Canadian Urological Association guideline: Erectile dysfunction

Question 1

Define Erectile Dysfunction (ED) and explain the physiological requirements for penile erection.

Answer 1

ED is the inability to achieve or maintain an erection sufficient for satisfactory sexual performance. Penile erection requires complex integration between vascular, neural, and endocrine systems leading to arterial dilatation, trabecular smooth muscle relaxation, and activation of the corporal veno-occlusive mechanism.

Question 2

What is the trabecular structure, and where is it found in the context of penile erection?

Answer 2

Trabecular refers to sponge-like regions in the erectile tissues of the penis, including the corpora cavernosa and corpus spongiosum. It consists of smooth muscle fibers, endothelial cells, and connective tissue.

Question 3

Explain the function of trabecular smooth muscle during sexual arousal and erection.

Answer 3

During sexual arousal, the smooth muscles within the trabeculae relax, allowing the spaces within to fill with blood. This leads to the expansion and erection of the penis.

Question 4

How can dysfunction or abnormalities in trabecular smooth muscle contribute to Erectile Dysfunction (ED)?

Answer 4

Dysfunction or abnormalities in the trabecular smooth muscle can hinder the relaxation necessary for the spaces within the trabeculae to fill with blood. This impairment can prevent the achievement of a full erection, contributing to ED.

Question 5

What is considered the cornerstone of assessing patients with Erectile Dysfunction (ED)?

Answer 5

The cornerstone of the assessment is a detailed history and physical exam. Screening laboratory testing should also be considered, depending on the clinical context.

Question 6

What key aspects should be included in a detailed history of a patient presenting with ED?

Answer 6

The history should include medical and psychological comorbidities, medications, substance use history, surgical and pelvic radiation history, history of pelvic trauma, previous treatments for sexual dysfunction, and a detailed psychosocial and sexual history.

Question 7

How may excessive pornography use be related to ED, and what is the current understanding of this association?

Answer 7

It has been hypothesized that excessive pornography use may contribute to sexual dysfunction during partnered sex, especially in younger patients with ED. However, this association is not clearly demonstrated in the empirical literature and requires further study.

Question 8

What are some of the key features to assess during the physical examination of a patient with ED?

Answer 8

Physical examination should assess the patient’s overall body habitus, level of virilization, and genital anatomy to identify any comorbid medical and/or sexual conditions.

Question 9

Which laboratory tests are recommended for patients with suspected vasculogenic or idiopathic ED?

Answer 9

Baseline hemoglobin A1C, fasting glucose, and lipid profile should be considered to rule out occult diabetes and dyslipidemia. Morning serum total testosterone level should be considered if symptoms of testosterone deficiency are present or if there is a failure of phosphodiesterase type-5 inhibitors (PDE5is).

Question 10

What is the role of specialized testing, such as nocturnal penile tumescence (NPT) and penile duplex ultrasound (PDU), in the assessment of ED?

Answer 10

Specialized testing is rarely required and can be used to differentiate between organic and non-organic causes of ED when the patient’s history is conflicting or in medico-legal cases. These tests provide little practical information beyond a detailed history and are usually obtained by subspecialists in sexual medicine.

Question 11

What characteristic often indicates psychogenic ED rather than organic ED regarding nocturnal erections?

Answer 11

The presence of nocturnal erections is often present in psychogenic ED, while it is reduced in organic ED.

Question 12

How does the presence of an erection during masturbation or with alternate partners differ between psychogenic and organic erectile dysfunction?

Answer 12

In psychogenic ED, erections are often present during masturbation or with alternate partners, while they are reduced in organic ED.

Question 13

How does significant recent psychosocial stress impact psychogenic and organic erectile dysfunction?

Answer 13

Psychogenic ED is strongly impacted by significant recent psychosocial stress, while organic ED has minimal impact.

Question 14

What are the feelings of performance anxiety around sexual activity in psychogenic ED compared to organic ED?

Answer 14

Psychogenic ED is characterized by a strong impact of feelings of performance anxiety around sexual activity, while organic ED has minimal impact.

Question 15

Explain the situational variability of erectile dysfunction in psychogenic and organic ED, such as improvement while on vacation.

Answer 15

Psychogenic ED has the potential for wide variability in situational contexts, including improvement while on vacation, whereas organic ED typically shows minimal variability.

Question 16

What is the Erection Hardness Scale (EHS) and how is it used in assessing erectile dysfunction?

Answer 16

The Erection Hardness Scale (EHS) is a self-reported assessment tool used to measure penile hardness. It ranges from 0 (no engorgement) to 4 (complete rigidity), providing an objective measure of erectile function.

Question 17

Explain the Sexual Health Inventory of Men (SHIM) as a tool for evaluating erectile dysfunction.

Answer 17

The Sexual Health Inventory of Men (SHIM) is a tool consisting of five questions that provide a score out of 25. It offers a subjective patient-reported assessment of erectile dysfunction, helping in the diagnosis and management of the condition.

Question 18

Describe the International Inventory of Erectile Function (IIEF) and its significance in assessing sexual function.

Answer 18

The International Inventory of Erectile Function (IIEF) is a comprehensive tool comprising fifteen questions that explore five domains of sexual function. These domains include desire, erectile function, intercourse satisfaction, orgasmic function, and overall sexual satisfaction. It is used to evaluate different aspects of sexual health and diagnose ED.

Question 19

Provide an overview of the validated assessment tools for erectile dysfunction, summarizing the main features of EHS, SHIM, and IIEF.

Answer 19

EHS: Self-reported penile hardness scale, ranging from 0 to 4.
SHIM: Five questions, scoring out of 25 for patient-reported assessment of ED.
IIEF: Fifteen questions across five domains (desire, erectile function, intercourse satisfaction, orgasmic function, and overall sexual satisfaction), providing a comprehensive evaluation of sexual function.

Question 20

Provide a general overview of the factors to be assessed during a physical examination for erectile dysfunction, as outlined in the Canadian Urological Association guideline.

Answer 20

The physical exam assesses factors in three key areas:

Overall: Blood pressure, body habitus, virilization, mood, gynecomastia.
Penis and groins: Penile length and girth, presence of penile plaques, phimosis, frenular tether, meatal stenosis, quality of femoral pulses.
Testicles: Volume and consistency.

Question 21

What specific factors are assessed in the “Overall” area during a physical examination for erectile dysfunction, and why are they significant?

Answer 21

The “Overall” area assesses blood pressure, body habitus, virilization, mood, and gynecomastia. These factors provide insights into systemic conditions that may influence ED, such as cardiovascular disease, hormonal imbalances, or psychological issues.

Question 22

Describe the importance of assessing the “Penis and groins” area during a physical examination for ED. What are the specific factors evaluated?

Answer 22

The “Penis and groins” assessment includes penile length and girth, presence of penile plaques, phimosis, frenular tether, meatal stenosis, and the quality of femoral pulses. This evaluation identifies anatomical or vascular abnormalities that may contribute to ED.

Question 23

What are the factors to be examined in the “Testicles” area during a physical examination for ED, and why are they significant?

Answer 23

The “Testicles” area assesses volume and consistency. This can reveal information about possible testicular atrophy or other abnormalities that might impact hormone levels and contribute to ED.

Question 24

Fig 1. Management summary of erectile dysfunction.

Question 25

List the conservative measures recommended for all patients with ED, especially if lifestyle habits are impacting erectile function.

Answer 25

Exercise/physical activity, smoking cessation, reducing alcohol and cannabis consumption, dietary changes. Note: L-arginine and citrulline have been evaluated but need more confirmation. Early referral for sexual counseling might also be considered.

Question 26

Explain the function and current clinical standing of Li-SWT as a treatment for mild to moderate ED in Canada.

Answer 26

Li-SWT induces angiogenesis and nerve regeneration to improve erectile function but is not Health Canada- or FDA-approved for clinical use in ED. It is widely offered but not within the standard guidelines.

Question 27

Describe the action, side effects, and contraindications of PDE5is (sildenafil, tadalafil, vardenafil) in ED treatment.

Answer 27

PDE5is promote vascular and cavernosal muscle relaxation. Side effects include headache, flushing, dyspepsia, and nasal stuffiness. Contraindications include the use of nitroglycerin or organic nitrates and hypersensitivity to any component of the tablet.

Question 28

Describe the position of Intraurethral Alprostadil in ED treatment and the reasons for its limited use.

Answer 28

A second-line option for ED with suboptimal efficacy and urethral discomfort. An “in-office” trial with dose titration is advised.

Question 29

Explain the function and considerations of the Vacuum Erection Pump Device in ED treatment.

Answer 29

Generates negative pressure to promote blood flow and trap it using a constriction ring. Associated with penile numbness, pain, and bruising. Suitable for those with contraindications to other options.

Question 30

Detail the usage, efficacy, and side effects of Intracavernosal Injection in ED.

Answer 30

Highly effective treatment with up to 94% success. Side effects include pain at the injection site, bruising, scarring, and priapism. “Trimix” is more efficacious but not approved by Health Canada.

Question 31

Describe the two types of penile prostheses and the associated considerations for their use in ED treatment.

Answer 31

Malleable and inflatable prostheses are implanted into the corporal bodies. Considerations include potential negative effect on penile length, satisfaction rates, mechanical failure, and rare complications like infection or device erosion.

Question 32

What are the Tmax values for Sildenafil, Tadalafil, and Vardenafil, and how are they affected by fatty meals?

Answer 32

Sildenafil: 30–120 minutes (median 60 minutes), delayed by 60 minutes with fatty meals
Tadalafil: 30–360 minutes (median 120 minutes), not affected by food
Vardenafil: 30–120 minutes (median 60 minutes), fatty meals reduce CMAX

Question 33

Compare the T½ and available doses for Sildenafil, Tadalafil, and Vardenafil.

Answer 33

T½ 4 hours, doses 25 mg, 50 mg, 100 mg PRN
Tadalafil: T½ 17.5 hours, doses 2.5 mg, 5 mg daily; 10 mg, 20 mg PRN
Vardenafil: T½ 4 hours, doses 5 mg, 10 mg, 20 mg PRN; 10 mg oral dissolvable tablet; 2.5 mg, 5 mg, 10 mg, 20 mg PRN

Question 34

What are the common dose adjustments needed for patients taking PDE5 inhibitors?

Answer 34

Adjustments may be needed for:

Patients >65 years
Hepatic impairment
Renal impairment (CrCl <30 ml/min)
Concomitant use of potent cytochrome P450 3A4 inhibitors (e.g., ritonavir, erythromycin)
Concomitant use of cimetidine

Question 35

Enumerate the contraindications and five most common side effects for Sildenafil, Tadalafil, and Vardenafil.

Answer 35

Contraindications: Any patient using organic nitrates either regularly or intermittently; known hypersensitivity to any tablet component
Sildenafil side effects: Headache, flushing, dyspepsia, nasal congestion, alteration in color vision
Tadalafil side effects: Headache, dyspepsia, back pain, myalgia, nasal congestion
Vardenafil side effects: Headache, flushing, rhinitis, dyspepsia, sinusitis

Question 36

What is the recommendation regarding the preferential use of daily tadalafil over on-demand tadalafil for patients with erectile dysfunction?

Answer 36

The recommendation is against the preferential use of daily tadalafil rather than on-demand tadalafil for patients with erectile dysfunction. (Conditional recommendation, low levels of certainty in evidence)

Question 37

Is low-intensity shockwave therapy (Li-SWT) recommended over no treatment for patients with erectile dysfunction?

Answer 37

The guideline suggests against the use of low-intensity shockwave therapy for patients with erectile dysfunction. (Conditional recommendation, low levels of certainty in evidence)

Question 38

Should testosterone replacement be used as monotherapy for patients with erectile dysfunction and a hypogonadal testosterone level?

Answer 38

The recommendation is against the use of testosterone as monotherapy for patients with erectile dysfunction and a hypogonadal testosterone level. (Conditional recommendation, low levels of certainty in evidence)

Question 39

Does increasing physical activity improve erectile function in patients with erectile dysfunction compared to usual activity?

Answer 39

The guideline suggests increasing physical activity, rather than usual activity, among patients with erectile dysfunction. (Conditional recommendation, low levels of certainty in evidence)

Question 40

Should penile rehabilitation with scheduled PDE5 inhibitor be used over no intervention for patients with post-prostatectomy erectile dysfunction?

Answer 40

The guideline suggests against the use of scheduled PDE5 inhibitor for penile rehabilitation among patients with post-prostatectomy erectile dysfunction. (Conditional recommendation, low levels of certainty in evidence)

Question 41

What is the panel’s recommendation regarding daily tadalafil vs. on-demand tadalafil for patients presenting with ED?

Answer 41

The panel conditionally recommends against preferentially prescribing daily tadalafil instead of on-demand tadalafil for patients with ED, as there is virtually no meaningful difference in side effects, discontinuation rates, or efficacy. However, certain patient-centered factors may influence the dosing regimen the patient ultimately chooses.

Question 42

Summarize the findings from RCTs comparing improvement in erectile function between on-demand tadalafil and daily tadalafil.

Answer 42

Eight RCTs compared these two dosing regimens over 8-12 weeks. The meta-analysis shows a mean increase in the IIEF-EF score of 0.8, favoring daily tadalafil, with moderate certainty of evidence. However, this small difference is not clinically significant. Both treatment regimens are similarly efficacious across various clinical subgroups.

Question 43

What are the patient-centered factors that influence the preference for daily dosing of tadalafil?

Answer 43

Daily tadalafil increases sexual spontaneity, improves self-confidence, reduces timing concerns, and anticipatory anxiety. It may also be preferred by female partners and is an approved treatment for comorbid lower urinary tract symptoms. Daily tadalafil may be more cost-effective depending on frequency of use and required dosage (2.5 mg or 5 mg).

Question 44

What is the panel’s recommendation regarding Li-SWT as a treatment for patients with ED, and why?

Answer 44

The panel conditionally recommends against Li-SWT for the treatment of ED at this time, given the trivial desirable effects on erectile function, significant heterogeneity between studies, uncertainty regarding evidence and long-term effects, concerns about cost-effectiveness, equity, and feasibility in the Canadian healthcare setting.

Question 45

Explain the results of the RCTs reviewed by the panel in assessing Li-SWT’s effectiveness for ED treatment, focusing on the mean increase in the IIEF-EF score.

Answer 45

Seven RCTs showed a mean increase in the IIEF-EF score of 4.08 (95% CI 1.57, 6.58) with very low certainty. Removing three studies with high risk of bias results in a mean increase of 2.07 (95% CI 0.19, 3.96) with moderate certainty, indicating that Li-SWT is unlikely to have noticeable clinical improvement in erectile function.

Question 46

What findings were obtained regarding the effect of Li-SWT on sexual quality of life in ED patients, and what was the certainty of the evidence?

Answer 46

Fojecki and colleagues collected quality of life data using the SQoL-M tool, and the Li-SWT arm scored 2.1 points higher (95% CI -7.9, 12.1) than the sham group. The evidence indicates no significant improvement in sexual quality of life between 10 vs. five Li-SWT treatments, with very low certainty of the evidence.

Question 47

Are there any concerns related to Li-SWT’s safety, and what further research or actions are required?

Answer 47

Li-SWT is believed to be safe with virtually no short-term adverse effects, but concerns about long-term effects, cost-effectiveness, equity, and feasibility exist. More research is required to assess longer-term adverse effects, and adequately powered RCTs focusing on patient safety and standardized protocols are needed before offering this modality outside of a clinical trial.

Question 48

What is the panel’s recommendation regarding the use of testosterone replacement as monotherapy in patients with Erectile Dysfunction (ED) and hypogonadal testosterone levels?

Answer 48

The panel conditionally recommends against using testosterone as monotherapy to improve erectile function in patients with a hypogonadal testosterone level.

Question 49

How does testosterone therapy affect overall sexual function and quality of life in patients with Testosterone Deficiency Syndrome (TDS)?

Answer 49

Testosterone therapy improves overall sexual function and sexual quality of life in patients with TDS, though it is unlikely to lead to a clinically significant improvement in erectile function as a monotherapy in hypogonadal patients.

Question 50

Summarize the findings of the six randomized controlled trials (RCTs) reviewed by the panel concerning testosterone replacement therapy in hypogonadal patients with ED.

Answer 50

The RCTs showed a mean increase in IIEF-EF score of 2.65 (95% CI 0.81, 4.48) with testosterone therapy compared to placebo, with moderate certainty in evidence. Despite some heterogeneity, this indicates that testosterone therapy alone unlikely leads to significant improvement in erectile function in this patient population.

Question 51

What evidence supports the use of testosterone in combination therapy to salvage patients who have failed PDE5is?

Answer 51

While monotherapy is not supported, some evidence supports testosterone’s use in combination therapy. Three RCTs showed a mean increase in IIEF-EF score of 1.68 (95% CI 0.30, 3.07) favoring testosterone combination therapy with low certainty of evidence. More controlled trials with longer follow-up are needed to confirm this claim.

Question 52

What is the panel’s recommendation regarding the increase of physical activity in patients with ED based on the GRADE evidence?

Answer 52

The panel conditionally recommends that patients with ED increase their physical activity to improve erectile function. This recommendation is based on a meta-analysis of five RCTs and considers the safety, low cost, accessibility, and acceptability of physical activity in the general population.

Question 53

How did the RCTs in the reviewed studies incorporate PDE5is in their design, and what conditions besides ED were participants diagnosed with?

Answer 53

Two of the five RCTs treated both the intervention and control arms with PDE5is as part of the study design. Participants in the RCTs had conditions such as obesity, ischemic heart disease, hypertension, and metabolic syndrome in addition to ED.

Question 54

Two of the five RCTs treated both the intervention and control arms with PDE5is as part of the study design. Participants in the RCTs had conditions such as obesity, ischemic heart disease, hypertension, and metabolic syndrome in addition to ED.

Answer 54

The evidence has a low certainty, and the meta-analysis shows a mean increase in the IIEF-EF score of 3.77 (95% CI 2.04, 5.50), favoring increased physical activity. The panel was influenced by the borderline clinical significance, safety, cost, accessibility, and the linear relationship between physical activity and overall health, including prevention strategies in conditions associated with ED.

Question 55

Summarize the common goals and routines across the trials concerning increased physical activity for ED treatment.

Answer 55

The common goal across the trials was to increase exercise tolerance through aerobic and/or resistance training. The exact prescribed physical activity and exercise routines differed among the trials, but they aimed to enhance overall physical fitness.

Question 56

What is the recommendation of the panel regarding penile rehabilitation with scheduled PDE5is following radical prostatectomy (RP) for post-prostatectomy ED?

Answer 56

The panel conditionally recommends against penile rehabilitation with scheduled PDE5is following RP. This conclusion is based on a very low certainty of evidence, and the pooled effect estimate indicates only a minimal and statistically insignificant difference in ED resolution compared to placebo.

Question 57

Describe the outcomes of Montorsi’s scheduled tadalafil vs. placebo RCT concerning sexual quality of life, and mention any significant differences in serious adverse events and treatment discontinuation between scheduled PDE5-inhibitor and placebo.

Answer 57

Montorsi’s scheduled tadalafil vs. placebo RCT found little to no difference in sexual quality of life after cessation of active therapy. The certainty of evidence regarding serious adverse events and treatment discontinuation is very low, and there were no significant differences found between scheduled PDE5-inhibitor and placebo.

Question 58

What is the stance of the panel concerning penile rehabilitation post-radiotherapy after treatment with EBRT and brachytherapy for prostate cancer?

Answer 58

There is insufficient evidence for the panel to make any recommendation for penile rehabilitation following treatment with EBRT and brachytherapy. Studies have shown short-term efficacy, but there is no evidence of long-term protective effects against future ED.

Question 59

Detail the findings from RCTs regarding penile rehabilitation with scheduled PDE5is in the post-RP population.

Answer 59

The panel reviewed five RCTs, randomizing patients to scheduled PDE5is or placebo. The follow-up period ranged from 24-48 weeks. The pooled effect estimate suggests that only 28 more patients per 1000 who receive penile rehabilitation with scheduled PDE5is experienced ED resolution compared to placebo (RR 1.11 [95% CI: 0.80, 1.55]), a result not statistically significant.

Question 60

Summarize the short-term and long-term effects of scheduled PDE5is taken around the time of radiation therapy (EBRT and/or brachytherapy).

Answer 60

Scheduled PDE5is have shown to be efficacious in the short-term after radiation therapy, with a cumulative increase in IIEF-EF score of 6.10 (95% CI 4.69, 7.52) compared to placebo after six weeks. However, limited evidence suggests that they do not offer any long-term protective effects against future ED.