Sex hormone-binding globulin (SHBG)
Sex hormone-binding globulin (SHBG) is a glycoprotein produced principally by the liver that binds to and transports sex steroids—mainly testosterone and oestradiol—in the bloodstream. By binding these hormones, SHBG regulates the amount that is biologically available to tissues. Higher SHBG generally reduces the free (unbound) fraction of testosterone and oestradiol, while lower SHBG increases it. Due to this buffering role, SHBG is a key determinant of hormonal balance in both men and women and is commonly measured alongside total testosterone and oestradiol to assist with interpretation.
Description
- 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
When SHBG is elevated, a larger proportion of testosterone and estradiol is protein-bound, which can reduce the free (bioavailable) fraction. High SHBG is often associated with increased oestrogen exposure (e.g., pregnancy or oestrogen therapy), hyperthyroidism, certain liver conditions, ageing, 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 to contextualise total hormone measurements. Together 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 approach enhances assessment when symptoms and total levels do not correspond, or when changes in binding proteins are suspected.
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