What are the differences in definition and normal values between total testosterone and free testosterone in adult men and women?

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Definitions and Normal Values: Total vs. Free Testosterone

Total testosterone measures all testosterone in the blood (bound and unbound), with normal ranges of 300-800 ng/dL in adult men and approximately 15-30 ng/dL in adult women, while free testosterone measures only the biologically active unbound fraction (approximately 2% of total), with normal ranges of approximately 50-200 pg/mL in men and 1-8 pg/mL in women. 1, 2

Total Testosterone: Definition and Normal Values

Total testosterone represents the sum of all testosterone circulating in the bloodstream, including testosterone tightly bound to sex hormone-binding globulin (SHBG), weakly bound to albumin, and the small free fraction. 2

Normal Values for Total Testosterone:

  • Adult Men: 300-800 ng/dL (10.4-27.8 nmol/L) in most laboratories 1

    • Some guidelines use 275-350 ng/dL as the lower threshold 1, 3
    • Values below 300 ng/dL on two separate morning measurements (8-10 AM) indicate hypogonadism 1, 3
  • Adult Women: Approximately 15-30 ng/dL 2

    • Circulating concentrations are approximately 15-25 times lower in women compared to men 2

Clinical Significance:

Total testosterone serves as the initial screening test for hypogonadism in men, but has important limitations. 1, 3 Total testosterone between 280-350 ng/dL is not sensitive enough to reliably exclude hypogonadism, and must exceed 350-400 ng/dL to reliably predict normal free testosterone. 4

Free Testosterone: Definition and Normal Values

Free testosterone represents the unbound, biologically active fraction of testosterone that is not attached to SHBG or albumin—this is the metabolically active form responsible for androgenic effects. 2 Free testosterone accounts for only approximately 2% of total testosterone. 2, 5

Normal Values for Free Testosterone:

  • Adult Men:

    • Approximately 50-200 pg/mL (0.17-0.69 nmol/L) 3
    • Reference range of 0.245-0.785 nmol/L (70-226 pg/mL) has been reported in healthy men aged 20-45 years 5
  • Adult Women:

    • Approximately 1-8 pg/mL 2
    • Significantly lower than men, reflecting the 15-25 fold difference in total testosterone 2

Clinical Significance:

Free testosterone measurement is essential when total testosterone is borderline (280-400 ng/dL), in men with obesity where low SHBG may artificially lower total testosterone, or when SHBG abnormalities are suspected. 1, 3, 4 Men with obesity and hypogonadism who have low total testosterone due solely to low SHBG may have normal free testosterone levels, while a subset will have frankly low free testosterone due to increased aromatization of testosterone to estradiol in adipose tissue. 1

Key Differences Between Total and Free Testosterone

Binding Status:

  • Total testosterone: Includes 98% bound (60% to SHBG, 38% to albumin) and 2% free 2, 5
  • Free testosterone: Only the unbound 2% fraction that is biologically active 2

Measurement Methods:

  • Total testosterone: Direct measurement by immunoassay or LC-MS/MS 6
  • Free testosterone: Best measured by equilibrium dialysis (reference method), though calculated free testosterone using total testosterone, SHBG, and albumin is commonly used in clinical practice 1, 3, 2, 5

Clinical Utility:

  • Total testosterone: First-line screening test, but can be misleading when SHBG is abnormal 1, 4
  • Free testosterone: More accurate reflection of androgen status, particularly in obesity, diabetes, thyroid disease, and when total testosterone is borderline 1, 3, 4, 7

Critical Clinical Pitfalls

Never rely on total testosterone alone when values are between 280-400 ng/dL—free testosterone measurement is mandatory in this range. 4 In men with obesity, low total testosterone may reflect low SHBG rather than true hypogonadism, making free testosterone assessment essential. 1, 3

The free androgen index (total testosterone/SHBG ratio) correlates poorly with calculated free testosterone and over-estimates free testosterone at low SHBG concentrations—it should not be used as a substitute for proper free testosterone measurement. 5

In women with hirsutism or suspected androgen excess, free testosterone has greater diagnostic efficiency than total testosterone and should be measured directly or calculated. 7

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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