No, One Injection of Nebido is Not Enough for Testosterone Replacement Therapy
One injection of Nebido (testosterone undecanoate) 1000 mg is insufficient for ongoing testosterone replacement therapy in hypogonadal men. While a single injection can maintain testosterone levels within the normal range for 7-12 weeks, TRT requires continuous treatment with repeated injections to sustain therapeutic benefit 1, 2, 3.
Standard Nebido Dosing Protocol
The FDA-approved and guideline-recommended dosing schedule for Nebido requires multiple injections 1, 4:
- Initial injection: 750-1000 mg intramuscularly
- Second injection: 4-6 weeks after the first dose
- Maintenance injections: Every 10-14 weeks thereafter (typically every 12 weeks)
This translates to approximately 4-5 injections per year for maintenance therapy, compared to 16+ injections annually with conventional testosterone enanthate or cypionate 2, 5.
Pharmacokinetic Rationale
The pharmacokinetics of testosterone undecanoate explain why repeated dosing is essential 6, 2:
- Serum testosterone peaks at the end of the first week after injection (reaching 47.8-54.2 nmol/L)
- Testosterone levels then progressively decline, reaching the lower-normal limit by days 50-60
- Terminal elimination half-life is 18-23 days
- Mean residence time is 21-23 days
Without a second injection at 4-6 weeks, testosterone levels will fall below the therapeutic range by 8-10 weeks, causing recurrence of hypogonadal symptoms 6, 3.
Clinical Evidence for Multi-Dose Regimens
Long-term studies demonstrate that sustained clinical benefit requires ongoing treatment 3, 7:
- In hypogonadal patients with erectile dysfunction, 58% respond to testosterone undecanoate therapy—but only with continued treatment 2
- Improvements in libido, erectile function, metabolic parameters, and quality of life are maintained only with regular injections every 10-14 weeks 7, 4
- Discontinuation of therapy results in return of hypogonadal symptoms as testosterone levels decline 3
Expected Treatment Outcomes with Proper Dosing
When Nebido is administered according to the recommended schedule, patients can expect 4, 8:
- Sexual function: Small but significant improvements (standardized mean difference 0.35)
- Quality of life: Modest improvements, primarily in sexual function domains
- Metabolic benefits: Improvements in fasting glucose, insulin resistance, triglycerides, and HDL cholesterol
- Minimal effects: Little to no benefit for physical functioning, energy, vitality, or cognition
Critical Monitoring Requirements
After initiating Nebido therapy, ongoing monitoring is mandatory 4, 1:
- Testosterone levels at 2-3 months after treatment initiation
- Hematocrit monitoring—withhold treatment if >54%
- PSA monitoring in men over 40 years
- Symptom reassessment at 12 months; discontinue if no improvement in sexual function
Common Pitfall to Avoid
Never assume a single injection constitutes adequate TRT. Hypogonadism is a chronic condition requiring lifelong treatment in most cases 4, 3. A single injection may temporarily normalize testosterone levels for 7-12 weeks, but this does not address the underlying deficiency. Patients must understand that TRT with Nebido requires commitment to regular injections every 10-14 weeks indefinitely to maintain therapeutic benefit 2, 5.
The convenience of Nebido lies in its reduced injection frequency (4-5 times yearly) compared to conventional testosterone esters (26+ times yearly), not in single-dose efficacy 2, 3.