Can testosterone cypionate be administered subcutaneously for testosterone replacement therapy in adult patients?

Subcutaneous Administration of Testosterone Cypionate

Yes, testosterone cypionate can be administered subcutaneously and is an effective, safe, and increasingly preferred alternative to intramuscular injection, using the same dosing regimens (50-100 mg weekly or 100-200 mg every 2 weeks). 1, 2

Route Equivalence and Efficacy

Both intramuscular (IM) and subcutaneous (subQ) injections achieve therapeutic testosterone levels with no significant difference in clinical outcomes. 1 Subcutaneous administration is increasingly preferred due to:

• Ease of self-administration – Patients can inject into the anterolateral thigh without assistance 1
• Less discomfort – Significantly lower pain scores during and after injection compared to IM 3
• Comparable efficacy – Therapeutic testosterone levels (450-600 ng/dL) are achieved across a wide BMI range (19.0-49.9 kg/m²) with doses of 50-150 mg weekly 1, 4

Critical FDA Labeling Caveat

The FDA-approved label for testosterone cypionate states it is "for intramuscular use only" and "should not be given intravenously," but notably does not mention subcutaneous administration. 5 This represents off-label use, though it is supported by high-quality clinical evidence and current practice guidelines. 1, 2

Dosing Recommendations

Start with 50-100 mg weekly via subcutaneous injection rather than the traditional biweekly IM dosing. 1, 2

• Weekly dosing (50-100 mg) provides more stable testosterone levels and reduces the problematic peaks and valleys inherent to testosterone esters 1, 2
• Biweekly dosing (100-200 mg every 2 weeks) can be used subcutaneously with the same doses as IM, but creates greater fluctuation 2
• These fluctuations may contribute to increased cardiovascular risk by causing extended periods in both supratherapeutic and subtherapeutic ranges 2

Pharmacokinetic Profile

Subcutaneous testosterone maintains stable serum levels between injections:

• Mean total testosterone levels remain 627 ± 206 ng/dL throughout the week with weekly dosing 6
• Mean free testosterone levels remain 146 ± 51 pg/mL between injections 6
• Total testosterone exposure (AUC) is comparable between subcutaneous and IM routes (1.7 vs 1.9 nmol·days/L/mg) 3

Safety Profile Advantages

Subcutaneous testosterone enanthate (a comparable ester) is independently associated with lower post-therapy estradiol and hematocrit compared to IM testosterone cypionate. 7

• Lower estradiol levels reduce gynecomastia risk 7
• Lower hematocrit reduces erythrocytosis risk, which occurs in 43.8% of IM patients vs 15.4% with more stable formulations 8
• Minor and transient local reactions occur in only 9 out of 63 patients (14%) 4
• No significant elevation in PSA or liver enzymes 7

Monitoring Protocol

Measure testosterone levels midway between injections 2-3 months after initiation or dose changes, targeting mid-normal values of 450-600 ng/dL. 1, 2

• For weekly dosing, check levels at any point during the week (levels remain stable) 6
• For biweekly dosing, check at trough (just before next injection) 2
• Once stable levels are confirmed, monitor every 6-12 months 2
• Monitor hematocrit at each visit due to dose-dependent erythrocytosis risk 8

Patient Preference Data

Among 22 patients who switched from IM to subcutaneous testosterone:

• All 22 had a mild (n=2) or marked (n=20) preference for subcutaneous injections 4
• None preferred IM injections 4
• Lower self-reported scores for preinjection anxiety, pain during injection, and postinjection pain 3

Practical Administration

Patients should inject into the subcutaneous tissue of the anterolateral thigh using the same supplies as IM injections:

• 18-gauge needle for drawing from vial 1
• 21-25 gauge, 1-1.5 inch needle for injection (though shorter needles may suffice for subcutaneous) 1
• 1-3 mL syringe 1
• Alcohol prep pads, gauze, bandages, and sharps container 1

Common Pitfalls to Avoid

• Do not assume FDA labeling prohibits subcutaneous use – The label specifies IM and warns against IV, but subcutaneous is well-supported by clinical evidence 5, 4, 6, 3, 7
• Do not continue biweekly dosing without considering weekly – Weekly dosing reduces fluctuations and associated risks 1, 2
• Do not skip hematocrit monitoring – Erythrocytosis remains a risk even with more stable subcutaneous levels 8, 7
• Do not inject into the abdomen – The thigh is the recommended subcutaneous site for testosterone 1