Editing Evaluation and Management of Erectile Dysfunction (section)

== Management ==

* '''Options (6):'''
*# '''Conservative treatment'''
*## '''Psychosexual counselling'''
*## '''Medication change'''
*## '''Lifestyle modifications'''
*# '''Phosphodiesterase type 5 inhibitors (PDE5i)'''
*# '''Vacuum erection device'''
*# '''Intraurethral alprostadil'''
*# '''Intracavernosal injections'''
*# '''Surgery'''
* '''Treatment approach as per 2021 CUA guidelines:'''
*# '''First-line: PDE5Is'''
*# '''Second-line: ICI or intraurethral alprostadil or vacuum device'''
*# '''Third-line: surgery'''

=== Cardiology referral ===

* '''2018 AUA'''
** '''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'''
* '''2021 CUA'''
** '''Controversial whether a diagnosis of ED alone should initiate a more thorough cardiovascular evaluation'''

=== Conservative treatment ===

* '''Psychosexual counselling'''
** May represent a spectrum of approaches from a simple open discussion with the primary care physician to psychologist, sexual therapists and/or psychiatrists
** 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.
* '''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, reducing alcohol, 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.
** Physical activity
*** Meta-analysis of 5 RCTs found a mean increase in the IIEF-EF score of 3.77 with increased physical activity level§

=== Oral medication ===

* '''Phosphodiesterase type 5 inhibitors (PDE5i)'''
** Facilitate a penile erection by promoting vascular and cavernosal smooth muscle relaxation in response to sexual stimulation
** '''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 (≈7 points, slightly higher with tadalafil§)
*** '''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
**** Potential advantages of daily dosing§
***** Increases sexual spontaneity
***** Improves sexual self-confidence
***** Less concern regarding timing of medication
***** Female partners preferred daily dosing compared to on-demand regimens.
***** In patients experiencing co-morbid lower urinary tract symptoms, daily tadalafil (5 mg) is an approved treatment option and has been shown to decrease symptom scores significantly more than on-demand dosing
***** May be more cost-effective than on-demand dosing, depending on the dosing and frequency of use
**** '''2021 CUA Guidelines conditionally recommend against preferentially prescribing daily tadalafil for patients presenting with erectile dysfunction.'''
***** No meaningful difference in side effects or discontinuation rates between either dosing regimen
*** 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'''
*** '''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'''
*** '''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)'''
*** '''Dose adjustment''' (2021 CUA Guidelines)
**** '''May be needed if (3):'''
****# '''Age >65'''
****# '''Hepatic impairment'''
****# '''Renal impairment (creatinine clearance <30 mL/min)'''
** '''Adverse events'''
*** Most AEs associated with the administration of PDE5i are mild to moderate and improve over time
**** Out of 1000 patients taking the drug on average 8 will experience a serious adverse event with sildenafil, 7 with tadalafil and 8 with vardenafil§
*** 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
*** '''Patients with an unsatisfactory response to PDE5is should first be counselled regarding proper use of the medication and may require a potential dose adjustment'''
** '''Characteristics of PDE5is'''

{| class="wikitable"
|'''PDE5i'''
|'''Onset of action'''
|'''Duration of action (T1/2)'''
|'''Available doses (maximum)'''
|'''Effect of food intake'''
|-
|'''Sildenafil'''
|'''30-60 min'''
|'''Up to 12 hours'''

'''(4 hours)'''
|25 mg, 50 mg, 100 mg PRN

(100mg daily)
|'''High-fat meal decreases efficacy'''
|-
|'''Vardenafil'''
|'''30-60 min'''
|'''Up to 10 hours'''

'''(4 hours)'''
|10 mg oral dissolvable tablet

2.5 mg, 5 mg, 10 mg, 20 mg PRN (20mg daily)
|'''High-fat meal decreases efficacy'''
|-
|'''Tadalafil'''
|'''60-120 min'''
|'''Up to 36 hours'''

'''(17.5 hours)'''
|2.5 mg, 5 mg daily

5 mg, 10 mg, 20 mg PRN

(20mg daily)
|'''Not affected'''
|-
|'''Avanafil'''
|'''15-30 min'''
|'''Up to 6 hours'''

'''(5 hours)'''
| 
|'''Not affected'''
|}
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

* '''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.

=== Vacuum erection device ===

* 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 which can be maintained safely for up to 30 minutes; then the vacuum is released and the device is removed.
* '''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.
* '''Effective and low-cost treatment option for select men with ED.'''
** '''Associated with high rates of patient and partner satisfaction'''
** Considered a more cumbersome and labour-intensive way to achieve an erection
** '''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
* No absolute contraindications making it a reasonable option for those who cannot tolerate or have contraindications to other medical or surgical options

* Adverse events: penile numbness, pain, bruising, and painful ejaculation

=== 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
* Known as MUSE (Medicated Urethral System for Erection)
* 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)
* '''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'''
* '''For patients 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) ===

* First pharmacologic treatment available for ED
* Involves the delivery of vasoactive agents directly into the corpus cavernosum prior to intercourse
* Effective in all subtypes of ED.
* '''Drugs commonly used in clinical practice (4) PAPA: Papaverine, Alprostadil, Phentolamine, and Atropine'''
** '''Only alprostadil is FDA and Health Canada 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
*** Shown to be even more efficacious than alprostadil monotherapy while maintaining an acceptable side effect profile and less penile pain
** '''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
* Outcomes
** Erectile Dysfunction Inventory of Treatment Satisfaction (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 EDITS (Erectile Dysfunction Inventory of Treatment Satisfaction) with higher EDITS scores correlating to greater satisfaction.
**** EDITS scores must be distinguished from the IIEF questionnaire, as EDITS scores tend to vary depending on comfort of the patient towards therapy.
** 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.

=== 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'''
*** Satisfaction rates are high for both implant naïve patients and those undergoing surgical revision of an existing device
** '''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.
*** While not all nonsurgical options need to be attempted prior to considering placement of a penile prosthesis, all nonsurgical options should at least be discussed with the patient prior to considering surgical intervention.
** '''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
**#* Glans will remain flaccid post implant
**# '''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).
**#* '''No evidence that diabetic men are at higher risk of prosthesis infection'''
**# '''Erosions'''
**# '''Device malfunction or failure'''
**#* Almost 50% will still be functional after 20 years of use
* '''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

=== Investigational (2) ===

* '''Low-intensity extracorporeal shock wave therapy (ESWT)'''
** Proposed treatment option for patients with mild to moderate ED
** Administered with a wand-like device delivering low intensity shockwaves to different areas of the penis in multiple sessions.
** Hypothesized to work by inducing angiogenesis through growth factor activation and inducing nerve regeneration
** Randomized sham-controlled trials that have evaluated low-intensity ESWT do not clearly indicate that benefits outweigh risks/burdens for men with ED
** Not Health Canada or FDA approved for clinical use for ED
** '''2018 AUA: Should only be used in investigational settings''' in the context of a clinical trial
** '''2021 CUA: conditionally recommends against low-intensity shockwave treatment (Li-SWT) as a treatment for patients with ED'''
* '''Intracavernosal stem cell therapy'''

=== Experimental ===

* '''Platelet-rich plasma (PRP) therapy'''
* '''Amniotic fluid matrices'''