What is the recommended route and site of administration for testosterone therapy in a male patient, via intramuscular (IM) injection or subcutaneous (subq) injection?

Testosterone Administration Route and Site for Male Patients

Both intramuscular (IM) and subcutaneous (subQ) injections are effective for testosterone therapy in males, with no significant difference in clinical outcomes between formulations, though subcutaneous administration is increasingly preferred due to ease of self-administration, less discomfort, and comparable efficacy. 1

Route Selection: IM vs SubQ

Intramuscular Administration (Traditional Standard)

• IM injection remains the FDA-approved route for testosterone cypionate and enanthate, with official labeling specifying deep gluteal muscle injection 2
• The American College of Gastroenterology recommends starting doses of 100-200 mg every 2 weeks or 50-100 mg weekly via IM route 3
• Weekly dosing (50-100 mg) provides more stable testosterone levels compared to biweekly administration, reducing fluctuations that may contribute to adverse effects including erythrocytosis and potentially cardiovascular risk 3, 4

Subcutaneous Administration (Emerging Preferred Alternative)

• SubQ injection achieves therapeutic testosterone levels equivalent to IM administration with doses of 50-150 mg weekly (median 75-80 mg), demonstrating effectiveness across a wide BMI range (19.0-49.9 kg/m²) 5
• Serum testosterone levels remain stable between weekly subQ injections, with mean total testosterone of 627 ± 206 ng/dL and free testosterone of 146 ± 51 pg/mL maintained throughout the dosing interval 6
• Among patients who switched from IM to subQ, 91% (20/22) had a marked preference for subQ injections, with none preferring to return to IM 5
• SubQ administration is easier to self-administer, associated with less discomfort, and has potential to improve patient adherence 7
• Minor and transient local reactions occur in only 14% (9/63) of patients receiving subQ testosterone 5

Injection Site Recommendations

For Intramuscular Injections

• Gluteal muscle (upper outer quadrant): FDA-approved site requiring deep IM injection 2
• Anterolateral thigh: Alternative IM site that allows for self-administration 3
• Use 21-23 gauge, 1-1.5 inch needles for IM injection (longer 1.5 inch needles for gluteal, shorter 1 inch for thigh in leaner patients) 3

For Subcutaneous Injections

• Anterior thigh or abdomen: Preferred sites for subQ self-administration 5, 7
• Allows easy self-injection with less discomfort compared to IM 5, 6
• Use appropriate subQ needles (typically shorter than IM needles) 7

Practical Implementation Algorithm

For new patients starting testosterone therapy:

1. Discuss both IM and subQ options with the patient, emphasizing that subQ is easier to self-administer and less painful 5, 7

2. If patient prefers self-administration or has concerns about injection discomfort: Start with subQ route at 50-100 mg weekly in anterior thigh or abdomen 3, 5

3. If patient has assistance for administration or prefers traditional approach: Use IM route at 50-100 mg weekly (gluteal if administered by another person, anterolateral thigh if self-administered) 3, 2

4. Monitor testosterone levels at 2-3 months after initiation, checking midway between injections and targeting mid-normal values (450-600 ng/dL) 3, 4

5. Adjust dose based on serum levels and clinical response, with typical range of 50-150 mg weekly for subQ or 50-200 mg for IM 3, 5

Critical Monitoring Considerations

• Weekly dosing is superior to biweekly dosing regardless of route, providing more stable testosterone levels and potentially reducing cardiovascular risk and erythrocytosis 3, 4
• Injectable testosterone (both IM and subQ) may carry greater cardiovascular risk compared to transdermal preparations, possibly due to fluctuating levels even with weekly dosing 3, 4
• Erythrocytosis occurs more frequently with injectable formulations compared to transdermal options 3
• Once stable levels achieved, monitor every 6-12 months with testosterone levels, hematocrit/hemoglobin, PSA, and digital rectal examination 1, 3, 4

Common Pitfalls to Avoid

• Avoid biweekly dosing when possible: The traditional 100-200 mg every 2 weeks causes excessive testosterone fluctuations; weekly dosing is superior 3
• Don't dismiss subQ route due to lack of FDA approval: While not officially FDA-approved, substantial evidence supports its safety and efficacy, with high patient preference 5, 7, 6
• Don't use testosterone undecanoate subQ: This long-acting formulation must be administered as gluteal IM injection only 3
• Ensure proper needle selection: Use 18-gauge for drawing from vial, then switch to 21-23 gauge for IM injection 3