Optimal Free Testosterone Range in Men
The optimal free testosterone range for adult men is 120-368 pg/mL (415-1274 pmol/L) for men aged 19-39 years, and 66-309 pg/mL (229-1072 pmol/L) for all adult men, measured using standardized equilibrium dialysis. 1
Target Range for Testosterone Replacement Therapy
When treating men with testosterone replacement therapy, the American Urological Association recommends targeting total testosterone levels in the middle tertile of the normal reference range (450-600 ng/dL), which corresponds to free testosterone levels that normalize symptoms while minimizing adverse effects. 2
- The goal is normalization of testosterone levels combined with improvement in symptoms, not simply achieving any particular number 2
- Treatment programs should use minimal dosing necessary to drive testosterone levels to the normal physiologic range 2
- For men on therapy, trough testosterone should be maintained within 300-1,000 ng/dL, though targeting mid-normal values (450-600 ng/dL) is preferred 2, 3
Clinical Context for Men with Mental Health Disorders
Free testosterone measurement becomes particularly important in men with mental health disorders because low free testosterone—even when total testosterone appears normal—is strongly associated with hypogonadal symptoms including depressed mood, fatigue, and decreased psychological energy. 4
- Men with normal total testosterone (≥10.5 nmol/L or ~303 ng/dL) but low calculated free testosterone (<220 pmol/L or ~63 pg/mL) reported significantly more sexual and physical symptoms, including depressed mood, compared to men with both normal total and free testosterone 4
- These men had higher SHBG and LH levels, indicating true androgen deficiency despite "normal" total testosterone 4
- Conversely, men with low total testosterone but normal free testosterone (due to low SHBG from obesity) had normal LH and lacked features of androgen deficiency 4
Diagnostic Thresholds and Gray Zones
The evidence reveals important cutoffs for clinical decision-making:
For free testosterone specifically:
- Free testosterone <220 pmol/L (~63 pg/mL) in the presence of symptoms indicates androgen deficiency requiring treatment consideration 4
- Free testosterone >220 pmol/L (~63 pg/mL) suggests adequate androgen action even if total testosterone is borderline low 4
For total testosterone context:
- Total testosterone <230 ng/dL usually benefits from replacement therapy in symptomatic men 2
- Total testosterone >350 ng/dL typically does not require replacement therapy 2
- Total testosterone 231-346 ng/dL represents a gray zone where free testosterone measurement becomes critical for decision-making 2
Age-Related Considerations
Reference intervals for free testosterone decline with age, but this natural decline does not automatically indicate pathology requiring treatment. 2, 1
- In men 19-39 years: 2.5th percentile is 120 pg/mL and 97.5th percentile is 368 pg/mL 1
- In all adult men: 2.5th percentile is 66 pg/mL and 97.5th percentile is 309 pg/mL 1
- The majority of elderly men maintain testosterone levels in the young adult range, and treatment decisions should be based on symptoms plus biochemical confirmation, not age alone 2
Measurement Methodology Matters
Free testosterone should be measured using equilibrium dialysis or calculated from total testosterone and SHBG using validated algorithms, not direct immunoassays. 1, 5
- Standardized equilibrium dialysis performed for 16 hours at 37°C using undiluted serum provides the gold standard 1
- Direct immunoassays for free testosterone are unreliable and should be avoided 5
- When total testosterone is borderline (7.0-12.5 nmol/L or ~200-360 ng/dL), free or bioavailable testosterone measurement is essential 6, 5
Common Pitfalls to Avoid
Do not rely solely on total testosterone in men with:
- Obesity (low SHBG artificially lowers total testosterone while free testosterone may be normal) 4
- Aging (high SHBG may maintain normal total testosterone while free testosterone is low) 4
- Mental health symptoms (depression and fatigue correlate more strongly with free testosterone than total testosterone) 4
Do not initiate therapy without:
- Two separate morning measurements confirming low testosterone 2
- Presence of hypogonadal symptoms (decreased libido, erectile dysfunction, depressed mood, fatigue, decreased physical stamina) 2
- Assessment of free testosterone when total testosterone is in the 231-346 ng/dL range 2
Monitoring During Treatment
Once on therapy, measure testosterone levels 2-3 months after initiation or dose changes, targeting mid-normal values of 450-600 ng/dL for total testosterone. 2, 3
- For injectable testosterone: measure midway between injections 2
- For transdermal preparations: levels can be measured at any time, with peak values occurring 6-8 hours after application 2
- Once stable, monitor every 6-12 months 2
- If patients fail to improve symptomatically despite reaching target levels, discontinue therapy 2