Sex hormone-binding globulin (SHBG)
Sex hormone-binding globulin (SHBG) is a glycoprotein primarily produced by the liver that binds and transports sex steroids—mainly testosterone and estradiol—in the bloodstream. By binding these hormones, SHBG controls how much is biologically available to tissues. Higher SHBG levels typically decrease the free (unbound) fraction of testosterone and estradiol, while lower SHBG levels increase it. Due to this regulatory function, SHBG plays a key role in hormonal balance for both men and women and is often measured alongside total testosterone and estradiol to help with interpretation.
Description
- Biological factors: sex, age, and genetic variation
- Hormonal milieu: estrogens tend to increase SHBG; androgens tend to decrease it
- Metabolic state: obesity, insulin resistance, and type 2 diabetes are linked to lower SHBG
- Thyroid function: hyperthyroidism → higher SHBG; hypothyroidism → lower SHBG
- Liver function: chronic liver disease can increase SHBG
- Physiological/medication effects: pregnancy and estrogen-containing therapies typically raise SHBG; anabolic-androgenic steroids can lower it
When SHBG levels are elevated, a larger portion of testosterone and estradiol binds to proteins, which can reduce the free (bioavailable) fraction. High SHBG is commonly associated with increased estrogen exposure (such as during pregnancy or estrogen therapy), hyperthyroidism, certain liver conditions, aging, and, in some cases, low body mass.
Low SHBG is associated with increased free androgen availability relative to total levels. It is commonly linked to obesity, insulin resistance/type 2 diabetes, hypothyroidism, polycystic ovary syndrome (PCOS), nephrotic syndrome, and the use of exogenous androgens.
SHBG helps provide context for total hormone measurements. Along with total testosterone or estradiol, SHBG allows for the calculation of free or bioavailable hormone (e.g., calculated free testosterone or a free-androgen index). This combined method enhances evaluation when symptoms and total levels don’t match, or when changes in binding proteins are suspected.
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