for men aged 70 years.³

Much more is now known about normal erectile function and understanding this informs current and future attempts to treat ED.⁶

• Erection is a neurovascular process involving penile erectile tissue. Specifically it particularly involves cavernous smooth muscle, smooth muscles of the arteriolar and arterial walls. Sexual arousal triggers release of neurotransmitters from cavernous nerve terminals causing:
  • Arterial and arteriolar dilatation (to increase blood flow into the penis)
  • Smooth muscle relaxation to accommodate the extra volume (sinusoidal expansion)
  • Activation of the corporeal veno-occlusive mechanism to increase pressure:
    • Trapping of incoming blood by expanding sinusoids
    • Reduction of venous outflow
  • Increase in P02 to about 90 mmHg (from 35)
  • Increase in intracavernous pressure to 100 mm Hg (achieves the erect state or full-erection phase)
  • Further increase with contraction of ischiocavernous muscles (rigid-erection phase)
• It is under hormonal control.

The nitric oxide-cyclic guanosine monophosphate system (NO-cGMP) is a biochemical pathway which stimulates relaxation of smooth muscle. Drugs such as sildenafil (a phosphodiesterase inhibitor) work by increasing release of nitric oxide and promoting smooth muscle relaxation.

ED shares risk factors with cardiovascular disease.⁷ For example the following are all associated with both cardiovascular disease and ED:

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

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

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).⁹ 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 above)
  • Medication should be listed.

History suggesting psychogenic causes:¹⁰

• 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 causes:¹⁰

• 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) and attention to the endocrine, neurological and vascular causes is appropriate (especially if indicated by the history).
• Pulse and blood pressure if recent readings not available.
• Rectal examination in patients over age 50.

These will be directed by the history and clinical findings.

General considerations

• Following guidelines.
  The availability of new and effective drugs for this relatively common disorder has led many men to seek advice. There has been a medicalisation of sexual behaviour which can ignore the social and relationship side of sex.¹¹ Unfortunately advice and treatment is often sought from physicians without the required knowledge and clinical experience.¹ This has prompted publication of helpful advice and guidelines. Underlying diseases should not go undetected or untreated and guidelines should be followed to avoid this happening.
  It is important to consider the possible risk factors and the potential benefits of modifying life style to reduce risk and improve symptoms. For example:
  • In one study men who initiated physical activity had a 70% reduced risk for ED relative to those who remained sedentary.³
  • Exercise and weight loss were shown to improve erectile function in another randomised study.¹
  • A recent meta-analysis suggested moderate and high levels of exercise were associated with lower incidence of ED.¹²
  Well-controlled, long-term studies are needed to show the benefits of lifestyle modification.¹
• The diagnostic work-up.
  Evaluation of ED should include:
  • Establishing a relaxed atmosphere at consultation to encourage rapport and appropriate full history.
  • Medical and psychological history of patient and ultimately the partner as well.
  • Explanation of the strategy towards diagnosis and treatment. Full explanation and reassurance, supported by written information regarding the problem and methods of treatment should be given to all patients.
• Cardiovascular disease and erectile dysfunction.
  It is worth considering that:
  • ED is common in patients with cardiovascular disease.
  • ED and cardiovascular disease share risk factors.
  • Initiating or resuming sexual activity in patients with ED and cardiovascular disease requires risk assessment and advice.
  A system of cardiac risk stratification has been devised following a conference in 2004.¹

Indications for referral¹

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

• Patients with primary erectile disorders (that is not secondary to organic or psychogenic cause).
• 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.
• Medicolegal reasons (for example sexual abuse).

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

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 workup (including duplex ultrasound and arteriography).
• Psychosexual causes:
  • This can be employed alone or with other treatments.
  • It is time consuming and results are variable.

Treating the symptom: first line therapy

Oral agents

• Phosphodiesterase inhibitors (sildenafil, tadalafil, and vardenafil). These 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. No double or triple blind multicenter trials to help choice. It should be remembered that nitrates are totally contraindicated with these drugs.
  • Sildenafil:
    • improves erectile function and is generally well tolerated4.
    • Efficacy reduced after fatty meals.
    • 50 mg is the recommended starting dose (change according to response).
    • Adverse events rare and drop-out rate similar to placebo.
  • Tadalafil:
    • Has a longer half life and 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 erectile dysfunction.
  • 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 erectile dysfunction.
    • Modest effect (equivalent to placebo) on psychogenic but not organic.
    • Not licensed for NHS treatment in UK but used as 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 Korea ginseng (unknown mechanism)
    • Limaprost is an alprostadil derivative.
    • Phentolamine derivatives are undergoing trials.

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 have been approved for use in ED treatment cannot be recommended.

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.¹⁰
• Adverse events include pain, petechiae, bruising and numbness.

Second-line therapy

Third-line therapy

• 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

Combination treatments

These can be used only with careful selection by specialists. Combination therapies are associated with more side effects.¹

Possible future treatments

Is medication available on the NHS?

Psychosexual counselling

The success of psychosexual therapy depends on the motivation of the patient and may be very time-consuming.
A review of all outcome studies in psychosexual therapy published since 1970 showed successful outcomes in 50-80% of patients.
Psychosexual therapy may be used in conjunction with physical therapies.