In summary, from a mechanistic standpoint, elevated Mets-IR may suppress ovulation through the following pathways: on one hand, insulin resistance can potentiate the stimulatory effect of LH on ovarian theca cells—for instance, by upregulating LH receptor or IGF-1 receptor expression—thereby promoting androgen synthesis and exacerbating the hyperandrogenic state in PCOS patients (33, 50). This evidence concerns the gene PLOD1 and polycystic ovary syndrome.