ED Guidelines
Summary of recommendations:
· Erectile Dysfunction (ED) is the preferred clinical term describing the inability to achieve and maintain a penile erection of sufficient rigidity to permit satisfactory sexual activity.
· Diagnosis and treatment of ED is often, most effectively performed by Primary-Care Physicians (PCP).
· The underlying risk factors associated with ED are common to cardiovascular disease in general, and therefore may represent the initial clinical sign of generalized vascular insufficiency.
· PCP’s, urologists, internists, psychiatrists, and other treating health-care professionals should be encouraged to initiate an open dialogue of sexual issues to identify men with ED who may not otherwise volunteer their sexual concerns.
· Frequently a careful history, physical exam, serum glucose, lipids and optional testosterone testing are all that are needed to make the diagnosis of ED and initiate therapy.
· Organic (physical) causes of ED are present in the majority of men, but situational contributing factors often play a contributory role and addressing these issues may enhance treatment efficacy.
· Once reversible causes of ED are ruled out, a trial of oral medication is recommended as first-line therapy, based on treatment efficacy, side effect profile and minimal invasiveness.
· Specialized testing and referral are generally reserved for cases where greater insight into the etiology is desired by the patient/physician and/or oral first-line treatment was unsuccessful or not appropriate.
· Second-line therapies although more invasive than oral agents, are generally well tolerated and effective.
· Surgery remains an important option for those men refractory to medical management, offering durable reliable relief from ED.
Background
Erectile dysfunction is a highly prevalent condition, which impacts on the quality of life of thousands of Canadian couples. Dramatic advances in our understanding of the pathophysiology of erection have led to the development of new highly effective, minimally invasive therapeutic agents. Traditionally, the choices of treatment for ED have been under the direction of urologists. Surgical approaches (malleable and inflatable penile implants) were the only genuinely effective therapy for decades. The introduction of intra-cavernous vasoactive agents in the mid-1980’s changed the balance of care with larger numbers of men seeking non-surgical options.
Primary care physicians are rapidly acquiring the diagnostic and therapeutic skills necessary to become the dominant healthcare providers for this condition. Armed with effective oral agents like the PDE-5 inhibitors, and the promise of a multitude of other new oral and sublingual agents in the research pipeline, ED is becoming more a medical clinical entity. Family physicians, internists, cardiologists and other medical specialists are being approached by couples with ED requesting treatment. In many cases longstanding relationships exist between the couple and their treating physician, fostering an important therapeutic alliance which may translate into improved clinical response to the selected treatment approach. A shared-care model for the treatment of ED,in which PCP initially identify and treat patients with ED and refer those individuals who require more invasive or specialized testing and treatment, is a valid concept. The combined experience and knowledge of primary care physicians coupled to the diverse knowledge of the specialist can ideally result in optimal care for the patient.
In spite of these changes in the approach to management of ED and the increasingly important role played by other healthcare providers, urologists remain an essential element in ED therapy for several important reasons.
1. In some cases anatomical penile deformity may play an important role in the ED (frequently requiring operative correction).
2. Intracavernous and intraurethral vasoactive therapy are considered by some primary care physicians as invasive techniques, which they are unable or unwilling to teach patients.
3. Historically, urologists were the consulting physicians for ED and are still the primary referral requested for the difficult, oral-refractory cases.
4. In a small but definable population (often those men with severe vascular disease or poorly controlled diabetes) the nonsurgical approaches may not succeed, requiring surgical options in the difficult to treat group.
5. Ongoing research into the basic and clinical consequences of ED is performed in urology labs and offices world-wide.
It is for these reasons that the Canadian Urological Association Guidelines Committee, in association with the Canadian Male Sexual Health Council undertook to develop an approach to management of the patient with ED. This is a rapidly expanding field with many new therapeutic options available to physicians and patients. We based our suggestions for management on peer reviewed literature, the 1999 WHO consensus panel, the evolving research on new medical approaches to ED management and placed these comments and recommendations into a Canadian perspective.
Global management objectives
1. To help the patient and partner establish their objectives of treatment.
2. To select diagnostic tests based on the patients presenting complaints and goals of therapy.
3. To utilize diagnostic tests in a cost effective and meaningful manner which impact choice of treatment.
4. To provide a diagnosis and understanding of the likely etiology of the erectile dysfunction to the patient and partner.
5. To offer treatment choices with comprehensive information on cost, likelihood of success and common side-effects.
6. To initiate therapy with the least invasive option which satisfies the patient and partner goals of treatment.
7. To provide patients with information concerning treatment related risks and benefits as well as ongoing support so as to maximize treatment success.
8. To re-establish the couples ability to achieve and maintain sexual intimacy in as natural a manner as possible.
9. To choose approaches which are reversible whenever possible.
Management approach Diagnosis
1. Determine that the problem is ED, not premature ejaculation, sexual dysfunction from other causes (Peyronie’s, low desire state).
2. Determine the timing of onset, nature of the problem and significance to the couple.
3. Evaluate whether a potentially reversible cause to the ED exists (medication, stress, depression, hormonal, tobacco, alcohol, drugs, partner specific issues).
4. Establish a likely underlying etiology based on the history, physical exam and lab testing (optional). A commonly used schema is:
· Vascular
· Endocrine
· Neurological
· Situational
· End organ (penile deformity)
· Mixed
Methodology
1. History and clinical questioning (this is the most important component of the ED evaluation).
2. Physical examination (directed at neural and vascular systems essential for erections).
3. Use of formalized questionnaire instruments (IIEF*,SHIM*).
4. Labs: serum glucose, hormonal screening (total Testosterone/ bioavailable), lipid screening.
5. Consultation with subspecialists (endocrinology, psychology, cardiology).
6. Specialized tests:
a. Combined injection and stimulation test (CIS)
b. Nocturnal penile tumescence testing (Rigiscan)
c. Duplex ultrasound with vasoactive penile injection/ sildenafil
d. Dynamic infusion cavernosography and cavernosometry (DICC)
e. Penile Angiogram
See in attached Appendix:
*Sexual Health Inventory for Men, *International Index of erectile function
Treatment options
1. Sexual counseling (this may represent a spectrum of approaches from a simple open discussion with the PCP to sexual therapists or psychiatry expert in intimacy building and sensate focus therapy).
2. Oral therapy (PDE-5 & hormonal).
3. Vacuum Therapy.
4. Local Therapy (intra-urethral or intracavernous agents).
5. Surgery:
a. Penile Implant
b. Peyronie’s Surgical Repair
c. Vascular bypass procedure (generally reserved for young men following traumatic penile vascular injury)
Diagnosis History
This is the cornerstone of the evaluation of sexual and erectile dysfunction. The history will provide the likely diagnosis in the vast majority of cases. There exist a variety of approaches to obtain a thorough history, with the most common feature being a supportive healthcare professional allowing the couple to relate their concerns and express their goals of treatment in an unhurried manner.
General domains of the History
· Determine specifics related to ED (onset, severity, significance and situations).
· Sexual desire, relationship issues, stress at home, work.
· Genital pain or altered shape.
· Lifestyle factors: smoking, substance use/abuse.
· Co-morbid conditions: hypertension, peripheral vascular disease, diabetes, and renal disease.
· Pelvic surgery, radiation.
· Medications.
· Psychiatric illness or conditions
Questionnaires
Use of validated questionnaires may be of significant benefit. These tools can be patient self-administered and provide much of the above information in an efficient non-threatening manner. There exist a number of validated instruments designed to evaluate sexual and erectile function. The greatest utility of these questionnaires may be in establishing a response to therapy and determining overall satisfaction with drug use over a specified length of time (i.e.4 weeks). In the attached appendix the Sexual Health Inventory for Men (SHIM) is included.
Physical exam
The consensus group found the physical to be most useful when performed in a focused manner, concentrating on the vascular and endocrine systems. A high association exists between erectile dysfunction and peripheral vascular disease and/or occult coronary syndromes. This may be an important opportunity to unmask these conditions. Assessment should include body habitus (secondary sexual characteristics), the peripheral circulation, neurological and genitourinary systems.
Identification of penile deformities may be best achieved in the erect state or by stretching the penis to make the plaque more pronounced.
Tests
Assessment for occult diabetes may be performed with a fasting glucose or HbA1c. Although recommended by the WHO consensus panel, a lipid screen is not a routine component of the Canadian ED assessment but is considered as a valuable addition to the evaluation and good general practice.
Hormonal profile screening remains a controversial aspect of the routine evaluation of ED. In the attached algorithm several suggested approaches are outlined, depicting the variety of views expressed by our consensus panel. There was a general agreement that in the man with ED and hypoactive desire, testing and treatment for low levels of testosterone is appropriate. In men with normal desire and ED the need for global testing is controversial and currently undetermined. Although beyond the scope of this document, hormonal supplementation is contraindicated in men with breast or prostate cancer. Once initiated on exogenous testosterone ongoing follow up is mandatory.
Optional testing such as TSH,LH, prolactin, CBC, and urinalysis are considered complimentary and not felt to be essential in the evaluation of ED in most cases.
Specialized testing
Psychological/psychiatric assessment. These assessments often provide important complimentary insight into relationships and
situational causes to ED. The lack of widespread availability and cost limit their use in most cases of ED treatment.
NPT testing
This is a minimally invasive means to measure and record nighttime erectile events (nocturnal penile tumescence). When not present little useful information is derived. Normally, measurement of 2-5 nighttime erections persisting with significant rigidity is recorded, reassurance of a normal neurovascular axis is possible. It’s greatest utility is in medico-legal cases and pharmacological studies to assess treatment impact.
Vascular testing
A variety of vascular tests exist. Historically a PBI or penile brachial index assessment was made. This noninvasive test records penile pressure as an index of arm pressure, providing a rough idea of vascular pressure into the penile circulation. The limitation was that the dorsal penile artery contributes to this index but in real life adds little to erectile function. In most research-based centers today availability of a duplex scan is common place. Use of the ultrasound scanner to localize and measure the size and flow through the cavernous vessels, pre- and post vasoactive injection allows a more refined assessment of the penile circulation. This test is currently performed less frequently in Canada since the advent of effective oral medications. Although minimally invasive the true utility of this study is present following an intracavernous injection. The logic of using an invasive test that may not alter treatment choice or management are the main reasons for this test’s lack of widespread use. Recent reports have described use of sildenafil prior to scanning to help evaluate penile flow, however this approach remains experimental at present.
Another approach to evaluate the penile vascular system is the DICC (dynamic infusion cavernosometry and cavernosography). A large number of varying diagnostic protocols exist for this procedure, all aiming to define how well the penile blood-trapping mechanism (the veno-occlusive mechanism) works. In brief, dye and fluid are delivered into the penis to induce an erection. Measurement of the rise and fall of intra-penile pressure with radiologic visualization of the veins draining the penis determine if a competent or incompetent veno-occlusive mechanism exists.
The most invasive diagnostic test reserved generally for cases of high-flow priapism or planned vascular bypass is the penile angiogram. This test allows visualization of the penile circulation and directs embolization for the unusual cases of penile injury induced high-flow priapism.
Endocrinological tests
Controversy still surrounds the ideal endocrine work up for men with ED. A morning total testosterone or bioavailable testosterone is logical in cases where sexual interest or significant reductions in ejaculate volume are aspects of the presenting complaint. Free testosterone measurement may have significant intra-assay variability which may limit it’s clinical utility.
Neuro-physiological testing
This form of testing generally allows for measurement of the sacral reflex arc, an indirect measure of the perineal neural integrity. Tests to directly measure the nonadrenergic noncholinergic nervous system via biopsy or surface electrodes have proven disappointing and are not clinically useful at present.
Conclusions
1. A careful history and physical exam are the essential elements of the ED work up in most cases.
2. Basic screening tests such as serum fasting glucose and testosterone are recommended.
3. An algorithmic treatment approach using the least invasive option is suggested.
4. In some cases where greater detailed information is desired or failure of the initial oral medication is encountered, trials of more invasive second –line treatment or investigations may be appropriate.
5. Surgery should be reserved for men in whom less invasive reversible treatment has not succeeded or is contraindicated.
6. Treatment should be individualized and follow up arranged to assess efficacy of treatment.
Comparison of the properties of PDE5 inhibitors
| PROPERTY | SILDENAFIL | TADALAFIL | VARDENAFIL |
| TMAX | 30-120 minutes (median 60 minutes) | 30-360 minutes (median 120 minutes) | 30-120 minutes (median 60 minutes) |
| T ½ | 4 hours | 17.5 hours | 4 hours |
| Absorption | Fatty meals cause a mean delay in TMAX of 60 minutes | Not affected by food | Fatty meals cause a reduction in CMAX |
| Available Doses | 25mg, 50mg, 100mg | 5mg, 10mg, 20mg | 2.5mg, 5mg, 10mg, 20mg |
| Maximum Dose | 100 mg daily | 20mg daily | 20mg daily |
| Efficacy | Each of the PDE5 inhibitors offers similar efficacy. |
||
| Dose adjustments may be needed | patients >65 hepatic impairment renal impairment concomitant use of potent cytochrome P450 3A4 inhibitors such as ritonavir and erythromycin concomitant use of cimetidine |
patients >65 hepatic impairment renal impairment concomitant use of potent cytochrome P450 3A4 inhibitors such as ritonavir and erythromycin |
patients >65 hepatic impairment renal impairment concomitant use of potent cytochrome P450 3A4 inhibitors such as ritonavir and erythromycin |
| Contraindications | any patient using organic nitrates either regularly or intermittently known hypersensitivity to any component of the tablet |
any patient using organic nitrates either regularly or intermittently known hypersensitivity to any component of the tablet |
any patient using organic nitrates either regularly or intermittently known hypersensitivity to any component of the tablet |
| Use with alpha blockers | Concomitant use of selective alpha blockers does not present a risk for significant hypotension. There is a potential risk of significant hypotension when using non-selective alpha blockers. | ||
| Side effects (top five in order of frequency when compared to placebo) | Headache, flushing, dyspepsia, nasal congestion, alteration in colour vision | Headache, dyspepsia, backpain, myalgia, nasal congestion | Headache, flushing, rhinitis, dyspepsia, sinusitis |
Please consult the individual product monographs for additional information. |
|||