What is the optimal time to assess serum testosterone levels in a male undergoing testosterone replacement therapy (TRT) with intramuscular injections of testosterone 200 milligrams (mg) every two weeks?

From the Guidelines

The best time to check testosterone levels for a male on 200mg testosterone replacement therapy every two weeks is at the midpoint between injections, typically 7 days after the last injection, as this timing provides the most accurate representation of average testosterone levels, avoiding both the peak and the trough 1. This approach is supported by the fact that peak serum levels occur 2 to 5 days after injection, and a return to baseline is usually observed 10 to 14 days after injection 1. Some key points to consider when monitoring testosterone levels include:

• Blood should be drawn in the morning between 8-10am when natural testosterone levels are highest
• Consistent monitoring should always be done at the same time of day and at the same point in the injection cycle
• If levels are too high or too low at the midpoint, the healthcare provider may adjust the dosage or recommend splitting the dose into weekly injections for more stable levels 1
• The goal of testosterone therapy is to achieve a total testosterone level in the middle tertile of the normal reference range, which is typically between 450-600 ng/dL 1
• Testosterone therapy should aim to use the minimal dosing necessary to drive testosterone levels to the normal physiologic range, and should be stopped if patients do not experience symptomatic relief after reaching the specified target testosterone levels or remain testosterone deficient in the setting of symptom/sign improvement 1

From the FDA Drug Label

For replacement in the hypogonadal male, 50 to 400 mg should be administered every two to four weeks The best time to check testosterone levels for a male who is taking testosterone replacement 200mg every two weeks is not directly stated in the label.

• Key consideration: The dosage is adjusted according to the patient's response and the appearance of adverse reactions.
• Monitoring: The label does not provide specific guidance on when to check testosterone levels, but it implies that monitoring should be based on the patient's response to the treatment.
• Clinical decision: It is reasonable to check testosterone levels before the next injection, approximately at the end of the dosing interval, to assess the patient's response to the current dose and adjust as needed 2.

From the Research

Monitoring Testosterone Levels

• The best time to check testosterone levels for a male taking testosterone replacement therapy (TRT) is not explicitly stated in the provided studies, but we can look at the timing of measurements in the studies to get an idea.
• In the study 3, measurements were taken at +2 hours and +23 hours after treatment onset, and it was found that serum testosterone levels were significantly lower at +23 hours compared to +2 hours.
• This suggests that testosterone levels may be highest shortly after injection and decrease over time, so it may be best to check levels at the trough (just before the next injection) to ensure that levels are not too low.

Testosterone Replacement Therapy

• The study 3 used a dose of 40 mg/day transdermal 2% testosterone gel, which is different from the 200mg every two weeks mentioned in the question.
• However, the study 4 mentions that injectable testosterone tends to produce the greatest effect on hematocrit, which may be relevant for someone taking 200mg every two weeks.
• The study 5 found that secondary polycythemia (defined as hematocrit ≥52%) increased the risk of major adverse cardiovascular events and venous thromboembolic events in men receiving testosterone therapy.

Timing of Measurements

• Based on the study 3, it may be best to check testosterone levels at two time points: shortly after injection (peak) and just before the next injection (trough).
• This would allow for a more complete understanding of the testosterone levels over time and ensure that levels are not too high or too low.
• However, the exact timing of these measurements is not specified in the studies, and more research may be needed to determine the optimal timing for checking testosterone levels in men taking TRT.