Abstract
While hyperinsulinemia is a common contributing mechanism in the pathogenesis of polycystic ovarian syndrome (PCOS), other mechanisms may give rise to or add to the effects of hyperinsulinemia, as well as other causes of hyperandrogenism, in the pathogenesis of PCOS. Such underappreciated causes may include autoimmune, insulin receptor mutations, mutations of post-receptor insulin signaling response elements, polymorphisms of LH, androgen, and estrogen signaling pathways, epigenetic alterations in hormonal signaling cascade response elements, infestations and infections with organisms capable of endocrine disruption by various mechanisms, as well as drugs and other chemicals which may be endocrine disruptors. In addition, alterations in the gut, oral, or vaginal biome may be associated with PCOS and insulin resistance and may, in some instances, have a role to play in its pathogenesis. In this chapter I plan to review what is known about these lesser-known causes of PCOS, in the hopes of alerting clinicians to consider them and stimulating investigators to better understand PCOS pathogenesis in general and, hopefully, develop more individualized, precision treatment and prevention strategies for the people in our care.