Testosterone Level Threshold for Starting TRT
Testosterone replacement therapy (TRT) should be initiated when total testosterone levels are consistently below 300 ng/dL on at least two separate early morning measurements, combined with symptoms and/or signs of testosterone deficiency. 1, 2, 3
Diagnostic Criteria for Testosterone Deficiency
- The diagnosis of testosterone deficiency requires BOTH low testosterone measurements AND the presence of symptoms and/or signs 1, 2
- Total testosterone threshold of <300 ng/dL (approximately 10.4 nmol/L) is the recommended cut-off by the American Urological Association 1
- At least two separate morning measurements showing consistently low levels are required for diagnosis 1, 2, 3
- Morning measurements (between 8 AM and 10 AM) are critical due to diurnal variation in testosterone levels 2, 3
Symptoms and Signs to Evaluate
- Reduced energy, reduced endurance, diminished work/physical performance 1
- Fatigue, poor concentration, impaired memory 1
- Depression, reduced motivation, irritability 1
- Reduced sex drive and changes in erectile function 1
- For ejaculation or orgasm disorders, testosterone therapy should be considered when total morning testosterone is <300 ng/dL 1
Special Considerations
- For patients with borderline testosterone levels (6.5-13.0 nmol/L), measurement of Sex Hormone-Binding Globulin (SHBG) and calculation of free testosterone is recommended 2
- In men with obesity, bioavailable testosterone measurement is particularly important as they may have low total testosterone due to low SHBG but normal free testosterone levels 3
- Free testosterone by equilibrium dialysis should be frankly low on at least 2 separate assessments in patients with obesity being considered for TRT 1
Common Pitfalls to Avoid
- Relying on a single testosterone measurement for diagnosis 1, 2
- Using calculated free testosterone when SHBG exceeds 170 nmol/L 2
- Failing to collect blood samples in the morning when testosterone levels are highest 2, 3
- Initiating TRT without proper diagnosis - up to 25% of men who receive testosterone therapy do not meet the criteria to be diagnosed as testosterone deficient 1, 3
- Not monitoring testosterone levels after initiating therapy - nearly half of men placed on testosterone therapy do not have their levels checked after therapy commences 1, 3
Monitoring After Initiation
- Testosterone levels should be tested 2-3 months after treatment initiation and/or after any dose change 1
- Once stable levels are confirmed, monitoring every 6-12 months is typically sufficient 1
- Treatment should be discontinued if there is no improvement in sexual function within 12 months 3
Safety Considerations
- TRT has been associated with increased hematocrit and hemoglobin levels 4
- Modest increases in PSA may occur with TRT, but studies suggest little effect on prostate tissue androgen levels and cellular functions in aging men with late-onset hypogonadism 5
- The FDA has required labeling changes to inform about a possible increased risk of heart attack and stroke with testosterone use for age-related hypogonadism 1
By following these evidence-based guidelines for initiating TRT at total testosterone levels consistently below 300 ng/dL with associated symptoms, clinicians can appropriately identify and treat patients with true testosterone deficiency while avoiding unnecessary treatment in those without clear indications.