SHBG

SHBG is synthesized primarily by hepatocytes and circulates in plasma, binding androgens and estrogens with high affinity (testosterone and DHT more than estradiol). Only free, unbound hormone is biologically active; SHBG-bound hormone serves as a reservoir. Factors that increase SHBG include hyperthyroidism, estrogen therapy/pregnancy, oral contraceptives, liver disease (cirrhosis), and aging—these states decrease free testosterone, which can cause symptoms of androgen deficiency despite normal total testosterone. Factors that decrease SHBG include obesity, insulin resistance/type 2 diabetes, hypothyroidism, and androgen excess (e.g., PCOS)—these increase free testosterone, contributing to hirsutism and virilization in conditions like PCOS. In women with PCOS, insulin resistance suppresses hepatic SHBG production, leading to elevated free testosterone and clinical hyperandrogenism (hirsutism, acne, oligomenorrhea) despite total testosterone being only mildly elevated. Clinically, measuring SHBG alongside total testosterone helps calculate free testosterone, which is more physiologically relevant especially in borderline cases. SHBG is also used as a marker of insulin sensitivity in some research contexts. In liver cirrhosis, decreased hepatic clearance of estrogen combined with increased SHBG can lead to relative hyperestrogenism, causing gynecomastia and other feminization signs in men. Testosterone replacement therapy monitoring should account for SHBG levels to accurately assess androgen status.