Testosterone, bioavailable

Bioavailable testosterone is an assessment of the biologically active testosterone in serum.

The concentrations of free and bioavailable testosterone are derived from mathematical expressions based on constants for the binding of testosterone to albumin and/or sex hormone binding globulin (SHBG).

Testosterone circulates in the blood in three forms:

1. Nearly half is bound tightly to a protein called SHBG (sex hormone binding globulin). In this form, testosterone is unable to enter cells.
2. The other half is more weakly bound to albumin. In this form, testosterone can eventually detach from albumin and increase the level of biologically active testosterone.
3. A very small fraction called “free testosterone” is not bound to any protein and can therefore freely enter cells and be used by the body.

→ The total quantity of albumin-bound (point 2 above) and free forms (point 3 above) is called “bioavailable testosterone.” 

→ All non-SHBG bound testosterone is considered bioavailable.

→ Total testosterone is the sum of the three forms of testosterone.

In the vast majority of cases, measuring the level of any fraction will provide the required clinical information. However, there are cases in which the total testosterone level is less representative of biological activity. When this happens, free or bioavailable testosterone must be measured.

Regardless of the fraction measured, it should be remembered that testosterone levels vary throughout the day. In young men, these levels can as much as double between a morning and mid-afternoon sample.

Total testosterone:

Generally represents the biological activity of natural or medicinal testosterone at the tissue level

SHBG:

Helps interpret abnormal testosterone levels

Bioavailable testosterone:

Lowered bioavailable testosterone levels are consistent in men with primary hypogonadism or hypogonadism secondary to a pituitary deficiency.

Free testosterone:

Lowered free testosterone levels are consistent in men with primary hypogonadism or hypogonadism secondary to a pituitary deficiency.

Usually, bioavailable (and free testosterone) levels parallel the total testosterone levels. However, a number of conditions and medications are known to increase or decrease the sex hormone-binding globulin (SHBG) concentration, which may cause total testosterone concentration to change without necessarily influencing the bioavailable or free testosterone concentration, or vice versa:

- Treatment with corticosteroids and sex steroids (particularly oral conjugated estrogen) can result in changes in SHBG levels and availability of sex-steroid binding sites on SHBG. This may make diagnosis of subtle testosterone abnormalities difficult.

- Inherited abnormalities in SHBG binding.

- Liver disease and severe systemic illness.

- In pubertal boys and adult men, mild decreases of total testosterone without LH abnormalities can be associated with delayed puberty or mild hypogonadism. In this case, either bioavailable or free testosterone measurements are better indicators of mild hypogonadism than determination of total testosterone levels.

- In polycystic ovarian syndrome and related conditions, there is often significant insulin resistance, which is associated with low SHBG levels. Consequently, bioavailable or free testosterone levels may be more significantly elevated.

References:

Kumar P, Kumar N, Thakur DS, Patidar A. Male hypogonadism: Symptoms and treatment. J Adv Pharm Technol Res. 2010 Jul;1(3):297-301. doi: 10.4103/0110-5558.72420. PMID: 22247861; PMCID: PMC3255409.