{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T11:52:37Z","timestamp":1792497157335,"version":"4.5.0"},"reference-count":79,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,3,6]],"date-time":"2022-03-06T00:00:00Z","timestamp":1646524800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women and a major cause of anovulatory infertility. A diagnosis of PCOS is established based the presence of two out of three clinical symptoms, which are criteria accepted by the ESHRE\/ASRM (European Society of Human Reproduction and Embryology\/American Society for Reproductive Medicine). Gonadotropin-releasing hormone (GnRH) is responsible for the release of luteinizing hormone, and follicle stimulating hormone from the pituitary and contributes a leading role in controlling reproductive function in humans. The goal of this review is to present the current knowledge on neuroendocrine determinations of PCOS. The role of such neurohormones as GnRH, and neuropeptides kisspeptin, neurokinin B, phoenixin-14, and galanin is discussed in this aspect. Additionally, different neurotransmitters (gamma-aminobutyric acid (GABA), glutamate, serotonin, dopamine, and acetylcholine) can also be involved in neuroendocrine etiopathogenesis of PCOS. Studies have shown a persistent rapid GnRH pulse frequency in women with PCOS present during the whole ovulatory cycle. Other studies have proved that patients with PCOS are characterized by higher serum kisspeptin levels. The observations of elevated serum kisspeptin levels in PCOS correspond with the hypothesis that overactivity in the kisspeptin system is responsible for hypothalamic-pituitary-gonadal axis overactivity. In turn, this causes menstrual disorders, hyperandrogenemia and hyperandrogenism. Moreover, abnormal regulation of Neurokinin B (NKB) is also suspected of contributing to PCOS development, while NKB antagonists are used in the treatment of PCOS leading to reduction in Luteinizing hormone (LH) concentration and total testosterone concentration. GnRH secretion is regulated not only by kisspeptin and neurokinin B, but also by other neurohormones, such as phoenixin-14, galanin, and Glucagon-like peptide-1 (GLP-1), that have favorable effects in counteracting the progress of PCOS. A similar process is associated with the neurotransmitters such as GABA, glutamate, serotonin, dopamine, and acetylcholine, as well as the opioid system, which may interfere with secretion of GnRH, and therefore, influence the development and severity of symptoms in PCOS patients. Additional studies are required to explain entire, real mechanisms responsible for PCOS neuroendocrine background.<\/jats:p>","DOI":"10.3390\/ijerph19053089","type":"journal-article","created":{"date-parts":[[2022,3,6]],"date-time":"2022-03-06T20:38:16Z","timestamp":1646599096000},"page":"3089","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":75,"title":["Neuroendocrine Determinants of Polycystic Ovary Syndrome"],"prefix":"10.3390","volume":"19","author":[{"given":"Anna","family":"Szeliga","sequence":"first","affiliation":[{"name":"Department of Gynecological Endocrinology, Poznan University of Medical Sciences, 60-535 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3936-5598","authenticated-orcid":false,"given":"Ewa","family":"Rudnicka","sequence":"additional","affiliation":[{"name":"Department of Gynecological Endocrinology, Medical University of Warsaw, 00-315 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marzena","family":"Maciejewska-Jeske","sequence":"additional","affiliation":[{"name":"Department of Gynecological Endocrinology, Poznan University of Medical Sciences, 60-535 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marek","family":"Kucharski","sequence":"additional","affiliation":[{"name":"Department of Gynecological Endocrinology, Medical University of Warsaw, 00-315 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Kostrzak","sequence":"additional","affiliation":[{"name":"Department of Gynecological Endocrinology, Poznan University of Medical Sciences, 60-535 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Hajbos","sequence":"additional","affiliation":[{"name":"Department of Gynecological Endocrinology, Medical University of Warsaw, 00-315 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Niwczyk","sequence":"additional","affiliation":[{"name":"Department of Gynecological Endocrinology, Poznan University of Medical Sciences, 60-535 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4420-5433","authenticated-orcid":false,"given":"Roman","family":"Smolarczyk","sequence":"additional","affiliation":[{"name":"Department of Gynecological Endocrinology, Medical University of Warsaw, 00-315 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blazej","family":"Meczekalski","sequence":"additional","affiliation":[{"name":"Department of Gynecological Endocrinology, Poznan University of Medical Sciences, 60-535 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,6]]},"reference":[{"key":"ref_1","first-page":"1","article-title":"Genetic, hormonal and metabolic aspects of PCOS: An update","volume":"14","author":"Musacchio","year":"2016","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Rotterdam ESHRE\/ASRM-Sponsored PCOS Consensus Workshop Group (2004). Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril., 81, 19\u201325.","DOI":"10.1016\/j.fertnstert.2003.10.004"},{"key":"ref_3","unstructured":"Taylor, H.S., Pal, L., and Seli, E. (2019). Speroff\u2019s Clinical Gynecologic Endocrinology and Infertility, Department of Obstetrics, Gynecology and reproductive Sciences, Yale School of Medicine. [9th ed.]."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1111\/j.1365-2605.2005.00623.x","article-title":"Development of polycystic ovary syndrome: Involvement of genetic and environmental factors","volume":"29","author":"Franks","year":"2006","journal-title":"Int. J. Androl."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1007\/s00109-007-0246-6","article-title":"Accumulation of dietary glycotoxins in the reproductive system of normal female rats","volume":"85","author":"Piperi","year":"2007","journal-title":"J. Mol. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"P1","DOI":"10.1530\/EJE-14-0253","article-title":"The polycystic ovary syndrome: A position statement from the European Society of Endocrinology","volume":"171","author":"Conway","year":"2014","journal-title":"Eur. J. Endocrinol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/0002-9378(91)90280-5","article-title":"Adrenal and ovarian steroid hormone responses to gonadotropin-releasing hormone agonist treatment in polycystic ovary syndrome","volume":"165","author":"Gonzalez","year":"1991","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1210\/er.2015-1018","article-title":"Scientific Statement on the Diagnostic Criteria, Epidemiology, Pathophysiology, and Molecular Genetics of Polycystic Ovary Syndrome","volume":"36","author":"Dumesic","year":"2015","journal-title":"Endocr. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1055\/s-2002-36706","article-title":"Regulation of gonadotropin secretion: Implications for polycystic ovary syndrome","volume":"20","author":"McCartney","year":"2002","journal-title":"Semin. Reprod. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.steroids.2011.12.007","article-title":"Neuroendocrine dysfunction in polycystic ovary syndrome","volume":"77","author":"Beller","year":"2012","journal-title":"Steroids"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2360","DOI":"10.1210\/jc.2008-2606","article-title":"Modulation of gonadotropin-releasing hormone pulse generator sensitivity to progesterone inhibition in hyperandrogenic adolescent girls\u2014implications for regulation of pubertal maturation","volume":"94","author":"Blank","year":"2009","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/S0303-7207(99)00239-7","article-title":"Follicular dynamics in the polycystic ovary syndrome","volume":"163","author":"Franks","year":"2000","journal-title":"Mol. Cell Endocrinol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1093\/humupd\/dmw027","article-title":"Interactions between androgens, FSH, anti-M\u00fcllerian hormone and estradiol during folliculogenesis in the human normal and polycystic ovary","volume":"22","author":"Dewailly","year":"2016","journal-title":"Hum. Reprod. Update."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1093\/humupd\/dmn015","article-title":"Follicle dynamics and anovulation in polycystic ovary syndrome","volume":"14","author":"Franks","year":"2008","journal-title":"Hum. Reprod. Update"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1111\/cen.13795","article-title":"Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome","volume":"89","author":"Teede","year":"2018","journal-title":"Clin. Endocrinol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1097\/AOG.0000000000002698","article-title":"Polycystic Ovary Syndrome","volume":"132","author":"Azziz","year":"2018","journal-title":"Obstet. Gynecol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1097\/00003081-197803000-00003","article-title":"Neuroendocrine regulation of the menstrual cycle","volume":"21","author":"Naftolin","year":"1978","journal-title":"Clin. Obstet. Gynecol."},{"key":"ref_18","first-page":"53","article-title":"The neuroendocrine control of the menstrual cycle","volume":"36","author":"Knobil","year":"1980","journal-title":"Recent Prog. Horm Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1073\/pnas.0409330102","article-title":"Kisspeptin directly stimulates gonadotropin-releasing hormone release via G protein-coupled receptor 54","volume":"102","author":"Messager","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e2009156118","DOI":"10.1073\/pnas.2009156118","article-title":"Direct evidence that KNDy neurons maintain gonadotropin pulses and folliculogenesis as the GnRH pulse generator","volume":"118","author":"Nagae","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5752","DOI":"10.1210\/en.2007-0961","article-title":"Kisspeptin neurons in the arcuate nucleus of the ewe express both dynorphin A and neurokinin B","volume":"148","author":"Goodman","year":"2007","journal-title":"Endocrinology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3479","DOI":"10.1210\/en.2010-0022","article-title":"Minireview: Kisspeptin\/neurokinin B\/dynorphin (KNDy) cells of the arcuate nucleus: A central node in the control of gonadotropin-releasing hormone secretion","volume":"151","author":"Lehman","year":"2010","journal-title":"Endocrinology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1210\/en.2009-0552","article-title":"Distribution and postnatal development of Gpr54 gene expression in mouse brain and gonadotropin-releasing hormone neurons","volume":"151","author":"Herbison","year":"2010","journal-title":"Endocrinology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2761","DOI":"10.1210\/en.2013-1268","article-title":"Regulation of arcuate neurons coexpressing kisspeptin, neurokinin B, and dynorphin by modulators of neurokinin 3 and \u03ba-opioid receptors in adult male mice","volume":"154","author":"Ruka","year":"2013","journal-title":"Endocrinology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2750","DOI":"10.1210\/en.2013-1231","article-title":"Neurokinin B activates arcuate kisspeptin neurons through multiple tachykinin receptors in the male mouse","volume":"154","author":"Boehm","year":"2013","journal-title":"Endocrinology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3187","DOI":"10.1210\/en.2018-00435","article-title":"Evidence That Dynorphin Acts Upon KNDy and GnRH Neurons During GnRH Pulse Termination in the Ewe","volume":"159","author":"Weems","year":"2018","journal-title":"Endocrinology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/0306-4522(92)90423-Y","article-title":"Localization of oestrogen receptors in preoptic neurons containing neurotensin but not tyrosine hydroxylase, cholecystokinin or luteinizing hormone-releasing hormone in the male and female rat","volume":"50","author":"Herbison","year":"1992","journal-title":"Neuroscience"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1111\/jne.12235","article-title":"The luteinising hormone surge-generating system is functional in male goats as in females: Involvement of kisspeptin neurones in the medial preoptic area","volume":"27","author":"Matsuda","year":"2015","journal-title":"J. Neuroendocrinol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2959","DOI":"10.1210\/en.2003-1305","article-title":"Evidence that dynorphin plays a major role in mediating progesterone negative feedback on gonadotropin-releasing hormone neurons in sheep","volume":"145","author":"Goodman","year":"2004","journal-title":"Endocrinology"},{"key":"ref_30","first-page":"3353","article-title":"Actions of sex steroids on kisspeptin expression and other reproduction-related genes in the brain of the teleost fish European sea bass","volume":"219","author":"Alvarado","year":"2016","journal-title":"J. Exp. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/j.tem.2018.08.005","article-title":"New Perspectives on the Pathogenesis of PCOS: Neuroendocrine Origins","volume":"29","author":"Walters","year":"2018","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"110561","DOI":"10.1016\/j.mce.2019.110561","article-title":"Pathological pulses in PCOS","volume":"498","author":"Coyle","year":"2019","journal-title":"Mol. Cell Endocrinol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.1016\/j.fertnstert.2005.11.044","article-title":"Plasma metastin levels are negatively correlated with insulin resistance and free androgens in women with polycystic ovary syndrome","volume":"85","author":"Panidis","year":"2006","journal-title":"Fertil. Steril."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"298","DOI":"10.3389\/fendo.2019.00298","article-title":"Kisspeptin and Polycystic Ovary Syndrome","volume":"10","author":"Tang","year":"2019","journal-title":"Front. Endocrinol"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1111\/cen.14402","article-title":"Clinical and biochemical discriminants between functional hypothalamic amenorrhoea (FHA) and polycystic ovary syndrome (PCOS)","volume":"95","author":"Phylactou","year":"2021","journal-title":"Clin. Endocrinol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2157","DOI":"10.1111\/jog.14767","article-title":"Serum kisspeptin levels in polycystic ovary syndrome: A meta-analysis","volume":"47","author":"Liu","year":"2021","journal-title":"J. Obstet. Gynaecol. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.ejogrb.2021.03.007","article-title":"Circulating kisspeptin and anti-m\u00fcllerian hormone levels, and insulin resistance in women with polycystic ovary syndrome: A systematic review, meta-analysis, and meta-regression","volume":"260","author":"Ornat","year":"2021","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_38","first-page":"1862","article-title":"Beyond GnRH, LH and FSH: The role of kisspeptin on hypothalalmic-pituitary gonadal (HPG) axis pathology and diagnostic consideration","volume":"71","author":"Khan","year":"2021","journal-title":"J. Pak. Med. Assoc."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"bqaa018","DOI":"10.1210\/endocr\/bqaa018","article-title":"Hyperactive LH Pulses and Elevated Kisspeptin and NKB Gene Expression in the Arcuate Nucleus of a PCOS Mouse Model","volume":"161","author":"Esparza","year":"2020","journal-title":"Endocrinology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1007\/s12020-018-1609-1","article-title":"Kisspeptin and LH pulsatile temporal coupling in PCOS patients","volume":"61","author":"Katulski","year":"2018","journal-title":"Endocrine"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1080\/09513590.2019.1597343","article-title":"Effects of kisspeptin on pathogenesis and energy metabolism in polycystic ovarian syndrome (PCOS)","volume":"35","author":"Wang","year":"2019","journal-title":"Gynecol. Endocrinol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2086","DOI":"10.1016\/j.dsx.2019.04.017","article-title":"Kisspeptin and body weight homeostasis in relation to phenotypic features of polycystic ovary syndrome; metabolic regulation of reproduction","volume":"13","author":"Rashad","year":"2019","journal-title":"Diabetes Metab. Syndr."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"13","DOI":"10.3121\/cmr.2.1.13","article-title":"Polycystic ovarian syndrome: Diagnosis and management","volume":"2","author":"Sheehan","year":"2004","journal-title":"Clin. Med. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"S210","DOI":"10.1542\/peds.2019-2056J","article-title":"Diagnosis and Management of Polycystic Ovary Syndrome in Adolescents","volume":"145","author":"Trent","year":"2020","journal-title":"Pediatrics"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.anireprosci.2005.05.032","article-title":"GnRHs and GnRH receptors","volume":"88","author":"Millar","year":"2005","journal-title":"Anim Reprod Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1055\/s-0039-3403461","article-title":"Kisspeptin, Neurokinin B and New Players in Reproduction","volume":"37","author":"Dhillo","year":"2019","journal-title":"Semin. Reprod. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1055\/s-0039-3400240","article-title":"Clinical Translational Studies of Kisspeptin and Neurokinin, B","volume":"37","author":"Hunjan","year":"2019","journal-title":"Semin. Reprod. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2239","DOI":"10.1210\/endo-128-5-2239","article-title":"Hypertrophy and increased gene expression of neurons containing neurokinin-B and substance-P messenger ribonucleic acids in the hypothalami of postmenopausal women","volume":"128","author":"Rance","year":"1991","journal-title":"Endocrinology"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1007\/s40618-019-01160-0","article-title":"Kisspeptin and neurokinin B analogs use in gynecological endocrinology: Where do we stand?","volume":"43","author":"Szeliga","year":"2020","journal-title":"J. Endocrinol. Investig."},{"key":"ref_50","first-page":"367","article-title":"Kisspeptin in the Hypothalamus of 2 Rat Models of Polycystic Ovary Syndrome","volume":"158","author":"Osuka","year":"2017","journal-title":"Endocrinology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"4313","DOI":"10.1210\/jc.2016-1202","article-title":"Neurokinin B Receptor Antagonism in Women with Polycystic Ovary Syndrome: A Randomized, Placebo-Controlled Trial","volume":"101","author":"George","year":"2016","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1007\/s10815-018-1338-7","article-title":"Altered expression of the kisspeptin\/KISS1R and neurokinin B\/NK3R systems in mural granulosa and cumulus cells of patients with polycystic ovarian syndrome","volume":"36","author":"Blasco","year":"2019","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.jpag.2014.09.017","article-title":"The Role of Kisspeptin in the Onset of Puberty and in the Ovulatory Mechanism: A Mini-review","volume":"28","author":"Carrera","year":"2015","journal-title":"J. Pediatr. Adolesc. Gynecol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3667","DOI":"10.1172\/JCI75730","article-title":"Kisspeptin-54 triggers egg maturation in women undergoing in vitro fertilization","volume":"124","author":"Jayasena","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3322","DOI":"10.1210\/jc.2015-2332","article-title":"Efficacy of Kisspeptin-54 to Trigger Oocyte Maturation in Women at High Risk of Ovarian Hyperstimulation Syndrome (OHSS) During In Vitro Fertilization (IVF) Therapy","volume":"100","author":"Abbara","year":"2015","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2495","DOI":"10.1093\/humrep\/dez205","article-title":"Kisspeptin treatment induces gonadotropic responses and rescues ovulation in a subset of preclinical models and women with polycystic ovary syndrome","volume":"34","author":"Skorupskaite","year":"2019","journal-title":"Hum. Reprod."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1093\/humupd\/dmu009","article-title":"The kisspeptin-GnRH pathway in human reproductive health and disease","volume":"20","author":"Skorupskaite","year":"2014","journal-title":"Hum. Reprod. Update."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1093\/humrep\/deaa104","article-title":"Kisspeptin and neurokinin B interactions in modulating gonadotropin secretion in women with polycystic ovary syndrome","volume":"35","author":"Skorupskaite","year":"2020","journal-title":"Hum. Reprod."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.bbrc.2017.09.048","article-title":"Central and peripheral expression sites of phoenixin-14 immunoreactivity in rats","volume":"493","author":"Prinz","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1111\/j.1365-2826.2012.02381.x","article-title":"A novel reproductive peptide, phoenixin","volume":"25","author":"Yosten","year":"2013","journal-title":"J. Neuroendocrinol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"118533","DOI":"10.1016\/j.bbamcr.2019.118533","article-title":"Phoenixin-14 stimulates proliferation and insulin secretion in insulin producing INS-1E cells","volume":"1866","author":"Billert","year":"2019","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1530\/REP-19-0025","article-title":"Effect of the neuropeptide phoenixin and its receptor GPR173 during folliculogenesis","volume":"158","author":"Nguyen","year":"2019","journal-title":"Reproduction"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1016\/j.bbrc.2020.05.101","article-title":"Levels of the neuropeptide phoenixin-14 and its receptor GRP173 in the hypothalamus, ovary and periovarian adipose tissue in rat model of polycystic ovary syndrome","volume":"528","author":"Kalamon","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_64","first-page":"479","article-title":"Galanin and glypican-4 levels depending on metabolic and cardiovascular risk factors in patients with polycystic ovary syndrome","volume":"65","author":"Altinkaya","year":"2021","journal-title":"Arch. Endocrinol Metab."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"344","DOI":"10.3109\/09513599909167578","article-title":"Neuropeptide Y, leptin, galanin and insulin in women with polycystic ovary syndrome","volume":"13","author":"Baranowska","year":"1999","journal-title":"Gynecol. Endocrinol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"140","DOI":"10.3389\/fendo.2014.00140","article-title":"The Effect of Liraglutide on Weight Loss in Women with Polycystic Ovary Syndrome: An Observational Study","volume":"5","author":"Rasmussen","year":"2014","journal-title":"Front. Endocrinol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"4565","DOI":"10.1210\/jc.2013-2350","article-title":"Diagnosis and Treatment of Polycystic Ovary Syndrome: An Endocrine Society Clinical Practice Guideline","volume":"98","author":"Legro","year":"2013","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1080\/17512433.2017.1292125","article-title":"GLP-1 receptor agonists in the treatment of polycystic ovary syndrome","volume":"10","author":"Lamos","year":"2017","journal-title":"Expert Rev. Clin. Pharmacol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1016\/j.ebiom.2019.05.065","article-title":"Activation of arcuate nucleus GABA neurons promotes luteinizing hormone secretion and reproductive dysfunction: Implications for polycystic ovary syndrome","volume":"44","author":"Silva","year":"2019","journal-title":"EBioMedicine"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1093\/humrep\/dex086","article-title":"Increased cerebrospinal fluid levels of GABA, testosterone and estradiol in women with polycystic ovary syndrome","volume":"32","author":"Kawwass","year":"2017","journal-title":"Hum. Reprod."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2230","DOI":"10.1210\/en.2019-00428","article-title":"Neuroendocrine Impairments of Polycystic Ovary Syndrome","volume":"160","author":"Ruddenklau","year":"2019","journal-title":"Endocrinology"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12958-018-0354-x","article-title":"GnRH dysregulation in polycystic ovarian syndrome (PCOS) is a manifestation of an altered neurotransmitter profile","volume":"16","author":"Chaudhari","year":"2018","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1210\/jcem-52-3-592","article-title":"beta-Endorphin stimulates the secretion of insulin and glucagon in humans","volume":"52","author":"Reid","year":"1981","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1055\/s-0035-1564094","article-title":"\u03b2-endorphins Plasma Level is Higher in Lean Polycystic Ovary Syndrome (PCOS) Women","volume":"124","author":"Milewicz","year":"2016","journal-title":"Exp. Clin. Endocrinol. Diabetes"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.2174\/138161206776055895","article-title":"Role of opioid antagonists in the treatment of women with glucoregulation abnormalities","volume":"12","author":"Guido","year":"2006","journal-title":"Curr. Pharm. Des."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2564","DOI":"10.1093\/humrep\/den273","article-title":"Naltrexone treatment in clomiphene resistant women with polycystic ovary syndrome","volume":"23","author":"Ahmed","year":"2008","journal-title":"Hum. Reprod."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/1477-7827-11-68","article-title":"Unilateral or bilateral vagotomy induces ovulation in both ovaries of rats with polycystic ovarian syndrome","volume":"11","author":"Linares","year":"2013","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Linares, R., Acu\u00f1a, X.N., Rosas, G., Vieyra, E., Ram\u00edrez, D.A., Chaparro, A., Espinoza, J.A., Dom\u00ednguez, R., and Morales-Ledesma, L. (2021). Participation of the Cholinergic System in the Development of Polycystic Ovary Syndrome. Molecules, 26.","DOI":"10.3390\/molecules26185506"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.fertnstert.2007.11.022","article-title":"Risk of depression and other mental health disorders in women with polycystic ovary syndrome: A longitudinal study","volume":"91","author":"Kerchner","year":"2009","journal-title":"Fertil. Steril."}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/19\/5\/3089\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:32:52Z","timestamp":1760135572000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/19\/5\/3089"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,6]]},"references-count":79,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,3]]}},"alternative-id":["ijerph19053089"],"URL":"https:\/\/doi.org\/10.3390\/ijerph19053089","relation":{},"ISSN":["1660-4601"],"issn-type":[{"value":"1660-4601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,6]]}}}