Half-Life of Intramuscular Testosterone
The half-life of intramuscular testosterone cypionate is approximately 8 days, while testosterone enanthate has a similar duration of action. 1
Pharmacokinetic Profile
The FDA-approved drug label for testosterone cypionate specifies that when injected intramuscularly, the half-life is approximately 8 days. 1 This extended half-life is due to the ester formulation being less polar than free testosterone, allowing for slow absorption from the lipid phase at the injection site. 1
Peak and Trough Timing
- Peak serum testosterone levels occur 2-5 days after intramuscular injection of standard testosterone esters (cypionate/enanthate). 2
- Testosterone levels often return to baseline by 10-14 days after injection, which explains why these formulations are typically dosed every 2-4 weeks. 2, 1
Clinical Implications for Your Patient
Elevated Hematocrit Concerns
Your 45-year-old patient with elevated hematocrit presents a specific concern, as intramuscular testosterone cypionate/enanthate formulations are associated with significantly higher increases in hematocrit compared to other testosterone formulations. 3
- Intramuscular testosterone enanthate/cypionate causes a mean hematocrit increase of 4.0% (95% CI 2.9-5.1%), which is significantly higher than transdermal patches. 3
- Men receiving 200 mg biweekly injections have an 8% risk of hematocrit rising above 54%, compared to only 1% risk with 100 mg weekly injections. 4
- If hematocrit rises above the reference range, you should temporarily withhold testosterone therapy, reduce the dose, or perform phlebotomy. 5, 6
Monitoring Requirements
Given the 8-day half-life and your patient's elevated hematocrit, you must monitor hematocrit/hemoglobin regularly, as erythrocytosis is more common with injectable testosterone formulations compared to topical preparations. 5
- Baseline hematocrit/hemoglobin measurement is mandatory before initiating therapy. 2, 5
- Follow-up visits should occur at 1-2 months initially, then at 3-6 month intervals for the first year, and yearly thereafter. 2
- Blood draws for testosterone level monitoring should account for the timing since last injection—peak levels at 2-5 days versus trough levels at 10-14 days. 2
Alternative Formulations to Consider
Given your patient's elevated hematocrit, subcutaneous testosterone enanthate autoinjector is independently associated with lower post-therapy hematocrit compared to intramuscular testosterone cypionate (p <0.001). 7 This may be a safer option for patients with baseline hematocrit concerns.