What are the options for testosterone replacement therapy (TRT) in Canada?

Testosterone Replacement Therapy Options in Canada

In Canada, testosterone replacement therapy is available in multiple formulations including transdermal gels, patches, and intramuscular injections, with transdermal gels generally preferred as first-line therapy due to superior cardiovascular safety and more stable testosterone levels. 1

Available Formulations

Transdermal Gels (Preferred First-Line)

• Testosterone gels provide the most stable day-to-day serum testosterone concentrations and have demonstrated better cardiovascular safety compared to injections. 1
• Available gel formulations include:
  • 1% testosterone gel (AndroGel, Testogel, Testim): 50-100 mg/day applied to shoulders, upper arms, abdomen, or thighs 2
  • 1.62% testosterone gel: 20.25-81 mg/day (1-4 pump actuations) applied to shoulders and upper arms only 3
  • 2% testosterone gel (Axiron solution): 30-120 mg/day applied to axilla; (Fortesta): 10-70 mg/day applied to thighs 2
• Gels achieve physiologic testosterone levels within 24 hours and maintain mid-normal range (500-600 ng/dL or 14-17.5 nmol/L) 4, 2
• Peak serum levels occur 6-8 hours after application 2

Intramuscular Injections

• Long-acting injections (testosterone enanthate or cypionate):

  • 100-200 mg every 2 weeks OR 50 mg weekly 2
  • Administered intramuscularly to thighs (self-injection) or gluteal region 2
  • Significantly less expensive than transdermal options (annual cost $156 vs $2,135 for transdermal) 1
  • Peak levels occur 2-5 days post-injection, with return to baseline by 10-14 days 2

• Extra-long-acting injections (testosterone undecanoate):

  • 750 mg initially, repeated at 4 weeks, then every 10 weeks 2
  • Gluteal intramuscular injection only 2
  • Provides less fluctuation in testosterone levels 2

Transdermal Patches

• Testosterone 24-hour patches (Androderm): 2-6 mg/day 2
• Applied to dry, intact skin 2
• Associated with high rates of skin reactions (up to 66% of users experience erythema or pruritus) 2, 1

Formulation Selection Algorithm

Start with transdermal gel for most patients due to:

• Superior cardiovascular safety profile (some evidence suggests injections carry greater risk of cardiovascular events, hospitalizations, and deaths) 1
• More stable testosterone levels without supratherapeutic/subtherapeutic fluctuations 1
• Better tolerability (gels cause skin reactions in only 5% vs 66% with patches) 2

Switch to intramuscular injections when:

• Maximum transdermal dose fails to achieve adequate serum testosterone levels 2
• Cost is prohibitive (injections are dramatically less expensive) 1
• Patient has reduced disease-management skills or resources for daily administration 1
• Patient preference (53% of patients choose injections primarily due to lower cost) 1

Dosing and Monitoring Protocol

Initial Dosing

• Confirm diagnosis first: Measure serum testosterone on at least two separate mornings; both values must be below normal range 3
• Starting dose for 1.62% gel: 40.5 mg daily (2 pump actuations) 3
• Starting dose for injections: 100-200 mg every 2 weeks 2

Baseline Testing Required

• PSA level 2
• Hematocrit or hemoglobin 2
• Digital rectal examination 2
• Voiding symptoms assessment (International Prostatic Symptoms Score) 2
• Sleep apnea history 2

Follow-Up Schedule

• First visit at 1-2 months to assess efficacy and consider dose escalation 2
• Measure testosterone levels at 2-3 months after initiation or dose change 2
• Visits every 3-6 months for first year, then yearly 2
• Once stable, monitor every 6-12 months 2

Monitoring at Each Visit

• Serum testosterone level (target mid-to-upper normal range, 500-600 ng/dL) 2
• PSA level 2
• Hematocrit or hemoglobin 2
• Digital rectal examination 2
• Symptomatic response, voiding symptoms, sleep apnea assessment 2

Timing of Testosterone Measurements

• For injections: Measure midway between injections, targeting mid-normal value 2
• For transdermal preparations: Can measure anytime, though peak occurs 6-8 hours post-application 2

Dose Adjustment Criteria

For 1.62% gel 3:

• If pre-dose morning testosterone >750 ng/dL: Decrease by 20.25 mg
• If 350-750 ng/dL: Continue current dose
• If <350 ng/dL: Increase by 20.25 mg

General principle: If clinical response is adequate, no dose adjustment needed even if levels are low-normal; if suboptimal response with low-normal levels, increase dose 2

Critical Safety Warnings

Secondary Exposure Risk (Gels Only)

• Children and women must avoid contact with unwashed or unclothed application sites 3
• Virilization has been reported in children secondarily exposed to testosterone gel 3
• Patients must wash hands immediately with soap and water after application 3
• Cover application sites with clothing after gel dries 3
• Wash application site thoroughly before anticipated skin-to-skin contact 3

Hematologic Monitoring

• If hematocrit rises above reference range: Temporarily withhold therapy, reduce dose, or perform phlebotomy 2

Prostate Cancer Surveillance

• Men with abnormal digital rectal exam or elevated PSA require negative prostate biopsy before initiating therapy 2
• Consider urologic referral if PSA increases >1.0 ng/mL in first 6 months OR >0.4 ng/mL per year thereafter 2
• Lower threshold for biopsy during first year of treatment due to theoretical risk of accelerated occult cancer growth 2

Cardiovascular Considerations

• FDA required labeling change in 2015 regarding possible increased risk of heart attack and stroke 2
• Injections may carry higher cardiovascular risk than gels, possibly due to time spent in supratherapeutic/subtherapeutic ranges 2, 1
• However, this remains controversial and may reflect high-risk patient populations rather than formulation effects 2

Common Pitfalls and Adverse Effects

Formulation-Specific Issues

• Gel transfer risk: Inadvertent transfer to partners/children via prolonged skin contact 1
• Injection site reactions: Local pain, soreness, bruising, erythema, swelling, nodules, furuncles 2, 1
• Patch irritation: Erythema or pruritus in up to 66% of users 2

General Adverse Effects

• Breast tenderness and swelling (small number of men) 2
• Testicular atrophy and compromised fertility due to gonadotropin down-regulation 2
• Fluid retention (use cautiously in heart failure or renal insufficiency) 2
• Acne, oily skin, increased body hair, flushing 2
• Sleep apnea exacerbation, particularly with higher parenteral doses 1

Contraindications

• Breast carcinoma 3
• Known or suspected prostate cancer 3
• Pregnancy (causes fetal harm) 3

Cost and Patient Preference Considerations

• 71% of patients prefer topical gel over injection or patch after >1 month use, citing convenience, ease of use, and non-staining of clothes 1
• 53% initially choose injections due to dramatically lower cost 1
• Annual cost differential is substantial: $2,135 for transdermal vs $156 for intramuscular formulations 1