Written by: Centre for Men's Health
Total testosterone is often seen as the go-to measure in terms of whether a man is suffering from low testosterone or testosterone deficiency. But it is also important to measure free testosterone – the portion of testosterone not bound up by blood proteins and available for use by the body.
Chief among these is sex hormone binding globulin (SHBG). This does exactly what its name suggests, binding up hormones, in this case testosterone, and making them unavailable for use by body tissues. Sex hormone binding globulin:
- Makes hormones biologically inactive;
- Regulates their availability for use by the body;
- Transports them to target cells;
- Stops them being broken down by the liver and kidneys until they are needed.
Another protein made by the liver and circulating in the blood, albumin, also binds testosterone but less strongly, with bonds that are more easily weakened.
So what is free testosterone?
Free testosterone is the tiny portion (2-5%) that is unbound to proteins like SHBG and albumin and can act on body tissues by binding to androgen receptors.
How do we measure free T?
While free testosterone can be measured directly, it can be calculated reliably using a formula based on levels of total testosterone, SHBG and albumin. Usually the lab will do this for you, but you can do it yourself as well https://www.pctag.uk/testosterone-calculator/ . A simpler way of looking at it is the Free Androgen Index, calculated by dividing your total testosterone level by your SHBG level and then multiplying the result by 100.
A separate measure, bioavailable testosterone, takes account of the fact that the bonds to albumin are comparatively weak and reversible. It is calculated by adding free testosterone to albumin-bound testosterone.
Why does free testosterone matter?
Free testosterone matters because it is possible to have normal levels of testosterone, but if you have high levels of SHBG, your free testosterone may actually be low. For this reason, for example the British Society of Sexual Medicine guidelines for male adult testosterone deficiency suggest treatment may be recommended for patients with Free T below 0.225 nmol/L even if total testosterone levels are within normal ranges.
What is the normal range for free testosterone?
Normal ranges will vary according to the laboratory, but very approximately 0.2 to 0.6 nmol/L is one example.
What impact does age have on free T?
Since SHBG generally increases with age, the normal range for Free T declines as men get older. This can be seen in the chart below. So while total testosterone falls rapidly after 45-50, free testosterone declines far faster and earlier in life.
What affects how much SHBG a man has?
Age is the leading factor in affecting SHBG levels in men. Others that may lead to it being higher include:
- Thyroid disorders;
- Advanced liver diseases like cirrhosis;
- Being underweight;
- Physical inactivity;
- Smoking;
- Low protein intake;
- Medications, including Metformin.
On the other hand SHBG levels may be decreased by:
- Obesity;
- Type 2 Diabetes;
- An underactive thyroid;
- Liver disease, such as non-alcoholic fatty liver disease;
- Steroid use;
- Excess growth hormone;
- High protein or high fat diet;
- Inflammatory cytokines;
- Genetic variation (which can influence SHBG levels either way)
Conclusions
Total testosterone is a key blood test marker, but measuring free testosterone gives a fuller picture of a man’s hormonal health and is essential in diagnosing low testosterone/testosterone deficiency and deciding whether he should have TRT.
References:
A practical guide on the assessment and management of testosteronedeficiency in adult men,
BSSM, 2017
SHBG and total testosterone levels in men with adult onset hypogonadism: what are we overlooking?
Stephen J Winters, Clin Diabetes Endocrinol 2020 Sep 29