Testosterone Undecanoate 1000 mg IM Dosing Regimen for Hypogonadism
The FDA-approved standard regimen for testosterone undecanoate (Aveed) is 750 mg (3 mL) intramuscularly at initiation, at 4 weeks, then every 10 weeks thereafter 1. However, the 1000 mg formulation commonly used internationally follows a different schedule: 1000 mg at initiation, at 6 weeks, then every 10-14 weeks for maintenance 2, 3.
Initial Dosing Protocol
- First injection: Administer 1000 mg testosterone undecanoate intramuscularly into the gluteal muscle 2, 3
- Second injection: Give at 6 weeks after the first injection 3
- Maintenance injections: Administer every 10-14 weeks thereafter 2, 3
The FDA label for the 750 mg formulation specifies a 4-week interval before the second dose and 10-week maintenance intervals 1, but clinical practice with 1000 mg formulations demonstrates that a 6-week interval before the second injection optimizes pharmacokinetics 3.
Pharmacokinetic Rationale
- Peak serum testosterone levels occur at the end of the first week after injection, reaching 47.8-54.2 nmol/L 4
- Testosterone levels decrease progressively and reach the lower-normal limit by day 50-60 4
- The terminal elimination half-life is approximately 23.7 days for the 1000 mg dose 4
- The second injection at 6 weeks (rather than immediately repeating at longer intervals) produces optimal pharmacokinetics with mean peak testosterone values remaining within normal range and persistence of normal levels for at least 7 weeks 4
Individualized Dosing Adjustments
While most patients (66%) maintain adequate levels with the standard 10-14 week interval 2, adjustments may be necessary:
- Shorten to every 10 weeks if testosterone levels fall below target before the next scheduled injection 3
- Extend to every 14 weeks if testosterone levels remain elevated throughout the dosing interval 3
- At 2 years of treatment, 91% of men receive the standard 1000 mg dose with 66% maintaining the 10-14 week interval 2
Monitoring Requirements
- Measure testosterone levels 2-3 months after treatment initiation and after any dose or interval change 5
- Target mid-normal testosterone values (500-600 ng/dL or 14-17.5 nmol/L) measured as trough levels before the next injection 5, 6
- Once stable on a given regimen, monitor every 6-12 months 5
- Observe patients for 30 minutes post-injection in the healthcare setting to monitor for serious pulmonary oil microembolism (POME) reactions or anaphylaxis 1
Safety Monitoring
- Hematocrit monitoring: Check periodically and withhold treatment if >54%; intramuscular testosterone carries higher erythrocytosis risk (up to 44%) compared to transdermal preparations (3-18%) 5, 7
- PSA monitoring: Check in men over 40 years and adjust treatment if significant increases occur 5
- Prostate examination: Assess for benign prostatic hyperplasia symptoms 5
Clinical Efficacy
- 72% of trough testosterone levels remain in the normal range with testosterone undecanoate therapy 2
- Significant improvements in health-related quality of life occur, with a 21.9% reduction in Aging Male Symptoms scale scores over 48 weeks 8
- The treatment is well-tolerated with 90.5% of men completing 2 years of therapy and only 3.9% discontinuing due to adverse effects 2
Important Caveats
- This long-acting formulation requires only 4-5 injections per year compared to approximately 16 injections annually with conventional testosterone enanthate 3
- The ease of administration makes testosterone undecanoate the preferred therapy for both patients and clinicians over more frequent injection schedules 2
- Absolute contraindications include active male breast cancer and men actively seeking fertility (testosterone suppresses spermatogenesis) 5
- The oral formulation of testosterone undecanoate is specifically contraindicated by the FDA for age-related hypogonadism not associated with structural or genetic etiologies 9