Metformin improves endotoxemia and alters folliculogenesis in women with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is associated with excessive ovarian androgen production, increased number of ovarian follicles and a wide range of other endocrine and metabolic derangements including endotoxemia. Metformin is often used in treatment of PCOS, especially to improve glucose metabolism. This study evaluated effects of metformin on endotoxemia, folliculogenesis and endocrine profiles. In a prospective trial, women with PCOS received metformin (500 mg t.i.d.) for three months and underwent baseline and post-treatment evaluations of their endocrine and metabolic profiles as well as detailed ultrasonographic evaluations of ovaries. Metformin treatment was associated with reduced lipopolysaccharides (LPS) by 19% (P<0.0001) and LPS binding protein (LPB) by 26% (P<0.0001). In parallel, the number of small antral follicles (<6mm) declined by 8% (P=0.005), total testosterone decreased by 13% (P=0.0003), ovarian testosterone production in response to hCG declined by 73% (P=0.03) and fasting insulin decreased by 19% (P=0.02). Reduction of testosterone following treatment with metformin may be due to a combination of multiple effects of metformin including improvement of endotoxemia, reduction of folliculogenesis and decreased insulin.