Study Eligibility Criteria and Selection Process

KQ 1. The clinical utility of routine blood tests—testosterone, prolactin, LH, FSH - in identifying and affecting therapeutic outcomes for treatable causes of ED was examined using reports of measurements of serum testosterone, FSH, LH, prolactin, and/or other hormone levels, (but not gonadotrophin-releasing hormone [GnRH], Inhibin, Activin, or Follistim). It was also examined in reports of the prevalence of reversible hormonal disorders in males with erectile dysfunction. The study selection criteria included the following:

Source: Primary study report published in English

Study design: Any (prevalence studies)

Population: Adults (age ≥ 18 years) diagnosed with ED with or without concurrent endocrinopathy (i.e., hypogonadism, hyperprolactinemia, abnormal levels of LH/FSH)

Intervention (experimental): Hormonal blood tests (i.e., testosterone/prolactin/LH/FSH)

Outcomes: Prevalence of endocrinopathies (i.e., hypogonadism, hyperprolactinemia, abnormal levels of LH/FSH)

KQ 2. Benefits of pharmaceutical treatments (e.g. oral, injections, hormonal, topical, intra-urethral suppositories) in males with ED. To address how patient specific characteristics (e.g. specific symptoms/origin, duration, severity of ED/comorbid conditions) affect prognosis/treatment success for ED patients. Evidence on the following treatment modalities was excluded from this review: Natural health products (e.g. herbals), yohimbine, vacuum constriction devices, and sex or surgical therapies (e.g. penile prosthesis implantation, penile arterial reconstructive surgery). Study selection criteria included the following:

Source: Primary study report published in English

Study design: RCTs (comparative efficacy and harms studies)

Population: Adults (age => 18 years) diagnosed with ED (with or without comorbidities)

Interventions (experimental/control): Oral (PDE-5 inhibitors, sublingual) injections (IC, cream)

Outcomes: Clinically relevant efficacy measures (i.e., scores for the IIEF “EF” domain, IIEF-Q3/Q4, SEP-Q2/Q3, GAQ-Q1, EDITS)

KQ 3. Harms of pharmaceutical treatments (e.g. oral, injections, hormonal, topical, intra-urethral suppositories) in males with ED. Evidence on the following treatment modalities was excluded from this review: Natural health products (e.g. herbals), yohimbine, vacuum constriction devices, and sex or surgical therapies (e.g. penile prosthesis implantation, penile arterial reconstructive surgery). Study selection criteria included the following:

Source: Primary study report published in English

Study design: RCTs (comparative efficacy and harms studies)

Population: Adults (age ≥ 18 years) diagnosed with ED (with or without comorbidities)

Interventions (experimental/control): Oral (PDE-5 inhibitors, sublingual) injections (IC, SC), hormonal (e.g. testosterone), intra-urethral suppositories, CPAP, and/or topical (e.g. patch, cream)

Outcomes: Any adverse events, serious adverse events, withdrawals due to adverse events, and specific adverse events.

KQ 3a. The incidence of specific harms such as Nonarteritic Anterior Ischemic Optic Neuropathy (NAION) and penile fibrosis associated with use of PDE-5 inhibitor and injection therapies, respectively. The review included reports of non-RCTs or observational studies. For identification of data on fibrosis related to use of injection therapies, only studies with at least 6 months of followup were included. Study selection criteria included the following:

Source: Primary study report published in English

Study design: Non-RCTs (experimental or observational case-control and cohort studies, case reports and case-series)

Population: Adults (age ≥ 18 years) diagnosed with ED (with or without comorbidities)

Interventions (experimental/control): Oral (PDE-5 inhibitors), injections (IC, SC)

Outcomes: NAION, penile fibrosis

Systematic and narrative reviews, case reports, editorials, commentaries or letters to the editor were excluded for all questions except Q3-a (specific harms). Studies evaluating interventions such as penile implant devices or natural health products used for the treatment of ED were also excluded.

The results of the literature search were uploaded to the software program TrialStat SRS version 4.0 along with screening questions developed by the review team and any supplemental instructions. A calibration exercise was undertaken to pilot and refine the screening process. One reviewer screened bibliographic records (i.e., title, authors, key words, abstract) using broad screening criteria (Appendix B). All potentially relevant records and those records that did not contain enough information to determine eligibility (e.g. no abstract was available) were retained. The reasons for exclusion are noted in the QUOROM flow diagram (Figure 2). Two reviewers independently performed full-text relevance screening. Disagreements were resolved by consensus. Reasons for exclusion were noted (Appendix E).