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Increased gonadotrophin releasing hormone (GnRH) pulsatility in the hypothalamus results in preferential luteinizing hormone (LH) secretion from the pituitary gland, leading to ovarian hyperandrogenism and oligo\/anovulation. The resultant hyperandrogenism reduces negative feedback from sex steroids such as oestradiol and progesterone to the hypothalamus, and thus perpetuates the increase in GnRH pulsatility. GnRH neurons do not have receptors for oestrogen, progesterone, or androgens, and thus the disrupted feedback is hypothesized to occur via upstream neurons. Likely candidates for these upstream regulators of GnRH neuronal pulsatility are Kisspeptin, Neurokinin B (NKB), and Dynorphin neurons (termed KNDy neurons). Growing insight into the neuroendocrine dysfunction underpinning the heightened GnRH pulsatility seen in PCOS has led to research on the use of pharmaceutical agents that specifically target the activity of these KNDy neurons to attenuate symptoms of PCOS. This review aims to highlight the neuroendocrine abnormalities that lead to increased GnRH pulsatility in PCOS, and outline data on recent therapeutic advancements that could potentially be used to treat PCOS. Emerging evidence has investigated the use of neurokinin 3 receptor (NK3R) antagonists as a method of reducing GnRH pulsatility and alleviating features of PCOS such as hyperandrogenism. We also consider other potential mechanisms by which increased GnRH pulsatility is controlled, which could form the basis of future avenues of research.<\/jats:p>","DOI":"10.1111\/cen.14704","type":"journal-article","created":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T11:51:42Z","timestamp":1646740302000},"page":"156-164","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Treatments targeting neuroendocrine dysfunction in polycystic ovary syndrome (PCOS)"],"prefix":"10.1111","volume":"97","author":[{"given":"Akanksha","family":"Garg","sequence":"first","affiliation":[{"name":"Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism Imperial College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bijal","family":"Patel","sequence":"additional","affiliation":[{"name":"Section of Investigative Medicine, Division of Diabetes, Endocrinology and 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