{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T12:32:56Z","timestamp":1777984376588,"version":"3.51.4"},"update-to":[{"DOI":"10.12688\/f1000research.168971.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T00:00:00Z","timestamp":1769990400000}}],"reference-count":25,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T00:00:00Z","timestamp":1769990400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100022072","name":"Fakultas Kedokteran, Universitas Indonesia","doi-asserted-by":"publisher","award":["NKB-1401\/UN2.RST\/HKP.05.00\/2022"],"award-info":[{"award-number":["NKB-1401\/UN2.RST\/HKP.05.00\/2022"]}],"id":[{"id":"10.13039\/501100022072","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns5:p>\n                    Background Dysregulation of the HPG axis in PCOS causes increased frequency and amplitude of gonadotropin-releasing hormone (GnRH) pulsatility in the hypothalamus. Single nucleotide polymorphisms (SNPs) in the KISS1 gene may be associated with altered neuroendocrine signaling in PCOS. The present study aims to evaluate the association between two\n                    <ns5:italic>KISS1<\/ns5:italic>\n                    polymorphisms (rs4889 and rs5780218), their haplotypes, and the odds of PCOS in Indonesian women. Methods A cross-sectional study was conducted at Yasmin Clinic, dr. Cipto Mangunkusumo General Hospital, Indonesia, involving 60 women with PCOS and 60 healthy controls. Hormonal levels were assessed using ELISA, and genomic DNA was analyzed by Sanger sequencing. Demographic data were compared using independent t-tests, and chi-square tests were used for genotype and allele frequency analysis. Results The genotypic distribution of rs4889 was significantly different between the PCOS and control groups (p&lt;0.05), where the distribution of mutant genotype GG was higher in PCOS than in control (18.3% and 1.7%, respectively). The allele distribution of rs4889 and rs5782018 KISS1 SNPs were significantly different between both groups (p&lt;0.01 and p&lt;0.05, respectively). The rs4889 polymorphism was significantly different between the PCOS and control groups for the codominant and recessive models (p&lt;0.01). Moreover, the rs5780218 polymorphism was significantly different between the PCOS and control groups for the codominant and dominant models (p&lt;0.05). From the haplotype analysis, the G-CT haplotype was significantly different, with an OR value of 2.57 (1.33\u20134.96, p=0.0057). Conclusions\n                    <ns5:italic>KISS1<\/ns5:italic>\n                    rs4889 and rs5780218 polymorphisms, as well as the G\u2013CT haplotype, are associated with increased odds of PCOS in Indonesian women. These findings support a potential role of upstream neuroendocrine genetic variation in PCOS susceptibility; however, causal inferences cannot be drawn from this cross-sectional study.\n                  <\/ns5:p>","DOI":"10.12688\/f1000research.168971.2","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T14:09:06Z","timestamp":1770041346000},"page":"889","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["rs4889 and rs5782018 polymorphisms of KISS1 gene as genetic predisposing factor for PCOS in Indonesian women"],"prefix":"10.12688","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5626-1283","authenticated-orcid":false,"given":"Gita","family":"Pratama","sequence":"first","affiliation":[{"name":"Reproductive Immunoendocrinology Division, Department of Obstetrics and Gynecology Jakarta Special Capital Region of Jakarta University of Indonesia Faculty of Medicine"},{"name":"Yasmin IVF Clinic Central Jakarta Jakarta Hospital Dr Cipto Mangunkusumo"},{"name":"Human Reproduction, Infertility, and Family Planning Cluster, Indonesia Reproductive Medicine Research and Training Center Jakarta Special Capital Region of Jakarta University of Indonesia Faculty of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4558-3161","authenticated-orcid":false,"given":"Ririn","family":"R Febri","sequence":"additional","affiliation":[{"name":"Human Reproduction, Infertility, and Family Planning Cluster, Indonesia Reproductive Medicine Research and Training Center Jakarta Special Capital Region of Jakarta University of Indonesia Faculty of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mila","family":"Maidarti","sequence":"additional","affiliation":[{"name":"Reproductive Immunoendocrinology Division, Department of Obstetrics and Gynecology Jakarta Special Capital Region of Jakarta University of Indonesia Faculty of Medicine"},{"name":"Yasmin IVF Clinic Central Jakarta Jakarta Hospital Dr Cipto Mangunkusumo"},{"name":"Human Reproduction, Infertility, and Family Planning Cluster, Indonesia Reproductive Medicine Research and Training Center Jakarta Special Capital Region of Jakarta University of Indonesia Faculty of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Budi","family":"Wiweko","sequence":"additional","affiliation":[{"name":"Reproductive Immunoendocrinology Division, Department of Obstetrics and Gynecology Jakarta Special Capital Region of Jakarta University of Indonesia Faculty of Medicine"},{"name":"Yasmin IVF Clinic Central Jakarta Jakarta Hospital Dr Cipto Mangunkusumo"},{"name":"Human Reproduction, Infertility, and Family Planning Cluster, Indonesia Reproductive Medicine Research and Training Center Jakarta Special Capital Region of Jakarta University of Indonesia Faculty of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asmarinah","family":".","sequence":"additional","affiliation":[{"name":"Department of Medical Biology Jakarta Special Capital Region of Jakarta University of Indonesia Faculty of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7952-2893","authenticated-orcid":false,"given":"Indah","family":"S Widyahening","sequence":"additional","affiliation":[{"name":"Department of Community Medicine Jakarta Special Capital Region of Jakarta University of Indonesia Faculty of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4264-7729","authenticated-orcid":false,"given":"Trinovita","family":"Andraini","sequence":"additional","affiliation":[{"name":"Department of Physiology Jakarta Special Capital Region of Jakarta University of Indonesia Faculty of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0832-7628","authenticated-orcid":false,"given":"Hartanto","family":"Bayuaji","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Bandung West Java University of Padjadjaran Faculty of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7424-679X","authenticated-orcid":false,"given":"Andon","family":"Hestiantoro","sequence":"additional","affiliation":[{"name":"Reproductive Immunoendocrinology Division, Department of Obstetrics and Gynecology Jakarta Special Capital Region of Jakarta University of Indonesia Faculty of Medicine"},{"name":"Yasmin IVF Clinic Central Jakarta Jakarta Hospital Dr Cipto Mangunkusumo"},{"name":"Human Reproduction, Infertility, and Family Planning Cluster, Indonesia Reproductive Medicine Research and Training Center Jakarta Special Capital Region of Jakarta University of Indonesia Faculty of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5623-3995","authenticated-orcid":false,"given":"Mulyoto","family":"Pangestu","sequence":"additional","affiliation":[{"name":"Education Program in Reproduction and Development, Department of Obstetrics and Gynecology, School of Clinical Sciences Clayton Victoria Monash University"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2560","published-online":{"date-parts":[[2026,2,2]]},"reference":[{"key":"ref1","first-page":"1-6","article-title":"Polycystic ovary syndrome (PCOS) and genetic predisposition: A review article.","volume":"3","author":"N Ajmal","year":"2019","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol.: X."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1-15","DOI":"10.3389\/fphys.2016.00124","article-title":"Poly Cystic Ovarian Syndrome: An updated overview.","volume":"7","author":"S El Hayek","year":"2016","journal-title":"Front. Physiol."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"249-260","DOI":"10.2147\/TACG.S200341","article-title":"Genetic Basis of Polycystic Ovary Syndrome (PCOS): Current Perspectives.","volume":"12","author":"M Khan","year":"2019","journal-title":"Appl. Clin. Genet."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"201-205","DOI":"10.1080\/09674845.2020.1864109","article-title":"Association analysis of KISS1 polymorphisms and haplotypes with polycystic ovary syndrome.","volume":"78","author":"M Farsimadan","year":"2021","journal-title":"Br. J. Biomed. Sci."},{"key":"ref5","first-page":"1-10","article-title":"Influence of KISS1 gene polymorphisms on the risk of polycystic ovary syndrome and its associated variables in Saudi women.","volume":"2","author":"M Daghestani","year":"2020","journal-title":"BMC Endocr. Disord."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"185-190","DOI":"10.1080\/09674845.2020.1726662","article-title":"Relevance of KISS1 gene polymorphisms in susceptibility to polycystic ovary syndrome and its associated endocrine and metabolic disturbances.","volume":"77","author":"M Daghestani","year":"2020","journal-title":"Br. J. Biomed. Sci."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"149-157","DOI":"10.1007\/s12020-018-1609-1","article-title":"Kisspeptin and LH pulsatile temporal coupling in PCOS patients.","volume":"61","author":"K Katulski","year":"2018","journal-title":"Endocrine."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"8229","DOI":"10.1038\/s41598-024-58064-0","article-title":"Mechanism of elevated LH\/FSH ratio in lean PCOS revisited: a path analysis.","volume":"14","author":"G Pratama","year":"2024 Apr 8","journal-title":"Sci. Rep."},{"key":"ref9","doi-asserted-by":"crossref","first-page":"1-6","DOI":"10.1186\/s12929-018-0452-2","article-title":"rs4889 polymorphism in KISS1 gene, its effect on polycystic ovary syndrome development and anthropometric and hormonal parameters in Saudi women.","volume":"25","author":"F Albalawi","year":"2018","journal-title":"J. Biomed. Sci."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"19-25","DOI":"10.1016\/j.fertnstert.2003.10.004","article-title":"Revised 2003 consensus on diagnostic criteria and long- term health risks related to polycystic ovary syndrome (PCOS).","volume":"81","year":"2004","journal-title":"Fertil. Steril."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"228-236","DOI":"10.1038\/sj.ejhg.5201755","article-title":"Methods for the selection of tagging SNPs: A comparison of tagging efficiency and performance.","volume":"15","author":"K Ding","year":"2007","journal-title":"Eur. J. Hum. Genet."},{"key":"ref12","first-page":"1-13","article-title":"GnRH dysregulation in polycystic ovarian syndrome (PCOS) is a manifestation of an altered neurotransmitter profile.","author":"N Chaudhari","year":"2018"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"51-57","DOI":"10.1016\/j.ygcen.2017.12.007","article-title":"Evaluation of different ranges of LH: FSH Ratios in Polycystic ovarian syndrome (PCOS) - Clinical based case control study Post-Graduate and Research Department of Zoology, St. Thomas College Kozhencherry.","volume":"260","author":"N Malini","year":"2017","journal-title":"Gen. Comp. Endocrinol."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"1-8","DOI":"10.1155\/2020\/6237141","article-title":"The Correlation between Hormonal Disturbance in PCOS Women and Serum Level of Kisspeptin.","volume":"2020","author":"R Ibrahim","year":"2020","journal-title":"Int. J. Endocrinol."},{"key":"ref15","doi-asserted-by":"crossref","first-page":"1-13","DOI":"10.3390\/ijerph19053089","article-title":"Neuroendocrine Determinants of Polycystic Ovary Syndrome.","volume":"19","author":"A Szeliga","year":"2022","journal-title":"Int. J. Environ. Res. Public Health."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"1711-1716","DOI":"10.1007\/s11845-021-02733-w","article-title":"Kisspeptin levels in relation to sex hormone profile among PCOS patients.","volume":"191","author":"E Zarei","year":"2022","journal-title":"Ir. J. Med. Sci."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"1-11","DOI":"10.1111\/jne.12590","article-title":"Emerging insights into hypothalamic-pituitary-gonadal axis regulation and interaction with stress signalling.","volume":"30","author":"A Acevedo-Rodriguez","year":"2018","journal-title":"J. Neuroendocrinol."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"1-7","DOI":"10.3389\/fendo.2019.00298","article-title":"Kisspeptin and Polycystic Ovary Syndrome.","volume":"10","author":"R Tang","year":"2019","journal-title":"Front. Endocrinol."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"1-12","DOI":"10.3390\/nu13051677","article-title":"Natural Molecules in the Management of Polycystic Ovary Syndrome (PCOS): An Analytical Review.","volume":"13","author":"M Iervolino","year":"2021","journal-title":"Nutrients."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"14-21","DOI":"10.14740\/jem716","article-title":"Luteinizing Hormone to Follicle-Stimulating Hormone Ratio Significantly Correlates With Androgen Level and Manifestations Are More Frequent With Hyperandrogenemia in Women With Polycystic Ovary Syndrome.","volume":"11","author":"S Morshed","year":"2021","journal-title":"J. Endocrinol. Metab."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"1-16","DOI":"10.1155\/2013\/762615","article-title":"Polycystic Ovary Syndrome: Effect and Mechanisms of Acupuncture for Ovulation Induction.","volume":"2013","author":"J Johansson","year":"2013","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"ref22","first-page":"1-26","article-title":"Polycystic Ovarian Syndrome: A Complex Disease with a Genetics Approach.","volume":"10","author":"H Nautiyal","year":"2022","journal-title":"Biomedicine."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"1-10","DOI":"10.1155\/2019\/6235680","article-title":"Association of Kiss1 and GPR54 Gene Polymorphisms with Polycystic Ovary Syndrome among Sri Lankan Women.","volume":"2019","author":"U Branavan","year":"2019","journal-title":"Biomed. Res. Int."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"344-358","DOI":"10.1038\/nrg3903","article-title":"Haplotype-resolved genome sequencing: Experimental methods and applications.","volume":"16","author":"M Snyder","year":"2015","journal-title":"Nat. Rev. Genet."},{"key":"ref25","doi-asserted-by":"publisher","author":"G Pratama","year":"2025, August 6","DOI":"10.17605\/OSF.IO\/KFM6C"}],"container-title":["F1000Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/f1000research.com\/articles\/14-889\/v2\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/14-889\/v2\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/14-889\/v2\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T08:49:09Z","timestamp":1776242949000},"score":1,"resource":{"primary":{"URL":"https:\/\/f1000research.com\/articles\/14-889\/v2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,2]]},"references-count":25,"URL":"https:\/\/doi.org\/10.12688\/f1000research.168971.2","relation":{"has-version":[{"id-type":"doi","id":"10.12688\/f1000research.168971.1","asserted-by":"subject"}],"has-review":[{"id-type":"doi","id":"10.5256\/f1000research.194949.r468339","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.194949.r468339","asserted-by":"object"}]},"ISSN":["2046-1402"],"issn-type":[{"value":"2046-1402","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,2]]},"assertion":[{"value":"Indexed","URL":"https:\/\/f1000research.com\/articles\/14-889\/v2#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.186221.r413858, Mukhri Hamdan, Universiti Malaya, Kuala Lumpur, Federal Territory of Kuala Lumpur, 16 Sep 2025, version 1, 1 approved, 1 approved with reservations","URL":"https:\/\/f1000research.com\/articles\/14-889\/v1#referee-response-413858","order":0,"name":"referee-response-413858","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Gita Pratama<\/b>; \n<i>Posted: 07 Jan 2026<\/i>; Dear Reviewer, We sincerely thank you for your thorough, constructive, and insightful review of our manuscript entitled&nbsp;\n<i>\u201crs4889 and rs5782018 polymorphisms of KISS1 gene as genetic predisposing factor for PCOS in Indonesian women.\u201d<\/i>&nbsp;We greatly appreciate your recognition of the study\u2019s strengths and your detailed recommendations, which have substantially improved the rigor, clarity, and transparency of our work. Below, we provide a point-by-point response to each comment.&nbsp;  1. Primary outcome specification We agree with the reviewer. In the revised manuscript, we now explicitly state in the&nbsp;\n<i>Statistical Analysis<\/i>&nbsp;section that the&nbsp;\n<b>primary outcome<\/b>&nbsp;was the association between KISS1 polymorphisms (rs4889 and rs5780218) and PCOS status, evaluated under predefined inheritance models (codominant, dominant, recessive, and overdominant). Model selection was guided by&nbsp;\n<b>AIC and BIC<\/b>, which was prespecified as an exploratory approach rather than confirmatory hypothesis testing.&nbsp;We have clarified that results across multiple models should be interpreted as&nbsp;\n<b>exploratory<\/b>, and we have added a statement in the&nbsp;\n<i>Limitations<\/i>&nbsp;section regarding multiple testing and the absence of formal correction.  2. Sample size and power considerations We acknowledge this limitation. As this was an exploratory candidate-gene study, no formal a priori power calculation was performed. In the revised manuscript, we have added a&nbsp;\n<b>post-hoc power estimation<\/b>&nbsp;(with explicit caveats) based on the observed minor allele frequencies and detectable odds ratios at \u03b1 = 0.05. We further revised the&nbsp;\n<i>Results<\/i>&nbsp;and&nbsp;\n<i>Discussion<\/i>&nbsp;sections to emphasize&nbsp;\n<b>cautious interpretation of large ORs<\/b>, particularly for rare genotypes (e.g., rs4889 GG), and explicitly note the potential for overestimation due to small cell counts.  3. Recruitment flow and attrition We thank the reviewer for this important observation. Reasons for exclusion included incomplete clinical data, withdrawal of consent, and failure to meet inclusion criteria upon reassessment.&nbsp;We have also clarified this information in the&nbsp;\n<i>Subjects<\/i>&nbsp;subsection of the&nbsp;\n<i>Methods<\/i>&nbsp;and confirmed that no significant demographic differences were observed between included and excluded participants.  4. Group definition and stratification (lean vs obese) We agree and have corrected this inconsistency. BMI stratification (lean vs obese) is now&nbsp;\n<b>explicitly defined<\/b>&nbsp;in the&nbsp;\n<i>Methods<\/i>&nbsp;section using standard WHO cut-offs (BMI &lt;25 kg\/m&sup2; and \u226525 kg\/m&sup2;). We clarify that BMI stratification was&nbsp;\n<b>preplanned for descriptive endocrine comparisons only<\/b>&nbsp;and not for primary genetic association testing.&nbsp;All references to \u201cfour groups\u201d have been aligned with this clarification, and subgroup results are now clearly labeled in tables and text.  5. Normality, summary measures, and statistical tests We have reassessed data distributions using normality testing. Variables with non-normal distributions are now presented as&nbsp;\n<b>median (IQR)<\/b>, and corresponding analyses were performed using&nbsp;\n<b>Mann\u2013Whitney U tests<\/b>. Normally distributed variables are reported as&nbsp;\n<b>mean &plusmn; SD<\/b>&nbsp;with appropriate parametric testing. All tables and text have been revised to ensure consistency between reported summary measures and statistical tests.  6. Genotyping quality control We have expanded the&nbsp;\n<i>Genotyping Methods<\/i>&nbsp;section to include detailed quality-control procedures, including:  Per-SNP and per-sample call rates Duplicate sample concordance Manual chromatogram re-evaluation for ambiguous calls Hardy\u2013Weinberg equilibrium testing in controls  We also clarify that&nbsp;\n<b>Fisher\u2019s exact test<\/b>&nbsp;was applied where expected cell counts were &lt;5.  7. Population structure and stratification bias We acknowledge this limitation. In the revised manuscript, we describe recruitment geography (Jakarta and surrounding regions) and explicitly discuss the&nbsp;\n<b>risk of population stratification<\/b>&nbsp;due to Indonesia\u2019s genetic diversity. As genome-wide markers were unavailable, adjustment using principal components was not feasible; this is now clearly stated as a limitation.  8. Confounding adjustment We have now included&nbsp;\n<b>multivariable logistic regression analyses<\/b>&nbsp;adjusting for age, BMI, and HOMA-IR. Both crude and adjusted odds ratios with 95% confidence intervals are presented in the revised results. Covariate selection was based on established PCOS risk factors and biological plausibility, as now stated in the&nbsp;\n<i>Statistical Analysis<\/i>&nbsp;section.  9. Haplotype and linkage disequilibrium reporting We have added&nbsp;\n<b>r&sup2; values<\/b>&nbsp;alongside D\u2032 to provide a more complete LD assessment. Haplotype frequencies with confidence intervals are now reported, and we discuss the&nbsp;\n<b>instability of low-frequency haplotypes<\/b>&nbsp;and limited inference power given the sample size.  10. Kisspeptin assay standardization and cycle timing We have expanded the&nbsp;\n<i>Hormone Measurements<\/i>&nbsp;section to include assay performance characteristics (limit of detection, intra- and inter-assay CVs, sample handling, and freeze\u2013thaw procedures).&nbsp;  11. Diagnostic criteria and androgen measurement We have clarified the definition of hyperandrogenism, acknowledged the limitations of immunoassay-based testosterone measurement compared with LC-MS\/MS, and provided laboratory reference ranges. The handling of cosmetic hair removal in Ferriman\u2013Gallwey scoring is now described, and inter-rater consistency procedures are noted where applicable.  12. Causal language in title and conclusions We fully agree and have revised the&nbsp;\n<b>results interpretation and conclusions<\/b>&nbsp;to replace causal language with&nbsp;\n<b>\u201cassociated with increased odds of PCOS.\u201d<\/b>&nbsp;This change has been applied consistently throughout the manuscript.  Once again, we thank the reviewer for their thoughtful and detailed critique. We believe these revisions substantially strengthen the methodological transparency and interpretability of our study, and we hope the revised manuscript satisfactorily addresses all concerns raised.  Sincerely, Authors","URL":"https:\/\/f1000research.com\/articles\/14-889\/v2#referee-comment-15219","order":1,"name":"referee-comment-15219","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.186221.r445139, Mushtak T. S. Al-Ouqaili, Department of Microbiology, University of Anbar, College of Medicine, Ramadi, 05 Jan 2026, version 1, 1 approved, 1 approved with reservations","URL":"https:\/\/f1000research.com\/articles\/14-889\/v1#referee-response-445139","order":2,"name":"referee-response-445139","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.194949.r468339, Mohd Faizal Ahmad, Department of Obstetrics & Gynecology, Faculty of Medicine, National University of Malaysia, Kuala Lumpur, 15 Apr 2026, version 2, indexed","URL":"https:\/\/f1000research.com\/articles\/14-889\/v2#referee-response-468339","order":3,"name":"referee-response-468339","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"The author(s) declared that no grants were involved in supporting this work","order":4,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}