What is the recommended dosage and treatment regimen for testosterone undecanoate (Intramuscular injection) in males with hypogonadism?

Testosterone Undecanoate Dosing for Male Hypogonadism

For intramuscular testosterone undecanoate (Aveed), administer 750 mg (3 mL) at initiation, at 4 weeks, and then every 10 weeks thereafter as the standard maintenance regimen. 1

Diagnostic Confirmation Required Before Initiation

Before starting testosterone undecanoate, you must confirm hypogonadism with two separate morning (8-10 AM) total testosterone measurements below 300 ng/dL on different days, along with specific symptoms of testosterone deficiency, particularly diminished libido and erectile dysfunction. 2, 1

• Measure serum LH and FSH after confirming low testosterone to distinguish primary from secondary hypogonadism, as this has critical treatment implications for fertility preservation. 2
• In men with obesity or borderline values, also measure free testosterone by equilibrium dialysis and sex hormone-binding globulin (SHBG) levels. 2

Standard Dosing Regimen

Loading Phase:

• 750 mg intramuscularly at baseline (week 0) 1
• 750 mg at week 4 1

Maintenance Phase:

• 750 mg every 10 weeks thereafter 1
• Alternative intervals of every 8-14 weeks may be considered based on individual trough testosterone levels, though the FDA-approved standard is every 10 weeks. 3, 4

Administration Requirements

Mandatory observation period: Observe patients in the healthcare setting for 30 minutes after each injection to monitor for serious pulmonary oil microembolism (POME) reactions or anaphylaxis, which can occur after any injection including the first dose. 1

• Inject deeply into the gluteal muscle following usual precautions for intramuscular administration of oily solutions. 1
• Testosterone undecanoate is available only through the Aveed REMS Program due to these serious risks. 1

Monitoring Schedule

Initial monitoring (2-3 months after starting):

• Measure trough testosterone levels (drawn just before the next scheduled injection) targeting mid-normal range of 500-600 ng/dL. 2, 5
• Check hematocrit/hemoglobin and PSA (in men over 40 years). 5

Ongoing monitoring (every 6-12 months once stable):

• Trough testosterone levels before injections 2
• Hematocrit—withhold treatment if >54% as intramuscular testosterone carries higher erythrocytosis risk (14% incidence). 6, 5, 7
• PSA levels and prostate examination for benign prostatic hyperplasia symptoms 5

Expected Pharmacokinetics

Following the week 4 injection and subsequent maintenance doses, testosterone undecanoate produces:

• Mean average serum testosterone of approximately 495 ng/dL during the 10-week dosing interval 8
• Peak levels occurring within the first week (mean 891 ng/dL), with 92% of patients maintaining peak concentrations below 1,500 ng/dL 8
• Trough levels reaching lower-normal range by weeks 10-14, with 72% of trough levels remaining in normal range 7
• Terminal elimination half-life of approximately 21-24 days 9

Dose Interval Adjustments

While the FDA-approved regimen is every 10 weeks, clinical practice allows individualization:

• Shorten to every 8 weeks if trough testosterone levels fall below 300 ng/dL or symptoms return before the next scheduled injection—this increases average testosterone by approximately 11% and trough levels by 10%. 3, 4
• Extend to every 12-14 weeks if trough levels remain consistently above 600 ng/dL. 3
• At 2 years, 91% of men receive the standard 1,000 mg dose with 66% at the standard 10-14 week interval, indicating most patients do well without adjustment. 7

Absolute Contraindications

Do not use testosterone undecanoate in:

• Men with breast cancer or known/suspected prostate cancer 1
• Men actively seeking fertility preservation (testosterone suppresses spermatogenesis and causes azoospermia—use gonadotropin therapy instead) 2, 5
• Women who are pregnant (causes fetal harm) 1
• Known hypersensitivity to testosterone undecanoate, refined castor oil, or benzyl benzoate 1

Realistic Outcome Expectations

Set appropriate expectations with patients:

• Small but significant improvements in sexual function and libido (standardized mean difference 0.35) 6, 2
• Little to no effect on physical functioning, energy, vitality, or cognition even in confirmed hypogonadism 6, 2
• Modest improvements in metabolic parameters including fasting glucose, insulin resistance, triglycerides, and HDL cholesterol 10
• Small reductions in waist circumference and body weight in men with metabolic syndrome 6, 10

Reevaluate at 12 months: If no improvement in sexual function is observed, discontinue testosterone therapy to avoid unnecessary long-term exposure to potential risks without benefit. 2

Critical Safety Considerations

Common adverse effects (≥2%): Acne, injection site pain, PSA increase, estradiol increase, fatigue, irritability, hemoglobin increase, insomnia, and mood swings. 1

Serious risks requiring monitoring:

• Erythrocytosis occurs in 14-25% of patients on intramuscular testosterone, with mean hematocrit increasing from 43.3% to 45.7% over 24 weeks. 6, 7, 8
• PSA increases (mean rise from 1.0 to 1.3 ng/mL over 24 weeks) require monitoring for prostate cancer risk. 8
• Venous thromboembolism (VTE) including deep vein thrombosis and pulmonary embolism have been reported—evaluate patients with suggestive symptoms. 1

Comparison to Alternative Formulations

Testosterone undecanoate offers dramatically reduced injection frequency compared to conventional testosterone esters:

• Approximately 4-5 injections per year with testosterone undecanoate versus 16-26 injections per year with testosterone enanthate or cypionate (every 2-3 weeks). 3
• Provides more stable testosterone levels than short-acting esters, which peak at 2-5 days and return to baseline by 10-14 days. 2
• However, transdermal preparations (gels, patches) remain preferred first-line by some guidelines due to even more stable day-to-day levels, though testosterone undecanoate was the preferred therapy for both patients and clinicians in comparative studies due to ease of administration. 2, 7