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:
→ 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.
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Total testosterone circulates primarily as protein-bound (nearly 50% bound to sex hormone binding globulin (SHBG) and 50% to albumin). Only 2-3% exists in free, biological active form. Testosterone is weakly bound to albumin and can be reversed easily, therefore albumin bound and free testosterone are considered to be bioavailable testosterone.
The highest testosterone level peaks at 30 to 40 years of age in adult men. The levels start to decline steadily after the fourth or fifth decade of adult male life.
The free testosterone test may be used to evaluate infertility, erectile dysfunction, or osteoporosis in men and to evaluate hirsutism, polycystic ovarian disease, and virilization in women. The test may also be used to monitor the efficacy of testosterone-lowering therapies in prostate cancer.
In adult men, testicular or androgen abuse might be suspected if testosterone levels exceed the upper limit of the normal range by more than 50%.
In women, high levels of bioavailable testosterone are consistent with overactive adrenal glands or ovaries (polycystic ovaries).
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In men, low levels of bioavailable testosterone are consistent with primary hypogonadism (testicular impairment) or secondary to a pituitary problem.
Andropause in men (decreased libido, erectile dysfunction, muscle weakness, etc.) is caused by secondary hypogonadism associated with aging.
It is important to determine if low levels of testosterone are due to aging or a pathological disorder.
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