Calculated Free Testosterone
The Vermeulen Equation, Equilibrium Dialysis, and Direct Assays
Evidence grade 4 of 5, Strong. Read how the Atlas grades evidence.
The written rationale for this grade is still being prepared.
- FDA
- Not applicable (laboratory methodology)
Reference only. Not medical advice.
What can go wrong
A free testosterone value is only as good as its method and the accuracy of its inputs. Direct analog free-T assays can mislead; calculated free T inherits any error in the SHBG or total-T assay; and reference ranges are method-specific. Treatment decisions should not rest on a single questionable free-T result.
This is something to take to a clinician. The Atlas can tell you what is known about calculated free testosterone in general. It cannot tell you what is happening in your body, and the difference matters most for exactly the symptoms that bring people to this page.
Free testosterone can be measured by equilibrium dialysis (a reference method), estimated by mass-action equations such as the Vermeulen formula from total testosterone, SHBG, and albumin, or reported by direct analog immunoassays. Guidelines generally favor equilibrium dialysis or a validated calculation over the cheap direct analog assay, which is widely regarded as unreliable. Each calculation has known biases, particularly at extreme SHBG.
How labs estimate the fraction of testosterone that can actually act, and why the method matters.
What people take it for
What it is taken for. Approval, where it exists, covers only some of these.
How it works
The Vermeulen equation applies the law of mass action to the competition between SHBG (high-affinity) and albumin (low-affinity, high-capacity) for testosterone, solving for the unbound fraction from total T, SHBG, and albumin. Equilibrium dialysis physically separates free from bound hormone and is the comparator against which calculations are judged.
Where the equations disagree
Calculation accuracy depends on SHBG. Reported analyses suggest the Vermeulen formula tends to perform better at higher SHBG and that calculated values can systematically over- or under-estimate dialysis results, with a meaningful fraction of samples deviating beyond acceptable limits regardless of equation. The direct analog immunoassay fares worst. The practical lesson: know which method your lab used before acting on a free-T number.
What has to be monitored
The bloodwork this needs, and the reason it belongs with a clinician rather than a website.
- Total testosterone (ideally LC-MS/MS)
- SHBG
- Albumin (for calculation)
What people get wrong
Often saidAll free testosterone numbers are equivalent
ActuallyNo. Equilibrium dialysis, calculated (Vermeulen), and direct analog immunoassay can give materially different values; the analog assay is the least trustworthy.
Who profits, and who pushes back
Nobody is named here yet, because we have not done that work on this entry. Read that as unfinished. Somebody almost certainly sells this, and somebody almost certainly disputes it. Assume both until we have checked.
Set against the alternatives
Equilibrium dialysis is most accurate but labor-intensive; the Vermeulen calculation is inexpensive and reasonable when SHBG and total T are measured well; the direct analog immunoassay is the least reliable and is discouraged by many guidelines.
At a glance
- Reference method
- Equilibrium dialysis (or ultrafiltration)
- Most common calculation
- Vermeulen equation
- Inputs
- Total testosterone, SHBG, albumin
- Weak method
- Direct analog free-T immunoassay
What this entry does not yet cover
What follows is unfinished work on our side, not a finding about Calculated Free Testosterone. A short entry is not a safe entry.
- Timeline. We have not built the dated record of research and regulatory events.
- Cost and market. We have not documented what it sells for or who sells it.
- Supply chain. We have not mapped where it is made.
- Who uses it. We have not documented the user groups.
- What could change. No forward-looking summary yet.
- Children and teenagers. We have not checked what is known about younger people.
- Where we land. We have not taken a position on this yet.
Sources
The studies below are named and described, but not linked. You cannot open them from here and check our reading against them, which means this page is our summary of the literature rather than a document you can verify. Weigh it accordingly until the links exist.
The studies that matter
Vermeulen et al., critical evaluation of free testosterone estimation1999
Proposed and validated the mass-action calculation against equilibrium dialysis
Comparison of free-T equations vs isotope-dilution equilibrium dialysis2010s
Accuracy differed between equations and by gender and SHBG, with a notable share of samples outside acceptable limits