Half-Life of Testosterone Cypionate (Depo-Testosterone)
The half-life of testosterone cypionate when injected intramuscularly is approximately 8 days. 1
Pharmacokinetic Profile
The FDA-approved drug label for testosterone cypionate clearly states that the elimination half-life is approximately 8 days following intramuscular injection. 1 This relatively long half-life allows for dosing intervals of 2-4 weeks, as the testosterone esters are absorbed slowly from the lipid phase after intramuscular injection. 1
Clinical Implications of the 8-Day Half-Life
Peak and trough variations are significant with this formulation:
Peak testosterone levels occur 2-5 days after injection, with serum testosterone rising approximately threefold above baseline. 2, 3
Testosterone levels decline progressively, returning to baseline by 10-14 days after injection. 2, 3
Many patients experience supranormal testosterone levels in the first week, followed by subnormal levels in the days before the next injection. 4
Monitoring Recommendations Based on Half-Life
Due to the fluctuating levels inherent to this 8-day half-life, specific timing of blood draws is critical:
Measure testosterone levels midway between injections (typically at 1 week for biweekly dosing), targeting 500-600 ng/dL in the mid-normal range. 5, 2, 6
Initial monitoring should occur at 2-3 months after starting therapy or any dose adjustment. 2, 6
Once stable, monitoring every 6-12 months is sufficient. 2, 6
Clinical Pitfalls Related to the 8-Day Half-Life
The relatively short half-life creates problematic pharmacokinetics:
Patients spend significant time in both supratherapeutic ranges (days 2-7) and subtherapeutic ranges (days 13-14 before next injection). 3
Non-SHBG-bound testosterone can reach several times the upper limit of normal shortly after injection. 3
This "roller coaster" effect is subjectively experienced as disagreeable by many patients. 4
Evidence suggests injectable testosterone may carry greater cardiovascular risk compared to transdermal preparations, possibly due to these wide fluctuations. 6
Comparison to Other Testosterone Formulations
Testosterone undecanoate has a substantially longer half-life:
Terminal elimination half-life of 18-23 days (more than double that of cypionate). 7
Allows for dosing intervals of 10-12 weeks rather than 2 weeks. 7, 4
Provides more stable testosterone levels without the pronounced peaks and valleys. 4
Transdermal preparations avoid the half-life issue entirely by providing continuous absorption and more physiologic, stable day-to-day testosterone levels. 5, 6