What is the recommended dosing regimen for testosterone undecanoate in the treatment of hypogonadism in adult males?

Testosterone Undecanoate Dosing for Hypogonadism

For intramuscular testosterone undecanoate, administer 750-1000 mg at baseline, 4 weeks, then every 10 weeks as the standard maintenance regimen, with trough testosterone levels measured before each injection targeting 500-600 ng/dL. 1

Initial Dosing Protocol

• Start with 750 mg intramuscular injection at baseline (week 0) 2
• Administer second injection at week 4 2, 3
• Begin maintenance dosing at week 14 with injections every 10 weeks thereafter 2, 3

This loading regimen achieves steady-state testosterone levels more rapidly than traditional testosterone esters, with 94% of patients maintaining serum testosterone within the normal range (300-1000 ng/dL) during the dosing interval. 2

Maintenance Dosing Considerations

• The standard 1000 mg dose every 10-14 weeks is effective for 91% of patients at 2 years 3
• For patients with suboptimal trough levels (<300 ng/dL), consider shortening the interval to 8 weeks rather than increasing the dose 4
• An 8-week maintenance regimen increases average testosterone concentration by approximately 11% and improves the percentage of patients maintaining trough levels >300 ng/dL by 10%, with minimal risk of supraphysiologic peaks. 4

The pharmacokinetic profile shows a terminal elimination half-life of 18-24 days, allowing for this extended dosing interval compared to testosterone cypionate or enanthate which require injections every 2-3 weeks. 5

Monitoring Requirements

• Measure trough testosterone levels 2-3 months after treatment initiation and after any dose or interval adjustment 1
• Target mid-normal testosterone values of 500-600 ng/dL measured as trough levels immediately before the next scheduled injection 1
• Once stable on a given regimen, monitor testosterone levels every 6-12 months 6
• Monitor hematocrit periodically and withhold treatment if >54%, as intramuscular testosterone carries higher erythrocytosis risk (14-25% incidence) compared to transdermal preparations 1, 3
• Check PSA in men over 40 years and assess for benign prostatic hyperplasia symptoms 1

Mean hematocrit increases from approximately 43% to 46% over 24 weeks, and PSA increases modestly from 1.0 to 1.3 ng/mL. 2

Dose Individualization Algorithm

If trough testosterone remains <300 ng/dL despite standard dosing:

• First, shorten the dosing interval to 8 weeks while maintaining the 1000 mg dose 4
• Only 9% of patients require dose or interval adjustments beyond the standard regimen 3

If peak testosterone exceeds 1500 ng/dL or hematocrit >54%:

• Extend the dosing interval to 12 weeks 3
• Consider switching to transdermal formulations if erythrocytosis persists 6

Critical Contraindications

• Oral testosterone undecanoate is specifically FDA-contraindicated for age-related hypogonadism not associated with structural or genetic etiologies due to demonstrated blood pressure increases and lack of established efficacy 7, 1
• Absolute contraindications for intramuscular testosterone undecanoate include active male breast cancer and men actively seeking fertility, as testosterone suppresses spermatogenesis and causes azoospermia 1
• For men desiring fertility preservation, gonadotropin therapy (hCG plus FSH) is mandatory instead of any testosterone formulation. 6

Comparative Advantages

• Testosterone undecanoate requires only 4 injections annually compared to 18-26 injections with cypionate/enanthate, improving compliance 8
• Long-term safety data extending to 8 years shows no serious adverse effects specific to this formulation 8
• 72% of trough testosterone levels remain in normal range with testosterone undecanoate compared to 53% with testosterone pellet implants, making it the preferred intramuscular option 3

Common Pitfalls to Avoid

• Never measure testosterone levels at peak (days 4-7 post-injection) - only trough levels before the next injection accurately guide dosing adjustments 1
• Do not increase the dose above 1000 mg - instead shorten the interval if trough levels are inadequate, as higher doses increase erythrocytosis risk without proportional benefit 4
• Do not initiate testosterone undecanoate without confirming both biochemical hypogonadism (two morning testosterone levels <300 ng/dL) and specific symptoms, particularly diminished libido or erectile dysfunction 6
• Recognize that testosterone therapy produces only small improvements in sexual function (standardized mean difference 0.35) and little to no effect on energy, vitality, physical function, or cognition. 7, 6