What is the recommended protocol for initiating testosterone injectable therapy in an adult male with confirmed low testosterone, including evaluation, dosing (100 mg weekly or 200 mg biweekly), needle gauge and length, injection site, and monitoring schedule?

Testosterone Injectable Therapy Protocol for Adult Males with Confirmed Hypogonadism

Diagnostic Confirmation Required Before Initiating Therapy

You must obtain two separate fasting morning total testosterone measurements (8–10 AM) both showing levels < 300 ng/dL to establish biochemical hypogonadism. 1, 2 A single measurement is insufficient due to diurnal variation and assay variability. 1

After confirming low testosterone, measure serum LH and FSH to differentiate primary (elevated gonadotropins) from secondary (low/normal gonadotropins) hypogonadism, as this distinction is critical for treatment selection and fertility counseling. 1, 2

Testosterone therapy is indicated only when both biochemical criteria are met AND the patient has diminished libido or erectile dysfunction. 3, 1, 2 Do not prescribe for fatigue, low energy, mood disturbances, or physical function complaints—these show little to no improvement with therapy. 3, 1

Pre-Treatment Baseline Testing

Before initiating testosterone injections, you must document:

• Hematocrit/hemoglobin – therapy is absolutely contraindicated if hematocrit > 54% 1, 4
• PSA and digital rectal exam for men ≥ 40 years; PSA > 4.0 ng/mL requires urologic evaluation and negative prostate biopsy before starting therapy 1, 4
• Confirm the patient does not desire current or future fertility – testosterone causes prolonged azoospermia; men seeking fertility require gonadotropin therapy (hCG ± FSH) instead 1, 2, 4
• Fasting glucose/HbA1c to exclude diabetes 1
• TSH to rule out thyroid dysfunction 1

Injectable Testosterone Dosing Protocol

The FDA-approved dosing for testosterone cypionate is 50–400 mg intramuscular every 2–4 weeks. 5 In clinical practice:

• Standard regimen: 100–200 mg intramuscular every 2 weeks 1, 6
• Alternative: 50–100 mg weekly for more stable levels 1
• Target serum testosterone: 500–600 ng/dL (mid-normal range) 1, 2, 6

Injection Technique

Administer deep intramuscular injection into the gluteal muscle. 5 Do not give intravenously. 5 Warm and shake the vial if crystals have formed during storage. 5

Needle Specifications

While specific gauge and length are not mandated in guidelines, standard practice uses:

• 21–23 gauge needle
• 1.5 inch length for gluteal injection in most adults 7

Monitoring Schedule

Initial Phase (First Year)

At 2–3 months after initiation:

• Measure serum testosterone midway between injections (days 5–7 for weekly dosing, days 7–10 for bi-weekly) 1, 6
• Check hematocrit/hemoglobin 1, 6, 4
• Measure PSA in men ≥ 40 years 1, 6
• Assess clinical response, particularly sexual function 1, 6

Every 3–6 months during year one:

• Repeat testosterone level (mid-interval timing) 1, 6
• Hematocrit monitoring 1, 6
• PSA measurement 1, 6
• Digital rectal examination 1, 6

Long-Term Monitoring (After First Year)

Every 6–12 months once stable:

• Testosterone level 1, 6
• Hematocrit 1, 6
• PSA and digital rectal exam 1, 6
• Symptom reassessment 1, 6

Critical Safety Thresholds

Withhold testosterone immediately if hematocrit rises > 54% and consider therapeutic phlebotomy in high-risk patients. 1, 4 Injectable testosterone carries a 44% risk of erythrocytosis compared to 15% with transdermal preparations. 1

Refer to urology if:

• PSA increases > 1.0 ng/mL within first 6 months 1, 6
• PSA rises > 0.4 ng/mL per year thereafter 1, 6
• Palpable prostate nodule or induration develops 1, 4

Expected Clinical Outcomes

You should counsel patients that testosterone therapy produces:

• Small but significant improvement in sexual function and libido (standardized mean difference 0.35) 3, 1, 2
• Little to no effect on physical functioning, energy, vitality, depressive symptoms, or cognition 3, 1, 2
• Modest quality of life improvements, primarily in sexual function domains 1, 2

Discontinue therapy at 12 months if there is no improvement in sexual function, as continued treatment without benefit exposes the patient to unnecessary risks. 3, 1, 6

Cost Considerations

Intramuscular testosterone is significantly more economical than transdermal formulations (approximately $156/year vs. $2,135/year), with similar clinical effectiveness. 3, 1 This makes injectable therapy the preferred option when cost is a concern. 3

Critical Pitfalls to Avoid

• Never initiate therapy without confirming the patient does not desire fertility – testosterone causes prolonged, potentially irreversible azoospermia 1, 2, 4
• Never diagnose hypogonadism on a single testosterone measurement – two morning values are required 1, 2
• Never draw testosterone levels at peak (days 2–5) or trough (days 13–14) – measure mid-interval to assess average exposure 1
• Never omit LH/FSH testing after confirming low testosterone – this guides therapy selection 1, 2
• Never continue therapy indefinitely without symptom reassessment – discontinue if no benefit after 12 months 3, 1, 6