From the Guidelines
Total testosterone level is important for assessing hormonal health, but free testosterone is generally considered more clinically relevant. When evaluating testosterone levels, it's essential to consider both total and free testosterone, as they provide different information about hormonal health. Free testosterone represents the biologically active hormone that can enter cells and exert effects on tissues, while total testosterone provides an overall picture of testosterone production and can help identify significant deficiencies 1. According to the American Urological Association (AUA) guideline, a total testosterone level below 300 ng/dL is considered a reasonable cut-off for the diagnosis of low testosterone, and the diagnosis should be made only after two total testosterone measurements are taken on separate occasions in an early morning fashion 1. However, in certain conditions, such as obesity, the relationship between total and free testosterone can be affected, and measuring both values is crucial for comprehensive hormone assessment 1. For example, men with obesity and hypogonadism may have low total testosterone due to low sex hormone-binding globulin, but normal free testosterone levels, highlighting the importance of measuring both values in clinical practice 1. In summary, while total testosterone level is important, free testosterone is generally considered more clinically relevant, and measuring both values provides complementary information for assessing hormonal health. Key points to consider when evaluating testosterone levels include:
- Measuring both total and free testosterone for comprehensive hormone assessment
- Using a total testosterone level below 300 ng/dL as a reasonable cut-off for the diagnosis of low testosterone
- Considering the relationship between total and free testosterone in certain conditions, such as obesity
- Measuring morning serum free testosterone and sex hormone-binding globulin levels in patients with obesity 1.
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. Generally, the amount of this sex-hormone binding globulin in the plasma will determine the distribution of testosterone between free and bound forms, and the free testosterone concentration will determine its half-life The total testosterone level is important as it includes both free testosterone and bound testosterone. However, free testosterone is the biologically active form that determines the half-life and activity of testosterone.
- Free testosterone is the form that binds to receptors and initiates transcription events and cellular changes related to androgen action.
- The total testosterone level is relevant because it can impact the amount of free testosterone available, as the amount of sex-hormone binding globulin in the plasma determines the distribution of testosterone between free and bound forms 2.
From the Research
Importance of Total Testosterone and Free Testosterone
- Total testosterone (TT) and free testosterone (FT) are both important parameters in assessing male hypogonadism, but their significance can vary depending on the context 3.
- Free testosterone is considered a more accurate indicator of androgen deficiency, as it reflects the biologically active form of testosterone that is available to bind with androgen receptors 3.
- Total testosterone, on the other hand, includes both bound and free testosterone, and its levels can be influenced by factors such as sex hormone-binding globulin (SHBG) and albumin 3.
Diagnostic Accuracy of Free Testosterone
- Routine assessment of free testosterone can improve the diagnostic accuracy of functional hypogonadism, especially in men with sexual symptoms 3.
- Free testosterone levels have been shown to correlate with clinical and biochemical parameters of androgen deficiency, such as age, hematocrit, gonadotropins, and symptoms of erectile dysfunction and low libido 3.
- In contrast, total testosterone levels may not always accurately reflect androgen deficiency, particularly in men with borderline total testosterone levels 3.
Treatment Efficacy and Satisfaction
- Both testosterone supplementation therapy and clomiphene citrate have been shown to be effective in improving serum total testosterone levels and alleviating symptoms of hypogonadism 4, 5, 6, 7.
- However, the efficacy of these treatments can vary depending on individual factors, such as age, gonadotropin levels, and the presence of comorbidities 5, 6.
- Patient satisfaction with treatment has been reported to be similar across different treatment modalities, including testosterone injections, gels, and clomiphene citrate 6, 7.