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Calculated vs Measured Free Testosterone

Last updated: June 2026

Calculated free testosterone is an estimate of the unbound, biologically active fraction, derived by feeding your total testosterone, SHBG, and albumin into the Vermeulen equation; measured free testosterone comes from physically separating that fraction by equilibrium dialysis and quantifying it on a mass spectrometer. For a typical man with a normal SHBG the two methods agree closely, but they can diverge sharply when SHBG runs very high or very low — which is exactly when free testosterone matters most.

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TL;DR — key takeaways

  • Calculated = a formula. It plugs total T, SHBG, and albumin into the Vermeulen equation. Cheap, fast, and available from any standard blood panel.
  • Measured = a lab method. Equilibrium dialysis with LC-MS/MS is the reference standard, but it is slower, costlier, and offered by few labs.
  • They usually agree when SHBG and albumin are normal — correlation with dialysis is strong.
  • They can diverge at SHBG extremes, because the calculation assumes fixed binding constants and a fixed albumin behaviour that do not hold for everyone.
  • Avoid the old "direct" analog immunoassay for free T — it has been criticised as unreliable.

What each method actually does

The calculated free testosterone (cFT) method never touches the free fraction directly. It applies the law of mass action: testosterone binds tightly to sex hormone-binding globulin (SHBG) and loosely to albumin, and whatever is left over is "free." Given total T, SHBG, and albumin concentrations plus published association constants, the Vermeulen equation solves for the unbound concentration. Because every input comes from a routine panel, cFT is what most clinics report.

The measured free testosterone (mFT) method separates the fractions physically. In equilibrium dialysis, undiluted serum sits across a semipermeable membrane against a buffer that mimics plasma; only unbound testosterone crosses, and at equilibrium the dialysate is quantified by liquid chromatography–tandem mass spectrometry (LC-MS/MS). This is the benchmark, but it is labour-intensive and offered by a handful of reference laboratories.

A third option still lingers on some panels: the direct analog immunoassay. It is cheap but was famously described as "an extraordinarily inaccurate assay," and major guidelines steer away from it. When this guide says "measured," it means equilibrium dialysis, not the analog assay.

Side-by-side comparison

PropertyCalculated (Vermeulen)Measured (equilibrium dialysis)
What it usesTotal T + SHBG + albuminThe physical free fraction
Underlying basisLaw of mass action, fixed binding constantsDirect separation + LC-MS/MS
Cost / availabilityLow; any standard panelHigher; few reference labs
TurnaroundSame as a routine drawSlower (specialist assay)
StatusAccepted algorithm in guidelinesReference standard
Weak pointAssumptions fail at SHBG extremesMethod varies between labs

The 2018 Endocrine Society guideline accepts either an established calculation (from total T, SHBG, and albumin) or equilibrium dialysis — and explicitly steers clinicians away from immunoassay-based free T. Reference ranges are method-specific, so a free T value only means something against the range from the same method.

Why SHBG drives the gap

The single biggest reason calculated and measured free T disagree is SHBG. Hold total testosterone constant and change only SHBG, and the calculated free fraction swings dramatically. The chart below uses a fixed total of 600 ng/dL and albumin of 4.3 g/dL, varying only SHBG.

SHBG (nmol/L) — total T fixed at 600 ng/dL Calc. free T (ng/dL) 17.915 13.430 8.560 6.190

Same total testosterone, free T nearly tripling from the high-SHBG to the low-SHBG end. This is why total T alone can mislead in men with abnormal SHBG — from thyroid disease, liver disease, obesity, or aging — and why a free T value is requested in the first place. It is also where the calculation is most stressed: its fixed binding constants are population averages, not your personal chemistry.

Worked examples

The free-testosterone figures below are outputs of the Vermeulen equation (the same maths the calculator runs); the unit conversions are exact arithmetic you can check by hand.

Example 1 — a typical normal-SHBG man

Total T 600 ng/dL, SHBG 30 nmol/L, albumin 4.3 g/dL.

Vermeulen calculated free T ≈ 13.4 ng/dL, i.e. 13.4 ÷ 600 = 2.2% of total. Here calculated and dialysis-measured values track each other closely.

Example 2 — high SHBG, same total

Keep total T at 600 ng/dL but raise SHBG to 90 nmol/L.

Calculated free T drops to ≈ 6.1 ng/dL (1.0% of total). The total looks healthy; the free fraction is less than half of Example 1. This is the case where you cannot judge status from total T alone.

Example 3 — low total, low SHBG

Total T 350 ng/dL (borderline-low), SHBG 15 nmol/L (low).

Calculated free T ≈ 9.9 ng/dL — higher than Example 2 despite a much lower total, because low SHBG releases more testosterone. A low total does not automatically mean a low free.

Example 4 — ng/dL to pg/mL

Labs often report free T in pg/mL. 1 ng/dL = 10 pg/mL, so 13.4 ng/dL × 10 = 134 pg/mL.

A published dialysis reference interval of 66–309 pg/mL therefore equals 6.6–30.9 ng/dL — check which units and which method your range uses before comparing.

Example 5 — total T ng/dL to nmol/L

To compare with a European report: multiply ng/dL by 0.0347. 600 ng/dL × 0.0347 = 20.8 nmol/L.

The conversion factor is just the reciprocal of testosterone's molar mass (288.4 g/mol) with the dL-to-L adjustment baked in.

Example 6 — the free fraction as a percentage

The "% free" is simply free T ÷ total T. In Example 2 that is 6.1 ÷ 600 = 1.02%; in Example 1, 2.23%.

Healthy men typically sit around 1.5–3% free — a fraction far outside that band is a prompt to re-check SHBG and the method used.

Calculated free testosterone by SHBG (total T = 600 ng/dL)

Vermeulen-equation outputs at a fixed total of 600 ng/dL and albumin 4.3 g/dL. Your own values will differ; confirm against your lab's method-specific range.

SHBG (nmol/L)Calc. free T (ng/dL)Free T (pg/mL)% free
15 (low)17.91792.98%
30 (mid)13.41342.23%
60 (high)8.5851.42%
90 (very high)6.1611.01%

When to prefer measured over calculated

For most men with mid-range SHBG, the calculation is good enough and far more practical. Direct equilibrium dialysis becomes worth the cost and wait when SHBG is markedly abnormal, in significant obesity (where binding behaviour shifts), or when the calculated value clashes with the clinical picture. Conversely, if SHBG and albumin are normal, paying for dialysis rarely changes the answer. The honest summary: calculated free T is an excellent screen, dialysis is the tiebreaker.

How this is calculated

The calculator uses the Vermeulen (1999) closed-form solution. It assumes a SHBG–testosterone association constant of about 1×109 L/mol and an albumin constant of about 3.6×104 L/mol, then solves a quadratic for the unbound concentration given total T, SHBG, and albumin. No step here is medical advice or a lab-validated result — it is the published equation worked transparently, so you can sanity-check a report or understand why two numbers from two methods differ. Binding constants are population averages, which is precisely why the estimate drifts from dialysis at the extremes.

Frequently asked questions

Is calculated free testosterone accurate?

For men with normal SHBG and albumin it correlates well with equilibrium dialysis and is accepted by major guidelines. Its accuracy falls when SHBG is very high or very low, because it relies on fixed average binding constants.

Which is better, calculated or measured free T?

Equilibrium dialysis is the reference standard, so it is "better" in pure accuracy. But calculated free T is cheaper, faster, and accurate enough for most people — reserve dialysis for abnormal SHBG or confusing results.

Why is my free T low when my total is normal?

High SHBG binds more of your testosterone, leaving a smaller free fraction. As Example 2 shows, a healthy-looking total of 600 ng/dL can pair with a free T under half of normal when SHBG is high.

Should I trust a "direct" free testosterone immunoassay?

Generally no. The direct analog immunoassay has long been criticised as unreliable; calculated free T or equilibrium dialysis is preferred.

What units should free testosterone be in?

Commonly pg/mL or ng/dL (1 ng/dL = 10 pg/mL), and sometimes pmol/L. Always compare against a reference range stated in the same units and from the same method.

Sources

  1. Vermeulen A, Verdonck L, Kaufman JM. A Critical Evaluation of Simple Methods for the Estimation of Free Testosterone in Serum (J Clin Endocrinol Metab 1999)
  2. Bhasin S, et al. Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline (J Clin Endocrinol Metab 2018)
  3. Goldman AL, et al. A Reappraisal of Testosterone's Binding in Circulation: Physiological and Clinical Implications (Endocr Rev 2017)
  4. Kacker R, et al. Free testosterone by direct and calculated measurement versus equilibrium dialysis in a clinical population (Aging Male 2013)
  5. Rosner W. An extraordinarily inaccurate assay for free testosterone is still with us (J Clin Endocrinol Metab 2001)
  6. Society for Endocrinology & ACB. Standardising the biochemical confirmation of adult male hypogonadism: a joint position statement (2023, PMC)
  7. Laboratory Assessment of Testicular Function (Endotext, NCBI Bookshelf)

This guide is for general educational purposes only and does not constitute medical advice. Always follow your prescriber’s specific instructions and consult a qualified clinician before changing any protocol.

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