boundandfreePhysiology 101

Think of hormones as keys, and the hormone receptors as locks. When the key fits into the right doorknob, the door will open. 

But you don’t always want the door to open—or at least you don’t want too many doors to open all at the same time. The way your body gets around this is to put “sheaths” on most of the keys; that way, even if they come in contact with the right doorknob, they won’t fit. The sheath is called a “binding globulin.” 

Different binding globulins are specific to different hormones. 

  • The Sex Hormone Binding Globulin (SHBG) binds androgens like testosterone, DHEA, and dihydrotestosterone, as well as estrogen.
  • The Thyroid Binding Globulin (TBG) binds thyroid.
  • The Corticosteroid Binding Globulin (CBG) binds progesterone, cortisol, and other corticosteroids.

Why Binding Globulins Matter

Only those hormones that are not “sheathed” by a binding globulin are what we call “bioavailable”: i.e. available to stimulate the receptors (unlock the doors). 

This is why it’s important to check, for instance “free” T3 and “free” T4 in a thyroid panel, not merely T3 and T4. It makes a difference how much hormone is actually unbound and bioavailable. This is also an important distinction for testosterone, since SHBG has a very high affinity for testosterone. A man can technically have a normal total testosterone level, but a low free testosterone level, which will still leave him with symptoms of low testosterone. 

What Makes “Bound” Hormones Go Up and Down

SHBG decreases when androgens are high, such as testosterone and DHEA. This can happen from supplementation, or from conditions that cause them to spike, such as Polycystic Ovarian Syndrome (PCOS). 

Hypothyroidism decreases SHBG as well, which may partially explain the correlation between hypothyroidism and other hormonal issues, such as PMS and menopausal symptoms. By the same token, high estrogen levels can increase the Thyroid Binding Globulin, leading to symptoms of hypothyroidism as well. 

Obesity and excess insulin triggers lower SHBG, and low SHBG also seems to increase the incidence of diabetes. This is partly why losing weight, minimizing sugar and increasing exercise is so effective at hormone balancing. Conversely, very thin or anorexic women often do not get their periods anymore, possibly due to elevated SHBG. 

The Upshot

You can test SHBG and TBG directly, and in some cases this is clinically useful. But the first step is to test the free, unbound forms of thyroid (T3 and T4). And of the sex hormones, it is especially helpful to test the free and total levels of testosterone in men.

Women with estrogen dominance symptoms or PCOS, on the other hand, would do well to increase SHBG with diet and lifestyle modifications. 

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