TNF and hyperandrogenism: As previously mentioned, TNF-ɑ is produced by M1 macrophages, neutrophils, and Th1 cells, which are all induced by the hyperandrogenism in PCOS; as a result, the significant increase in TNF-ɑ then inhibits the tyrosine kinase function of the insulin receptor, impairing the signal transduction pathway for insulin and ultimately leading to the insulin resistance seen in PCOS (Fig. 4) [33].