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Sex hormone-binding globulin (SHBG)
Sex hormone-binding globulin (SHBG) is a glycoprotein produced mainly by the liver that binds to and transports sex steroids—primarily testosterone and oestradiol—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 oestradiol, 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 oestradiol to aid interpretation.
Description
What affects SHBG levels?
- Biological factors: sex, age, and genetic variation
- Hormonal milieu: oestrogens 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 oestrogen-containing therapies typically raise SHBG; anabolic-androgenic steroids can lower it
What might a high SHBG level indicate?
When SHBG is elevated, a larger proportion of testosterone and estradiol is protein-bound, which can reduce the free (bioavailable) fraction. High SHBG is commonly observed with increased oestrogen exposure (e.g., pregnancy or oestrogen therapy), hyperthyroidism, certain liver conditions, ageing, and in some cases with low body mass.
What might a low SHBG level indicate?
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 the use of exogenous androgens.
How is SHBG used alongside testosterone or estradiol results?
SHBG helps to put total hormone measurements into context. Alongside 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 approach enhances assessment when symptoms and total levels don’t match, or when changes in binding proteins are suspected.
