Can testosterone be administered subcutaneously (under the skin) every 2 weeks (biweekly)?

Subcutaneous Testosterone Administration Every 2 Weeks

Yes, testosterone can be administered subcutaneously biweekly, using the same dosing regimens established for intramuscular injections (100-200 mg every 2 weeks), though weekly dosing may provide more stable levels and is increasingly preferred. 1, 2

Route of Administration: Subcutaneous vs Intramuscular

Subcutaneous testosterone is an effective and safe alternative to intramuscular injection, achieving comparable serum testosterone levels with similar or lower doses. 3, 4

• Subcutaneous administration results in predictable testosterone levels within the normal male range (300-1,000 ng/dL) when dosed appropriately 3, 4
• In a study of 63 transgender men, all patients achieved normal male testosterone ranges with subcutaneous doses of 50-150 mg (median 75-80 mg), demonstrating effectiveness across a wide BMI range (19.0-49.9 kg/m²) 3
• Pharmacokinetic profiles are comparable between routes, though subcutaneous absorption may be slightly slower than intramuscular 2

Dosing Frequency Considerations

While biweekly dosing is feasible, weekly subcutaneous administration (50 mg weekly) is increasingly favored over biweekly dosing (100-200 mg every 2 weeks) because it reduces the problematic peaks and troughs inherent to testosterone esters. 1, 5

• Both intramuscular and subcutaneous injections produce "fluctuating serum testosterone levels with peaks and valleys" when given biweekly 1
• These fluctuations may contribute to increased cardiovascular risk by causing extended periods in both supratherapeutic and subtherapeutic ranges 1
• Weekly dosing provides more stable serum concentrations with smaller peak-trough fluctuations 5
• A 52-week study demonstrated that weekly subcutaneous testosterone enanthate (dose-adjusted 50-100 mg) maintained steady levels with 92.7% of patients achieving target ranges 5

Practical Implementation

Subcutaneous injection offers significant advantages for self-administration with minimal discomfort and high patient satisfaction. 3, 4

• Among 22 patients who switched from intramuscular to subcutaneous, all preferred subcutaneous (20 marked preference, 2 mild preference), with none preferring intramuscular 3
• Over 95% of patients reported no injection-related pain with subcutaneous administration 5
• Self-administration is easier with subcutaneous route, potentially improving adherence 4
• Minor and transient local reactions occurred in only 9 of 63 patients (14%) 3

Monitoring Protocol

Monitor testosterone levels midway between injections (at trough for biweekly dosing) 2-3 months after initiation or dose changes, targeting mid-normal values of 500-600 ng/dL. 1, 2

• Once stable levels are confirmed, monitoring every 6-12 months is sufficient 1
• The same monitoring approach used for intramuscular injections applies to subcutaneous administration 2
• Dose adjustments should be made based on these trough levels to maintain therapeutic range 1, 5

Common Pitfalls to Avoid

• Don't assume subcutaneous requires different dosing than intramuscular - the same dose ranges (100-200 mg every 2 weeks or 50 mg weekly) are effective for both routes 1, 2
• Don't overlook the cardiovascular concerns with biweekly dosing - the FDA required labeling changes in 2015 regarding possible increased cardiovascular risk, which may be related to the fluctuating levels from less frequent dosing 1
• Don't forget to counsel on injection site reactions - while rare, local reactions can occur and patients should be prepared 3
• Don't measure levels at the wrong time - always measure at trough (midway between injections for biweekly dosing) to avoid misleading peak values 1