Sex hormone-binding globulin ( SHBG ) is a glycoprotein that binds to sex hormones, specifically testosterone and estradiol. Other steroid hormones such as progesterone, cortisol, and other corticosteroids are bound by transcortin.

Testosterone and estradiol circulate in the bloodstream, bound mostly to SHBG and to some degree bound to serum albumin. Only a small fraction is unbound, or "free," and thus biologically active and able to enter a cell and activate its receptor . The SHBG inhibits the function of these hormones. Thus bioavailability of sex hormones is influenced by the level of SHBG. SHBG has a higher affinity for Dihydrotestosterone than for Testosterone or for Estradiol making it essential in women for regulating the bio-availability of Dihydrotestosterone.

SHBG is produced most by the liver and is released into the bloodstream. Other sites that produce SHBG include the brain, uterus, testes, and placenta. Testes-produced SHBG is called androgen-binding protein. The gene for SHBG is located on chromosome 17.

SHBG levels appear to be controlled by a delicate balance of enhancing and inhibiting factors. Its level is decreased by high levels of insulin and insulin-like growth factor 1 ( IGF-1) (see: milk ). Also, high androgen and transcortin levels decrease SHBG, while high growth hormone, estrogen and thyroxine levels increase it.

However, recent evidence suggests that it is the liver's production of fats that reduces SHBG levels, not any direct effect of insulin and specific genetic mechanisms have been found that do this.

Conditions with low SHBG include polycystic ovary syndrome, diabetes, and hypothyroidism. Conditions with high SHBG include pregnancy, hyperthyroidism, and anorexia nervosa. There has recently been research to link high SHBG levels with breast and testicular cancer as well.

When determining levels of circulating estradiol or testosterone, either a total measurement could be done that includes the "free" and the bound fractions, or only the "free" hormone could be measured.

A free androgen index expresses the ratio of testosterone to the sex hormone binding globulin and can be used to summarize the activity of free testosterone.

The total testosterone is likely the most accurate measurement of testosterone levels and should always be measured at 8 o'clock in the morning. Sex hormone binding globulin can be measured separate from the total fraction of testosterone.

• Androgen binding protein