Sex Hormone-Binding Globulin (SHBG)

SHBG is a liver-produced glycoprotein that binds sex hormones (primarily testosterone and oestradiol) in the bloodstream, regulating their bioavailability.

Sex hormone-binding globulin (SHBG) is a glycoprotein synthesised in the liver that binds with high affinity to testosterone and oestradiol. By controlling how much sex hormone is unbound and biologically active, SHBG is a key modulator of androgen and oestrogen action — and a sensitive biomarker for metabolic and endocrine state.

Function

SHBG circulates in blood, binding roughly two-thirds of circulating testosterone (the remainder is bound to albumin or free). Only the free fraction is immediately bioavailable; albumin-bound is loosely available.

Calculated free testosterone (Vermeulen formula from total T, SHBG, and albumin) is the standard clinical method for assessing bioavailable testosterone, as direct free-T immunoassays are unreliable at low concentrations.

Clinical significance

High SHBG: caused by hyperthyroidism, oestrogen excess, chronic alcohol, hepatitis, ageing, and severe calorie restriction. Reduces free testosterone availability.

Low SHBG: strongly associated with insulin resistance, NAFLD, hypothyroidism, obesity, and exogenous androgen use. Low SHBG often precedes overt metabolic dysfunction.

SHBG is therefore both a diagnostic adjunct (interpreting testosterone) and an independent marker of metabolic and endocrine health.

References

Related concepts

Testosterone — Testosterone is the primary male sex hormone, an androgen produced mainly in the testes that regulates libido, muscle mass, bone density, red blood cell production, and mood.
Estradiol in Men — Estradiol (E2) is the most potent oestrogen, produced in men primarily through aromatisation of testosterone in adipose, brain, and bone tissue, and is essential for bone health, libido, cognition, and cardiovascular function.