How this instrument works
Most testosterone circulating in blood is bound to two proteins: sex hormone-binding globulin (SHBG), which binds tightly, and albumin, which binds much more loosely. Only a small fraction is truly free and immediately available to tissues. The total measurement counts everything — bound and free together — which is why two people with an identical total reading can have meaningfully different amounts actually free if their SHBG levels differ.
Vermeulen, Verdonck, and Kaufman (1999) derived a way to calculate the free fraction from three routine values: total testosterone, SHBG, and albumin. The method starts from the known binding affinities of the hormone for SHBG and albumin and the mass-balance relationship between bound and free forms, and it reduces algebraically to a single quadratic equation in the unbound concentration. That quadratic is solved directly with the quadratic formula — this is a genuinely closed-form calculation, not an iterative approximation, even though some other free-hormone methods in the literature are iterative.
This calculator uses the association constants from the original 1999 paper: 3.6×10⁴ L/mol for the albumin binding affinity (Ka) and 1×10⁹ L/mol for the SHBG binding affinity (Ks), along with a carrier-protein molecular weight of 69,000 g/mol for albumin and 288.42 g/mol for the hormone itself. These same values are used in the reference calculator hosted by the International Society for the Study of the Aging Male (ISSAM) at issam.ch, built with the involvement of one of the original paper's co-authors, which serves as a useful cross-check on this calculator's output. A small minority of secondary sources online cite a different Ks constant, but that alternate figure could not be traced to any authoritative source, so this calculator uses the better-supported, ISSAM-corroborated values instead.
- Enter total testosterone in ng/dL.
- Enter SHBG in nmol/L.
- Enter albumin in g/dL.
- Read the calculated free testosterone in pg/mL.
Worked example — total T 500 ng/dL, SHBG 30 nmol/L, albumin 4.3 g/dL
A total T of 500 ng/dL, SHBG of 30 nmol/L, and albumin of 4.3 g/dL — a typical adult male profile — converts to a calculated free T of about 111.0 pg/mL once solved through the quadratic.
Lower the total reading to 300 ng/dL but raise SHBG to 60 nmol/L (albumin 4.0 g/dL), and the calculated free amount drops to about 40.3 pg/mL — a bigger relative drop than the total value alone would suggest, because more SHBG locks up a larger share of whatever's present.
Conversely, an 800 ng/dL total reading with a low SHBG of 15 nmol/L (albumin 4.5 g/dL) calculates to about 245.8 pg/mL free — proportionally much more available than the first example, despite starting from a total only 60% higher. This is the core reason the free and total numbers can tell different stories: SHBG changes how much of the total is actually unbound.
Questions
Why not just measure free testosterone directly?
Direct free-hormone assays (typically equilibrium dialysis) are considered a gold standard but are expensive, slow, and not widely available in routine clinical labs. A calculated result from total T, SHBG, and albumin — using an equation like Vermeulen's — is a widely used, far more practical substitute for everyday clinical use, and correlates well with equilibrium dialysis results in most circumstances.
Is the Vermeulen formula iterative or a direct calculation?
It is a direct, closed-form calculation. The relationships between total, bound, and free testosterone reduce algebraically to a single quadratic equation, which is solved exactly with the quadratic formula. No iteration or successive approximation is involved, though some other free-hormone estimation methods described in the literature are iterative.
Where do the association constants (Ka and Ks) in this calculator come from?
They come from the original Vermeulen, Verdonck, and Kaufman (1999) paper: 3.6×10⁴ L/mol for albumin's binding affinity to the hormone, and 1×10⁹ L/mol for SHBG's. These are the same values used in the ISSAM reference calculator at issam.ch, built with the involvement of one of the paper's original co-authors. A different Ks value circulates in a minority of secondary sources, but it could not be traced back to any authoritative origin, so this calculator does not use it.
Why does SHBG matter so much for free testosterone?
SHBG binds testosterone far more tightly than albumin does, so even modest changes in SHBG concentration can noticeably shift how much testosterone stays free. SHBG itself varies with age, thyroid status, liver function, obesity, and other factors, which is part of why two people with the same total testosterone can have meaningfully different free testosterone.
Can this calculator diagnose low testosterone (hypogonadism)?
No. It performs a calculation from values you provide; interpreting whether a result is low, and what to do about it, requires a clinician weighing symptoms, timing of the blood draw (testosterone is typically measured in the morning), repeat testing, and the reference range used by the reporting lab. Treat a calculated result as one input to that clinical conversation, not a standalone diagnosis.
Do total testosterone, SHBG, and albumin need to come from the same blood draw?
Yes, ideally — using values from the same sample, drawn under the same conditions (morning, fasting status consistent with your lab's protocol), gives the most physiologically meaningful result. Mixing values from different days or different physiological states can produce a calculated free testosterone that doesn't reflect any single real moment.
References
- 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;84(10):3666-72.
- PubMed — Vermeulen et al. 1999, PMID 10523012
- ISSAM (International Society for the Study of the Aging Male) — Free & Bioavailable Testosterone Calculator
Read this first: This instrument computes a screening figure from population formulas — it is not a diagnosis, and it cannot see the whole picture a clinician can. Use it to inform a conversation, not to replace one.