Clinical doses of metformin may slightly lower circulating estrogen or cause no change in circulating sex hormone-binding globulin (SHBG) levels in postmenopausal women44,45, while premenopausal polycystic ovarian syndrome (PCOS) patients taking clinical doses of metformin showed a modest increase in circulating SHBG and estrogen levels46. Here, SHBG is linked to polycystic ovary syndrome.