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

If you've ever had your testosterone tested, chances are the lab checked "total testosterone" and maybe flagged it as normal or low. But 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.

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 gauges go beyond what a standard hormone panel tells you and give your provider genetic context that makes lab results more meaningful.