{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T18:57:22Z","timestamp":1781636242211,"version":"3.54.5"},"reference-count":23,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T00:00:00Z","timestamp":1771891200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"vor","delay-in-days":34,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100009232","name":"University of Debrecen","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100009232","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Women's Health"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Transition metals such as iron and manganese are critical for cellular metabolism, redox balance, and immune function, and they also influence host\u2013pathogen interactions. Vaginitis is characterized by mucosal inflammation that may alter local trace-element homeostasis. We hypothesize that inflammatory conditions such as vaginitis may be associated with altered cervicovaginal iron and manganese levels. We performed a prospective, single-center cohort study at the University of Debrecen (Hungary) between April 2023 and April 2024, enrolling 80 women\u2009\u2265\u200918 years with vulvovaginal complaints. Participants were assessed at baseline and at weeks 4, 8, and 12 with clinical evaluation and cervicovaginal lavage (CVL) sampling, collected using metal-free instruments. Participants were randomized 1:1 to receive either fluconazole alone or a single baseline oral fluconazole plus an intravaginal zinc-containing hydrogel. CVL samples were digested and analyzed for iron and manganese using ICP-OES. Group comparisons were performed using linear mixed-effects models with a random intercept for participant. CVL Fe concentrations were higher in women with culture-positive vaginitis compared with controls (mean\u2009\u00b1\u2009SD: 56.36\u2009\u00b1\u200924.84 vs. 44.64\u2009\u00b1\u200920.11), with a significant between-group difference in mixed-effects models (\u0394\u2009=\u20098.82, 95% CI 0.74 to 16.89;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.032). Mn concentrations did not differ between vaginitis and controls (1.42\u2009\u00b1\u20090.73 vs. 1.09\u2009\u00b1\u20090.77;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.542). In subgroup analyses, Fe remained significantly higher in vaginitis compared with controls among women who did not use the hydrogel (60.69\u2009\u00b1\u200926.53 vs. 47.27\u2009\u00b1\u200921.87;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.041), whereas the difference was attenuated and no longer significant among hydrogel users (53.64\u2009\u00b1\u200923.62 vs. 41.75\u2009\u00b1\u200917.71;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.148). Within the vaginitis cohort, Fe and Mn concentrations were similar across culture-defined phenotypes (bacterial-positive vs. fungal-positive) and between fungal culture-negative and fungal-positive samples. Culture-positive vaginitis was associated with higher total cervicovaginal iron concentrations, while manganese remained largely unchanged. Adjunct topical zinc therapy appeared to temper the vaginitis-associated elevation in iron, consistent with improved mucosal integrity and reduced inflammation-driven iron availability. Total Fe and Mn concentrations in CVL did not distinguish vaginitis phenotypes, supporting their use primarily as reference values and motivating future work focused on bioavailable metal fractions and metal-binding host proteins. The study protocol was approved by the Hungarian National Institutional Review Medical Research Council (approval No. 3282-7\/2023\/EUIG).\n                  <\/jats:p>","DOI":"10.1186\/s12905-026-04339-9","type":"journal-article","created":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T23:24:58Z","timestamp":1771889098000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cervicovaginal lavage fluid iron and manganese levels in women with and without vaginitis"],"prefix":"10.1186","volume":"26","author":[{"given":"Barbara","family":"Kozma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Ratonyi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bence","family":"Kozma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Takacs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Attila G.","family":"Sipos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,24]]},"reference":[{"issue":"2","key":"4339_CR1","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1016\/j.cbpa.2009.11.008","volume":"\u201304","author":"TE Kehl-Fie","year":"2010","unstructured":"Kehl-Fie TE, Skaar EP. Nutritional immunity beyond iron: a role for manganese and zinc. Curr Opin Chem Biol. 2010;\u201304(2):218\u201324.","journal-title":"Curr Opin Chem Biol"},{"key":"4339_CR2","doi-asserted-by":"crossref","unstructured":"Waldron KJ, Rutherford JC, Ford D, Robinson NJ. Metalloproteins and metal sensing. Nature. 2009-08-13;460(7257):823\u201330.","DOI":"10.1038\/nature08300"},{"issue":"11","key":"4339_CR3","doi-asserted-by":"publisher","first-page":"105352","DOI":"10.1016\/j.isci.2022.105352","volume":"25","author":"H Sui","year":"2022","unstructured":"Sui H, Chen Q, Yang J, Srirattanapirom S, Imamichi T. Manganese enhances DNA- or RNA-mediated innate immune response by inducing phosphorylation of TANK-binding kinase 1. iScience. 2022;25(11):105352. https:\/\/doi.org\/10.1016\/j.isci.2022.105352. PMID: 36325059; PMCID: PMC9619380).","journal-title":"iScience"},{"key":"4339_CR4","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.mib.2019.05.006","volume":"\u201312","author":"U Roy","year":"2019","unstructured":"Roy U, Kornitzer D. Heme-iron acquisition in fungi. Curr Opin Microbiol. 2019;\u201312:52:77\u201383.","journal-title":"Curr Opin Microbiol"},{"key":"4339_CR5","doi-asserted-by":"crossref","unstructured":"Schaible UE, Kaufmann SHE. Iron and microbial infection. Nat Rev Microbiol. 2004 -12;2(12):946\u201353.","DOI":"10.1038\/nrmicro1046"},{"key":"4339_CR6","doi-asserted-by":"publisher","unstructured":"Dickson KB, Zhou J. Role of reactive oxygen species and iron in host defense against infection. Front Biosci (Landmark Ed). 2020-03-01;25(8):1600\u20131616. https:\/\/doi.org\/10.2741\/4869.","DOI":"10.2741\/4869"},{"key":"4339_CR7","doi-asserted-by":"publisher","unstructured":"Erikson KM, Aschner M, Manganese. Its role in disease and health. Met Ions Life Sci. 2019-01-14;19:\/books\/9783110527872\/9783110527872,016.xml https:\/\/doi.org\/10.1515\/9783110527872-016.","DOI":"10.1515\/9783110527872-016"},{"key":"4339_CR8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/bs.pmbts.2016.05.002","volume":"142","author":"JL Kelliher","year":"2016","unstructured":"Kelliher JL, Kehl-Fie TE. Competition for manganese at the host-pathogen interface. Prog Mol Biol Transl Sci. 2016;142:1\u201325.","journal-title":"Prog Mol Biol Transl Sci"},{"key":"4339_CR9","doi-asserted-by":"crossref","unstructured":"Foster AW, Osman D, Robinson NJ. Metal preferences and metallation. J Biol Chem 2014-10-10;289(41):28095\u2013103.","DOI":"10.1074\/jbc.R114.588145"},{"key":"4339_CR10","doi-asserted-by":"crossref","unstructured":"Marnach ML, Wygant JN, Casey PM. Evaluation and Management of Vaginitis. 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Clin Obstet Gynecol. 2008;51(3):549.","journal-title":"Clin Obstet Gynecol"},{"key":"4339_CR18","doi-asserted-by":"crossref","unstructured":"Gonzalez-Martin R, Palomar A, Qui\u00f1onero A, Pellicer N, Fernandez-Saavedra R, Conde-Vilda E, et al. The impact of essential trace elements on ovarian response and reproductive outcomes following single euploid embryo transfer. Int J Mol Sci. 2023-06-30;24(13):10968.","DOI":"10.3390\/ijms241310968"},{"key":"4339_CR19","doi-asserted-by":"publisher","unstructured":"Gonzalez-Martin R, Palomar A, Perez-Deben S, Salsano S, Qui\u00f1onero A, Caracena L et al. Higher concentrations of essential trace elements in women undergoing IVF May be associated with poor reproductive outcomes following single euploid embryo transfer. 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Genomic analyses identify manganese homeostasis as a driver of group B Streptococcal vaginal Colonization. mBio. 2022-06-28;13(3):e0098522.","DOI":"10.1128\/mbio.00985-22"}],"container-title":["BMC Women's Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12905-026-04339-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12905-026-04339-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12905-026-04339-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T18:44:06Z","timestamp":1781635446000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12905-026-04339-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,24]]},"references-count":23,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["4339"],"URL":"https:\/\/doi.org\/10.1186\/s12905-026-04339-9","relation":{},"ISSN":["1472-6874"],"issn-type":[{"value":"1472-6874","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,24]]},"assertion":[{"value":"15 October 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 February 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 February 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study protocol was approved by the Hungarian National Institutional Review Medical Research Council (approval No. 3282-7\/2023\/EUIG). Each participant signed a written informed consent form. All procedures performed in studies involving human participants were under the ethical standards of the Hungarian National Institutional Review Medical Research Council and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"185"}}