What is the recommended treatment regimen for an adult male with diagnosed hypogonadism using Nebido (Testosterone Undecanoate) 1000 mg for Testosterone Replacement Therapy (TRT)?

Nebido 1000 mg Treatment Regimen for Testosterone Replacement Therapy

For adult males with confirmed hypogonadism, Nebido (testosterone undecanoate) 1000 mg should be administered intramuscularly with the second injection at 6 weeks, then every 10-12 weeks thereafter, providing superior pharmacokinetic stability compared to shorter-acting formulations. 1, 2

Diagnostic Confirmation Required Before Initiating

• Two separate morning (8-10 AM) total testosterone measurements below 300 ng/dL are mandatory to establish biochemical hypogonadism 3, 1
• Measure serum LH and FSH to distinguish primary from secondary hypogonadism, as this determines fertility preservation options 1
• Free testosterone by equilibrium dialysis should be obtained if total testosterone is borderline or if obesity/diabetes is present 1
• Specific symptoms must be present, particularly diminished libido and erectile dysfunction—symptoms alone without biochemical confirmation are insufficient 3, 1

Standard Nebido Dosing Protocol

The established regimen is 1000 mg intramuscularly, with the second injection 6 weeks after the first, followed by injections every 12 weeks. 2 This schedule reduces annual injections to 4-5 compared to 16 injections yearly with testosterone enanthate 2.

• Individualized adjustment is possible: shorten intervals to every 10 weeks if testosterone levels trend low, or extend to every 14 weeks if levels remain elevated 2
• Nebido provides sustained eugonadal testosterone levels without supraphysiologic peaks or subtherapeutic troughs characteristic of shorter-acting preparations 2

Pre-Treatment Mandatory Assessments

• Baseline hematocrit/hemoglobin must be documented, as hematocrit >54% is an absolute contraindication 1
• PSA level and digital rectal examination in men over 40 years—PSA >4.0 ng/mL requires urologic evaluation before starting 1
• Fertility counseling is mandatory: testosterone therapy causes azoospermia and is absolutely contraindicated in men seeking fertility 3, 1
• Screen for active breast cancer, untreated severe sleep apnea, and recent cardiovascular events within 3-6 months 3, 1

Monitoring Schedule During Treatment

• First testosterone level check at 2-3 months after treatment initiation, targeting mid-normal range (500-600 ng/dL) 1
• Once stable, monitor testosterone levels every 6-12 months 1
• Hematocrit monitoring at each visit—withhold treatment if >54% and consider phlebotomy in high-risk cases 3, 1
• PSA monitoring in men over 40: urologic referral if PSA increases >1.0 ng/mL in first 6 months or >0.4 ng/mL per year thereafter 1

Expected Treatment Outcomes

Testosterone therapy produces small but significant improvements in sexual function and libido (standardized mean difference 0.35), but little to no effect on physical functioning, energy, vitality, depressive symptoms, or cognition. 3, 1

• In hypogonadal patients with erectile dysfunction, 58% respond to testosterone undecanoate alone, with best results in diabetic hypogonadal patients 2
• Metabolic improvements include reduced body fat, improved insulin resistance, and favorable changes in triglycerides and HDL cholesterol 1, 4
• Bone mineral density improves, with lumbar spine BMD increasing 3.2% and femoral neck BMD by 1.4% 5

Absolute Contraindications

• Active desire for fertility preservation—use gonadotropin therapy (hCG plus FSH) instead 3, 1
• Active or treated male breast cancer 3, 1
• Hematocrit >54% 3, 1
• Untreated severe obstructive sleep apnea 1
• Recent cardiovascular events within 3-6 months 1

Critical Clinical Pitfalls to Avoid

Never initiate testosterone therapy in eugonadal men (normal testosterone levels), even if symptomatic—the European Association of Urology strongly recommends against this practice. 3, 1

• Do not diagnose hypogonadism based on symptoms or screening questionnaires alone, as these lack specificity 3
• Never start testosterone without confirming the patient does not desire fertility, as suppression of spermatogenesis can be prolonged 1, 4
• Avoid testing during acute illness, as this artificially lowers testosterone levels 3
• Do not continue therapy indefinitely without reassessing benefit—discontinue if no improvement in sexual function after 12 months 1, 6

Comparative Advantages of Nebido

Nebido provides more stable day-to-day testosterone levels compared to shorter-acting intramuscular preparations (cypionate/enanthate), which peak at days 2-5 and return to baseline by days 10-14 1, 7. This stability may reduce the risk of erythrocytosis compared to conventional injections 1, 7. However, transdermal preparations (gel, patch) remain the preferred first-line formulation per European guidelines due to even greater stability 3, 1.

When to Consider Alternative Formulations

• If cost is the primary concern, testosterone cypionate/enanthate (annual cost $156) is more economical than transdermal gel ($2,135 annually) 1
• For patients preferring convenience and self-administration, transdermal gel may be preferred despite higher cost 1
• For secondary hypogonadism with fertility concerns, gonadotropin therapy (recombinant hCG plus FSH) is mandatory, not testosterone 3, 1