Testosterone Replacement Therapy Threshold
Testosterone replacement therapy should be initiated when two separate fasting morning total testosterone measurements are both below 300 ng/dL, accompanied by symptoms of hypogonadism. 1
Diagnostic Testosterone Thresholds
The diagnostic approach requires understanding specific testosterone level cutoffs:
- Below 230 ng/dL: These symptomatic men typically benefit from testosterone replacement therapy and represent clear-cut hypogonadism 1
- 231-346 ng/dL: This represents a gray zone where a 4-6 month therapeutic trial may be considered in symptomatic men after careful risk-benefit discussion 1
- Above 350 ng/dL: Testosterone levels in this range typically do not require replacement therapy 1
The American Urological Association defines testosterone below 300 ng/dL as the reasonable cut-off to support the diagnosis of low testosterone across all adult age groups. 1
Critical Measurement Requirements
Proper diagnosis demands strict adherence to testing protocols:
- Two separate measurements are mandatory - both must be obtained on different days in the early morning when testosterone levels naturally peak 1
- Fasting morning testosterone levels provide the most accurate assessment 1
- Single random measurements are insufficient and lead to misdiagnosis 1
Common pitfall: Approximately 20-25% of men receiving testosterone therapy do not meet diagnostic criteria, often because proper two-sample morning testing was not performed 1
Required Symptoms for Treatment
Laboratory values alone are insufficient - patients must demonstrate hypogonadal symptoms including:
- Decreased libido and spontaneous erections 1
- Erectile dysfunction 1
- Decreased physical stamina and strength 1
- Depressed mood and fatigue 1
- Increased visceral adiposity 1
- Sleep disturbance and poor concentration/memory 1
The presence of both low testosterone levels AND symptoms is required - testosterone therapy should not be initiated in eugonadal individuals regardless of symptoms 1
Special Considerations for Borderline Cases
Men with "low-normal" testosterone (301-350 ng/dL) who have symptoms may still benefit from therapy:
- These patients may have low bioavailable testosterone not reflected in total testosterone values 2
- Free testosterone measurement should be obtained in obese men, as obesity affects sex hormone-binding globulin levels 1
- Free testosterone below 1.5 ng/dL supports the diagnosis even when total testosterone appears borderline 2
Target Levels After Initiating Therapy
Once treatment begins, monitoring ensures appropriate dosing:
- Target total testosterone in the middle tertile of normal range: 450-600 ng/dL 1
- Measure levels 2-3 months after treatment initiation or dose changes 1
- For injectable testosterone, measure midway between injections targeting mid-normal values (500-600 ng/dL) 1
- Use minimal dosing necessary to achieve the physiologic range of 450-600 ng/dL 1
If patients fail to experience symptomatic relief after reaching target testosterone levels, or remain testosterone deficient despite symptom improvement, testosterone therapy should be stopped. 1