Erectile Dysfunction

Description
  • Erectile dysfunction (ED) is a persistent inability to attain or maintain an erection satisfactory for sexual activity.
  • Approximately 52% of Canadian men between the ages of 40 and 70 have some degree of ED.
  • ED affects physical and psychosocial well-being and quality of life for men, their partners, and their families.
  • ED can be associated with many different diseases and conditions. Patients should receive an initial medical evaluation before treatment is considered.
  • ED may be a marker of underlying cardiovascular disease and / or diabetes.
  • Medications are implicated in up to 25% of ED cases.
  • Risk factors for ED:
    • Age
    • Diabetes
    • Hypertension
    • Metabolic syndrome
    • Lower urinary tract symptoms
    • Obesity
    • Smoking
    • Prostatectomy (conflicting evidence)
    • Bicycle riding (conflicting evidence)

  For more information, go to:

Signs and Symptoms
  • Inability to achieve and maintain a penile erection of sufficient rigidity to permit satisfactory sexual intercourse during 75 percent of attempts for at least 3 months.
    • An occasional failure to have an erection followed by successful attempts later does not constitute ED.

  • Normal erectile physiology is a complex interaction involving the vascular, neurologic, hormonal and psychological systems. Biopsychosocial stimulation causes the local release of nitric oxide via the parasympathetic system increasing formation of cyclo-guanosine monophosphate (cGMP) which causes relaxation of the cavernosal smooth muscle. This compresses the small veins in the penis preventing venous return and erection occurs. 
    • Various mechanisms can interfere with this pathway and reduce of 3’5’-cGMP concentration below the level necessary for an erection.

  • The Sexual Health Inventory for Men (SHIM) can help with assessment of ED severity.  Available here.
  • ED can be classified as organic (Table 1), psychogenic (Table 2) or mixed.

Table 1: Organic (physiologic) causes of ED

Disorder type

Examples

Vasculogenic

Generalized cardiovascular disease, hypertension, hyperlipidemia, diabetes mellitus, smoking

Neurogenic

Multiple sclerosis, Parkinson's disease, tumours, stroke, spinal disorders, diabetes mellitus, alcoholism, uremia, polyneuropathy, surgery (e.g. prostatectomy)

Anatomical or structural

Peyronie's disease, congenital curvature of the penis, hypospadias, pelvic area trauma

Endocrinological

Hypogonadism, hyperprolactinaemia, hyperthyroidism, hypothyroidism, diabetes mellitus

Other systemic iseases

Hepatic disease, renal disease, chronic obstructive pulmonary disease 

Lifestyle

Smoking, obesity, recreational drug use, alcoholism, sedentary lifestyle

 

Table 2: Psychogenic Causes of ED

Predisposing

(risk factors)

Lack of sexual knowledge, past sexual problems, relationship problems, religious or cultural beliefs, restrictive upbringing, unclear sexual or gender preference, previous sexual abuse, physical or mental health problem, other sexual problems in the man or in his partner

Precipitating

(trigger symptoms)

New relationship, acute relationship problems, family or social pressures, pregnancy and childbirth, other life event, acute physical or mental health problems, lack of knowledge about normal changes or ageing, other sexual problems in the man or in his partner

Maintaining

(persistent symptoms)

Relationship problems, poor communication between partners, ongoing physical or mental health problems, other sexual problems in the man or in his partner

Differential Assessment
  • Premature ejaculation: Patients reporting weak erections may have premature ejaculation rather than erectile dysfunction
  • Delayed or inhibited ejaculation: No difficulty acquiring and maintaining an erection but cannot climax and ejaculate. May be caused by certain medications, e.g. SSRIs.
  • Lack of libido (sexual desire) – may be associated but most patients with ED do not complain of loss of libido.
  • Drug-induced erectile dysfunction - many commonly used drugs can cause or contribute to erectile dysfunction. (Table 3)

Table 3: Drugs associated with erectile dysfunction

Drug class

Examples

Diuretics

Thiazides, spironolactone

Antihypertensives

Methyldopa, clonidine, beta-blockers*, calcium channel blockers

Fibrates

Clofibrate, gemfibrozil

Antipsychotics

Chlorpromazine, haloperidol, risperidone, olanzapine

Antidepressants

Tricyclics, monoamine oxidase inhibitors , selective serotonin reuptake inhibitors, venlafaxine, lithium

Histamine (H2)-antagonists

Cimetidine, ranitidine

Hormones and hormone-modifying drugs

Estrogens (for example estradiol), progesterone, corticosteroids (for example prednisone), cyproterone acetate

Cytotoxics

Cyclophosphamide, methotrexate

Anti-arrhythmics and anticonvulsants

Disopyramide, carbamazepine, amiodarone, digoxin

5-alpha reductase inhibitors

Finasteride, dutasteride

*Beta-blockers may cause reduced sexual activity frequency and loss of libido (annual risk 5 per 1000 patients) but are not generally associated with erectile dysfunction

When to Refer
  • No medical assessment or prior diagnosis of erectile dysfunction
  • History of trauma to genital area, pelvis or spine since medical assessment
  • Non-response after an adequate trial of PDE-5 inhibitors
  • Contraindications to PDE-5 inhibitors
  • If the safety of sexual activity is a concern, for example:
    • Unstable heart disease (e.g., angina)
    • Recent myocardial infarction
    • Poorly compensated heart failure
    • Unstable arrhythmias
  • Poor control or recent emergence of symptoms of potentially contributing conditions (e.g. diabetes, hypertension)
  • Medication therapy which has the potential to cause or exacerbate erectile dysfunction (Table 3).There is a strong temporal relationship between starting a drug and appearance of ED.  If this relationship is not evident (eg. no medication changes in several months prior to emergence of ED), ED is unlikely to be medication-induced.
    • Consider making a recommendation to the doctor for alternatives with a lower risk of erectile dysfunction such as:
      • Antihypertensive: ACE inhibitors
      • Diuretics:  Loop diuretics
      • Fibrates: Statins
      • Histamine-antagonists: Proton-pump inhibitors
      • Antidepressants: Limited evidence; bupropion least risk of sexual dysfunction
Treatment
  • Non-pharmacologic treatment

    • ED may respond significantly to lifestyle changes and should be encouraged for every patient:
      • Lose weight (if overweight or obese)
      • Stop smoking
      • Reduce alcohol consumption
      • Increase exercise
      • Consult a sexual health counsellor if psychological factors are identified as factors in ED; this website may aid in finding a therapist in your area.

  • Pharmacologic treatment
    • Consider discontinuing a medication known to cause or worsen ED if there is a strong temporal relationship as outlined above.
    • Phosphodiesterase-5 (PDE-5) inhibitors are the first-line treatment. (Table 5)
      • Includes sildenafil, tadalafil and vardenafil
      • Facilitate erection by inhibiting the PDE-5 enzyme responsible for the degradation of cGMP in the cavernous smooth muscles - prolongs activity of cGMP which maintains smooth muscle relaxation necessary for rigid penile erections.
      • Main effect is on sexual performance not libido.
      • Sexual stimulation is required to trigger process of erection.
      • Well-established efficacy across many trials and meta-analyses; NNT of 2 to 3 for satisfactory intercourse.
      • All PDE-5 inhibitors considered equally efficacious.
        • Decision on which agent to use will depend on differences in side-effect profile, frequency of intercourse.

TABLE 4: Comparison of phosphodiesterase-5 Inhibitors

 

Onset (minutes)

Duration
(hours)

Cost per usual dose

Side-effect differences

Comments

Sildenafil

30-60

4-8
(May last up to 12)

$12

More visual disturbances
More nasal congestion

Requires planning

Tadalafil

45

Up to 36

$17.50

More myalgia vs. others

Less planning
Longer acting (so may be more cost-effective)

Vardenafil

30

4-8
(May last up to 12)

$15.50

(9$ for generic Staxyn®)

QT prolongation

Requires planning

Available in potentially faster acting oral disintegrating tablet

 

    • Common side effects: (most patients tolerate therapy well)
      • Flushing (10%)
      • Diarrhea (4%)
      • Dizziness (2%)
      • Headache (>10%)
      • Dyspepsia (<8%)
      • Visual disturbances (>10% at high doses)
      • Myalgia (6%)
      • Nasal congestion (up to 9%)
      • Rash (up to 3%) 
    • Serious side-effects are rare but require immediate medical attention, for example:
      • Nonarteritic anterior ischemic optic neuropathy (NAION) - severe, persistent visual acuity loss in either upper or lower half of vision
      • QT prolongation with vardenafil

    • Dosage adjustment may be required if >65,  and in liver or renal impairment 

Table 5: Dose adjustments for age, renal and hepatic dysfunction

 

Normal initial dose /
dosage range (per 24h)

Over 65 initial dose

Renal impairment initial dose (CrCl)

Hepatic disease

Sildenafil

50mg /
25-100mg

25mg

<30ml/min: 25mg

25mg

Tadalafil

20mg /

10-20mg

Depends on CrCl

31-80ml/min: 10mg per 48h, max of 3 doses per week

<30ml/min: Do not use

10mg

Vardenafil

10mg /

10-20mg

5mg

No adjustment needed

5mg

 

    • Drug interactions with PDE-5 inhibitors (Check PIP before prescribing)
      • Increased hypotension with:
        • Nitrates (severe and life-threatening; absolute contraindication)
        • α-1 blockers, especially terazosin, doxazosin - should be on a stable dose before starting a  PDE-5 inhibitor; start at the lowest recommended dose
        • Antihypertensives (caution – monitor for symptoms of hypotension)
        • CYP 3A4 inhibitors: increase concentration and half-life of PDE-5 inhibitors: azole antifungals, cimetidine, ciprofloxacin, erythromycin, clarithromycin, doxycycline, grapefruit, isoniazid, protease inhibitors, quinidine, verapamil
          • If must use interacting drug, use lowest dose of PDE-5 inhibitors and increase interval of dosing to 24h; maximum vardenafil dose not to exceed 5 mg
          • Concurrent use of vardenafil with indinavir, ritonavir, ketoconazole, or itraconazole is contraindicated
      • CYP 3A4 inducers can significantly reduce therapeutic effect: carbamazepine, phenytoin, phenobarbital, rifampin

    • High fat meals can delay onset time for sildenafil, and may reduce overall effectiveness of vardenafil; no effect on tadalafil.

    • Begin at usual initial dose, and increase up to the maximum dose as necessary and tolerated.

    • High response to first dose but may take three to eight attempts (2–8 weeks) to attain maximum effect.

    • Non-response is defined as four to six unsuccessful attempts at the maximum dose of a PDE-5 inhibitor under optimal conditions.

    • Options if unsatisfactory response to adequate trial of a PDE-5 inhibitor:
      • Switching to the long-acting PDE-5 inhibitor (tadalafil) if shorter-acting agents are not successful.
      • Daily dosing of PDE-5 inhibitors is also an option for non-responders to as-needed PDE-5 inhibitor therapy. This may also be preferable for men for whom planning intercourse is not feasible.  This is not in the current scope of pharmacist prescribing – refer patients to discuss this option with their doctor or nurse practitioner.
      • For true non-responders, switching to a different PDE-5 inhibitor is unlikely to be successful – 5 to 8% response rate reported.

    • Second line treatments: (not in scope of pharmacist prescribing)
      • Testosterone replacement (if levels are below normal range). Can be used in combination with PDE-5 inhibitors.
      • Urethral therapy (alprostadil), penile injection (alprostadil, papaverine, phentolamine), vacuum pump therapy.
General Advice / Monitoring
  • This medication will not produce an erection on its own; sexual stimulation is still required.
  • Wait at least 1 hour before attempting sexual intercourse.
  • Take sildenafil and vardenafil on an empty stomach (not necessary for tadalafil).
  • Most side effects are mild and not serious but contact a healthcare provider immediately if any of the following occur:
    • Prolonged, painful erection
    • Sudden loss of vision
    • Chest pain
    • Dizziness, faintness

  • Monitoring:
    • Arrange to follow-up with the patient to assess effectiveness and tolerability in 2 to 4 weeks.
      • Effective: Continue as needed, provide refills for up to 1 year, then reassess or refer.
      • Ineffective or partial effectiveness:
        • Increase to maximum dose if tolerated
        • Re-counsel on appropriate use
        • Consider a trial of tadalafil if taking a short-acting PDE-5 inhibitor
      • Cannot tolerate side effects: reduce dose (if agent is working) or trial a different PDE-5 inhibitor.
    • Re-evaluate any co-morbid conditions and modifiable risk factors (eg. blood pressure, cardiac health, weight, psychological factors).
Products

Detailed information on contraindications, cautions, adverse effects and interactions is available in individual drug monographs in the CPS (e-CPS), Lexi-Comp, AHFS, www.drugs.com or other reliable drug monograph references. For comprehensive drug comparisons, see RxFiles charts (www.rxfiles.ca).

This information should be routinely consulted before prescribing.

 

Ingredient

Dosage

Sildenafil

25-100mg

Tadalafil

10-20mg

Vardenafil

10-20mg

 

Prescribing and Billing Details
  • Fee pseudoDIN 00951320; maximum of 1 claim per year
  • May prescribe sufficient quantity for up to 6 attempts initially. Refill for 1 year, then reassess or refer.
  • Only products with an official indication from Health Canada for erectile dysfunction and/or recommended by reputable and reliable guidelines are considered for these guidelines. Only the active ingredients in the "products" section are approved for pharmacist prescribing.

 

Treatment Flowchart
Pharmacist Assessment Documents

Note:  The PAR automatic fillable short-form will be made available soon.

  • The Sexual Health Inventory for Men (SHIM) to aid in assessment available here
References / Suggested Reading
  1. Hirsh I. Erectile Dysfunction (Impotence; ED). In Merck Manual on-line. Available at:  http://www.merckmanuals.com/professional/genitourinary-disorders/male-sexual-dysfunction/erectile-dysfunction. (Free access)
  2. Smiley D. Male Sexual Dysfunction. In Minor Ailments, RxTx  online databases. CPhA. Available in Saskatchewan through SHIRP (www.shirp.ca).
  3. Basson R.  Male Sexual Dysfunction. In CTC, RxTx  online databases. CPhA. Available in Saskatchewan through SHIRP (www.shirp.ca).
  4. Kim, E.  Erectile Dysfunction Treatment and Management. In Medscape online. Available at http://emedicine.medscape.com/article/444220-treatment. (free access, requires registration).
  5. Rove K. Erectile Dysfunction. In DynaMed [Internet]. Ipswich (MA): EBSCO Information Services. 1995- . [updated 2015 Sep 15, cited March 2016). Available from http://search.ebscohost.com/login.aspx?direct=true&db=dnh&AN=113875&site=dynamed-live&scope=site. Registration and login required. 
  6. Cunningham G. Treatment of male sexual dysfunction. In UpToDate online. Available at www.uptodate.com by subscription.
  7. Shamloul R, Ghanem H. Erectile dysfunction. Lancet. 2013;381:153-65.
  8. Porst H, Burnett A, Brock G, et al; ISSM Standards Committee for Sexual Medicine. SOP conservative (medical and mechanical) treatment of erectile dysfunction. J Sex Med. 2013;10:130-71.
  9. Nam Cheol Park, Tae Nam Kim, Hyun Jun Park. Treatment Strategy for Non-Responders to PDE5 Inhibitors World J Mens Health. 2013; 31: 31–35. 
Written by Terry Damm, BSP; Karen Jensen, MSc, BSP
Posted May 2018; Updated Oct 2018