What weekly dose of intramuscular testosterone should a 28‑year‑old male with hypogonadism receive if he is currently on 100 mg weekly and his serum total testosterone is 300 ng/dL?

Dose Adjustment for Testosterone Replacement Therapy

Increase the weekly dose to 150–200 mg intramuscular testosterone cypionate or enanthate, targeting a mid-normal testosterone level of 500–600 ng/dL measured midway between injections. 1

Current Situation Analysis

Your patient's trough testosterone of 300 ng/dL on 100 mg weekly is at the lower diagnostic threshold for hypogonadism and well below the target mid-normal range of 500–600 ng/dL recommended by the American Urological Association for men on testosterone replacement therapy. 1, 2

• With 100 mg weekly intramuscular testosterone, the expected steady-state mean testosterone is approximately 422–537 ng/dL, but individual pharmacokinetic variation means some patients achieve lower levels. 3, 4
• The current level of 300 ng/dL suggests suboptimal dosing for this patient's metabolism and clearance rate. 1

Recommended Dose Escalation

Increase to 150 mg weekly as the next step, with reassessment at 2–3 months. 1

• If 150 mg weekly produces a mid-cycle testosterone of 400–500 ng/dL but symptoms persist, escalate to 200 mg weekly. 1, 5
• The standard FDA-approved dosing range is 50–400 mg every 2–4 weeks, but weekly dosing at 100–200 mg provides more stable levels and reduces peak-related adverse effects. 1, 5
• Studies demonstrate that 200 mg every 2 weeks produces mean testosterone levels of 536 ng/dL, whereas 100 mg weekly produces 422 ng/dL—your patient needs an intermediate or higher dose. 3, 5

Monitoring Protocol

Measure testosterone levels 2–3 months after each dose adjustment, drawn midway between injections (days 3–4 after injection for weekly dosing). 1, 2

• For weekly injections, peak testosterone occurs on days 2–5, and levels return toward baseline by days 10–14, so mid-cycle sampling (days 3–4) captures average exposure. 1, 4
• Target a mid-normal testosterone of 500–600 ng/dL at this mid-cycle timepoint. 1, 2
• Once stable levels are achieved, monitor every 6–12 months. 1

Monitor hematocrit at each visit—withhold testosterone if hematocrit exceeds 54% and consider dose reduction or phlebotomy. 1

• Injectable testosterone carries a 43.8% risk of erythrocytosis (hematocrit >52%), significantly higher than transdermal preparations (15.4%). 1
• The 200 mg biweekly regimen produces higher average testosterone exposure and is associated with an 8% incidence of hematocrit >54%, compared to 1% with 100 mg weekly—your patient's escalated dose will increase this risk. 5

Monitor PSA in men over 40 years, with urologic referral if PSA increases >1.0 ng/mL in the first 6 months or >0.4 ng/mL per year thereafter. 1

Alternative: Consider Transdermal Testosterone

If dose escalation to 200 mg weekly produces erythrocytosis or supraphysiologic peaks, switch to transdermal testosterone gel 1.62% at 40.5–81 mg daily, which provides more stable day-to-day levels and lower erythrocytosis risk. 1

• Transdermal preparations are favored over intramuscular injections due to stable testosterone levels and reduced hematocrit elevation. 1
• Subcutaneous testosterone enanthate autoinjector (100 mg weekly) is another option that produces lower estradiol and hematocrit than intramuscular cypionate while achieving similar testosterone levels (mean 552 ng/dL). 6

Expected Clinical Outcomes

Small but significant improvements in sexual function and libido (standardized mean difference 0.35) are the primary proven benefits of testosterone therapy. 1

• Little to no effect on physical functioning, energy, vitality, depressive symptoms, or cognition should be expected, even with optimized testosterone levels. 1
• If sexual function does not improve after 12 months despite achieving target testosterone levels of 500–600 ng/dL, discontinue therapy to avoid unnecessary long-term exposure. 1

Critical Pitfalls to Avoid

Do not draw testosterone levels at the peak (days 2–5 after injection), as this will show supraphysiologic levels and lead to inappropriate dose reduction. 1

Do not draw levels at the trough (days 10–14), as testosterone may have returned to baseline, potentially leading to unnecessary dose escalation. 1

Never continue testosterone therapy in men actively seeking fertility—testosterone suppresses spermatogenesis and causes prolonged azoospermia; use gonadotropin therapy (hCG plus FSH) instead. 1