Clinical Information

Sex hormone-binding globulin (SHBG), a 95 kDa homodimer, is the blood transport protein for testosterone and estradiol. SHBG is mainly produced in the liver and has a half-life of approximately seven days. SHBG binds reversibly to sex steroids. SHBG has a relatively high-binding affinity to dihydrotestosterone (DHT), medium affinity to testosterone and estradiol, and exhibits a low affinity to estrone, dehydroepiandrosterone, androstenedione, and estriol. Albumin, which exists at physiologically higher concentrations than SHBG, also binds to sex steroids, although with a much lower binding affinity (eg, about 100 times lower for testosterone).

Decreased SHBG serum concentrations are associated with conditions in which elevated androgen concentrations are present, or the effect of androgen on its target organs is excessive. Because of the high-binding affinity of SHBG to DHT, as compared to estradiol, SHBG has profound effects on the balance between bioavailable androgens and estrogens. Increased SHBG concentrations may be associated with signs and symptoms of hypogonadism in men, while decreased concentrations can result in androgenization in women. SHBG is regulated by insulin, and a low SHBG concentration often indicates insulin resistance and, consequently, may be a predictor of type 2 diabetes.

Endogenous or exogenous thyroid hormones or estrogens increase SHBG concentrations. In men, there is also an age-related gradual rise, possibly secondary to the mild age-related fall in testosterone production. This process can result in bioavailable testosterone concentrations that are much lower than would be expected based on total testosterone measurements alone.