Hormone Biomarkers: Bioavailable Testosterone in Men

Optimal Takeaways

Bioavailable testosterone represents the amount of circulating free testosterone along with that bound loosely to albumin, which can easily become available. A decrease in bioavailable testosterone is associated with rheumatoid arthritis, hypertension, prostate cancer, and cognitive impairment. High levels may reflect overproduction or over-supplementation with testosterone.

Standard Range: 110 - 575 ng/dL (3.81 - 19.94 nmol/L)

Optimal Dx’s Optimal Range: 375 - 575 ng/dL (13 - 19.94 nmol/L)

Low bioavailable testosterone can be seen with advancing age and can be associated with rheumatoid arthritis, and compromised cognition, memory, and visuospatial function (Bain 2007). Low bioavailable testosterone is also associated with increased risk of hypertension (Yang 2019), and prostate cancer (Bayar 2017).

High bioavailable testosterone may be associated with over-supplementation with testosterone, overproduction of testosterone, or reduced sex hormone binding globulin.

Overview

Bioavailable testosterone (BT) is that portion not bound to sex hormone-binding globulin (SHBG). It may be loosely bound to albumin or circulating freely and unbound (Clapauch 2008). A decrease in BT may be more significant clinically than a decline in total testosterone as it indicates the amount of testosterone readily available for use.

A low BT of 104 ng/dL (3.6 nmol/L) or below was associated with a 4.9-fold greater detection of prostate cancer in men with a high suspicion of the disease. An elevated SHBG of 66.25 nmol/L or above was associated with prostate cancer in this group as well (Garcia-Cruz 2013). In another study of men with prostate cancer, a lower BT of 125 ng/dL (4.3 nmol/L) was associated with a higher grade/severity of cancer (Bayar 2017).

Men with rheumatoid arthritis were found to have lower BT, a common finding in this group. Testosterone has anti-inflammatory properties and is able to suppress immune inflammatory reactions. In a small study of hypogonadal men, 8 out of 13 had some form of rheumatic autoimmune disease, e.g., rheumatoid arthritis, lupus, ankylosing spondylitis, or dermatomyositis), a disease with a prevalence of less than 1% in the general public. In another group of men with rheumatoid arthritis, 33 of 104 had low BT compared with 7 out of 99 controls (Bain 2007).

Low bioavailable testosterone was also associated with increased risk of hypertension in a group of 253 men undergoing routine health checkups. Risk of hypertension was highest with a BT of 127 ng/dL (4.4 nmol/L) and risk was lowest with a BT above 196 ng/dL (6.8 nmol/L) (Yang 2019).

A higher bioavailable testosterone may be indicative of greater metabolic health in men. A number of research studies observe that a higher bioavailable testosterone is associated with increased insulin sensitivity and decreased risk of metabolic syndrome when both testosterone and SHBG were adequate. In fact, researchers note an inverse relationship with total and bioavailable testosterone, SHBG, and prominent risk factors for metabolic syndrome. However, one study found that men who were obese and infertile had significantly lower total testosterone but significantly higher bioavailable testosterone and estradiol, presumably due to significantly lower SHBG (Kasturi 2008).

References

Bain, Jerald. “The many faces of testosterone.” Clinical interventions in aging vol. 2,4 (2007): 567-76. doi:10.2147/cia.s1417

Bayar, Göksel et al. “Low free and bioavailable testosterone levels may predict pathologically-proven high-risk prostate cancer: a prospective, clinical trial.” Turkish journal of urology vol. 43,3 (2017): 289-296. doi:10.5152/tud.2017.35467

Clapauch, Ruth et al. “Laboratory diagnosis of late-onset male hypogonadism andropause.” Arquivos brasileiros de endocrinologia e metabologia vol. 52,9 (2008): 1430-8. doi:10.1590/s0004-27302008000900005

García-Cruz, Eduardo et al. “Higher sex hormone-binding globulin and lower bioavailable testosterone are related to prostate cancer detection on prostate biopsy.” Scandinavian journal of urology vol. 47,4 (2013): 282-9. doi:10.3109/00365599.2012.747562

Kasturi, Sanjay S et al. “The metabolic syndrome and male infertility.” Journal of andrology vol. 29,3 (2008): 251-9. doi:10.2164/jandrol.107.003731

Yang, Qingtao et al. “Association of total testosterone, free testosterone, bioavailable testosterone, sex hormone-binding globulin, and hypertension.” Medicine vol. 98,20 (2019): e15628. doi:10.1097/MD.0000000000015628