When considering our findings, it may be reasonable to speculate that metformin may act to optimize oocyte development and production by the local and/or systemic reduction of hyperinsulinemia, androgen and leptin production, as well as by the reduction of inappropriately high intrafollicular estradiol levels (seen in PCOS patients) by attenuation of aromatase activity as highlighted previously [46,49]. The gene discussed is LEP; the disease is hyperinsulinism.