SHBG and Hyperinsulinemia: Hyperinsulinemia further aggravates PCOS by inhibiting the production of insulin-like growth factor (IGF-1) binding protein in the liver, which causes elevated circulating IGF-1 levels, in turn stimulating more ovarian thecal cell androgen production, as well as reducing the production of sex-hormone-binding globulin (SHBG), thereby leading to increased free testosterone levels, further exacerbating symptoms of hyperandrogenism [20].