Half-Life of Testosterone Cypionate
The elimination half-life of intramuscular testosterone cypionate is approximately 8 days.
Pharmacokinetic Profile
Testosterone cypionate has a terminal elimination half-life of approximately 8 days when administered via intramuscular injection, according to FDA labeling. 1
After a standard 200 mg intramuscular injection, serum testosterone peaks between days 2–5, then progressively declines to baseline by days 13–14. 2
The mean residence time (the average time testosterone molecules remain in the body) is approximately 21.7 days for a 500 mg dose of testosterone undecanoate, though this differs from cypionate's shorter half-life. 3
Clinical Implications of the 8-Day Half-Life
Because of this 8-day half-life, standard dosing intervals are every 2–4 weeks (most commonly every 2 weeks at 100–200 mg), which allows serum levels to decline toward baseline before the next injection. 1, 4
The relatively short half-life compared to longer-acting esters creates a "roller-coaster" pattern of supraphysiologic peaks (days 2–5) followed by progressive decline to low-normal or subnormal levels by days 10–14. 2, 5
This pharmacokinetic profile explains why weekly dosing (50–100 mg) produces more stable testosterone levels than bi-weekly administration, reducing the magnitude of peak-to-trough fluctuations. 4, 6
Comparison with Other Testosterone Esters
Testosterone enanthate has a nearly identical half-life and pharmacokinetic profile to cypionate, making them clinically interchangeable. 4
Testosterone undecanoate has a much longer terminal elimination half-life of 18.3–23.7 days, allowing for injection intervals of 10–12 weeks once steady state is achieved. 3, 7
Monitoring Considerations Based on Half-Life
For patients receiving testosterone cypionate, testosterone levels should be measured midway between injections (approximately days 5–7 for weekly dosing, or days 7–10 for bi-weekly dosing) to capture representative trough-to-mid-cycle values and avoid the supraphysiologic peak. 5, 4
Peak levels occur 2–5 days post-injection and often exceed the upper limit of normal, while trough levels at days 13–14 may return to hypogonadal range with bi-weekly dosing. 2, 5
Safety Implications of the Short Half-Life
The short 8-day half-life and resulting supraphysiologic peaks are associated with a 43.8% incidence of erythrocytosis with intramuscular testosterone cypionate, compared to only 15.4% with transdermal preparations that provide more stable levels. 5, 6
Elevated blood viscosity from erythrocytosis can exacerbate coronary, cerebrovascular, and peripheral vascular disease, particularly in older adults—a risk directly linked to the peak-trough pattern created by the 8-day half-life. 5