T/Free T refers to the ratio of total testosterone (T) to free testosterone (Free T) in the blood. This ratio is used to assess the levels of testosterone that are biologically active and available for use by the body, as opposed to testosterone that is bound to proteins and not readily available. Total testosterone includes all the testosterone in the blood, both bound and unbound, with most of it bound to proteins such as sex hormone-binding globulin (SHBG) and albumin, making it biologically inactive. Free testosterone, on the other hand, is the fraction of testosterone that is not bound to any proteins and is therefore biologically active. This form of testosterone can enter cells and exert its effects on various tissues.
The T/Free T ratio is important because it provides a more accurate picture of the hormonal status and potential clinical conditions than total testosterone alone. For instance, in conditions like hypogonadism, the total testosterone levels might be normal, but the free testosterone levels could be low, indicating a deficiency in biologically active testosterone. Several methods are used to measure free testosterone, including equilibrium dialysis (considered the gold standard but not suitable for routine clinical use), direct immunoassay (which may not be as accurate), calculated free testosterone derived from total testosterone and SHBG concentrations, and the Free Androgen Index (FAI), which is the ratio of total testosterone to SHBG, providing an estimate of free testosterone levels. Accurate measurement of free testosterone is crucial for diagnosing and managing conditions like hypogonadism, polycystic ovary syndrome (PCOS), and other endocrine disorders. Standardization and validation of these measurement methods are essential for reliable clinical assessment.
Further Reading:
- Carlström, K., Gershagen, S., & Rannevik, G. (1987). Free Testosterone and Testosterone/SHBG Index in Hirsute Women: A Comparison of Diagnostic Accuracy. Gynecologic and Obstetric Investigation, 24(4), 256–261. https://doi.org/10.1159/000298811
- El-Eshmawy, M. M., Ibrahim, A., Bahriz, R., Shams-Eldin, N., & Mahsoub, N. (2022). Serum uric acid/creatinine ratio and free androgen index are synergistically associated with increased risk of polycystic ovary syndrome in obese women. BMC Endocrine Disorders, 22(1). https://doi.org/10.1186/s12902-022-01240-y
- Cumming, D. C., & Wall, S. R. (1985). Non-Sex Hormone-Binding Globulin-Bound Testosterone as a Marker for Hyperandrogenism*. The Journal of Clinical Endocrinology and Metabolism, 61(5), 873–876. https://doi.org/10.1210/jcem-61-5-873
- Patil, P., Neevan D'Souza, Ghate, S. D., Lakshmi Nagendra, & Girijashankar, H. B. (2022). Free-androgen Index in Women with Polycystic Ovarian Syndrome: A Meta-Analysis. Journal of Health and Allied Sciences NU, 13(03), 380–388. https://doi.org/10.1055/s-0042-1757445
- Abouroab, A. S., Ismail, S. R., & Marzok, H. F. A. (2021). Free Serum Testosterone Versus Total Testosterone/Estradiol Ratio in Low Sexual Desire in Old Men. The Egyptian Journal of Hospital Medicine, 83(1), 1062–1067. https://doi.org/10.21608/ejhm.2021.160618
- Vermeulen, A., Verdonck, L., & Kaufman, J. M. (1999). A critical evaluation of simple methods for the estimation of free testosterone in serum. The Journal of Clinical Endocrinology and Metabolism, 84(10), 3666–3672. https://doi.org/10.1210/jcem.84.10.6079
- Reinhardt, W., Patschan, D., Pietruck, F., Philipp, T., Janssen, O. E., Mann, K., Friedrich Jockenhövel, & Witzke, O. (2005). Free Androgen Index Is Superior to Total Testosterone for Short-Term Assessment of the Gonadal Axis after Renal Transplantation. Hormone Research in Paediatrics, 64(5), 248–252. https://doi.org/10.1159/000089292