Which testosterone preparation is most appropriate for subcutaneous injection?

Subcutaneous Testosterone: Optimal Formulation

Testosterone enanthate or cypionate are the best preparations for subcutaneous injection, started at 50-100 mg weekly, as these formulations achieve therapeutic testosterone levels equivalent to intramuscular administration with superior tolerability. 1

Recommended Formulations for SubQ Administration

• Testosterone enanthate and testosterone cypionate are equally effective for subcutaneous injection, with both demonstrating dose-proportional pharmacokinetics and steady serum testosterone profiles when dosed weekly 1, 2

• Testosterone undecanoate is NOT recommended for subcutaneous use as it must be administered as gluteal intramuscular injection only, despite one research study showing technical feasibility 1

Dosing Protocol for SubQ Testosterone

• Start at 50-100 mg weekly via subcutaneous injection, which provides more stable testosterone levels compared to biweekly intramuscular dosing 1

• Dose range of 50-150 mg weekly is effective across a wide BMI range (19.0 to 49.9 kg/m²), with median effective dose of 75-80 mg in clinical studies 1, 2

• Target mid-normal testosterone levels of 450-600 ng/dL measured midway between injections at 2-3 months after initiation or dose adjustment 1

Clinical Advantages of SubQ Route

• SubQ injection achieves therapeutic testosterone levels equivalent to IM administration with no significant difference in total testosterone exposure (mean AUC 1.7 vs 1.9 nmol·days/L/mg) 3

• Superior tolerability compared to IM injection, with lower patient-reported scores for pre-injection anxiety, pain during injection, and post-injection pain 3

• Easier self-administration using shorter needles (typically 27-gauge, five-eighths inch) compared to the 21-23 gauge, 1-1.5 inch needles required for IM gluteal or thigh injections 1, 4

• 92.7% of patients achieve target testosterone levels (300-1,100 ng/dL) with dose-adjusted subcutaneous testosterone enanthate, with more than 95% reporting no injection-related pain 5

Injection Technique and Sites

• Abdomen and thigh are appropriate subcutaneous injection sites for testosterone, though specific anatomical guidance is limited in current guidelines 1

• Use smaller gauge needles (27-gauge, five-eighths inch) which are adequate for subcutaneous administration of testosterone in oil-based vehicles 4

• Minor and transient local reactions occur in approximately 14% of patients (9 out of 63) but do not typically require discontinuation 2

Monitoring Requirements

• Measure testosterone levels at 2-3 months after initiation or any dose change, checking midway between injections and targeting 450-600 ng/dL 1

• Monitor hematocrit/hemoglobin at each visit, as injectable testosterone (including SubQ) carries risk of erythrocytosis, though weekly dosing reduces this risk compared to biweekly administration 1

• Once stable levels achieved, monitor every 6-12 months including testosterone, hematocrit, PSA (if age-appropriate), and lipid profiles 1

Critical Safety Considerations

• Weekly SubQ dosing produces more stable testosterone levels than biweekly IM dosing, which reduces adverse effects including erythrocytosis and potentially cardiovascular risk 1

• Erythrocytosis occurs in 43.8% with IM injections versus 15.4% with transdermal preparations, though specific SubQ rates are not well-defined; weekly dosing mitigates peak supraphysiological levels 1

• No clinically significant hepatotoxicity occurs with injectable testosterone enanthate or cypionate, as these formulations bypass first-pass hepatic metabolism and are not 17-α-alkylated 1

Common Pitfalls to Avoid

• Do not use testosterone undecanoate subcutaneously in routine practice, as it is FDA-approved only for gluteal IM injection despite one research study showing technical feasibility 1, 6

• Do not assume SubQ requires different total weekly doses than IM administration; the same 50-100 mg weekly starting dose applies to both routes 1, 2

• Do not forget to prescribe appropriate supplies: 27-gauge needles for SubQ (not the 21-23 gauge, 1-1.5 inch needles used for IM), 1-3 mL syringes, alcohol prep pads, and sharps container 1