When a man gets his testosterone tested and the result comes back low, there is a natural follow-up question that his physician may or may not think to ask: is that low total testosterone number telling us the full story?
It often isn’t.
Testosterone in the bloodstream doesn’t travel alone. Roughly 40–45% of it is tightly bound to a protein called sex hormone binding globulin (SHBG). Another 50–55% is loosely bound to albumin. Only about 1–3% circulates as “free” testosterone — the fraction that is not bound to any protein and can move freely into cells and exert its biological effects.
When we talk about “free testosterone” or “bioavailable testosterone,” we’re talking about this unbound fraction plus the loosely albumin-bound fraction. The tightly SHBG-bound testosterone is effectively inactive from a tissue perspective — it cannot enter cells, cannot bind to androgen receptors, cannot do the things testosterone does.
In obesity, this binding system gets disrupted in a way that is simultaneously predictable, complicated, and clinically important.
What Insulin Resistance Does to SHBG
SHBG is produced by the liver. Its production rate is sensitive to several hormonal signals, one of the most powerful of which is insulin. Elevated insulin — the central feature of insulin resistance, which is nearly ubiquitous in moderate to severe obesity — suppresses hepatic SHBG production.
The effect is substantial. Men with insulin resistance or type 2 diabetes typically have significantly lower SHBG levels than metabolically healthy men of comparable age. A 2014 review by Grossmann and colleagues documented that moderate obesity is predominantly associated with reductions in total testosterone, with this effect largely mediated by the insulin-driven suppression of SHBG.
Here is where it gets counterintuitive: if SHBG is the binding protein that “sequesters” testosterone in an inactive form, then lower SHBG should, in theory, increase the proportion of testosterone that is free and biologically active. This is mathematically true in the short term, and some clinicians have observed that in mildly overweight men with slightly low total testosterone, free testosterone can appear normal or even high-normal on initial testing.
But this apparent compensation is misleading for two reasons.
First, it is temporary and incomplete. As obesity progresses and the HPT axis becomes more suppressed (through the aromatase, inflammatory cytokine, and leptin mechanisms discussed in the previous post), total testosterone production falls. Lower SHBG shifts a higher proportion of a smaller total — and eventually, even free testosterone declines. In men with BMI above 35 kg/m², both total and free testosterone are typically reduced compared to lean controls.
Second, SHBG itself has biological functions beyond simply binding testosterone. SHBG appears to interact directly with cell receptors and may have signaling properties independent of its carrier function. A man with very low SHBG is not simply a man with “more available testosterone” — he is a man with a disrupted hormonal transport system that may affect tissue testosterone delivery in ways that total and free testosterone measurements don’t fully capture.
Visceral Fat vs. Subcutaneous Fat: Not All Fat Is Equal
One of the more important insights from the obesity-testosterone literature is that where fat is stored matters as much as how much is stored. Visceral adipose tissue (VAT) — the fat that accumulates around the internal organs, in the mesentery and omentum, contributing to the “belly fat” appearance of central obesity — is metabolically distinct from subcutaneous adipose tissue (SAT), the fat deposited under the skin.
VAT is more metabolically active. It has higher rates of lipolysis (fat breakdown releasing free fatty acids into portal circulation), higher aromatase activity relative to tissue volume, and a higher density of inflammatory macrophages. VAT is more strongly correlated with insulin resistance, metabolic syndrome, cardiovascular risk, and — specifically relevant here — HPT axis suppression than subcutaneous fat.
This distinction matters clinically because body mass index (BMI) does not differentiate between fat types or distributions. A man with a BMI of 28 who carries most of his excess weight as subcutaneous abdominal fat has a different metabolic and hormonal profile than a man with the same BMI whose excess fat is predominantly visceral. Waist circumference, and particularly waist-to-hip ratio, are better proxies for VAT burden than BMI alone.
Multiple studies have shown that waist circumference predicts testosterone levels more accurately than BMI in men of comparable body weight. The European Male Aging Study documented significant negative correlations between waist circumference and testosterone levels across its 3,000+ person cohort. Waist circumference is also a better predictor of metabolic syndrome components — the insulin resistance, dyslipidemia, and hypertension that compound the hormonal picture.
The “Normal Free Testosterone” Trap
For clinicians interpreting testosterone panels in obese men, this creates a diagnostic challenge that is worth naming explicitly.
A moderately obese man in his late 40s presents with symptoms consistent with hypogonadism — low energy, reduced libido, difficulty maintaining muscle mass, increased abdominal fat. His total testosterone comes back at 320 ng/dL — technically above most laboratory cutoffs for hypogonadism (which commonly use 300 ng/dL as a threshold). His SHBG, if measured, is low. His free testosterone, if calculated or measured directly, may appear normal.
A superficial reading of these labs says: “testosterone is normal.” But what the labs actually show is: a suppressed HPT axis producing reduced total testosterone, with the proportion of free testosterone artificially elevated by insulin-resistance-suppressed SHBG, resulting in a free testosterone number that masks the total hormonal deficiency.
The 2014 Grossmann review noted that in moderate obesity, free testosterone levels may remain within the reference range even when total testosterone is reduced, precisely because of this SHBG dynamic — and that this creates underestimation of the extent of hormonal disruption in moderately obese men.
The practical implication: in obese men with symptoms of hypogonadism, total testosterone alone is an insufficient diagnostic workup. SHBG measurement, free testosterone calculation or direct measurement, and clinical symptom assessment all contribute to a complete picture.
The Baseline Problem
This diagnostic complexity also means that interpreting lab results in obese hypogonadal men who start TRT requires some care. As fat mass decreases — either from lifestyle change, pharmacotherapy with GLP-1 agonists, or bariatric surgery — SHBG will tend to rise. A man who begins TRT with low SHBG and an apparently normal free testosterone may, as he loses weight, see SHBG normalize upward. His total testosterone will also change as his endogenous production changes, his body composition changes, and his insulin sensitivity improves.
In other words, the hormonal picture in an obese man on TRT who is also actively losing weight is not static. It requires monitoring at appropriate intervals, with adjustments to dosing as the metabolic context evolves.
Understanding this is not an argument against treatment. It is an argument for treating the whole patient — weight, insulin sensitivity, body composition, and hormone levels — as an integrated metabolic system rather than a single lab value that either does or doesn’t cross a threshold.
Next up: Post 4 — “The Bidirectional Trap: How Low Testosterone Causes Fat Gain, and How Fat Gain Causes Low Testosterone — the Cycle That Locks Men In.”
