From the Guidelines
Serum testosterone and free testosterone levels are two different measurements of testosterone in the body, with serum testosterone measuring the total amount of testosterone and free testosterone measuring the biologically active portion. The difference between serum testosterone and free testosterone levels is crucial in evaluating testosterone status, as only free testosterone can bind to receptors in tissues to produce effects like muscle growth, libido, and mood regulation 1. About 98% of testosterone is bound to proteins like sex hormone-binding globulin (SHBG) and albumin, while only 1-2% circulates as free testosterone. Conditions that alter binding protein levels, such as obesity, liver disease, or thyroid disorders, can create situations where total testosterone appears normal while free testosterone is abnormal, or vice versa 1. For this reason, symptoms of testosterone deficiency should prompt testing of both forms, as treatment decisions are best made with complete information about both total and bioavailable hormone levels 1. Key points to consider when evaluating testosterone status include:
- Measuring both total and free testosterone levels provides a more complete picture of hormonal health
- Conditions that alter binding protein levels can affect testosterone measurements
- Symptoms of testosterone deficiency should prompt testing of both total and free testosterone levels
- Treatment decisions should be based on complete information about both total and bioavailable hormone levels. In men with diabetes, mean levels of testosterone are lower compared to age-matched men without diabetes, but obesity is a major confounder 1. Testosterone replacement in men with symptomatic hypogonadism may have benefits, including improved sexual function, well-being, muscle mass and strength, and bone density 1. In summary, measuring both serum testosterone and free testosterone levels is essential in evaluating testosterone status, and treatment decisions should be based on complete information about both total and bioavailable hormone levels.
From the FDA Drug Label
Testosterone in plasma is 98 percent bound to a specific testosterone-estradiol binding globulin, and about 2 percent is free. The main difference between serum testosterone and free testosterone levels is the amount of testosterone that is bound to proteins in the blood.
- Serum testosterone refers to the total amount of testosterone in the blood, including both bound and free testosterone.
- Free testosterone refers to the small amount of testosterone that is not bound to proteins, about 2% of the total testosterone, and is the active form of the hormone that can enter cells and exert its effects. The amount of testosterone bound to proteins, such as sex-hormone binding globulin, determines the distribution of testosterone between free and bound forms, and the free testosterone concentration determines its half-life 2.
From the Research
Difference between Serum Testosterone and Free Testosterone Levels
The main difference between serum testosterone and free testosterone levels is the way they are measured and their clinical significance.
- Serum testosterone refers to the total amount of testosterone present in the blood, including both bound and free testosterone 3.
- Free testosterone, on the other hand, refers to the amount of testosterone that is not bound to proteins in the blood and is available to enter cells and exert its effects 4.
Clinical Significance
- Serum testosterone levels are used to diagnose and monitor conditions such as hypogonadism, a condition where the testes do not produce enough testosterone 5.
- Free testosterone levels are also important in diagnosing and monitoring hypogonadism, as well as other conditions such as polycystic ovary syndrome and hirsutism in women 4.
- The measurement of free testosterone is important because it is the metabolically active fraction of testosterone, and changes in free testosterone levels can have significant effects on the body 4.
Measurement and Variability
- There are different methods available for measuring serum testosterone and free testosterone levels, including immunoassays, equilibrium dialysis, and liquid chromatography-tandem mass spectrometry 3, 4, 6.
- However, there can be significant variability between different measurement methods and kits, particularly for free testosterone levels 6, 7.
- This variability can make it difficult to interpret results and diagnose conditions, highlighting the need for standardized measurement methods and reference ranges 6.
Reference Ranges
- Reference ranges for serum testosterone and free testosterone levels can vary between laboratories and populations, and are often based on limited studies with unknown medical and reproductive histories 6.
- The use of standardized reference ranges and measurement methods is important for accurate diagnosis and monitoring of conditions related to testosterone levels 6.