{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T23:16:56Z","timestamp":1788131816613,"version":"build-2803163510"},"reference-count":42,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,6,8]],"date-time":"2022-06-08T00:00:00Z","timestamp":1654646400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and objectives: Kisspeptin, also named metastin, showed important roles in initiating the secretion of gonadotropin-releasing hormone (GnRH) and is an essential factor in the development of polycystic ovaries syndrome (PCOS). Several research studies noticed associations between kisspeptin levels and patients with anovulatory cycles due to PCOS with an increased LH\/FSH ratio. The aim of our study was to bring scientific evidence regarding the correlation between high kisspeptin and luteinizing hormone values in subfertile women due to PCOS. Materials and Methods: A prospective case-control study was conducted in \u201cElena Doamna\u201d Hospital of Obstetrics and Gynecology between 4 January 2021 and 1 March 2022. All patients agreed to participate in our study, had ages between 18 and 45 years old, and had a body mass index between 18.5 and 30 kg\/m2. The study group consisted of subfertile patients with PCOS and menstrual disturbances, including amenorrhea or oligomenorrhea. The control group consisted of healthy patients with ovulatory cycles and no other reproductive or endocrinology pathologies. During the follicular phase of their menstrual cycle, patients had blood samples taken with the dosage of kisspeptin, LH, FSH, estradiol, insulin, glycemic levels, testosterone, and prolactin. Pelvic ultrasounds and clinical examinations were performed as well. Results: Significant differences were observed in kisspeptin, LH, FSH, and estradiol levels between patients with PCOS and the control group. After the univariate analysis, PCOS was significantly associated with increased kisspeptin, increased LH, and decreased FSH. There was no significant association between PCOS, estradiol, prolactin, and insulin. Conclusions: kisspeptin serum values are higher in subfertile PCOS patients, supporting the hypothesis that an over-stimulation of the KISS1 system might cause the hyper-stimulation of the HPG-axis.<\/jats:p>","DOI":"10.3390\/medicina58060776","type":"journal-article","created":{"date-parts":[[2022,6,12]],"date-time":"2022-06-12T22:37:20Z","timestamp":1655073440000},"page":"776","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Kisspeptin Variations in Patients with Polycystic Ovary Syndrome\u2014A Prospective Case Control Study"],"prefix":"10.3390","volume":"58","author":[{"given":"Mona","family":"Akad","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Medicine and Pharmacy \u201cGr. T. Popa\u201d, 700115 Ia\u0219i, Romania"},{"name":"Clinical Hospital of Obstetrics and Pharmacy \u201cElena Doamna\u201d, 700398 Ia\u0219i, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8969-8016","authenticated-orcid":false,"given":"R\u0103zvan","family":"Socolov","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Medicine and Pharmacy \u201cGr. T. Popa\u201d, 700115 Ia\u0219i, Romania"},{"name":"Clinical Hospital of Obstetrics and Pharmacy \u201cElena Doamna\u201d, 700398 Ia\u0219i, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Furnic\u0103","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Medicine and Pharmacy \u201cGr. T. Popa\u201d, 700115 Ia\u0219i, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7386-0859","authenticated-orcid":false,"given":"Roxana","family":"Covali","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Medicine and Pharmacy \u201cGr. T. Popa\u201d, 700115 Ia\u0219i, Romania"},{"name":"Clinical Hospital of Obstetrics and Pharmacy \u201cElena Doamna\u201d, 700398 Ia\u0219i, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catalina Daniela","family":"Stan","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Medicine and Pharmacy \u201cGr. T. Popa\u201d, 700115 Ia\u0219i, Romania"},{"name":"Clinical Hospital of Obstetrics and Pharmacy \u201cElena Doamna\u201d, 700398 Ia\u0219i, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduard","family":"Crauciuc","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Medicine and Pharmacy \u201cGr. T. Popa\u201d, 700115 Ia\u0219i, Romania"},{"name":"Clinical Hospital of Obstetrics and Pharmacy \u201cElena Doamna\u201d, 700398 Ia\u0219i, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioana","family":"Pavaleanu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Medicine and Pharmacy \u201cGr. T. Popa\u201d, 700115 Ia\u0219i, Romania"},{"name":"Clinical Hospital of Obstetrics and Pharmacy \u201cElena Doamna\u201d, 700398 Ia\u0219i, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1093\/jnci\/88.23.1731","article-title":"KiSS-1, a novel human malignant melanoma metastasis-suppressor gene","volume":"88","author":"Lee","year":"1996","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_2","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_3","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1038\/35079135","article-title":"Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor","volume":"31","author":"Ohtaki","year":"2001","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.tem.2008.10.005","article-title":"Kisspeptins and GnRH neuronal signalling","volume":"20","author":"College","year":"2009","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3920","DOI":"10.1523\/JNEUROSCI.5740-08.2009","article-title":"Discovery of potent kisspeptin antagonists delineate physiological mechanisms of gonadotropin regulation","volume":"29","author":"Roseweir","year":"2009","journal-title":"J. Neurosci."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Li, X.F., Kinsey-Jones, J.S., Cheng, Y., Knox, A.M., Lin, Y., Petrou, N.A., Roseweir, A., Lightman, S.L., Milligan, S.R., and Millar, R.P. (2009). Kisspeptin signalling in the hypothalamic arcuate nucleus regulates GnRH pulse generator frequency in the rat. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0008334"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3958","DOI":"10.1210\/jc.2007-1116","article-title":"Kisspeptin-54 stimulates gonadotropin release most potently during the preovulatory phase of the menstrual cycle in women","volume":"92","author":"Dhillo","year":"2007","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"10714","DOI":"10.1073\/pnas.0704114104","article-title":"Hypogonadotropic hypogonadism in mice lacking a functional Kiss1 gene","volume":"104","author":"Fagg","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/S0079-6123(02)41090-4","article-title":"Hypothalamic control of gonadotropin secretion","volume":"141","author":"McCann","year":"2002","journal-title":"Prog. Brain Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"E953","DOI":"10.1210\/jc.2013-1569","article-title":"Increasing LH pulsatility in women with hypothalamic amenorrhoea using intravenous infusion of Kisspeptin-54","volume":"99","author":"Jayasena","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_11","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_12","unstructured":"National Institute of Health (2019, October 01). Evidence-Based Methodology Workshop on Polycystic Ovary Syndrome (3\u20135 December 2012). Executive Summary, Available online: https:\/\/Prevention.nih.gov\/docs\/programs\/pcos\/FinalReport.pdf."},{"key":"ref_13","first-page":"364","article-title":"Recommendations from the international evidence-based guideline for the assessement and management of polycystic ovary syndrome","volume":"110","author":"Teede","year":"2018","journal-title":"Human Reprod."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.mce.2006.04.030","article-title":"Kisspepeptin-gpr54 signaling in the neuroendocrine reproductive axis","volume":"254","author":"Gottsch","year":"2006","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.brainresrev.2007.05.006","article-title":"Estrogen positive feedback to gonadotropin-releasing hormone (GnRH) neurons in the rodent: The case for the rostral periventricular area of the third ventricle (RP3V)","volume":"57","author":"Herbison","year":"2008","journal-title":"Brain Res. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1159\/000356903","article-title":"Neuroanatomy of the human hypothalamic kisspeptin system","volume":"99","author":"Hrabovszky","year":"2014","journal-title":"Neuroendocrinology"},{"key":"ref_17","first-page":"E776","article-title":"FSH secretory pattern and degree of concordance with LH in amenorrheic, fertile and postmenopausal women","volume":"264","author":"Genazzani","year":"1993","journal-title":"Am. J. Physiol."},{"key":"ref_18","first-page":"577","article-title":"Use of metformin in the treatment of polycystic ovary syndrome","volume":"6","author":"Genazzani","year":"2010","journal-title":"Women\u2019s Health"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1016\/j.fertnstert.2016.01.029","article-title":"Spontaneous endogenous pulsatile release of kisspeptin is temporally coupled with luteinizing hormone in healthy women","volume":"105","author":"Meczekalski","year":"2016","journal-title":"Fertil. Steril."},{"key":"ref_20","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":"Human Reprod."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1080\/09513590.2018.1519792","article-title":"Serum Kisspeptin levels in unexplained infertility, polycystic ovary syndrome, and male factor infertility","volume":"35","author":"Kaya","year":"2019","journal-title":"Gynecol. Endocrinol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"73","DOI":"10.17816\/JOWD66673-80","article-title":"Kisspeptin and polycystic ovary syndrome\u2014Is there any connection?","volume":"66","author":"Yarmolinskaya","year":"2017","journal-title":"J. Obstet. Women\u2019s Dis."},{"key":"ref_23","first-page":"5","article-title":"Kisspeptin and galanin-like peptide (GALP) levels in women with PCOS","volume":"4","author":"Nyagolova","year":"2016","journal-title":"Int. J. Pharm. Med. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1007\/s00404-017-4509-3","article-title":"Kisspeptin expression features in the arcuate and anteroventral periventricular nuclei of hypothalamus of letrozole-induced polycystic ovarian syndrome in rats","volume":"296","author":"Aliabadi","year":"2017","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"510","DOI":"10.6061\/clinics\/2017(08)09","article-title":"Hypothalamic transcriptional expression of the kisspeptin system and sex steroid receptors differs among polycystic ovary syndrome rat models with different endocrine phenotypes","volume":"72","author":"Marcondes","year":"2017","journal-title":"Clinics"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1530\/JOE-16-0568","article-title":"Effect of androgen on Kiss1 expression and luteinizing hormone release in female rats","volume":"233","author":"Iwata","year":"2017","journal-title":"J. Endocrinol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"157","DOI":"10.5144\/0256-4947.2015.157","article-title":"Serum kisspeptin levels in normal and overweight Saudi females and its relation with anthropometric indices","volume":"35","author":"Rafique","year":"2015","journal-title":"Ann. Saudi Med."},{"key":"ref_28","first-page":"45","article-title":"Serum levels of spexin and kisspeptin negatively correlate with obesity and insulin resistance in women","volume":"16","author":"Korek","year":"2018","journal-title":"Physiol. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1159\/000350217","article-title":"Kisspeptin, leptin, and retinol-binding protein 4 in women with polycystic ovary syndrome","volume":"75","author":"Jeon","year":"2013","journal-title":"Gynecol. Obstet. Investig."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1080\/09513590.2017.1379499","article-title":"Is there a role for kisspeptin in pathogenesis of polycystic ovary syndrome?","volume":"34","author":"Gorkem","year":"2018","journal-title":"N. Gynecol. Endocrinol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"718","DOI":"10.3109\/09513590.2016.1161019","article-title":"Role of kisspeptin in polycystic ovary syndrome (PCOS)","volume":"32","author":"Ozay","year":"2016","journal-title":"Gynecol. Endocrinol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4315","DOI":"10.1210\/jc.2009-0406","article-title":"Subcutaneous Injection of Kisspeptin-54 Acutely Stimulates Gonadotropin Secretion in Women with Hypothalamic Amenorrhea, But Chronic Administration Causes Tachyphylaxis","volume":"94","author":"Jayasena","year":"2009","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1038\/clpt.2010.204","article-title":"Twice-Weekly Administration of Kisspeptin-54 for 8 Weeks Stimulates Release of Reproductive Hormones in Women With Hypothalamic Amenorrhea","volume":"88","author":"Jayasena","year":"2010","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_34","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_35","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_36","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.ejogrb.2016.02.004","article-title":"Immunohistochemical expression pattern of metastasis suppressors KAI1 and KISS1 in endometriosis and normal endometrium","volume":"199","author":"Timologou","year":"2016","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1210\/en.2009-0803","article-title":"Critical roles of kisspeptins in female puberty and preovulatory gonadotropin surges as revealed by a novel antagonist","volume":"151","author":"Pineda","year":"2010","journal-title":"M. Endocrinol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Nakamura, S., Uenoyama, Y., Ikegami, K., Dai, M., Watanabe, Y., Takahashi, C., Hirabayashi, M., Tsukamura, H., and Maeda, K.-I. (J. Neuroendocrinol., 2016). Neonatal kisspeptin is steroid-independently required for defeminisation and peripubertal kisspeptin-induced testosterone is required for masculinisation of the brain: A behavioural study using Kiss1 KO rats, J. Neuroendocrinol., in press.","DOI":"10.1111\/jne.12409"},{"key":"ref_39","unstructured":"Anushree, D., and Amitbah, K. (2019, January 19\u201321). The role of GnIH and GnIH-antagonist in ameliorating PCOS-like features in the ovary of DHEA-treated PCOS-mice. Proceedings of the International Conference on Reproduction, Endocrinology and Development, Navrachana University, Vadodara, India."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1111\/jne.12084","article-title":"Kisspeptin neurones do not directly signal to RFRP-3 neurones but RFRP-3 may directly modulate a subset of hypothalamic kisspeptin cells in mice","volume":"25","author":"Poling","year":"2013","journal-title":"J. Neuroendocrinol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"6215","DOI":"10.7314\/APJCP.2013.14.11.6215","article-title":"Kisspeptins (KiSS-1): Essential players in suppressing tumor metastasis","volume":"14","author":"Prabhu","year":"2013","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"5875","DOI":"10.1210\/en.2012-1747","article-title":"Single-cell analyses reveal that KISS1R-expressing cells undergo sustained kisspeptin-induced signaling that is dependent upon an influx of extracellular Ca2+","volume":"153","author":"Babwah","year":"2012","journal-title":"Endocrinology"}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/58\/6\/776\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:26:01Z","timestamp":1760138761000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/58\/6\/776"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,8]]},"references-count":42,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,6]]}},"alternative-id":["medicina58060776"],"URL":"https:\/\/doi.org\/10.3390\/medicina58060776","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,8]]}}}