{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:52:40Z","timestamp":1790297560875,"version":"4.1.0"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Premature ovarian insufficiency (POI) is a major long-term adverse effect of cyclophosphamide (CYC) therapy in systemic lupus erythematosus (SLE). Reported prevalence varies due to differences in populations, protocols, and diagnostic criteria. Objective: To estimate the prevalence of POI in women with SLE exposed to CYC and explore sources of heterogeneity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>MEDLINE, Embase, Web of Science, Scopus, and LILACS were searched from inception through October 2024. Twenty-one studies were included in the systematic review; 12 CYC-exposed cohorts contributed to the primary meta-analysis. Two reviewers independently extracted data and assessed study quality using the Joanna Briggs Institute checklist.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The pooled prevalence of POI in SLE treated with CYC was 15% (95% CI 7-26%), with substantial heterogeneity (I\n                      <jats:sup>2<\/jats:sup>\n                      \u00a0=\u00a085%; Cochran\u2019s Q\u00a0=\u00a073.98 p &amp;lt;0.0001; tau\n                      <jats:sup>2<\/jats:sup>\n                      \u00a0=\u00a00.0353). In contrast, prevalence among unselected SLE populations was markedly lower, confirming the potential gonadotoxic effect of CYC. Temporal analysis showed reduced prevalence in studies published after 2005 (9%) compared with pre-2005 (29%), coinciding with adoption of Euro-Lupus low-dose protocols. Meta-regression identified age at exposure as a significant predictor (\u03b2 = 0.21, 95% CI: 0.04-0.38, p = 0.017). Cumulative CYC dose was not independently associated with prevalence, likely reflecting the widespread adoption of lower-dose regimens after 2005. Methodological sensitivity analyses using logit transformation (20.0%, 95% CI 12.7-30.1) and GLMM (14.5%, 95% CI 7.1-27.2) were added to assess model robustness. Funnel-plot and the Egger\u2019s test indicated no evidence of publication bias (p = 0.91).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Women with SLE treated with CYC show a substantial burden of POI, with an estimated prevalence of approximately 15%. These results underscore the need for standardized diagnostic criteria, fertility counseling, and individualized treatment decisions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic review registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/www.crd.york.ac.uk\/PROSPERO\/view\/<\/jats:ext-link>\n                      , identifier CRD42025641213.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1775060","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T04:52:10Z","timestamp":1779943930000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Premature ovarian insufficiency in patients with systemic lupus erythematosus on cyclophosphamide: a systematic review and 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