{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T04:37:30Z","timestamp":1777523850640,"version":"3.51.4"},"reference-count":28,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T00:00:00Z","timestamp":1743638400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["21737001"],"award-info":[{"award-number":["21737001"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>Despite previous clinical studies providing some evidence of an association between metformin treatment and polycystic ovary syndrome(PCOS), these findings remain controversial. To investigate whether the association reflect causality, a two-sample Mendelian randomization (MR) method was conducted.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>Data from genome-wide association studies were analyzed, with the exposure factor being metformin and the outcome variable being PCOS. The inverse variance weighted(IVW) was used as the primary method for MR analysis. In addition, MR\u2013Egger, weighted median, heterogeneity tests, and sensitivity analyses were performed.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>The initial and validation MR analyses indicated that genetically predicted metformin treatment had no effects on PCOS. Sensitivity analyses provided additional confirmation of the reliability of the MR results.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Our two-sample MR analysis did not find genetic evidence supporting a significant association between metformin treatment and PCOS.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0321380","type":"journal-article","created":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T19:10:18Z","timestamp":1743707418000},"page":"e0321380","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Mendelian randomization study showed no causality between metformin treatment and polycystic ovary syndrome"],"prefix":"10.1371","volume":"20","author":[{"given":"Liting","family":"Lin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huan","family":"Shen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9030-7754","authenticated-orcid":true,"given":"Yanbin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,4,3]]},"reference":[{"issue":"10","key":"pone.0321380.ref001","doi-asserted-by":"crossref","first-page":"2447","DOI":"10.1210\/clinem\/dgad463","article-title":"Recommendations from the 2023 international evidence-based guideline for the assessment and management of polycystic ovary syndrome","volume":"108","author":"HJ Teede","year":"2023","journal-title":"J Clin Endocrinol Metab"},{"issue":"2","key":"pone.0321380.ref002","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1210\/clinem\/dgab613","article-title":"Health care-related economic burden of polycystic ovary syndrome in the united states: Pregnancy-related and long-term health consequences","volume":"107","author":"C Riestenberg","year":"2022","journal-title":"J Clin Endocrinol Metab"},{"issue":"1","key":"pone.0321380.ref003","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1210\/jcem-50-1-113","article-title":"Correlation of hyperandrogenism with hyperinsulinism in polycystic ovarian disease","volume":"50","author":"GA Burghen","year":"1980","journal-title":"J Clin Endocrinol Metab"},{"issue":"8","key":"pone.0321380.ref004","doi-asserted-by":"crossref","first-page":"4110","DOI":"10.3390\/ijms23084110","article-title":"Controversies in the pathogenesis, diagnosis and treatment of pcos: Focus on insulin resistance, inflammation, and hyperandrogenism","volume":"23","author":"D Armanini","year":"2022","journal-title":"Int J Mol Sci"},{"issue":"1","key":"pone.0321380.ref005","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1056\/NEJMct0707092","article-title":"Metformin for the treatment of the polycystic ovary syndrome","volume":"358","author":"JE Nestler","year":"2008","journal-title":"N Engl J Med"},{"issue":"2","key":"pone.0321380.ref006","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1007\/s11605-020-04900-3","article-title":"The impact of bariatric surgery compared to metformin therapy on pregnancy outcomes in patients with polycystic ovarian syndrome: A systematic review and meta-analysis","volume":"25","author":"C Chang","year":"2021","journal-title":"J Gastrointest Surg"},{"issue":"3","key":"pone.0321380.ref007","first-page":"CD003053","article-title":"Insulin-sensitising drugs (metformin, troglitazone, rosiglitazone, pioglitazone, D-chiro-inositol) for polycystic ovary syndrome","author":"JM Lord","year":"2003","journal-title":"Cochrane Database Syst Rev"},{"issue":"5","key":"pone.0321380.ref008","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1093\/humupd\/dmv025","article-title":"Metformin and lifestyle modification in polycystic ovary syndrome: Systematic review and meta-analysis","volume":"21","author":"N Naderpoor","year":"2015","journal-title":"Hum Reprod Update"},{"issue":"3","key":"pone.0321380.ref009","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1016\/j.fertnstert.2017.06.026","article-title":"Role of metformin for ovulation induction in infertile patients with polycystic ovary syndrome (PCOS): A guideline","volume":"108","author":"Practice Committee of the American Society for Reproductive Medicine. 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