{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T13:11:27Z","timestamp":1792069887220,"version":"4.4.0"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:00:00Z","timestamp":1775692800000},"content-version":"vor","delay-in-days":22,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Galala University"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Women's Health"],"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n Recurrent vulvovaginal candidiasis is a substantial personal and healthcare burden. This systematic review assessed the effects of topical versus oral maintenance antifungal therapy in women with recurrent vulvovaginal candidiasis to improve outcomes.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n We conducted a comprehensive search of bibliographic databases (CENTRAL, MEDLINE\/PubMed), citation indexes (Web of Science, Scopus), and clinical trial registries (ClinicalTrials.gov, WHO ICTRP) from inception to March 2025, without language or publication status restrictions. We screened reference lists of relevant studies and systematic reviews. We included randomized trials comparing topical versus oral maintenance antifungal therapy for recurrent vulvovaginal candidiasis. Three reviewers independently screened the records, assessed the full texts, extracted the data, and assessed the risk of bias. The primary outcome was the proportion of participants with no clinical or mycological recurrence at the end of follow-up. We performed a common-effect meta-analysis. We used the GRADE approach to assess the certainty of evidence and generate a summary of findings table.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n We identified six eligible trials (1224 participants), five completed trials with results (792 participants) and one completed trial awaiting results (432 participants). All studies included women with recurrent vulvovaginal candidiasis. In the oral arm, five studies used fluconazole and one study used itraconazole. In the topical arm, three studies used clotrimazole, one used a combination of clotrimazole-diclofenac, one used fenticonazole, and one used nystatin. Five studies continued outcome measurement for six months after completion of the maintenance phase. Most of the included studies were judged to be at high risk of bias. The pooled estimates of the effects are not significantly different across all outcomes, including clinical or mycological recurrence, satisfaction, and adverse events. The evidence for all outcomes was very uncertain due to serious methodological concerns and imprecision.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n The evidence is very uncertain about the benefits and harms of oral versus topical antifungal maintenance therapy for women with recurrent vulvovaginal candidiasis. Given the substantial personal and healthcare burden of the condition, the uncertainty of the evidence leaves a crucial gap in guidance for clinicians and patients when choosing a maintenance strategy.<\/jats:p>\n <\/jats:sec>\n \n Review registration<\/jats:title>\n \n OSF\n osf.io\/g7fzy<\/jats:ext-link>\n .\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1186\/s12905-026-04356-8","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:46:22Z","timestamp":1773794782000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Oral versus topical maintenance antifungal therapy for recurrent vulvovaginal candidiasis: a systematic review and meta-analysis"],"prefix":"10.1186","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-5877-4722","authenticated-orcid":false,"given":"Sara Ibrahim","family":"Abdelkader","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6686-8019","authenticated-orcid":false,"given":"Sally Aboelthana","family":"Aboelenin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2662-9863","authenticated-orcid":false,"given":"Rahma Alaa","family":"Abdelhafez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4572-2210","authenticated-orcid":false,"given":"Ashraf Fawzy","family":"Nabhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,18]]},"reference":[{"key":"4356_CR1","doi-asserted-by":"publisher","unstructured":"Denning DW, Kneale M, Sobel JD, Rautemaa-Richardson R. Global burden of recurrent vulvovaginal candidiasis: a systematic review. The Lancet Infectious Diseases. 2018;18:e339\u201347. Available from: https:\/\/doi.org\/10.1016\/S1473-3099(18)30103-8.","DOI":"10.1016\/S1473-3099(18)30103-8"},{"key":"4356_CR2","first-page":"3306","volume":"61","author":"JD Sobel","year":"2000","unstructured":"Sobel JD. Treatment of recurrent vulvovaginal candidiasis. Am Family Phys. 2000;61:3306\u201312.","journal-title":"Am Family Phys"},{"issue":"12","key":"4356_CR3","doi-asserted-by":"publisher","first-page":"1124","DOI":"10.1177\/0956462420943034","volume":"31","author":"GDGC Edwards","year":"2020","unstructured":"Saxon (Lead Author), Edwards GDGC, Rautemaa-Richardson A. British Association for Sexual Health and HIV national guideline for the management of vulvovaginal candidiasis (2019). Int J STD AIDS. 2020;31(12):1124\u201344.","journal-title":"Int J STD AIDS"},{"key":"4356_CR4","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.ajog.2015.06.067","volume":"214","author":"JD Sobel","year":"2016","unstructured":"Sobel JD. Recurrent vulvovaginal candidiasis. Am J Obstet Gynecol. 2016;214:15\u201321.","journal-title":"Am J Obstet Gynecol"},{"key":"4356_CR5","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1111\/ajo.12592","volume":"57","author":"A Matheson","year":"2017","unstructured":"Matheson A, Mazza D. Recurrent vulvovaginal candidiasis: A review of guideline recommendations. Aust N Z J Obstet Gynaecol. 2017;57:139\u201345.","journal-title":"Aust N Z J Obstet Gynaecol"},{"key":"4356_CR6","doi-asserted-by":"crossref","unstructured":"Rosati D, Bruno M, Jaeger M, Oever J ten, Netea MG. Recurrent vulvovaginal candidiasis: An immunological perspective. Microorganisms. 2020;8:144.","DOI":"10.3390\/microorganisms8020144"},{"key":"4356_CR7","doi-asserted-by":"publisher","unstructured":"DondersG, Sziller IO, Paavonen J, Hay P, de Seta F, Bohbot JM, et al. Management of recurrent vulvovaginal candidosis: narrative review of the literature and European expert panel opinion. Front Cell Infect Microbiol. 2022;12:934353. https:\/\/doi.org\/10.3389\/fcimb.2022.934353.","DOI":"10.3389\/fcimb.2022.934353"},{"key":"4356_CR8","doi-asserted-by":"publisher","first-page":"S162","DOI":"10.1093\/cid\/ciab1057","volume":"74","author":"P Nyirjesy","year":"2022","unstructured":"Nyirjesy P, Brookhart C, Lazenby G, Schwebke J, Sobel JD. Vulvovaginal Candidiasis: A Review of the Evidence for the 2021 Centers for Disease Control and Prevention of Sexually Transmitted Infections Treatment Guidelines. Clin Infect Dis. 2022;74:S162\u20138.","journal-title":"Clin Infect Dis"},{"key":"4356_CR9","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1093\/cid\/ciad002","volume":"76","author":"JD Sobel","year":"2023","unstructured":"Sobel JD. New Antifungals for Vulvovaginal Candidiasis: What Is Their Role? Clin Infect Dis. 2023;76:783\u20135.","journal-title":"Clin Infect Dis"},{"key":"4356_CR10","unstructured":"Kiss H. A phase IIb\/III study of prof-001 for the treatment of patients with recurrent vulvovaginal candidiasis (RVVC). 2021. Available from: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04734405."},{"key":"4356_CR11","doi-asserted-by":"publisher","unstructured":"Cooke G, Watson C, Deckx L, Pirotta M, Smith J, van Driel ML. Treatment for recurrent vulvovaginal candidiasis (thrush). Cochrane Database of Systematic Reviews. 2022;2022. Available from: https:\/\/doi.org\/10.1002\/14651858.CD009151.pub2.","DOI":"10.1002\/14651858.CD009151.pub2"},{"key":"4356_CR12","unstructured":"Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, et al. editors. Cochrane handbook for systematic reviews of interventions, version 6.5 (updated august 2024). Cochrane; 2024. Available from: https:\/\/www.training.cochrane.org\/handbook."},{"key":"4356_CR13","doi-asserted-by":"crossref","unstructured":"Abdelkader SI, Aboelenin SA, AbdelHafez RA, Nabhan AF. Oral versus topical maintenance antifungal therapy for recurrent vulvovaginal candidiasis. OSF; 2025. Available from: https:\/\/osf.io\/g7fzy.","DOI":"10.21203\/rs.3.rs-6605031\/v1"},{"key":"4356_CR14","doi-asserted-by":"publisher","first-page":"n160","DOI":"10.1136\/bmj.n160","volume":"372","author":"MJ Page","year":"2021","unstructured":"Page MJ, Moher D, Bossuyt PJ, Boutron I, Hoffmann T, Mulrow CD, et al. PRISMA 2020 explanation and elaboration: Updated guidance and exemplars for reporting systematic reviews. BMJ. 2021;372:n160.","journal-title":"BMJ"},{"key":"4356_CR15","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.jclinepi.2016.01.021","volume":"75","author":"J McGowan","year":"2016","unstructured":"McGowan J, Sampson M, Salzwedel DM, Cogo E, Foerster V, Lefebvre C. PRESS peer review of electronic search strategies: 2015 guideline statement. J Clin Epidemiol. 2016;75:40\u20136.","journal-title":"J Clin Epidemiol"},{"key":"4356_CR16","first-page":"1","volume":"1","author":"C Lefebvre","year":"2019","unstructured":"Lefebvre C, Glanville J, Briscoe S, Littlewood A, Marshall C, Metzendorf MI, et al. Cochrane highly sensitive search strategies for identifying randomized trials in MEDLINE. Cochrane Methods. 2019;1:1\u201311.","journal-title":"Cochrane Methods"},{"key":"4356_CR17","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1186\/s13643-016-0384-4","volume":"5","author":"M Ouzzani","year":"2016","unstructured":"Ouzzani M, Hammady H, Fedorowicz Z, Elmagarmid A. Rayyan\u2014a web and mobile app for systematic reviews. Syst Reviews. 2016;5:210.","journal-title":"Syst Reviews"},{"key":"4356_CR18","unstructured":"Higgins JPT, Savovi\u0107 J, Page MJ, Elbers RG, Sterne JAC et al. Chapter 8: Assessing risk of bias in a randomized trial. In: Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, editors. Cochrane handbook for systematic reviews of interventions. Version 6.5. Cochrane; 2024. Available from: https:\/\/training.cochrane.org\/handbook."},{"key":"4356_CR19","doi-asserted-by":"publisher","first-page":"l4898","DOI":"10.1136\/bmj.l4898","volume":"366","author":"JAC Sterne","year":"2019","unstructured":"Sterne JAC, Savovi\u0107 J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: A revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366:l4898.","journal-title":"BMJ"},{"key":"4356_CR20","unstructured":"Higgins JP, Eldridge S, Li T et al. Chapter 23: Including variants on randomized trials. In: Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, editors. Cochrane handbook for systematic reviews of interventions version 65. Cochrane; 2024. Available from: https:\/\/www.training.cochrane.org\/handbook."},{"key":"4356_CR21","unstructured":"Deeks JJ, Higgins JPT, Altman DG, McKenzie JE, Veroniki AA et al. Chapter 10: Analysing data and undertaking meta-analyses. In: Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, editors. Cochrane handbook for systematic reviews of interventions. Version 6.5. Cochrane; 2024. Available from: https:\/\/training.cochrane.org\/handbook."},{"key":"4356_CR22","unstructured":"R Core Team. R: A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing. 2024. Available from: https:\/\/www.R-project.org\/."},{"key":"4356_CR23","unstructured":"Schwarzer G, Carpenter JR, R\u00fccker G, Meta. General package for meta-analysis. 2024. Available from: https:\/\/cran.r-project.org\/package=meta."},{"key":"4356_CR24","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1136\/bmj.315.7109.629","volume":"315","author":"M Egger","year":"1997","unstructured":"Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629\u201334.","journal-title":"BMJ"},{"key":"4356_CR25","unstructured":"Page MJ, Higgins JPT, Sterne JAC et al. Chapter 13: Assessing risk of bias due to missing evidence in a meta-analysis. In: Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, editors. Cochrane handbook for systematic reviews of interventions. Version 6.5. Cochrane; 2024. Available from: https:\/\/training.cochrane.org\/handbook."},{"key":"4356_CR26","unstructured":"Sch\u00fcnemann HJ, Higgins JPT, Vist GE, Glasziou P, Akl EA, Skoetz N et al. Chapter 14: Completing summary of findings tables and grading the certainty of the evidence. In: Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, editors. Cochrane handbook for systematic reviews of interventions. Version 6.5. Cochrane; 2024. Available from: https:\/\/training.cochrane.org\/handbook."},{"key":"4356_CR27","unstructured":"GRADE Working Group. GRADE handbook. 2025. Available from: https:\/\/gdt.gradepro.org\/app\/handbook\/handbook.html."},{"key":"4356_CR28","unstructured":"McMaster, University. Evidence Prime. GRADEpro GDT: GRADEpro guideline development tool. 2023. Available from: https:\/\/www.gradepro.org."},{"key":"4356_CR29","doi-asserted-by":"publisher","first-page":"e1230","DOI":"10.1002\/cl2.1230","volume":"18","author":"NR Haddaway","year":"2022","unstructured":"Haddaway NR, Page MJ, Pritchard CC, McGuinness LA. PRISMA2020: An r package and shiny app for producing PRISMA 2020-compliant flow diagrams, with interactivity for optimised digital transparency and open synthesis. Campbell Syst Reviews. 2022;18:e1230.","journal-title":"Campbell Syst Reviews"},{"key":"4356_CR30","doi-asserted-by":"publisher","first-page":"148","DOI":"10.18565\/aig.2024.241","volume":"102024","author":"DYE Dobrokhotova","year":"2024","unstructured":"Dobrokhotova DYE, Borovkova BEI, Burdenko BMV, Kovler S, Kovler SE. Long-term outcomes of prolonged fenticonazole therapy in patients with recurrent vulvovaginal candidiasis. Akusherstvo i ginekologiia. 2024;102024:148\u201357.","journal-title":"Akusherstvo i ginekologiia"},{"key":"4356_CR31","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1007\/s11046-014-9827-4","volume":"179","author":"S Fan","year":"2014","unstructured":"Fan S, Liu X, Wu C, Xu L, Li J. Vaginal Nystatin Versus Oral Fluconazole for the Treatment for Recurrent Vulvovaginal Candidiasis. Mycopathologia. 2014;179:95\u2013101.","journal-title":"Mycopathologia"},{"key":"4356_CR32","first-page":"17","volume":"2","author":"Z Fardyazar","year":"2007","unstructured":"Fardyazar Z, Habibzadeh S, Fard SA, Tello M. Vaginal azoles versus oral fluconazole in treatment of recurrent vulvovaginal candidiasis. Iran J Clin Infect Dis. 2007;2:17\u201322.","journal-title":"Iran J Clin Infect Dis"},{"key":"4356_CR33","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1136\/sti.68.6.374","volume":"68","author":"IW Fong","year":"1992","unstructured":"Fong IW. The value of chronic suppressive therapy with itraconazole versus clotrimazole in women with recurrent vaginal candidiasis. Sex Transm Infect. 1992;68:374\u20137.","journal-title":"Sex Transm Infect"},{"key":"4356_CR34","unstructured":"NCT04734405. Phase IIb\/III parallel-arm, randomized, active-controlled, double-blind, double-dummy, multicenter, non-inferiority study in patients with recurrent vulvovaginal candidiasis to compare the efficacy, safety and tolerability of topically administered ProF-001 versus oral fluconazole. ClinicalTrials.gov Identifier: NCT04734405. Available from: https:\/\/clinicaltrials.gov\/study\/NCT04734405. Accessed 16 Feb 2026."},{"key":"4356_CR35","first-page":"27","volume":"33","author":"AEE Shaheen","year":"2020","unstructured":"Shaheen AEE, Omran LAA, Kandil M, Sayyed TM. Oral versus topical antifungal treatment for recurrent vulvovaginal candidiasis. Menoufia Med J. 2020;33:27.","journal-title":"Menoufia Med J"},{"key":"4356_CR36","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1016\/j.ejogrb.2024.09.040","volume":"302","author":"B Gardella","year":"2024","unstructured":"Gardella B, Cassani C, Dominoni M, Pasquali MF, Spinillo A. Maintenance pharmacological therapy of recurrent vulvovaginal candidiasis. A Bayesian network meta-analysis of randomized studies. Eur J Obstet Gynecol Reproductive Biology. 2024;302:310\u20136.","journal-title":"Eur J Obstet Gynecol Reproductive Biology"},{"key":"4356_CR37","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1590\/1806-9282.20210916","volume":"68","author":"J L\u00edrio","year":"2022","unstructured":"L\u00edrio J, Giraldo PC, Sarmento AC, Costa APF, Cobucci RN, Saconato H, et al. Antifungal (oral and vaginal) therapy for recurrent vulvovaginal candidiasis: A systematic review and meta-analysis. Revista da Associa\u00e7\u00e3o M\u00e9dica Brasileira. 2022;68:261\u20137.","journal-title":"Revista da Associa\u00e7\u00e3o M\u00e9dica Brasileira"},{"key":"4356_CR38","doi-asserted-by":"publisher","unstructured":"Denison HJ, Worswick J, Bond CM, Grimshaw JM, Mayhew A, Gnani Ramadoss S et al. Oral versus intra-vaginal imidazole and triazole anti-fungal treatment of uncomplicated vulvovaginal candidiasis (thrush). Cochrane Database of Systematic Reviews. 2020;2020. Available from: https:\/\/doi.org\/10.1002\/14651858.CD002845.pub3.","DOI":"10.1002\/14651858.CD002845.pub3"}],"container-title":["BMC Women's Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12905-026-04356-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12905-026-04356-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12905-026-04356-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T20:21:52Z","timestamp":1781641312000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12905-026-04356-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,18]]},"references-count":38,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["4356"],"URL":"https:\/\/doi.org\/10.1186\/s12905-026-04356-8","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-6605031\/v1","asserted-by":"object"}]},"ISSN":["1472-6874"],"issn-type":[{"value":"1472-6874","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,18]]},"assertion":[{"value":"6 May 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 February 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 March 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":"Not applicable.","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":"196"}}