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Bioavailable Testosterone

What is bioavailable testosterone?

Bioavailable testosterone refers to the proportion of testosterone in the blood that is actually available to the body for its biological functions. It consists of free testosterone and testosterone bound to albumin.

In contrast, the proportion bound to sex hormone-binding globulin (SHBG) is very tightly bound and is generally not immediately available to the body's cells.

Since bioavailable testosterone better reflects the actually usable amount of hormone than total testosterone alone, it plays an important role, especially in investigating testosterone deficiency.

What is bioavailable testosterone composed of?

Testosterone circulating in the blood exists in three different forms:

  • free testosterone
  • testosterone bound to albumin
  • testosterone bound to SHBG

Bioavailable testosterone includes:

  • free testosterone
  • albumin-bound testosterone

Since the binding to albumin is relatively loose, this testosterone can easily be made available to the body's cells.

What is the difference between bioavailable and free testosterone?

The terms bioavailable testosterone and free testosterone are often confused, but they describe different proportions of testosterone in the blood.

Free testosterone includes only the very small proportion of the hormone that circulates unbound in the blood. Bioavailable testosterone, on the other hand, includes both free testosterone and the proportion bound to albumin, as this is only loosely bound and is also easily available to the body's cells.

Bioavailable testosterone is therefore always higher than free testosterone and is also considered an important marker of the biologically available proportion of the hormone. Especially with altered SHBG levels, considering free and bioavailable testosterone together can provide additional diagnostic information.

What role does SHBG play?

SHBG (sex hormone-binding globulin) is a transport protein that binds testosterone in the blood.

The higher the SHBG level, the greater the proportion of testosterone that is tightly bound and therefore initially unavailable to the body. This can lead to a deficiency of biologically active testosterone despite normal total testosterone.

Conversely, low SHBG levels often mean that a larger proportion of testosterone is bioavailable.

Therefore, SHBG is often determined together with testosterone when investigating testosterone deficiency.

Why is bioavailable testosterone important?

Bioavailable testosterone indicates how much testosterone is actually available to the target tissues.

This is particularly important when the SHBG level is altered. In such cases, total testosterone may show a normal value even though the biologically available proportion is reduced.

Determining or calculating bioavailable testosterone can therefore help to more accurately assess testosterone deficiency.

When is bioavailable testosterone determined?

It is usually determined as part of an extended hormone diagnostic test.

Typical reasons include:

In many cases, bioavailable testosterone is not measured directly, but calculated using total testosterone, SHBG, and albumin—similar to how free testosterone is calculated using the Vermeulen formula.

What can cause low bioavailable testosterone?

Low bioavailable testosterone can have various causes.

These include, among others:

  • reduced testosterone production
  • elevated SHBG levels
  • primary or secondary hypogonadism
  • age-related hormonal changes
  • certain liver diseases
  • hyperthyroidism

The cause should always be assessed in connection with other laboratory values.

Which laboratory values are assessed together?

To provide a meaningful assessment of bioavailable testosterone, other laboratory values are often taken into account.

These include, in particular:

  • total testosterone
  • free testosterone
  • SHBG
  • albumin
  • LH
  • FSH

Considering these values together allows for a better assessment of the hormonal situation.

Conclusion

Bioavailable testosterone includes free testosterone and testosterone bound to albumin, and describes the proportion of the hormone that is actually available to the body.

Especially with altered SHBG levels, bioavailable testosterone provides important additional information and helps to more accurately assess testosterone deficiency.

 

Sources

Vermeulen, A., Verdonck, L., & Kaufman, J. M. (1999). A critical evaluation of simple methods for the estimation of free testosterone in serum. The Journal of Clinical Endocrinology & Metabolism, 84(10), 3666–3672. https://doi.org/10.1210/jcem.84.10.6079

de Ronde, W., van der Schouw, Y. T., Pols, H. A., Gooren, L. J., Muller, M., Grobbee, D. E., & de Jong, F. H. (2006). Calculation of bioavailable and free testosterone in men: A comparison of 5 published algorithms. Clinical Chemistry, 52(9), 1777–1784. https://doi.org/10.1373/clinchem.2005.063354

Yang, J., Hamilton, C., Robyak, K., & Zhu, Y. (2023). Discrepancies in four algorithms for the calculation of free and bioavailable testosterone. Clinical Chemistry, 69(12), 1429–1431. https://doi.org/10.1093/clinchem/hvad177

Fiers, T., Wu, F., Moghetti, P., Vanderschueren, D., Lapauw, B., & Kaufman, J. M. (2018). Reassessing free-testosterone calculation by liquid chromatography-tandem mass spectrometry direct equilibrium dialysis. The Journal of Clinical Endocrinology & Metabolism, 103(6), 2167–2174. https://doi.org/10.1210/jc.2017-02360

Bhasin, S., Brito, J. P., Cunningham, G. R., Hayes, F. J., Hodis, H. N., Matsumoto, A. M., Snyder, P. J., Swerdloff, R. S., Wu, F. C., & Yialamas, M. A. (2018). Testosterone therapy in men with hypogonadism: An Endocrine Society clinical practice guideline. The Journal of Clinical Endocrinology & Metabolism, 103(5), 1715–1744. https://doi.org/10.1210/jc.2018-00229