What is SHBG and why does it matter?

SHBG (sex hormone-binding globulin) is a liver-made protein that binds testosterone and estrogen in your bloodstream. Bound hormone is inactive; only the unbound, or free, portion is biologically active. Two people with the same total testosterone can have very different free testosterone depending on their SHBG.

Why would normal testosterone still come with low-T symptoms?

If total testosterone looks normal but SHBG is high, more of that testosterone is bound and unavailable, leaving less free testosterone for your cells. Knowing your genetic tendency for SHBG helps a provider decide whether to test free T and SHBG directly.

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Beyond Total Testosterone: SHBG, Free T, and the Genetics Most Labs Miss

Total testosterone only tells part of the story. What matters just as much is how much is actually available to your cells, and that depends on SHBG, a binding protein whose level is strongly shaped by your genetics.

By Mosaic BiodataFebruary 28, 20261 min read

Beyond Total Testosterone: SHBG, Free T, and the Genetics Most Labs Miss

Total testosterone only tells part of the story — what matters just as much is how much of that testosterone is actually available to your cells, and that depends on a protein called SHBG. Two people can have identical total testosterone and very different amounts of free, usable testosterone, and your genetics help set where you land.

What SHBG does

SHBG (sex hormone-binding globulin) is a protein produced by your liver that binds to testosterone and estrogen in your bloodstream. When testosterone is bound to SHBG, it's inactive; your cells can't use it. Only "free" testosterone (the unbound portion) is biologically active.

This means two people can have the same total testosterone level but very different amounts of free testosterone, depending on their SHBG levels. High SHBG binds more testosterone, leaving less available. Low SHBG leaves more free testosterone circulating.

The genetic influence

SHBG levels are significantly influenced by genetics. Variants in the SHBG gene itself, along with genes involved in liver function and insulin sensitivity, can determine whether your baseline SHBG tends to run higher or lower. This is true for both men and women, and it affects how both testosterone and estrogen behave in your body.

There's also the DHT (dihydrotestosterone) pathway to consider. The 5-alpha reductase enzyme converts testosterone into DHT, a more potent androgen. Genetic variants affect this conversion rate too, which influences everything from hair growth patterns to prostate health.

What this means for you

If your labs show "normal" total testosterone but you're experiencing symptoms associated with low T, SHBG might be the missing piece. Knowing your genetic tendency for SHBG production can help your provider interpret your bloodwork more accurately and decide whether additional testing (free T, SHBG levels) is warranted.

What Mosaic covers

Your Mosaic report includes SHBG tendency, testosterone metabolism, and DHT conversion in the Hormones section. These readings go beyond what a standard hormone panel tells you and give your provider genetic context that makes lab results more meaningful. If hormones are your focus, the hormone optimization landing page is a good next step.

Keep exploring: the Insights Library breaks down the 108 traits Mosaic reads from your DNA, and the reports show how they come together.