Sex Hormone Binding Globulin (SHBG)

Sex hormone-binding globulin (SHBG) is a protein produced by the liver that is responsible for carrying sex steroids including testosterone and estradiol. It binds to sex hormones far more strongly than albumin, so is considered the primary transport protein for sex hormones. Approximately 96-99% of testosterone is bound to SBHG and albumin. SHBG levels change in response to many factors, notable age and obesity, though a number of medications can also have an effect on circulating protein levels. Testosterone is bound to SHBG tightly. Naturally, higher levels of SHBG can result in lower levels of free circulating testosterone, as more testosterone is bound to SHBG than floating in the bloodstream in an unbound state.

Total Testosterone is calculated by adding free testosterone to albumin-bound testosterone and SHBG-bound testosterone.

Abnormal SHBG levels can be found in the following circumstances:

Higher SHBG: Liver disease, hyperthyroidism, aging, HIV, high estrogen concentrations (i.e. from oral contraceptives in women), pregnancy, psychological stress, anti-epileptic drugs
Lower SHBG: obesity, diabetes, insulin resistance, taking anabolic steroids, taking glucocorticoids (i.e. prednisone), kidney disease, taking progesterone

When is measuring SHBG useful?

Sex Hormone Binding Globulin binds with a greater affinity for androgen (male) hormones than female hormones. We know that sex hormone-binding globulin binds to testosterone tightly, so for a male with a normal testosterone level who has symptoms of testosterone deficiency, a high SHBG would explain symptoms of testosterone deficiency because of lower circulating levels of free testosterone.

Low SBHG, when controlled for age, has been associated as a biomarker for metabolic syndrome risk (elevated waist circumference, low HDL, elevated blood pressure) and diabetes.

What lowers SHBG levels?