Erectile Dysfunction (ED)

“All men with ED should be evaluated for the presence of cardiovascular risk factors and any identified risk should be addressed.”

British Society for Sexual Medicine (BSSM) guideline on the management of erectile dysfunction in men (2017)

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Definition

ED is the persistent inability to attain and/or maintain an erection sufficient for satisfactory sexual performance.
The physical and psychosocial effects of ED can significantly affect the quality of life of patients and their partners

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Prevalence

According to data from the Massachusetts Male Aging Study, up to 52% of men between the ages of 40 and 70 are affected by ED.
The prevalence of 5.1% in 20- to 39-year-old men increases to 70.2% in men 70 years of age and older.

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Aetiology

ED is caused by various vascular, neuronal, hormonal and metabolic factors, mediated by endothelial and smooth-muscle dysfunction.

Although most causes of ED are physical, some are due to psychosexual issues.

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ED is predictive of cadiovascular disease

ED is a cardiovascular (CV) risk factor, posing a risk equivalent to that of current, moderate smoking.

ED is also an important marker for future CV events, with symptoms occurring some 3–5 years before an event

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Risk factors

Cardiovascular disease (CVD)

Including risk factors for CVD: older age, sedentary lifestyle, obesity, smoking, hypercholesterolaemia and metabolic syndrome

Testosterone Deficiency (TD)

Associated with lower urinary tract symptoms (LUTS) and/or benign prostatic hyperplasia (BPH)

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Assessment

History taking

1. Symptom duration – precipitating factors (if identified)

2. Previous/current treatment interventions

3. Reported tumescence (cucumber, closed banana, peeled banana, tofu) and if there is any deviation of the penis during tumescence

4. Signs of testosterone deficiency : loss of early morning erections and low sexual desire

5. Ejaculatory timing - screen for premature or delayed ejaculation, decreased volume of ejaculate

6. Cardiovascular risk factors- screen for hypertension, diabetes, dyslipidaemia

7. Risk factors for STIs and prostatitis

8. Psychosexual factors (hence useful to assess with their partner present)

9. Psychological symptoms

10. Prescribed drugs (antihypertensives, antidepressants, antipsychotics, cytotoxic drugs), alcohol intake, smoking status and recreational drug use (as potential reversible causes of ED)

Physical examination

1. Cardiorespiratory and metabolic syndrome parameters:HR, BP, waist circumference, BMI

2. Signs of tesosterone deficiency: visceral obesity, decreased body hair, gynaecomastia, small testes

3. Penis, scrotum, testicular examination; any penile scarring suggestive of Peyronie’s Disease

4. Conduct a DRE of the prostate if there are genitourinary or protracted secondary ejaculatory symptoms

Investigations

Blood tests

• Fasting glucose, HbA1C, lipids, fasting testosterone (before 11am), PSA (with shared decision-making), TFTs

• If low (TT <8 nmol/L) or borderline (TT 8–12 nmol/L), repeat TT, albumin, SHBG (to determine free testosterone) and serum LH/FSH/PRL (primary or secondary TD); consider TFTs

Urinalysis

• If suspected prostatitis or STI

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Management of ED in primary care

1. Consider efficacy and safety of the different treatments

2. Consider patient and partner preferences

3. Manage comorbidities (such as hypertension, diabetes, dyslipidaemia), including lifestyle factors (exercise/weight management, smoking cessation, reduced alcohol consumption)

4. Consider specialist referral to
   Endocrinology, before initiating testosterone therapy for testosterone deficiency
   Cardiology, if at high CV risk
   Urology, for men with Peyronie’s Disease, in cases where PDE-inhibitors are contra-indicated, or cases of PDE5I non-responder
   Psychosexual counsellors- if indicated

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ED Therapies

1st line treatment
Lifestyle and risk factor modification + ral phosphodiesterase type-5 inhibitor PDE5I or Vacuum erection device
Avanafil, sildenafil and vardenafil are short-acting drugs and are suitable for occasional use as required
Tadalafil is a longer-acting drug and can be used as a regular lower daily dose to allow for spontaneous sexual activity

PDE5I non-responder criteria (equating to criteria for referral to a specialist)
6 doses of an individual PDE5I at the maximum dose (with sexual stimulation)
Fail to respond to the maximum dose of at least two different PDE5I.

2nd line treatment- any of the following:
Intracavernous injection of alprostadil (prostaglandin E1) 
Intraurethral alprostadil
Alprostadil topical cream
Low-intensity extracorporeal shock wave therapy

3rd line treatment
Penile prosthesis

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Cautions with PDE5I

Contraindications

1. Any nitrate based medications: sublingual nitroglycerin, amyl nitrite, and isosorbide mononitrate or dinitrate

2. Hereditary degenerative retinal disorders

3. History of non-arteritic anterior ischaemic optic neuropathy

4. Recent history of myocardial infarction; recent history of stroke

5. Hypotension: avoid if systolic blood pressure below 90 mmHg;

6. Patients in whom vasodilation or sexual activity are inadvisable

7. Recent unstable angina

Caution

1. Predisposition to priapism

2. Cardiovascular disease:
   Myocardial infarction, stroke, or life-threatening arrhythmia in the last 6 months
   Resting hypotension (blood pressure [BP] <90/50 mmHg) or hypertension (BP >170/100 mmHg)
   Unstable angina or angina during sexual intercourse
   Congestive heart failure categorized as New York Heart Association Class IV

3. Anti-hypertensive co-administration, particularly alpha-blockers (often used for benign prostatic hyperplasia) as risk of profound hypotension

Concomitant use of moderate and potent inhibitors of CYP3A4

1. PDE5 inhibitors are metabolied predominantly through the hepatic isoenzyme cytochrome P450 (CYP) 3A4 pathway.

2. Manufacturer advises using a lower starting dose of PDE5I with concurrent use of moderate and potent inhibitors of CYP3A4

3. The concomitant use of potent CYP3A4 inhibitors increases plasma concentrations of PDE5I.

4. Examples of potent CYP3A4 inhibitors include: erythromycin, saquinavir, ritonavir, ketoconazole, itraconazole, clarithromycin

Side effects
Headache, flushing, dyspepsia, dizziness, rhinitis, visual abnormalities, chest pain

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Priapism associated with alprostadil

Priapism (erection lasting four hours or more) is a medical emergency.
Application of an ice pack to the upper-inner thigh (alternating between the left and right thighs every two minutes for up to ten minutes) may result in reflex opening of the venous valves.
Treatment options by Emergency physicians or Urologists include:

1. Initial therapy by penile aspiration: using aseptic technique, 20–50mL of blood should be aspirated using a 19–21 gauge butterfly needle inserted into the corpus cavernosum; if necessary the procedure may be repeated on the opposite side

2. Lavage: if initial aspiration is unsuccessful, a second 19–21 gauge butterfly needle can be inserted into the opposite corpus cavernosum; sterile physiological saline can be injected through the first needle and drained through the second;

3. If aspiration and lavage of are unsuccessful, intracavernosal injection of a sympathomimetic with action on alpha-adrenergic receptors can be given, with continuous monitoring of blood pressure and pulse— see phenylephrine hydrochloride [unlicensed indication], adrenaline/epinephrine [unlicensed indication], and metaraminol [unlicensed indication]. Extreme caution is required in patients with coronary heart disease, hypertension, cerebral ischaemia and in patients taking a monoamine-oxidase inhibitor (facilities for managing hypertensive crisis should be available when administered to patients taking MAOIs);

4. If necessary the sympathomimetic injections can be followed by further aspiration of blood through the same butterfly needle;

5. If administration of a sympathomimetic drug is unsuccessful, urgent referral for surgical management is required.

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