Effectiveness and safety of dydrogesterone versus dienogest after laparoscopic cystectomy for ovarian endometrioma: a multicenter prospective cohort study

Effectiveness and safety of dydrogesterone versus dienogest after laparoscopic cystectomy for ovarian endometrioma: a multicenter prospective cohort study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Effectiveness and safety of dydrogesterone versus dienogest after laparoscopic cystectomy for ovarian endometrioma: a multicenter prospective cohort study Jiao Liu, Wenjing Lu, Huazhang Miao, Xiaowan Luo, Xinke Zhao, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-11504446/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 13 You are reading this latest preprint version Abstract Background Prospective evidence to guide the choice between dydrogesterone and dienogest after laparoscopic cystectomy for ovarian endometrioma remains limited. This study compared their effectiveness and safety in women of reproductive age to inform individualized postoperative treatment. Methods This prospective multicenter cohort enrolled women aged 18–45 years who underwent laparoscopic cystectomy for histologically confirmed ovarian endometrioma at four hospitals in Guangdong Province, China. Patients and clinicians jointly selected postoperative therapy with either dydrogesterone (10 mg twice daily on cycle days 5–25) or continuous dienogest (2 mg daily) during routine care. The primary outcome was the change in visual analog scale (VAS) pain score from preoperative baseline to week 24. Between-group differences were estimated using covariate-adjusted analysis of covariance with HC3 robust standard errors. The study was registered at ClinicalTrials.gov (NCT05976529) on 25 April 2023. Results A total of 242 women were enrolled: 109 initiated dydrogesterone and 133 initiated dienogest; 234 (96.7%) had VAS data available at week 24. The adjusted between-group difference in VAS pain score change was 0.00 points (95% CI, − 0.44 to 0.43; P = 0.983; dydrogesterone minus dienogest), and estimates were similar across sensitivity analyses. At week 24, the improvement in the Mental Component Summary score of the 12-Item Short Form Health Survey was greater with dydrogesterone (adjusted mean difference, 5.32 points; 95% CI, 2.28 to 8.35; Benjamini-Hochberg [BH]-adjusted P = 0.004). Cyclic bleeding was the predominant bleeding pattern in the dydrogesterone group, whereas no bleeding was the predominant pattern in the dienogest group. Through week 24, any adverse event was reported in 38.1% of the dydrogesterone group versus 54.3% of the dienogest group (BH-adjusted P = 0.063); anxiety or depression (5.7% vs 22.5%; BH-adjusted P = 0.009) and insomnia (4.8% vs 17.8%; BH-adjusted P = 0.018) were reported less frequently with dydrogesterone than with dienogest. Conclusions After adjustment, the improvement in VAS pain score at 24 weeks did not differ significantly between dydrogesterone and dienogest. Differences in mental well-being, adverse events, and bleeding patterns may help guide individualized postoperative treatment decisions. ovarian endometrioma dydrogesterone dienogest postoperative treatment VAS pain score Full Text Additional Declarations No competing interests reported. Supplementary Files Supplementarymaterial.docx Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: Revision requested 08 Nov, 2026 Reviews received at journal 07 Nov, 2026 Reviews received at journal 07 Nov, 2026 Reviewers agreed at journal 31 Oct, 2026 Reviewers agreed at journal 31 Oct, 2026 Reviews received at journal 30 Oct, 2026 Reviewers agreed at journal 30 Oct, 2026 Reviewers agreed at journal 30 Oct, 2026 Reviewers agreed at journal 30 Oct, 2026 Reviewers invited by journal 29 Oct, 2026 Editor assigned by journal 26 Oct, 2026 Submission checks completed at journal 26 Oct, 2026 First submitted to journal 25 Oct, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About In Review Editorial Policies Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-11504446","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":752449006,"identity":"225b304b-f83a-4e77-af71-b48bf89fc85e","order_by":0,"name":"Jiao Liu","email":"","orcid":"","institution":"Guangdong Province Women and Children Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jiao","middleName":"","lastName":"Liu","suffix":""},{"id":752449007,"identity":"c937ae6f-c3c0-414d-b185-d0eafbe88f3b","order_by":1,"name":"Wenjing Lu","email":"","orcid":"","institution":"Guangdong Province Women and Children 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study","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"reproductive-biology-and-endocrinology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"rbej","sideBox":"Learn more about [Reproductive Biology and Endocrinology](http://rbej.biomedcentral.com)","snPcode":"12958","submissionUrl":"https://submission.nature.com/new-submission/12958/3","title":"Reproductive Biology and Endocrinology","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"ovarian endometrioma, dydrogesterone, dienogest, postoperative treatment, VAS pain score","lastPublishedDoi":"10.21203/rs.3.rs-11504446/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-11504446/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eProspective evidence to guide the choice between dydrogesterone and dienogest after laparoscopic cystectomy for ovarian endometrioma remains limited. This study compared their effectiveness and safety in women of reproductive age to inform individualized postoperative treatment.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis prospective multicenter cohort enrolled women aged 18\u0026ndash;45 years who underwent laparoscopic cystectomy for histologically confirmed ovarian endometrioma at four hospitals in Guangdong Province, China. Patients and clinicians jointly selected postoperative therapy with either dydrogesterone (10 mg twice daily on cycle days 5\u0026ndash;25) or continuous dienogest (2 mg daily) during routine care. The primary outcome was the change in visual analog scale (VAS) pain score from preoperative baseline to week 24. Between-group differences were estimated using covariate-adjusted analysis of covariance with HC3 robust standard errors. The study was registered at ClinicalTrials.gov (NCT05976529) on 25 April 2023.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eA total of 242 women were enrolled: 109 initiated dydrogesterone and 133 initiated dienogest; 234 (96.7%) had VAS data available at week 24. The adjusted between-group difference in VAS pain score change was 0.00 points (95% CI, \u0026minus;\u0026thinsp;0.44 to 0.43; P\u0026thinsp;=\u0026thinsp;0.983; dydrogesterone minus dienogest), and estimates were similar across sensitivity analyses. At week 24, the improvement in the Mental Component Summary score of the 12-Item Short Form Health Survey was greater with dydrogesterone (adjusted mean difference, 5.32 points; 95% CI, 2.28 to 8.35; Benjamini-Hochberg [BH]-adjusted P\u0026thinsp;=\u0026thinsp;0.004). Cyclic bleeding was the predominant bleeding pattern in the dydrogesterone group, whereas no bleeding was the predominant pattern in the dienogest group. Through week 24, any adverse event was reported in 38.1% of the dydrogesterone group versus 54.3% of the dienogest group (BH-adjusted P\u0026thinsp;=\u0026thinsp;0.063); anxiety or depression (5.7% vs 22.5%; BH-adjusted P\u0026thinsp;=\u0026thinsp;0.009) and insomnia (4.8% vs 17.8%; BH-adjusted P\u0026thinsp;=\u0026thinsp;0.018) were reported less frequently with dydrogesterone than with dienogest.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eAfter adjustment, the improvement in VAS pain score at 24 weeks did not differ significantly between dydrogesterone and dienogest. Differences in mental well-being, adverse events, and bleeding patterns may help guide individualized postoperative treatment decisions.\u003c/p\u003e","manuscriptTitle":"Effectiveness and safety of dydrogesterone versus dienogest after laparoscopic cystectomy for ovarian endometrioma: a multicenter prospective cohort study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-11-12 10:28:11","doi":"10.21203/rs.3.rs-11504446/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision 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