Bound, loosely bound, and free
Testosterone does not travel alone. Roughly half of what circulates is bound tightly to sex hormone-binding globulin (SHBG); most of the remainder is loosely bound to albumin; and only about 1–3% circulates unbound. "Free testosterone" is that small unbound fraction. "Bioavailable testosterone" is the free fraction plus the loosely albumin-bound fraction.
Because the SHBG-bound share is large and tightly held, changes in SHBG move free testosterone without necessarily moving total testosterone. That is the mechanism behind the most common confusing pattern on a TRT panel: a total testosterone that looks unremarkable next to a free testosterone that does not.
Why two men with the same total T are not in the same place
Give two men an identical total testosterone of, say, mid-range on the same report. If one has high SHBG and the other low, the unbound fraction differs — and the fraction is what tissues see. This is why clinicians order free testosterone when the total number and the clinical picture disagree, and why SHBG belongs on the panel next to it rather than as an afterthought.
It is also why comparing your numbers with someone else's is close to meaningless, even before assay differences enter the picture.
Three ways free testosterone gets reported
| Method | How it works | What to know |
|---|---|---|
| Equilibrium dialysis | Physically separates the unbound fraction before measurement. | The reference method. Slower and more expensive, so it is not the default everywhere. |
| Calculated (Vermeulen) | Derived from total testosterone, SHBG and albumin using published binding constants. | Vermeulen and colleagues concluded that free testosterone calculated from total testosterone and immunoassayed SHBG "appears to be a rapid, simple, and reliable index of bioavailable T", suitable for clinical routine — with pregnancy as a stated exception. |
| Direct analog immunoassay | Measures the free fraction directly with a tracer-based immunoassay. | Widely available and widely criticised for poor agreement with dialysis at the extremes. Check which method produced your number before comparing it with anything. |
The practical rule is the same one that governs every other marker: compare like with like. A calculated result and a direct-analog result are not two points on one trend line. Switching method starts a new series.
What changes SHBG
SHBG is not a fixed personal constant. Factors clinicians weigh when a value looks unusual include age, thyroid status, liver disease, insulin resistance and obesity, significant caloric restriction, oral oestrogen exposure and certain medications. Some of those push SHBG up and some push it down.
The reason this belongs in a tracking guide rather than a treatment guide: an SHBG that has moved changes how every testosterone number on the panel should be read. If your free testosterone shifted while total testosterone did not, SHBG is the first place a clinician will look — and a documented trend for both is more useful than a single pair of values. Note too that high-dose biotin supplements can interfere with immunoassays, SHBG platforms included, which the FDA has documented.
Tracking free T and SHBG together
Three habits make this readable: pick one laboratory and one method and stay with them; put SHBG on the same requisition as total and free testosterone so the pair is always dated together; and record the position in your injection interval, because free testosterone rises and falls with total testosterone across the interval. Timing conventions are covered in the lab timing guide.
TRT AI keeps total testosterone, free testosterone and SHBG on one timeline with the protocol underneath, so the question "did my free T actually change, or did my SHBG?" has an answer that does not depend on memory.
Common questions
Is calculated free testosterone accurate enough?
Vermeulen and colleagues found the calculation from total testosterone and immunoassayed SHBG to be a rapid, simple and reliable index of bioavailable testosterone, suitable for clinical routine. Equilibrium dialysis remains the reference method, and your clinician decides which is appropriate for your case.
Why is my free testosterone low when my total is normal?
The usual explanation is SHBG — a high SHBG binds more of the total, leaving a smaller unbound fraction. Assay method and draw timing also contribute. It is a pattern worth showing your clinician with SHBG values attached, not a diagnosis.
Can I lower my SHBG?
SHBG responds to a range of clinical factors, and changing it is not a self-directed project. If SHBG is distorting your panel, that is a conversation for the clinician managing your therapy.