Sex hormone-binding globulin (SHBG)
Sex hormone-binding globulin (SHBG) is a glycoprotein produced mainly by the liver that binds and transports sex steroids—primarily testosterone and estradiol—in the bloodstream. By binding these hormones, SHBG regulates how much is biologically available to tissues. Higher SHBG generally reduces the free (unbound) fraction of testosterone and estradiol, while lower SHBG increases it. Because of this buffering role, SHBG is an important determinant of hormonal balance in both men and women and is commonly measured alongside total testosterone and estradiol to aid 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 share of testosterone and estradiol is protein-bound, which can lower the free (bioavailable) fraction. High SHBG is often seen with higher estrogen exposure (e.g., pregnancy or estrogen therapy), hyperthyroidism, some liver conditions, aging, and in some cases with low body mass.
Low SHBG is associated with greater free androgen availability relative to total levels. It is commonly linked with obesity, insulin resistance/type 2 diabetes, hypothyroidism, polycystic ovary syndrome (PCOS), nephrotic syndrome, and exogenous androgen use.
SHBG helps contextualize total hormone measurements. Together with total testosterone or estradiol, SHBG enables calculation of free or bioavailable hormone (e.g., calculated free testosterone or a free-androgen index). This combined approach improves assessment when symptoms and total levels do not align, or when binding protein changes are suspected.
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