“Sex-hormone-binding globulin,” and “luteinizing hormone” are the top two clusters, representing two common mechanisms of IR increasing PCOS free testosterone level (14, 15): First, insulin receptors in the pituitary gland are triggered to release luteinizing hormone, and second, the synthesis of sex hormone-binding globulin (SHBG) in the liver is inhibited. Here, INSR is linked to polycystic ovary syndrome.