AUA GUIDELINE: ERECTILE DYSFUNCTION (2018)
Content includes 2015 CUA ED Guidelines
See ED Evaluation and Management Chapter Notes
Diagnosis and Evaluation
- UrologySchool.com Summary:
2018 AUA | 2021 CUA | |
Mandatory |
|
|
Recommended |
|
|
Optional |
|
|
- History and Physical Exam
- History (medical, sexual, and psychosocial)
- Determine that the problem is erectile dysfunction versus other aspects of the sexual response cycle (desire, ejaculation, orgasm) or from other causes (Peyronie’s disease, lifestyle factors including illicit drug use, quality of partners relationship)
- Onset of symptoms (the timing of specific symptoms should be ascertained in relation to the onset of ED as these symptoms may be primary causes of ED or secondary effects of the ED condition), symptom severity, degree of bother, whether symptoms have been stable or are progressive (worsening symptoms may suggest progressive underlying comorbidities, particularly cardiovascular comorbidities)
- Changes in libido, orgasm, ejaculation, genital pain and penile morphology (possible presence of Peyronie’s disease)
- Situational factors (e.g., occurring only in specific contexts, only when with a partner, only with specific partners), circumstances that facilitate or hinder erectile function
- Presence of nocturnal and/or morning erections (suggests, but does not confirm, a psychogenic component to ED symptoms that would benefit from further investigation), masturbatory erections
- Prior use of erectogenic therapy
- Evaluation of psychological factors (i.e., depression, anxiety, relationship conflict, stressors at home or work) and psychosexual issues addresses psychogenic contributions to clinical presentations. Men may not appreciate that depression, anxiety, stress, and relationship conflicts can interfere with the physiological processes necessary for erectile function. Thoughtful discussion of these issues with men and their partners is a key component of patient education and can promote acceptance of incorporating a mental health/sexuality expert into the treatment plan.
- In situations in which sudden or severe ED is likely to develop (e.g., men considering definitive therapy for pelvic cancers) early inclusion of psychosexual expertise on the treatment team is critical to development of an effective and feasible treatment plan
- Comorbid medical conditions: hypertension, peripheral vascular disease, diabetes, obesity, and renal disease
- Comorbid sexual conditions: premature ejaculation, anorgasmia, low libido, and Peyronie's
- Pelvic surgery, radiation or trauma
- Medications
- Lifestyle factors: smoking, substance use/abuse, sedentary lifestyle
- Because of the complexity of sexuality and the impact of a sexual relationship on a man’s life, it is strongly advised that a male’s partner be invited to participate in this process whenever possible and clinically appropriate.
- Physical exam
- Vitals (hypertensive may contribute to ED)
- Body habitus (waist circumference, BMI)
- Signs of testosterone deficiency (e.g., gynecomastia, under-developed facial/pubic/axillary hair)
- Genital exam (including assessment of penile skin lesions and placement/configuration of the urethral meatus)
- Examination of the penis for occult deformities or plaque lesions should occur with the penis held stretched and palpated from the pubic bone to the coronal sulcus.
- Scrotal exam
- General assessment of the scrotal skin
- Palpation of the testicles to assess for size, consistency, and location.
- Digital rectal examination is NOT required for evaluation of ED; however, BPH is a common comorbid condition in men with ED and may merit evaluation and treatment.
- History (medical, sexual, and psychosocial)
- Laboratory
- 2018 AUA
- All men (2):
- Fasting glucose or hemoglobin A1c (screen for occult diabetes)
- Morning total testosterone
- Optional
- Fasting lipids
- Serum BUN/Cr
- Other: optional testing such as thyroid-stimulating hormone (TSH), luteinizing hormone (LH) and follicle-stimulating hormone (FSH), prolactin, complete blood count (CBC), and urinalysis are added when dictated by clinical context.
- All men (2):
- 2021 CUA
- Fasting glucose or hemoglobin A1c in patients with either suspected vasculogenic or idiopathid ED
- Fasting lipids in patients with either suspected vasculogenic or idiopathid ED
- Morning total testosterone if (2):
- Symptoms of testosterone deficiency
- Failure of phosphodiesterase type-5 inhibitors
- Validated questionnaires
- Uses
- Assess severity of ED
- Measure treatment effectiveness
- Guide future management
- 2018 AUA: recommended
- 2021 CUA: can be useful
- Examples include the Erection Hardness Score (EHS) and the Sexual Health Inventory for Men (SHIM); for specialty practices when the presenting issue is ED, a more detailed instrument such as the full form of the International Index of Erectile Function (IIEF) may be more useful.
- The IIEF consists of 15 questions that quantify 5 domains (follows typical sequence):
- Sexual desire
- Erectile function
- Intercourse satisfaction
- Ejaculatory/orgasmic function
- Overall sexual satisfaction
- The IIEF consists of 15 questions that quantify 5 domains (follows typical sequence):
- IIEF validated in heterosexual population, but has been shown to be efficacious in then men who have sex with men (MSM) population
- Specialized testing
- Can be used to differentiate between organic and non-organic causes of ED when the patient’s history is conflicting and in medico-legal cases
- 2021 CUA: rarely required in the routine assessment of patients with ED
- 2018 AUA: For some men with ED, specialized testing and evaluation may be necessary to guide treatment. Specialized testing should only occur if findings will affect management
- Situations that may require more detailed evaluation include men with ED who are
- Young
- Strong likelihood of primary psychogenic etiology
- Strong family history of cardiac illness
- Concomitant PD
- History of pelvic trauma
- Failed prior ED therapies
- Lifelong ED
- Nocturnal Penile Tumescence and Rigidity (NPTR) testing
- Quantifies the number, duration, and rigidity of nocturnal erections
- Involves placement of two strain gauges on the penile shaft to measure radial rigidity during sleep; the device is used over several nights’ sleep
- Historically used to differentiate psychogenic from organic causes of ED, with the presumption that men with psychogenic ED would have preservation of nocturnal penile erections. However, test is prone to false negatives and may be less useful in men with impaired sleep schedules.
- Recommended criteria for normal NPTR include:
- 4-5 erectile episodes per night
- Mean duration >30 minutes
- Increase in circumference >3cm at the base and >2cm at the tip
- Maximal rigidity >70% at both base and tip
- Limited availability in Canada and costs are not covered by most provinces
- Audiovisual and vibratory stimulation
- Erotic stimulation by explicit videotape material with monitoring has been used as a reliable as well as a time- and cost-effective alternative to NPTR to differentiate psychogenic from organic causes of ED
- In-office testing (3)
- Intracavernosal injection (ICI)
- An erectogenic agent (e.g., prostaglandin E1, papaverine, and/or phentolamine) is injected into the corpora cavernosa of the penis. Erectile response is assessed 5-10 minutes post injection and typically after sexual stimulation (e.g. masturbation, exposure to audiovisual sexual stimulation). The erectile response is observed and rated by an independent assessor.
- The test is designed to bypass neurologic and hormonal influences involved in the erectile response and evaluates veno-occlusive function of penis. A normal test, based on the assessment of a sustainably rigid erection, signifies normal erectile hemodynamics. Alternative diagnoses of psychogenic, neurogenic, or endocrinogenic ED may then be considered.
- For some men, the sympathetic tone and anxiety involved with in-office penile injection may override the injection agent’s activity, leading to a false positive diagnosis of ED. Repeat dosing is recommended in such cases.
- In addition to providing information on penile vascular status, ICI may be useful to assess for penile deformities such as Peyronie’s disease
- Penile duplex ultrasound
- Currently the gold-standard (most reliable, least invasive) in penile vascular evaluation
- Evaluates both cavernous arterial inflow and the veno-occlusive capacity of the penis
- Used to localize and measure the size and flow through the cavernous vessels, pre- and post-vasoactive injection which allow a more refined assessment of penile circulation. The test adds an imaging dimension and a quantification component to the evaluation of blood flow in the penis, distinct from the ICI evaluation, which relies on the assessor’s judgment alone
- Uses (4):
- Differentiation of primary psychogenic versus organic etiology for ED
- Identification of men with severe veno-occlusive dysfunction resulting in ED who are unlikely to respond to medical therapy
- Identification of young men who may be candidates for penile revascularization procedures
- Assessment of arterial function in men who may warrant assessment by a cardiologist (i.e., men with predominantly vascular ED)
- Key parameters derived from penile duplex ultrasound include peak systolic velocity ([PSV], cavernosal artery blood flow rate at start of systole) and end diastolic velocity ([EDV], cavernosal artery blood flow rate at the end of diastole)
- PSV <25-30 cm/s is considered evidence of arterial insufficiency (arteriogenic or vascular ED)
- PSV consistently > 35 cm/s defines normal cavernous arterial inflow
- EDV >5 cm/s is consistent with veno-occlusive dysfunction, though different cut-points have been applied.
- Resistive Index (PSV – EDV) / PSV) <0.80 is indicative of veno-occlusive dysfunction
- PSV <25-30 cm/s is considered evidence of arterial insufficiency (arteriogenic or vascular ED)
- Biothesiometry (not mentioned in CUA guidelines)
- Non-specific term for testing intended to assess for peripheral neuropathies
- Has been applied to the penis, most commonly by applying a device that administers vibrations of controlled and consistent intensity
- Intracavernosal injection (ICI)
- Invasive testing (2)
- Cavernosometry and cavernosography
- Cavernosometry quantifies intracorporal pressure after ICI and is useful primarily for establishing a diagnosis of veno-occlusive dysfunction.
- Typically, cavernosometry is performed in conjunction with cavernosography (intracorporal installation of radio-opaque dye) which permits detailed localization of any area(s) of leak
- Previously used in select patients who were suspected of having a site-specific vasculogenic leak resulting from perineal or pelvic trauma or who have had lifelong ED (primary ED). Rarely performed in the modern era since surgery for veno-occlusive dysfunction is not recommended, making anatomical localization from cavernosography largely irrelevant.
- Selective internal pudendal angiography
- Accurately defines the arterial inflow of the penis
- Commonly reserved for
- Young patient with ED secondary to a traumatic arterial disruption or the patient with a history of penile compression injury, who is being considered for penile revascularization surgery
- Non-ischemic priapism
- Cavernosometry and cavernosography
Management
- Men should be counseled that ED is a risk marker for underlying cardiovascular disease (CVD) and other health conditions that may warrant evaluation and treatment
- ED is as strong of a risk factor for CVD as is smoking and family history
- Sexual activity has been associated with increased risk for cardiac events, although the absolute risk is small, particularly in men who regularly engage in other physical activities
- Low-risk patients (men without cardiac disease who are able to exercise with no to minimal cardiac symptoms, men with diagnosed cardiac disease who have undergone successful revascularization procedures (e.g., coronary artery stenting, coronary artery bypass graft), men with controlled asymptomatic hypertension, and men with low grade heart failure (i.e., New York Heart Association Class I and II heart failure) may be treated for ED without additional cardiovascular evaluation.
- All other men with cardiovascular conditions require a cardiology consultation and additional cardiac evaluation; if there is uncertainty regarding a man’s exercise tolerance and fitness for sexual activity, then he should be referred for in-depth evaluation of cardiac reserve by a cardiologist
- Consider referral to a mental health professional to promote treatment adherence, reduce performance anxiety, and integrate treatments into a sexual relationship
- Many men avoid using ED treatments or discontinue using effective ED treatments because of beliefs about loss of masculinity and distress related to possible failure in a sexual situation.
- Psychogenic ED is generally driven by a man’s anxiety related to the ability to achieve an erection. Medical treatments can be effective in these situations, but the addition of psychotherapy or psychosexual counseling may help men to use the medications more effectively and ultimately transition off medical ED therapies.
- Psychosexual therapy
- May represent a spectrum of approaches from a simple open discussion with the primary care physician to psychologist, sexual therapists and/or psychiatrists
- Medication change
- Certain medications are associated with ED. If this is found, consider changing to a different dose or type of medication entirely, this may reverse ED in some patients
- Offending drugs such as estrogens, morphine, sedatives, and neuroleptics should be discontinued
- Lifestyle modifications
- Changes in diet, discontinuation of cigarette smoking and increased physical activity, improve overall health and may improve erectile function
- A change to a no-nose saddle from a conventional saddle has been shown to recover erectile function, presumably by alleviating perineal trauma, in a short-term interventional study of men with ED associated with occupational bicycle riding.
- Oral medication
- Phosphodiesterase type 5 inhibitors (PDE5i)
- FDA-approved oral PDE5i available for management of ED (4):
- Sildenafil
- Tadalafil
- Vardenafil
- Avanafil
- All have similar efficacy and tolerability, though limited data available on avanafil;
- Mean change in IIEF-EF scores is similar across drugs (≈8 points, slightly higher with sildenafil)
- Only tadalafil is currently FDA-approved for daily dosing
- On-demand dosing versus daily dosing for tadalafil appears to produce the same level of efficacy
- In general, these agents effectively result in successful sexual intercourse rates of ≈70%. There is no sustained erectile function improvement after discontinuing PDE5i
- Mechanism of action
- Inhibits the phosphodiesterase type 5 enzyme from breaking down cyclic guanasine monophosphate (cGMP) to 5’GMP
- This results in increased concentration of penile cavernosal cGMP that then causes smooth muscle relaxation in the corpus cavernosum vasculature.
- Smooth muscle relaxation results in increased erection hardness and duration in men with ED who have sufficient intact vasculature
- This results in increased concentration of penile cavernosal cGMP that then causes smooth muscle relaxation in the corpus cavernosum vasculature.
- Augments but does not induce the erectile response
- Initiation of erection requires the release of nitric oxide from penile nerve endings and vascular endothelium under the influence of sexual stimulation
- Contraindications:
- Absolute (2):
- Concomitant use of nitrate-containing medications (e.g., sublingual nitroglycerin, isosorbide dinitrate, other nitrate preparations used to treat angina, amyl nitrite, and amyl nitrate “poppers”); combination with a PDE5i can cause a precipitous drop in blood pressure
- If angina occurs during sex when using a PDE5i, patients should stop having sex and seek emergency care immediately. They should inform medical personnel that a PDE5i was taken and should avoid nitroglycerin use for a period of 24 hours for sildenafil and vardenafil and 48 hours for tadalafil
- No pharmacologic antidote to the PDE5i/nitrate interaction exists
- Known hypersensitivity to any component of the tablet
- Concomitant use of nitrate-containing medications (e.g., sublingual nitroglycerin, isosorbide dinitrate, other nitrate preparations used to treat angina, amyl nitrite, and amyl nitrate “poppers”); combination with a PDE5i can cause a precipitous drop in blood pressure
- Relative (5):
- Severe renal or liver disease; in men with mild to moderate hepatic or renal impairment or men with spinal cord injury, dose adjustment should be considered given the potential for delayed metabolism
- CUA guidelines do not include severe renal or liver disease as contraindication, but do suggest dose adjustment
- Severe cardiac disease
- Controlled and post-marketing studies have shown that PDE5i do not cause an increase in myocardial infarction or death rates when compared with expected rates in study control populations.
- Caution is advised for the use of PDE5i in patients with certain conditions: aortic stenosis, left ventricular outflow obstruction, hypotension, and hypovolemia.
- FDA recommends against use in patients with MI in last 6 months
- Concomitant use of non-selective alpha blockers
- Caution is advised when PDE5i are co-administered with α-adrenergic blockers, because both agents are vasodilators with blood pressure lowering effects.
- There is a potential risk of significant hypotension when using non-selective alpha blockers (terazosin, alfuzosin, doxazosin)
- Concomitant use of selective alpha blockers (silodosin, tamsulosin) does not present a risk for significant hypotension.
- Concomitant use of anti-arrhythmics
- Vardenafil is not recommended in (2):
- Patients who take type 1A (e.g., quinidine or procainamide) or type 3 (e.g., sotalol or amiodarone) anti-arrhythmics
- Congenital prolonged QT syndrome
- Known hereditary degenerative retinal disorders
- FDA recommends against use in patients with known hereditary degenerative retinal disorders, such as retinitis pigmentosa
- Metabolism
- Metabolized by the cytochrome P450 3A4 enzyme
- Dose increase required with concomitant use of (inducers of this enzyme):
- Rifampin
- Dose reduction required with concomitant use of (inhibitors of this enzyme):
- Ketoconazole, itraconazole, fluconazole
- Ritonavir, indinavir
- Cimetidine
- Macrolide antibiotics (e.g. erythromycin)
- CUA guidelines suggest that dose adjustment may be needed in patients >65 years old
- Adverse events
- Most AEs associated with the administration of PDE5i are mild to moderate and improve over time
- Side effects prompt discontinuation only in a few patients
- The most common reason for discontinuation of PDE5i is lack of treatment efficacy (e.g., hardness of erection)
- Most AEs follow a dose-response pattern
- Generally, daily dosing associated with lower rates of AEs
- The most frequently reported AEs (occurring in ≥2% of patients): HARD DICK F***S MY NIGHT DAMN VISION
- Headache (7-16%)
- Dyspepsia (4-10%)
- Flushing (4-10%)
- Myalgia/back pain (0-3%)
- Dizziness
- Nasal congestion (3-4%)
- Visual disturbances (e.g., photophobia, blue vision) (0-3%)
- Sildenafil and vardenafil associated with higher rates of visual disturbance
- Sildenafil and vardenafil cross-react to a greater extent with PDE type 6, which is expressed in the retina, than tadalafil and avanafil.
- Tadalafil associated with higher rates of back pain and myalgia
- Vardenafil associated with higher rates of nasal congestion
- Non-arteritic Anterior Ischemic Optic Neuropathy (NAION)
- A rare visual condition characterized by the sudden onset of loss of vision in one eye
- Several studies have suggested that PDE5i use is associated with an increased risk of NAION, although the absolute risk is small (3 additional cases per 100,000 men age ≥ 50).
- Men in higher-risk groups (e.g., older males, males of Caucasian ethnicity, males with vascular risk factors) should be counseled about this small increased risk, including the fact that the absolute risk of NAION is extremely low with or without the use of PDE5i, and that the association does not imply causation.
- Patients should be advised to stop use of PDE5i and to seek immediate medical attention as a safety measure in the event of a sudden loss of vision
- No increased risk of skin cancers or prostate cancer recurrence after prostate cancer treatment
- Instructions regarding onset and duration of action and effect of food intake should be provided to maximize benefit/efficacy.
- Studies of men who report non-response to PDE5i indicate that incorrect use (e.g., lack of sexual stimulation, medication taken with a large meal) accounts for 56-81% of treatment failures
- Characteristics of PDE5is
PDE5i |
Onset of action |
Duration of action (T1/2) |
Available doses (maximum) |
Effect of food intake |
Sildenafil |
30-60 min |
Up to 12 hours |
25 mg, 50 mg, 100 mg PRN |
High-fat meal decreases efficacy |
Vardenafil |
30-60 min |
Up to 10 hours |
10 mg oral dissolvable tablet |
High-fat meal decreases efficacy |
Tadalafil |
60-120 min |
Up to 36 hours |
2.5 mg, 5 mg daily |
Not affected |
Avanafil |
15-30 min |
Up to 6 hours |
|
Not affected |
- The dose should be titrated to provide optimal efficacy
- Given that men with diabetes or post-prostatectomy often present with more severe levels of ED, consider initiating therapy at a higher dose.
- Dose-response effects across PDE5i medications are small and non-linear (i.e., doubling the dose does not double the effect)
- As part of the process of identifying the optimal dose, males may be offered dosing frequency changes or different PDE5i.
- Few studies focused on special populations (diabetes, metabolic syndrome, post-prostatectomy, etc.), but in general, findings are similar to those reported in the general ED population. For example, for males with diabetes, sildenafil, tadalafil, and vardenafil appear equally effective with limited data reported for avanafil.
- Erectile function recovery after radical treatment for prostate cancer
- Radical prostatectomy (RP)
- Erectile function may improve over time
- The interval of spontaneous erectile function recovery usually occurs 12-24 months after RP, although recovery may still be possible as much as 36 months after surgery.
- Relatively few men recover baseline erectile function, particularly those age > 60 at the time of surgery
- A meta-analysis of studies with >12 months follow-up post-RP reported that use of a bilateral nerve-sparing technique was associated with a 60% erectile function recovery rate compared to a rate of 47% for use of a unilateral nerve-sparing technique.
- Erectile function may improve over time
- Rradiotherapy (RT)
- Erectile function may worsen over time
- Onset of ED is delayed and may occur 24-36 months after treatment
- Erectile function may worsen over time
- Radical prostatectomy (RP)
- Men who desire preservation of erectile function after treatment for prostate cancer (by RP or RT) should be informed that early use of PDE5i post-treatment may NOT improve spontaneous, unassisted erectile function
- Penile rehabilitation refers to use of PDE5 inhibitors in some regularly scheduled fashion following radical prostatectomy to promote recovery of spontaneous erectile function. Trials have not demonstrated that early PDE5i use (i.e., within 45 days of prostate cancer therapy) improves unassisted erectile function.
Advantage of sildenafil and vardenafil over tadalafil: faster onset
Advantages of tadalafil over sildenafil and vardenafil: longer duration of action and not affected by meals
- Vacuum erection device
- Principle is to mechanically create negative pressure surrounding the penis to engorge it with blood and then restrain outflow from the organ to maintain the erection-like effect.
- Although the treatment does not produce a truly physiologic erection and the engorged blood predominantly consists of venous blood, the effect resembles a normal erection and is sufficient for coitus.
- The standard vacuum erection device consists of a plastic suction cylinder and vacuum-generating source (manual or battery-operated pump) in one piece. It is placed directly over the flaccid penis and operated, and after the penis is erected an elastic constriction ring or band is positioned at the base of the penis; then the vacuum is released and the device is removed.
- Vacuum devices are associated with high rates of patient and partner satisfaction and are an effective and low-cost treatment option for select men with ED.
- Effective in the general ED population as well as in men with diabetes, spinal cord injury, post-prostatectomy, and other conditions
- Useful in patients with glanular insufficiency
- May have a role as a “rescue” device in men who are PDE5i non-responders
- Intraurethral (IU) alprostadil
- Relies on the absorption of the medication into the surrounding corpus spongiosum, with passage via small vascular channels into the corpora cavernosa, the main erectile bodies
- MUSE uses a suppository inserted into the urethral opening that dispenses a semisolid pellet (1x3mm) of alprostadil (125, 250, 500, and 1000mcg dosages) into the distal urethra (3cm from the external urethral meatus)
- Has inferior efficacy compared to PDE5 inhibitors and ICI
- Treatment option when:
- Patient prefers to avoid oral medication and avoid needles required for ICI medications
- PDE5i are contraindicated
- The main indications are patients who are non-responsive to PDE5 inhibitors resulting from damage of the autonomic penile nerve supply (e.g., radical prostatectomy, cystectomy, and trauma) or those who wish to use the therapy in combination with PDE5 inhibitors.
- The most common adverse events are genital pain, minor urethral trauma/bleeding, urethral pain or burning, and dizziness. Episodes of hypotension or syncope are rare. No reports of priapism
- Although episodes of priapism were not reported in IU alprostadil trials, the man should be thoroughly educated about priapism and instructed on safe responses and maneuvers in a prolonged erection situation.
- Contraindications to MUSE (3):
- Hypersensitivity
- Abnormal penile anatomy
- Conditions that increase the risk of priapism
- AUA: For men with ED who are considering the use of IU alprostadil, an in-office test should be performed.
- Most studies proceeded with chronic treatment only in men who had erections firm enough for intercourse in response to in-office testing. The success rates among men who used the medication chronically, therefore, are relevant to responsive intra-office testing – not men with ED in general.
- IU alprostadil should not be prescribed until a man has undergone instruction in the method, an initial dose-titration in the office, and detailed counseling regarding possible adverse events and actions to take in response to potentially serious adverse events.
- MUSE seems safe for female partners, producing only a 5.8% incidence of vaginal burning or itching, although it should be used with a condom for intercourse with a pregnant woman
- Intracavernosal injections (ICI)
- Effective in all subtypes of ED.
- Drugs commonly used in clinical practice (4) PAPA: Papaverine, Alprostadil, Phentolamine, and Atropine
- Only alprostadil is FDA-approved for ICI injection and is the only medication typically used as a single agent.
- Combination therapy (trimix is alprostadil + papaverine + phentolamine) offers a synergistic mechanism of the vasoactive agents to elicit maximal erectile responses, particularly among patients who have failed monotherapy
- Alprostadil
- MOA: synthetic form of prostaglandin E1 and induces tissue relaxation via increased cAMP
- Advantages: lower incidences of prolonged erection, systemic side effects, penile fibrosis
- Disadvantages: higher incidence of painful erection, higher cost, has a shortened half-life if not refrigerated after reconstitution into liquid from powder.
- Rare systemic side effects that include vasodilation, inhibition of platelet aggregation and stimulation of intestinal activity.
- Papaverine
- MOA: non-specific PDE inhibitor that prevents the degradation of cAMP and cGMP thereby promoting tissue relaxation; decreases venous outflow
- Advantages: inexpensive and stable at room temperature
- Disadvantages: commonly observed liver enzyme elevations, priapism risk (up to 35%), and penile fibrosis risk (1-33%) have led to its abandonment as monotherapy
- Phentolamine
- MOA: non-selective, reversible, competitive, α1-blocker (stimulation of α1-adrenergic receptor inhibits erection), no effect on venous outflow
- Advantages: limited success when administered intracavernosally as a sole agent, short half-life
- Disadvantages: systemic hypotension, reflex tachycardia, nasal congestion, and gastrointestinal upset.
- VIP in combination with phentolamine is currently being sought for regulatory approval in the US
- Treatment option for men who have contraindications to the use of PDE5i, prefer not to take an oral medication, or find that PDE5i are inadequate or ineffective
- Effective in the general ED population as well as in men with diabetes, cardiovascular risk factors, men post-prostatectomy, and men with spinal cord injuries
- Adverse events
- Most serious adverse event is priapism. Other adverse events include prolonged erection (does not require treatment, unlike priapism), pain, ecchymosis, penile fibrosis, plaque, or curvature and other deformities (injection site nodules)
- Patients should be thoroughly educated about priapism and instructed in actions to take in a prolonged erection situation.
- Commonly-used strategies (but for which there is no evidence) include attempting ejaculation and, if unsuccessful, then oral pseudephedrine followed by the application of an ice pack to the penis for 30 minutes to an hour. If a painful, non-bendable erection persists after these strategies, then the man should proceed to the emergency room within 2-4 hours of medication administration.
- ICI with PGE1 alone appears to have lower rates of priapism but is associated with more pain and higher risk of complications.
- Repeated penile trauma from ICI inevitably causes penile
fibrosis
- ICI should be limited to 10 injections monthly to reduce risk of penile fibrosis
- ICI induced fibrosis appears to be partially reversible, is often unnoticed by patients and does not contribute significantly to the development of meaningful penile curvature.
- AUA: in-office injection test should be performed for men with ED considering ICI therapy
- Men should first have an in-office injection test to determine the appropriate dose and medication(s) to produce sufficient duration of response and to minimize adverse events. Start with a small dose of medication
- Contraindications (5):My Direct Pinches Cause Instant Priapism
- Use of Monoamine oxidase inhibitors (risk of precipitating a life-threatening hypertensive crisis if an intracavernosal α-adrenergic agonist is used to reverse a priapic episode)
- Reduced manual Dexterity (although the partner can be trained in the injection technique)
- Psychological instability
- Severe Coagulopathy or unstable Cardiovascular disease
- Anti-coagulation therapy is not a contraindication
- Infection (systemic, cutaneous, or urinary tract infection)
- History or risk for Priapism
- Obesity (relative, from 2019 AUA Update on ICI)
- Application
- Injections
should be conducted at 3 and 9 o’clock positions to avoid
neurovascular structures on the dorsum of the penis and the
urethra ventrally
- Injections should be at 90° to the penile surface
- Injections
should be conducted at 3 and 9 o’clock positions to avoid
neurovascular structures on the dorsum of the penis and the
urethra ventrally
- Outcomes
- EDITS scores were not
significantly different between ICI and oral therapy. However,
EDITS scores were significantly higher with implants than with
ICI or oral therapy
- Patient satisfaction is often measured
using the EDITS (Erectile Dysfunction Inventory of Treatment
Satisfaction) with higher EDITS scores correlating to greater satisfaction. This score must be distinguished from the IIEF questionnaire, as the former tends to vary depending on comfort of the patient towards therapy.
- Patient satisfaction is often measured
using the EDITS (Erectile Dysfunction Inventory of Treatment
- Patient attrition from ICI has been reported as 30-60%
by 6 months and up to 80% beyond that time.
- A majority of men who discontinued use were younger.
- Attrition has been
attributed to modifiable issues, such as inadequate penile rigidity
and anxiety, and unmodifiable issues, such as lack of spontaneity,
unnaturalness, lack of interest and health concerns.
- Such high attrition rates in the modifiable category could be due to inadequate medication titration, injection technique or perhaps high expectations and anxiety that may be alleviated by psychological intervention.
- EDITS scores were not
significantly different between ICI and oral therapy. However,
EDITS scores were significantly higher with implants than with
ICI or oral therapy
- Surgery
- Indications (4):
- Penile injury resulting from genital or pelvic trauma
- Penile structural deformity occurring in association with Peyronie disease
- Cavernosal fibrosis secondary to prolonged ischemic priapism or infection
- Medical therapy for ED is contraindicated, unsuccessful, or undesirable
- Penile prosthesis
- See Surgery for Erectile Dysfunction Chapter Notes
- Effective in men from the general ED population as well as men from a variety of special populations
- Patients should understand that this treatment choice is best conceptualized as irreversible
- Although prostheses can be removed, it is unlikely that a man’s penis will be reliably responsive to other ED therapies after prosthesis explant.
- Several devices are currently available: malleable (non-inflatable) vs. two- or three-piece inflatable penile prostheses
- 2019 AUA Best Practice Policy on Antibiotic Prophylaxis recommend an aminoglycoside with either a first- or second-generation cephalosporin or vancomycin 1 hour before surgery and up to 24 hours after surgery for implanted prosthetic devices (AUS, penile prosthesis, sacral neuromodulators)
- The potential risks of prosthesis surgery include (5):
- Risks inherent in the surgical procedure (penile edema or hematoma, corpus injury, urethral injury, acute urinary retention, and crura injury)
- Possible changes in the appearance of the penis
- When objective measures are used, small length decreases may be documented
- Infection
- A serious adverse event that typically occurs within the first 3 months after surgery and usually requires removal of the prosthesis
- In select cases, an infected prosthesis can be removed, the location of the device washed out using an antibiotic salvage procedure and a new device immediately placed.
- This approach should be restricted to men without evidence of sepsis or severe local infection.
- More typically, the infected device is removed, the infection is addressed with antibiotics, and the tissues are allowed to heal (for 6 weeks to 6 months).
- In select cases, an infected prosthesis can be removed, the location of the device washed out using an antibiotic salvage procedure and a new device immediately placed.
- No evidence that diabetic men are at higher risk of prosthesis infection
- Erosions
- Device malfunction or failure
- Penile arterial reconstruction
- May be considered for young men with (3):
- ED and
- Focal pelvic/penile arterial occlusion and
- Without documented generalized vascular disease or veno-occlusive dysfunction
- Usually used for internal pudendal artery stenosis
- Penile venous reconstruction
- Not recommended; overall, data indicate that penile venous ligation surgery is unlikely to result in long-term successful management of ED for the overwhelming majority of men and delays treatment with other more reliable options such as penile prosthesis surgery
- Hormonal therapy in patients with hypogonadism
- Testosterone may be used alone for hypogonadism, or in combination with oral PDE5-inhibitor therapy when ED is present.
- Men with ED and testosterone deficiency who are considering ED treatment with a PDE5i should be informed that PDE5i may be more effective if combined with testosterone therapy.
- Current recommendations suggest that a short (e.g. 3-month) therapeutic trial of testosterone is justified in men with hypogonadism, and in the absence of a response, testosterone administration should be discontinued
- Once treatment with exogenous testosterone is initiated, ongoing follow-up is mandatory.
- Men should be advised that testosterone therapy is not an effective mono-therapy for ED.
- Alternative hormonal replacement therapies have been suggested, but because of insufficient evidence they are not currently recommended for use
Investigational (2)
- Low-intensity extracorporeal shock wave therapy (ESWT)
- Randomized sham-controlled trials that have evaluated low-intensity ESWT do not clearly indicate that benefits outweigh risks/burdens for men with ED
- Should only be used in investigational settings in the context of a clinical trial
- Intracavernosal stem cell therapy
Experimental
- Platelet-rich plasma (PRP) therapy
Treatment approach as per CUA guidelines:
- First-line: oral medications (PDE5Is)
- Second-line: local therapy (ICI or intraurethral alprostadil) or vacuum device
- Third-line: surgery
Questions
- What are the mandatory investigations in a patient with erectile dysfunction as per the AUA/CUA?
- What are the recommended investigations in a patient with erectile dysfunction as per the AUA/CUA?
- As per the 2015 CUA Guidelines on Erectile Dysfunction, what are the indications to measure serum testosterone?
- What are the 5 domains of the International Index of Erectile Function (IIEF)?
- List potential specialized testing options in the evaluation of erectile dysfunction
- List the FDA-approved PDE5 inhibitors for the treatment of ED
- What are the contraindications to PDE5 inhibitors?
- Which PDE5 inhibitor is not recommended in patients who take type 1A antiarrhythmics (e.g., quinidine or procainamide) or type 3 antiarrhythmics (e.g., sotalol or amiodarone) or in patients with congenital prolonged QT syndrome?
- What are potential adverse events related to the use of a PDE5i?
- Which PDE5 inhibitors have higher rates of visual disturbances? Myalgia?
- What is the onset of action, T1/2, and effect of food intake on the different PDE5 inhibitors?
- What are the non-surgical treatment options for erectile dysfunction?
- What are the contraindications to intraurethral alprostadil?
- What are the typical medications in intracavernosal injection?
- What are the contraindications to intracavernosal injections?
- What are potential complications of penile prosthesis surgery?
Answers
- What are the mandatory investigations in a patient with erectile dysfunction as per the AUA/CUA?
- AUA: history, physical, diabetes screen (fasting glucose or HbA1c), serum testosterone
- CUA: history, physical, diabetes screen (fasting glucose or HbA1c)
- What are the recommended investigations in a patient with erectile dysfunction as per the AUA/CUA?
- AUA and CUA: questionnaire
- As per the 2015 CUA Guidelines on Erectile Dysfunction, what are the indications to measure serum testosterone?
- Decreased interest
- Decreased ejaculatory volume
- Failure of PDE5 inhibitor treatment
- Delayed ejaculation
- Diabetes
- What are the 5 domains of the International Index of Erectile Function (IIEF)?
- Sexual desire
- Erectile function
- Intercourse satisfaction
- Ejaculatory/orgasmic function
- Overall sexual satisfaction
- List potential specialized testing options in the evaluation of erectile dysfunction
- Nocturnal Penile Tumescence and Rigidity testing
- Intracavernosal injection
- Penile duplex ultrasound
- Biothesiometry
- Cavernosometry and cavernosograophy
- Arteriography
- List the FDA-approved PDE5 inhibitors for the treatment of ED
- Sildenafil
- Tadalafil
- Verdenafil
- Avanafil
- What are the contraindications to PDE5 inhibitors?
- Absolute:
- Hypersensitivity
- Concomitant use of nitrates
- Relative:
- Severe liver disease
- Concomitant use of alpha-blocker
- Severe cardiac disease
- Concomitant use of antiarrhythmics
- Known hereditary degenerative retinal disorders
- Which PDE5 inhibitor is not recommended in patients who take type 1A antiarrhythmics (e.g., quinidine or procainamide) or type 3 antiarrhythmics (e.g., sotalol or amiodarone) or in patients with congenital prolonged QT syndrome?
- Vardenafil
- What are potential adverse events related to the use of a PDE5i?
- Headache
- Dyspepsia
- Flushing
- Myalgia
- Nasal congestion
- Visual disturbances
- NAION
- Which PDE5 inhibitors have higher rates of visual disturbances? Myalgia?
- Sildenafil and vardenafil
- Tadalafil
- What is the onset of action, T1/2, and effect of food intake on the different PDE5 inhibitors?
- Sildenafil: 30-60 mins, 4 hours, high-fat meal decreases efficacy
- Verdenafil: 30-60 mins, 4 hours, high-fat meal decreases efficacy
- Tadalafil: 60-120 mins, 17.5 hours, no effect
- Avanafil: 15-30 mins, 5 hours, no effect
- What are the non-surgical treatment options for erectile dysfunction?
- Oral PDE5 inhibitors
- Vacuum erection device
- Intraurethral alprostadil
- Intracavernosal injections
- What are the contraindications to intraurethral alprostadil?
- Patients with known hypersensitivity to alprostadil
- Abnormal penile anatomy
- Conditions that increase the risk of priapism
- What are the typical medications in intracavernosal injection?
- Papaverine (PDE5 inhibitor)
- Alprostadil (prostaglandin)
- Phentolamine (alpha-blocker)
- Atropine (anticholinergnic)
- What are the contraindications to intracavernosal injections?
- Concomitant use of monoamine oxidase inhibitors
- Reduced manual dexterity
- Psychological instability
- Severe coagulopathy and/or unstable cardiovascular disease
- History or risk of priapism
- What are potential complications of penile prosthesis surgery?
- Intra-operative: corpus injury, urethral injury, crura injury, bleeding
- Early post-operative: infection, urinary retention
- Late post-operative: erosion, change in appearance of penis, device malfunction