Published June 13 2016
When hormones such as thyroxine, estradiol, and testosterone are not in the free form, they travel through the bloodstream while bound to a protein. When they are not bound to a protein they are considered to be in the free state. However, most of these hormones are bound to a protein, as only about 1 to 2% are in the free state. Sex hormone binding globulin (SHBG) is a protein that binds to the hormones testosterone, dihydrotestosterone, and estradiol. Thyroid binding globulin (TBG) binds to the thyroid hormones thyroxine (T4) and triiodothyronine (T3).
But why are most hormones bound to a protein? Well, the way it works is that SHBG helps to regulate the circulating concentrations of some of the sex hormones. So it helps to transport the hormones to the target tissues, and then as they are needed they are released by the body. By the way, even though testosterone and estrogen mainly bind to SHBG, I should mention that approximately 30% of these hormones bind to another protein called albumin . As for TBG, this binding protein helps to transport thyroid hormone throughout the body, and it releases thyroid hormone as needed.
Factors That Increase Sex Hormone Binding Globulin
There are certain factors that can increase SHBG. When SHGB increases, more of the sex hormones are bound to this protein, especially testosterone, which has a greater affinity for SHBG than estradiol. As a result of testosterone binding to SHBG there is less free testosterone in the system. On a blood test this usually will show up as high SHBG and low free testosterone. I’ll list some of the main factors below that can increase SHBG. You’ll notice that high levels of thyroid hormone (i.e. hyperthyroidism) will increase SHBG (1).
Here is a list of some of the factors that increase SHBG (1) (2) (3):
Hyperthyroidism
Pregnancy
Taking estrogen in the form of hormone replacement therapy or oral contraceptives
Cirrhosis
Caffeine
Factors That Decrease Sex Hormone Binding Globulin
There are also certain factors that can decrease SHBG. When SHBG is decreased, this means that less testosterone is bound to this protein, and so free testosterone is likely to be higher. Low levels of thyroid hormone (i.e. hypothyroidism) will cause a decrease in SHBG. When viewing the list below you’ll notice that some other factors which can decrease SHBG include obesity and insulin. In fact, low SHBG can be used as a marker of insulin resistance (4) (5), and the research also shows it’s a predictor of type 2 diabetes (6) (7).
Here is a list of some of the factors that decrease SHBG (8) (9) (10):
Hypothyroidism
Obesity
Androgens (i.e. testosterone)
Insulin
Cortisol
Progestins
Factors That Increase Thyroid Binding Globulin
Let’s take a look at some of the factors which can increase thyroid binding globulin. Just as a reminder, when thyroid binding globulin is high, this means that more thyroid hormone is bound to this protein, and thus the free thyroid hormone levels will be lower. Below I’ll list a few other factors which can increase TBG, which in turn will lead to a decrease in thyroid hormone:
Here is a list of some of the factors that increase TBG (11) (12) (13):
Hypothyroidism
Estrogen
Pregnancy
Liver disease
Factors That Decrease Thyroid Binding Globulin
When thyroid binding globulin is low, the free thyroid hormone levels will be high. Thus, we would expect TBG to be low in cases of hyperthyroidism, and a few other conditions can potentially decrease TBG as well.
Here is a list of some of the factors that decrease TBG (14) (15):
Hyperthyroidism
Acute illness
Malnutrition
Nephrotic syndrome
How Can You Measure These Binding Proteins?
Both of these markers can be tested through the blood. Most major labs will offer both of these tests. I don’t test these markers on all of my patients, especially TBG. And the reason for this is because it usually isn’t going to change my approach, as my focus will be more on the thyroid hormone levels. So for example, if a patient of mine has elevated thyroid hormone levels, I am going to assume that they have low TBG levels. But even if the TBG levels weren’t low on a blood test it still wouldn’t change my approach, which is to help lower the thyroid hormone levels, while of course trying to address the cause of the problem.
However, SHBG can be valuable in certain situations. As I mentioned earlier, having a low SHBG can be a marker for insulin resistance, and a predictor of type 2 diabetes. Of course you can also look at other factors to determine insulin resistance as well, such as hemoglobin A1C, and the triglyceride/HDL ratio, which should be less than three.
What Can You Do To Normalize SHBG and TBG levels?
There are a few different things you can do to help normalize SHBG and TBG levels. Since both hyperthyroidism and hypothyroidism can affect these binding proteins then of course you want to do what is necessary to balance the thyroid hormones. I also mentioned how blood sugar disorders such as insulin resistance and type 2 diabetes can lead to a decrease of SHBG, and so it is important to have healthy insulin and blood glucose levels. Remember that elevated cortisol levels can decrease both SHBG and TBG.
In summary, hormones such as thyroxine, estradiol, and testosterone are usually bound to a protein, which help to transport the hormones to the target tissues. Thyroid hormone binds to thyroid binding globulin (TBG), while estradiol and testosterone bind to sex hormone binding globulin. Certain factors that increase TBG include hypothyroidism, estrogen, and pregnancy, while hyperthyroidism and malnutrition can decrease TBG. Hyperthyroidism, pregnancy, and oral contraceptives are some factors which can increase SHBG, while hypothyroidism, obesity, and insulin can decrease SHBG. In order to have normal TBG and SHBG levels you of course want to balance the hormones, and you also might have to address other factors, such as insulin resistance.
