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 to these hormones, SHBG regulates their biological availability to tissues. Higher SHBG levels typically decrease the free (unbound) fraction of testosterone and estradiol, while lower SHBG levels increase it. Due to this buffering function, SHBG plays a crucial role in maintaining hormonal balance in both men and women and is frequently measured alongside total testosterone and estradiol to support clinical 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 is elevated, a larger proportion of testosterone and estradiol binds to proteins, which can reduce the free (bioavailable) fraction. Elevated SHBG is commonly observed with increased estrogen levels (such as during pregnancy or estrogen therapy), hyperthyroidism, certain liver disorders, aging, and occasionally in individuals with low body mass.
Low SHBG is linked to increased availability of free androgens compared to total levels. It is often associated with obesity, insulin resistance/type 2 diabetes, hypothyroidism, polycystic ovary syndrome (PCOS), nephrotic syndrome, and the use of external androgens.
SHBG helps put total hormone measurements into perspective. Along with total testosterone or estradiol, SHBG allows for the calculation of free or bioavailable hormone (for example, calculated free testosterone or a free androgen index). This combined method improves evaluation when symptoms and total levels don’t match, or when changes in binding proteins are suspected.
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