Two men can have the same total testosterone and very different amounts of it available to their tissues. The difference is SHBG — a carrier protein that binds testosterone tightly enough to take it out of circulation, biologically speaking. Understanding that gap is the difference between a lab result that answers your question and one that misleads you.
Testosterone circulates in three states
Testosterone does not travel through blood as free molecules. It circulates bound to carrier proteins, in three fractions:
Tightly bound to SHBG. Sex hormone-binding globulin binds testosterone with high affinity. While bound, it cannot interact with androgen receptors in tissue.
Loosely bound to albumin. Albumin's grip is weak, so testosterone dissociates from it readily and remains available to tissue.
Free. Unbound to any protein. Only about 1% to 4% of circulating testosterone is in this state.[1]
Free plus albumin-bound is usually described as the bioavailable fraction — the portion that can actually reach tissue. Total testosterone, the number on your lab report, is the sum of all three, including the SHBG-bound portion that cannot act.
A caution on the numbers: the exact percentage split is quoted inconsistently, because it depends on an individual's SHBG concentration and because the underlying model is contested. A 2017 review in Endocrine Reviews argued that the conventional assumptions about testosterone-SHBG binding — the stoichiometry, the dynamics, the affinity — "are not supported by published experimental data," and proposed a multistep model with allosteric regulation instead.[1] Treat any precise-sounding percentage you see quoted for this with some suspicion, including on other sites.
What moves SHBG
SHBG is a glycoprotein made mainly in the liver, and its level varies substantially between men.
Rises with: age, liver disease, hyperthyroidism, and some medications including certain anticonvulsants.
Falls with: obesity, insulin resistance, and type 2 diabetes.
The age effect matters most for interpretation. SHBG climbs as men get older, binding a larger share of whatever testosterone is produced — which means bioavailable testosterone can decline faster with age than total testosterone alone suggests.
When SHBG changes the answer
Take two men who both test at a total testosterone of 380 ng/dL.
The first has high SHBG. More of his testosterone is bound and inactive, so his calculated free testosterone may land below the reference range. He may have a genuine functional deficiency despite a total that reads as merely low-normal.
The second has low SHBG. Less of his testosterone is bound, so his free testosterone can sit comfortably in range. Same total, adequate bioavailable hormone.
Total testosterone alone cannot separate these two men. This is why Endocrine Society guidance recommends measuring free or bioavailable testosterone when total testosterone is near the diagnostic threshold, when an SHBG abnormality is suspected, or when symptoms and total testosterone disagree.[2]
How free testosterone gets measured — and which methods to trust
Equilibrium dialysis physically separates the unbound fraction. It is the reference method, and it is expensive and not universally available.
Calculated free testosterone derives the value from total testosterone, SHBG, and albumin. The Vermeulen equation is the standard formula. Its authors found it to be "a rapid, simple, and reliable index of bioavailable T, comparable to" equilibrium dialysis and suitable for routine clinical use.[3] This is what most labs report as "calculated free testosterone."
Direct analog immunoassay measures free testosterone directly, and is the one to be wary of. The same evaluation found direct immunoassays and the Free Androgen Index unreliable, with values that shifted depending on SHBG concentration — the exact variable you are trying to see through.[3]
If a panel reports free testosterone, it is worth knowing which of these produced the number.
Frequently asked questions
Should I ask for free testosterone as well as total? It is reasonable when your total is near the threshold and you have symptoms, or when the symptoms and the total do not line up. Guidance supports adding free or bioavailable testosterone in exactly those situations.[2] A fuller panel typically also includes SHBG, LH, and FSH.
What counts as a high SHBG? Reference ranges vary by laboratory and by age, so the lab's own range is the one that matters. Because SHBG rises with age, a value that reads high for a younger man may be unremarkable for an older one — while still reducing his bioavailable testosterone.
My total testosterone is normal but I have symptoms. Can SHBG explain that? It can. High SHBG can leave free and bioavailable testosterone genuinely reduced while total testosterone still reads as adequate, which is why free testosterone measurement is recommended when symptoms and total testosterone disagree.[2] Whether that pattern warrants treatment is a clinical judgment, not a number.
Does testosterone therapy change SHBG? Testosterone therapy tends to lower SHBG over time, which shifts more of the circulating hormone into the free and bioavailable fractions.
Reading your results with the full picture
A total testosterone value is a starting point. If it is borderline and you have symptoms, SHBG and free testosterone are what turn an ambiguous number into an interpretable one.
Keen connects you with a licensed clinical team for a telehealth consultation and lab review. If your testosterone is clinically low, treatment is Keen Testosterone Spray Rx — a once-daily topical spray powered by Hypospray® transdermal delivery.
Related reading: why testosterone declines with age — rising SHBG is one of the three mechanisms — plus low libido after 40 and low testosterone and fatigue.
References
3 sources
- Goldman AL, Bhasin S, Wu FCW, et al. A Reappraisal of Testosterone's Binding in Circulation: Physiological and Clinical Implications. Endocr Rev. 2017;38(4):302–324. doi:10.1210/er.2017-00025 · PMID 28673039
- Bhasin S, Brito JP, Cunningham GR, et al. Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2018;103(5):1715–1744. doi:10.1210/jc.2018-00229 · PMID 29562364
- 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):3666–3672. doi:10.1210/jcem.84.10.6079 · PMID 10523012
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