Educational content, not medical advice. Testing and treatment decisions belong with a physician.
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Total, bound and free testosterone
A standard testosterone test reports total testosterone: everything in the sample, bound and unbound. In circulation, roughly half is tightly bound to sex hormone-binding globulin (SHBG), most of the rest is loosely bound to albumin, and only about 1 to 3 percent is free. The free fraction and the albumin-bound fraction together are often called bioavailable testosterone, because albumin releases its testosterone easily in the tissues. The SHBG-bound part is held back.
That is why the same total value can mean different things in two men. If one man has a low SHBG and another a high SHBG, the man with high SHBG has less testosterone available at the same total number.
SHBG rises with age
In the Baltimore Longitudinal Study of Aging, Harman and colleagues (JCEM, 2001) followed men with repeated measurements over decades. Total testosterone fell with age, but the free testosterone index fell faster, because SHBG rose at the same time. By the age of 80, a much larger share of men were low on the free index than on total testosterone.
The European Male Ageing Study (EMAS, Wu et al., NEJM 2010) pointed the same way. In about 3,300 men aged 40 to 79, the authors defined late-onset hypogonadism as three sexual symptoms (fewer morning erections, low libido and erectile problems) together with total testosterone below 11 nmol/L and free testosterone below 220 pmol/L. Free testosterone was part of the definition, not an afterthought. The study is also a reminder that a number without symptoms is not a diagnosis.
The Danish population surveys analysed by Andersson and colleagues (JCEM, 2007) and the Finnish cohort data from Perheentupa (2013) show that both testosterone and SHBG have shifted between generations. A reference range built on yesterday's men does not automatically describe men today.
What raises and lowers SHBG
SHBG is made in the liver and responds to many signals. Higher SHBG is seen with:
- increasing age
- an overactive thyroid
- liver disease, including heavy alcohol use
- estrogen, and some anti-epileptic drugs
- low energy availability, such as hard dieting or a lot of endurance training on too little food
Lower SHBG is seen with:
- overweight and especially abdominal fat
- insulin resistance and type 2 diabetes
- an underactive thyroid
- nephrotic syndrome
- use of anabolic steroids or other androgens
The pattern works in both directions. A man with insulin resistance can have a low total testosterone that is partly explained by a low SHBG, while his free value is less affected. A lean older man can have the opposite: a total value that looks acceptable, with a high SHBG and a free value at the bottom of the range.
How free testosterone is measured or calculated
The reference method for free testosterone is equilibrium dialysis, which is laborious and rarely used outside specialised labs. Most labs therefore calculate free testosterone from total testosterone, SHBG and albumin with the formula described by Vermeulen and colleagues (JCEM, 1999). The calculated value agrees well with dialysis in most men and is the approach recommended in the Endocrine Society guideline (Bhasin et al., JCEM 2018) when total testosterone is borderline or SHBG is likely to be abnormal.
Direct "analogue" immunoassays for free testosterone are a different matter. They are cheap but known to be unreliable, and guidelines advise against using them. If your lab report lists free testosterone, it is worth checking whether it was calculated or measured directly.
Practical: what to measure
A useful first test takes one fasting morning sample, ideally before 10 a.m., because testosterone is highest early in the day:
- Total testosterone
- SHBG
- Albumin, so free testosterone can be calculated
- LH and FSH, to see whether the signal from the brain is low or high
A low or borderline result should be repeated on another morning before any conclusion is drawn. Illness, a bad night, intense training the day before or a period of very low food intake can all push the numbers down temporarily.
The total number alone hides part of the story. Read together with SHBG and with how you actually feel, it becomes much more useful. Whether treatment is relevant is a decision for a doctor who sees the whole picture, not something a single number can answer.
Questions & answers
What is SHBG?
Sex hormone-binding globulin is a protein made in the liver that binds testosterone in the blood. Bound testosterone is not directly available to the tissues.
Why measure SHBG together with testosterone?
Free testosterone is calculated from total testosterone, SHBG and albumin. Without SHBG, a normal total value can hide low free testosterone.
What raises or lowers SHBG?
Ageing, an overactive thyroid, liver disease, some medicines and very low energy intake raise it. Obesity and insulin resistance lower it.