Target Testosterone Level in Testosterone Replacement Therapy (TRT)
The recommended target for testosterone replacement therapy is a total testosterone level in the middle tertile of the normal reference range, specifically 450-600 ng/dL (15.6-20.8 nmol/L). 1
Target Ranges and Monitoring
- The American Urological Association recommends targeting total testosterone levels in the middle tertile of the normal reference range (450-600 ng/dL or 15.6-20.8 nmol/L) as the goal for testosterone replacement therapy 1
- The FDA-approved testosterone products recommend adjusting dosage based on pre-dose morning serum testosterone concentrations, with a target range of 350-750 ng/dL (12.1-26.0 nmol/L) 2
- Testosterone levels should be tested 2-3 months after treatment initiation and/or after any dose adjustment to ensure target levels are being achieved 1
- Once stable levels are confirmed on a given dose, monitoring every 6-12 months is typically sufficient 1
Dose Adjustment Guidelines
- For injectable testosterone: measure levels midway between injections, targeting a mid-normal value (500-600 ng/dL or 17.3-20.8 nmol/L) 1
- For transdermal preparations: levels can be measured at any time, with the understanding that peak values occur 6-8 hours after application 1, 3
- Dose adjustments should follow these criteria 2:
- If pre-dose morning total serum testosterone > 750 ng/dL (26.0 nmol/L): Decrease daily dose
- If pre-dose morning total serum testosterone is 350-750 ng/dL (12.1-26.0 nmol/L): No change in dose
- If pre-dose morning total serum testosterone < 350 ng/dL (12.1 nmol/L): Increase daily dose
Clinical Considerations and Pitfalls
- The diagnosis of low testosterone should only be made after two total testosterone measurements are taken on separate occasions, both conducted in early morning 1
- Many men receive testosterone therapy without proper diagnosis - studies estimate that up to 25% of men who receive testosterone therapy do not meet the criteria to be diagnosed as testosterone deficient 1
- Nearly half of men placed on testosterone therapy do not have their testosterone levels checked after therapy commences 1
- Treatment programs should use the minimal dosing necessary to drive testosterone levels to the normal physiologic range 1
- If patients do not experience symptomatic relief after reaching the specified target testosterone levels, testosterone therapy should be stopped 1
Formulation-Specific Considerations
- Transdermal testosterone preparations (gel, patch) show less fluctuation in testosterone levels compared to injectable forms 1, 4
- Injectable testosterone may produce supraphysiological peak concentrations (mean 71 nmol/L or 2048 ng/dL) 24-48 hours after injection, followed by a decline to baseline over 2-3 weeks 5
- Testosterone gel applications can show marked variability both between subjects and within the same subject on different occasions 3, 6
- When using transdermal gels, serum testosterone levels can be significantly lower at +23 hours compared to +2 hours after application, with many patients falling below target range by the end of the dosing period 3
Safety Considerations
- Exogenous testosterone therapy should not be prescribed to men who are currently trying to conceive 1
- Testosterone therapy should not be commenced for a period of three to six months in patients with a history of cardiovascular events 1
- The FDA requires labeling to inform healthcare professionals and patients of a possible increased risk of heart attack and stroke with testosterone preparations used to treat age-related hypogonadism 1
- Dihydrotestosterone (DHT) levels should be monitored as they can become elevated, particularly with certain formulations like transdermal gels 6, 4
By maintaining testosterone levels within the recommended range of 450-600 ng/dL (15.6-20.8 nmol/L), clinicians can optimize the benefits of testosterone replacement therapy while minimizing potential risks.