Written by Keen Meds · Reviewed by Licensed Clinical Providers · March 1, 2026
Key Insight: Up to 60% of circulating testosterone is tightly bound to sex hormone-binding globulin (SHBG) and biologically inactive. Only the "free" testosterone fraction, along with the loosely albumin-bound fraction, can actually act on tissue.
When you get a testosterone blood test, the number on the report is total testosterone. Most labs flag a value below 300 ng/dL as low. But total testosterone is not the whole picture -- and in a significant number of men, it is not even the most clinically relevant number. Sex hormone-binding globulin (SHBG) is a protein that binds testosterone tightly and renders it biologically inactive. A man with a total testosterone of 420 ng/dL and high SHBG may have less biologically active testosterone available to his tissues than a man with a total testosterone of 310 ng/dL and low SHBG. This is not theoretical -- it affects real clinical decisions about diagnosis and treatment. Understanding how testosterone is distributed in blood, what SHBG does, and how to interpret the full picture is one of the most useful things a patient can know before discussing lab results with their provider.
How Testosterone Exists in Blood: Three Forms
Testosterone in the bloodstream does not float freely as individual molecules. It circulates bound to carrier proteins. The specific distribution across three fractions determines what is biologically active.
The first and largest fraction is tightly bound to sex hormone-binding globulin (SHBG). Approximately 60% of circulating testosterone is in this state. The binding between testosterone and SHBG is high-affinity -- the protein holds testosterone so firmly that it cannot interact with androgen receptors in tissue. This fraction is biologically inactive.
The second fraction is loosely bound to albumin, the most abundant protein in blood. Approximately 38% of circulating testosterone is albumin-bound. Because albumin's binding is weak and low-affinity, testosterone can dissociate easily from it and become available to tissue. This fraction is considered bioavailable.
The third fraction is truly free testosterone -- unbound to any protein, circulating freely in the aqueous phase of blood. This represents approximately 2% of total testosterone. It is the fraction that most directly diffuses into cells and acts on androgen receptors. Free testosterone is the most biologically potent fraction on a per-molecule basis, though albumin-bound testosterone also contributes meaningfully to bioavailable activity.
Total testosterone is the sum of all three fractions: tightly SHBG-bound (inactive), albumin-bound (bioavailable), and free (active). When a lab reports total testosterone, it is reporting the full sum, including the approximately 60% that cannot act on tissue.
What SHBG Is and What Affects It
Sex hormone-binding globulin is a glycoprotein produced primarily in the liver. Its primary job is to serve as a carrier protein for sex hormones, including testosterone, estradiol, and dihydrotestosterone (DHT). By binding testosterone tightly, SHBG regulates how much biologically active testosterone is available to tissues at any given time.
SHBG levels vary substantially between individuals and are influenced by a range of physiological and pathological factors.
SHBG increases with age. This is one of the reasons why testosterone availability declines more sharply with age than total testosterone measurements might suggest -- SHBG rises as men age, binding more of whatever testosterone the body produces and reducing the free and bioavailable fractions further.
SHBG increases with liver disease. The liver produces SHBG, and liver inflammation or cirrhosis often drives SHBG production upward. Men with liver conditions may have high SHBG masking functional testosterone deficiency.
SHBG increases with hyperthyroidism. Thyroid hormones stimulate SHBG production, so men with elevated thyroid function often have elevated SHBG.
SHBG increases with certain medications, including some statin cholesterol medications and some anticonvulsants. Men on these drug classes should discuss whether SHBG testing is appropriate.
Conversely, SHBG decreases with obesity, insulin resistance, and type 2 diabetes. Men who are significantly overweight often have low SHBG, which means their bioavailable testosterone fraction is higher relative to their total testosterone. This is one reason why a low total testosterone in an obese man may be less clinically symptomatic than the same level in a lean man with elevated SHBG.
When SHBG Changes the Clinical Picture
The clinical importance of SHBG becomes apparent when total testosterone and free testosterone tell different stories.
Consider two men, both with a total testosterone of 380 ng/dL -- a value many labs would report as low-normal, below the 400 ng/dL threshold some clinicians use for concern.
Man A has elevated SHBG of 60 nmol/L. With that much SHBG binding his testosterone, his calculated free testosterone is genuinely low -- potentially below the normal reference range for free testosterone. He has low bioavailable testosterone despite a borderline total level.
Man B has low SHBG of 18 nmol/L. With less SHBG binding his testosterone, his calculated free testosterone is in the normal range. He has adequate bioavailable testosterone despite the same total level as Man A.
These two men have very different clinical realities despite identical total testosterone values. Man A may have genuine functional testosterone deficiency and would benefit from hormonal evaluation and possibly treatment. Man B does not. A total testosterone number alone cannot distinguish them.
The Endocrine Society recommends measuring free or bioavailable testosterone in situations where total testosterone is borderline, where SHBG abnormality is suspected, or where symptoms and total testosterone do not align.
How Free Testosterone Is Measured
Free testosterone can be assessed in two ways. The most accurate method is equilibrium dialysis -- a laboratory technique that physically separates the unbound fraction. This is the reference method but is expensive and not available in all labs.
The more commonly used clinical approach is calculating free testosterone from total testosterone, SHBG, and albumin using a validated mathematical formula. The Vermeulen equation is the most widely accepted formula for this calculation and is what most labs use when they report a "calculated free testosterone." It is a reliable approximation for most clinical purposes, though it is slightly less accurate than equilibrium dialysis in some edge cases.
Some labs offer direct analog immunoassay measurement of free testosterone. This method is generally considered less accurate than equilibrium dialysis or calculated free testosterone and is not recommended by most endocrinology guidelines for clinical decision-making.
Frequently Asked Questions
Should I ask for free testosterone testing, not just total testosterone?
If your total testosterone is borderline (approximately 300 to 450 ng/dL) and you have hypogonadal symptoms, asking your provider about adding free testosterone and SHBG to your panel is clinically appropriate. The Endocrine Society recommends it when SHBG abnormality is suspected or when symptoms and total testosterone do not align. A complete picture includes total testosterone, free testosterone, SHBG, LH, and FSH.
What SHBG level is considered elevated?
Reference ranges vary by lab and age. As a general guideline, SHBG above 40 to 50 nmol/L in middle-aged men is elevated and warrants investigation into the cause and clinical relevance. SHBG tends to rise with age, so an older man's "elevated" SHBG may be expected, but it still reduces his effective testosterone availability.
Does testosterone therapy affect SHBG levels?
Yes. Testosterone therapy tends to lower SHBG over time. This is actually a positive feedback mechanism in some respects: as SHBG decreases, more of the administered testosterone remains in the free and bioavailable fractions rather than being bound and inactivated. This partially explains why some men respond well to TRT at doses that initially look borderline -- the reduction in SHBG amplifies the effective hormone delivery.
If my total testosterone is normal but I have symptoms, can SHBG be the problem?
Yes. This scenario is sometimes called "functional" or "relative" hypogonadism -- total testosterone appears adequate by standard lab ranges, but SHBG is high enough that free and bioavailable testosterone are genuinely reduced. The Endocrine Society acknowledges that in men with symptoms consistent with hypogonadism and normal total testosterone, free testosterone measurement should be performed to rule out this pattern. A clinical provider can interpret whether treatment is appropriate based on the complete hormonal picture and symptom context.
What This Means for Your Treatment Decisions
A total testosterone number is a starting point, not the complete answer. SHBG and free testosterone provide the full picture of how much testosterone is actually available to your tissues. If your results are borderline and you have symptoms, the full panel matters.
Keen Meds connects you with licensed clinical providers for a telehealth evaluation and lab review. If your testosterone is clinically low, you may qualify for Testosterone Spray Rx.
