From the Guidelines
Bioavailable testosterone and free testosterone are distinct measurements of testosterone, with bioavailable testosterone being more clinically relevant as it represents all testosterone that can be readily used by tissues. The difference between these two measurements is crucial in understanding testosterone's role in the body. Free testosterone refers only to testosterone molecules that are completely unbound to any proteins in the bloodstream, accounting for about 2-3% of total testosterone 1. On the other hand, bioavailable testosterone includes both free testosterone and testosterone that is bound to albumin protein, which is approximately 35-40% of total testosterone. However, it does not include testosterone bound to sex hormone-binding globulin (SHBG), which is tightly bound and unavailable for use.
Key points to consider:
- Bioavailable testosterone is a more comprehensive measure of usable testosterone in the body.
- Free testosterone is a smaller subset of bioavailable testosterone.
- The measurement of bioavailable or free testosterone is particularly important in conditions where SHBG levels might be abnormal, such as diabetes, as noted in the standards of medical care in diabetes-2018 1.
- In men with diabetes who have symptoms or signs of hypogonadism, measuring morning total testosterone and considering free or bioavailable testosterone levels, especially when total testosterone is near the lower limit, can provide a more accurate assessment of testosterone availability and guide treatment decisions 1.
Given the information from the standards of medical care in diabetes-2018 1, it's clear that understanding the difference between bioavailable and free testosterone is vital for the accurate diagnosis and treatment of hypogonadism, particularly in men with diabetes. Therefore, when evaluating testosterone levels, especially in clinical contexts like diabetes, measuring bioavailable testosterone is considered more informative because it reflects the total amount of testosterone available for use by the body's tissues.
From the FDA Drug Label
Testosterone in plasma is 98 percent bound to a specific testosterone-estradiol binding globulin, and about two percent is free Generally, the amount of this sex-hormone binding globulin (SHBG) in the plasma will determine the distribution of testosterone between free and bound forms, and the free testosterone concentration will determine its half-life Testosterone esters are less polar than free testosterone
The main difference between bioavailable testosterone and free testosterone is not explicitly stated in the provided drug labels. However, it can be inferred that:
- Free testosterone refers to the 2% of testosterone that is not bound to any proteins in the blood.
- The concept of bioavailable testosterone is not directly mentioned, but it is generally understood to refer to the fraction of testosterone that is available to bind to androgen receptors, which includes both free testosterone and testosterone that is bound to albumin (a protein that can release testosterone to tissues). Since the labels do not provide a clear distinction between bioavailable and free testosterone, no definitive conclusion can be drawn 2, 3.
From the Research
Definition of Bioavailable and Free Testosterone
- Bioavailable testosterone refers to the fraction of testosterone that is available to bind with androgen receptors, including both free testosterone and testosterone bound to albumin [(4,5)].
- Free testosterone, on the other hand, is the fraction of testosterone that is not bound to any protein in the blood and is therefore available to enter cells and bind with androgen receptors [(4,6)].
Difference Between Bioavailable and Free Testosterone
- The main difference between bioavailable and free testosterone is that bioavailable testosterone includes both free testosterone and testosterone bound to albumin, whereas free testosterone only includes the unbound fraction 4.
- Bioavailable testosterone is considered a better indicator of the amount of testosterone available to the body's tissues, as it takes into account both free and albumin-bound testosterone 5.
Measurement of Bioavailable and Free Testosterone
- Accurate measurement of total and free testosterone is essential for making the diagnosis of androgen disorders 6.
- Bioavailable testosterone can be measured by calculating the fraction of testosterone that is not bound to sex hormone-binding globulin (SHBG) 4.
- Free testosterone can be measured directly using techniques such as liquid chromatography tandem mass spectrometry 6.