Normal Bioavailable Testosterone in Men in Their 40s
For men in their 40s, bioavailable (non-SHBG-bound) testosterone typically ranges from approximately 2.5 to 9.7 nmol/L (72-280 ng/dL), though this represents tissue-available testosterone rather than total testosterone, which normally ranges from 8.7-31.7 nmol/L (251-914 ng/dL) in this age group. 1
Understanding Bioavailable vs. Total Testosterone
Bioavailable testosterone includes both free testosterone and albumin-bound testosterone—essentially all testosterone available to tissues except that bound to sex hormone-binding globulin (SHBG). 2 This measurement provides a more accurate assessment of physiologically active androgen than total testosterone alone, particularly in men with obesity or conditions affecting SHBG levels. 3
Key Measurement Considerations
Total testosterone in healthy men in their 40s ranges from 8.7-31.7 nmol/L (251-914 ng/dL), representing the 2.5th to 97.5th percentile. 1
Non-SHBG-bound testosterone (bioavailable testosterone) can be measured using 50% ammonium sulfate precipitation, which removes SHBG-bound testosterone and provides a reasonable assessment of tissue-available hormone. 2
The diagnosis of low testosterone should only be made after two total testosterone measurements taken on separate occasions, both conducted in early morning (between 8-10 AM), as testosterone levels naturally fluctuate throughout the day with highest levels in the morning. 4, 5
Clinical Thresholds for Men in Their 40s
Total testosterone below 8.7 nmol/L (251 ng/dL) is considered abnormally low for men in their 40s, corresponding to the 2.5th percentile. 1
The general clinical threshold of total testosterone below 300 ng/dL is used across all adult age groups to support a diagnosis of low testosterone. 4, 5
When total testosterone falls in the "grey zone" between 8-12 nmol/L (231-346 ng/dL), measurement of free or bioavailable testosterone becomes essential for accurate diagnosis. 6
Special Considerations for Canadian Practice
In Canada, total testosterone measurement remains the most cost-effective first-line test and will be sufficient in over 75% of cases for diagnosing hypogonadism. 7
When evaluating low total testosterone in men with obesity, morning serum free testosterone measurement is essential, as obesity-related decreases in testosterone are frequently attributable to low SHBG concentrations, and these men may have normal free testosterone despite low total testosterone. 3, 4
Direct (analog) free testosterone assays are considered unreliable in the clinical context and should be avoided; calculated free testosterone or precipitated bioavailable testosterone are preferred methods. 7
Age-Related Changes in Bioavailable Testosterone
Bioavailable testosterone decreases more significantly with age than total testosterone, making it a more sensitive indicator of androgen deficiency in aging men. 2
While total testosterone peaks around age 19 and falls to approximately 13.0 nmol/L by age 40, there is no evidence for further decline in mean total testosterone after age 40, though variance increases substantially. 8
The decrease in bioavailable testosterone appears to begin by middle age (40s-50s), even when total testosterone and LH levels remain normal. 2
Common Pitfalls to Avoid
Do not rely on single testosterone measurements—two separate early morning measurements are required for accurate diagnosis. 4, 5
Avoid non-fasting or afternoon measurements, as these can significantly underestimate true testosterone levels. 5
Do not use direct free testosterone assays—these are technically unreliable and should not guide clinical decisions. 7
When total testosterone is low-normal but clinical suspicion remains high, measure bioavailable or calculated free testosterone rather than assuming adequacy based on total testosterone alone. 3, 6