SHBG: Why Total Testosterone Alone Can Mislead
Sex hormone-binding globulin determines how much testosterone is actually available to tissues. Why physicians read it alongside total testosterone, what moves it, and how free testosterone is calculated.
By UAE Peptide Clinic Research Desk
Total testosterone is one of the most requested hormone tests in men's health, and increasingly in women's health too. Yet a single number rarely tells the full story. Most testosterone in the blood is not free to act; it is carried by proteins, and the main carrier is sex hormone-binding globulin, or SHBG. Two people with identical total testosterone can have very different amounts of biologically available hormone depending on their SHBG. This is why independent DHA-licensed physicians who review hormone panels before any protocol usually ask for SHBG alongside the total figure.
What SHBG is and what it does
SHBG is a glycoprotein made mainly in the liver. It binds testosterone and dihydrotestosterone tightly, and oestradiol somewhat less tightly, carrying them through the bloodstream. In men, roughly 40 to 60 percent of circulating testosterone is bound to SHBG, most of the remainder is loosely attached to albumin, and only around 1 to 3 percent circulates free. The free fraction and the albumin-bound fraction together are often called bioavailable testosterone, because albumin releases hormone readily at the tissue level while SHBG does not.
Because SHBG holds hormone out of action, a change in SHBG changes how much testosterone is available even if the testes are producing exactly the same amount. The laboratory total reflects everything, bound and unbound; it cannot distinguish between them.
What moves SHBG up or down
SHBG is unusually responsive to metabolic and endocrine signals, which is part of why physicians find it informative.
- Insulin and body weight: higher insulin levels and central adiposity suppress hepatic SHBG production, so SHBG tends to be low in insulin resistance, type 2 diabetes and obesity. A low SHBG is one of the earlier laboratory signals of metabolic strain.
- Thyroid hormone: thyroxine raises SHBG. Hyperthyroidism is a classic cause of high SHBG, and hypothyroidism can lower it.
- Oestrogen: oral oestrogen, including the combined contraceptive pill, raises SHBG substantially through first-pass exposure in the liver. Transdermal oestrogen has a much smaller effect.
- Age: SHBG rises steadily with age in men, which is one reason total testosterone can look stable while the free fraction declines.
- Liver function: SHBG is synthesised in the liver, so chronic liver disease can push it in either direction; cirrhosis commonly raises it.
- Androgens and growth hormone: exogenous androgens lower SHBG. Research on growth hormone administration has also reported reductions in SHBG, which is one reason physicians monitoring GH-axis protocols may track it over time.
Why the same total can mean different things
Consider two men, both with a total testosterone of 14 nmol/L, a value most laboratories place inside the reference range. The first has an SHBG of 20 nmol/L; the second has an SHBG of 70 nmol/L. The first man has a considerably larger free fraction. The second may have a calculated free testosterone that sits below the range even though his total looks unremarkable. Without SHBG, these two results are indistinguishable on paper.
The reverse also happens. A man with obesity and insulin resistance may have a low total testosterone driven largely by low SHBG, while his free testosterone is closer to the middle of the range. Interpreting the low total as a straightforward production problem would miss the metabolic picture underneath it.
SHBG does not change what the body makes. It changes how much of it is available, and that is the number the tissues respond to.
Calculated versus measured free testosterone
Directly measuring free testosterone by equilibrium dialysis is the reference method, but it is expensive and not widely available. Most clinical laboratories therefore calculate free testosterone from total testosterone, SHBG and albumin using published equations such as the Vermeulen formula. So-called direct free testosterone immunoassays also exist, but several endocrine societies advise against relying on them because of poor agreement with the reference method. If a report shows a free testosterone value, it is worth knowing which method produced it.
Timing matters too. Testosterone follows a morning peak, so samples are typically drawn before 10am, fasting where possible, and an abnormal result is usually repeated on a second morning before any conclusion is drawn. SHBG itself is relatively stable across the day, which makes it a dependable anchor for interpreting the more variable total.
Where this fits in a peptide consultation
SHBG is not a target of peptide therapy, and this article does not suggest any compound for any result. Its value is as context. Many of the pathways that peptide research has examined, including the GH axis, insulin signalling and thyroid function, also happen to move SHBG. A physician reviewing a baseline panel will therefore often read total testosterone, SHBG, calculated free testosterone, fasting insulin, HbA1c and thyroid function together rather than one line at a time, and may retest SHBG during a protocol to see whether the broader metabolic picture is shifting. For women, SHBG is read in the same way alongside total testosterone, with low values prompting attention to insulin resistance and conditions such as polycystic ovary syndrome, and high values often explained by oral oestrogen.
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