Sex Hormone-Binding Globulin (SHBG)

Take-home points

• SHBG regulates the amount of testosterone that is readily available.
• Both low and high SHBG levels can explain symptoms of abnormal testosterone levels, even if the total testosterone level is within the normal range.
• It is important to consult a health professional if you experience symptoms of abnormal testosterone levels.

What is sex-hormone binding globulin?

Sex hormone-binding globulin (SHBG) is a protein made by the liver with a couple of vital bodily functions. First, it binds to and transports sex hormones (such as testosterone) around the body. Second, it helps to control the amount of these sex hormones actively working in the body.

The biological activity of sex hormones is mostly determined by whether they are bound to SHBG, as detailed by the ‘free hormone hypothesis’.¹ For example, on average, approximately 50% of testosterone is readily available (i.e., bioavailable) because it is not bound to SHBG; it is either free or bound to albumin (a diffrent protein that helps transports hormones around the body).² The other 50% of testosterone is bound to SHBG and cannot enter tissues to exert an effect.  

What is the relationship between testosterone and SHBG?

The body tries to balance testosterone and SHBG to keep the amount of bioavailable testosterone within a normal range. If total testosterone or SHBG levels change, then the amount of bioavailable testosterone also changes.  

Potential health issues arise when bioavailable testosterone deviates from normal levels. That is, when SHBG levels are high but total testosterone levels are not. Or when SHBG levels are low but total testosterone levels are not.  

Low SHBG levels are associated with a higher incidence of hypertension, inflammation, insulin resistance, type 2 diabetes, coronary heart disease, stroke, and liver disease.³ On the other hand, high levels of SHBG are associated with certain symptoms of low testosterone, especially when total testosterone levels are already low. These symptoms include infertility, a decreased sex drive, and erectile dysfunction.⁴

Rises in SHBG and slight reductions in total testosterone also explain why bioavailable testosterone levels tend to reduce linearly over the lifespan.⁵ Some reports find that bioavailable testosterone can reduce by 50% by age 75 .⁶

What do SHBG test results mean?

Measuring your SHBG level provides information about how much of your testosterone is active. A healthcare professional usually advises an SHBG test if you have signs and symptoms of having too much or too little testosterone.  

The normal range for SHBG concentrations in adult men is 10 – 57 nanomoles per litre (nmol/L). Therefore, a test score under 10 nmol/L indicates low SBHB, and a test score above 57 nmol/L indicates high SBHB.  

What do I do if my SHBG test results are high or low?

Whether a high or low SHBG level is a potential health concern depends on how your health professional interprets this result alongside your total testosterone levels. As mentioned, if your SHBG levels are high or low, it may suggest you have a health condition causing these abnormal levels. In this case, your healthcare professional will be able to provide you with all the information regarding any treatments and your next steps.  

How to interpret Testosterone Test results? Find out here‍

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References

1. Mendel CM. Endocr Rev 1989;10(3):232-74.

2. Dunn JF et al. J Clin Endocrinol Metab 1981;53(1):58-68.

3. Wang J. Clin Endocrinol Metab 2021;106(10):e3946-e3956.

4. Caldwell JD, Jirikowski GF. Horm Metab Res 2009;41(3):173-82.

5. Fabbri E, et al. J Gerontol A Biol Sci Med Sci 2016;71(9):1202–1209.

6. Vermeulen A, et al. J Clin Endrocrinol Metab 1996;81(5):1821-6.