The reason for this observation may be a reduced negative feedback on the pituitary of E2 since we noticed that E2 levels of patients in PCOS-NIR and PCOS-NOW groups were lower than those of patients in control-NIR and control-NOW groups, and they showed higher level of LH than PCOS-IR and PCOS-OW, in which we hypothesized that their pituitary had a higher sensitivity to GNRH, or got less negative feedback on their pituitary due to low level of E2. This evidence concerns the gene PLOD1 and polycystic ovary syndrome.