Abstract
BACKGROUND: Endometriosis and uterine fibroids are estrogen-dependent gynecological disorders with an increasing burden to women's health worldwide. Despite overlapping symptoms and long-term consequences, the magnitude of their co-occurrence remains unclear. METHODS: We systematically searched PubMed, Embase, and Scopus up to July 21st, 2025, for studies reporting data on fibroids occurrence in patients with and without endometriosis. Effect estimates (adjusted or, if unavailable, crude) were pooled using random-effects models. Age and body mass index (BMI) were explored in uni- and multivariate meta-regressions. Subgroup analyses considered study design, data source, geographic location, parity, age and study quality. Sensitivity analysis included only asymptomatic controls without endometriosis. Study quality and certainty of evidence were assessed using the Newcastle-Ottawa Scale and Grading of Recommendations Assessment, Development, and Evaluation guidelines, respectively. The protocol was registered on PROSPERO (CRD42024614711). FINDINGS: 4351 articles were identified, of which 23 met eligibility criteria, including 3,109,231 patients (118,716 with endometriosis and 2,990,515 controls). Endometriosis was associated with higher odds of fibroids (pooled OR 2.91; 95% CI, 1.78-4.75). BMI influenced estimates (p < 0.01). Between-group differences in data source (p < 0.01) and study quality (p = 0.03) were observed. Parity showed a trend effect: OR 1.56 (95% CI: 0.53-4.59) for studies with >50% nulliparous women, 4.52 (95% CI: 2.53-8.10) for those with >50% multiparous, 5.23 (95% CI, 2.09-13.04) for studies with >95% multiparous women. In sensitivity analysis with only asymptomatic controls (n = 3,103,146), the OR increased to 7.01 (95% CI: 4.72-10.41). INTERPRETATION: This first meta-analysis on the co-occurrence of endometriosis and fibroids shows that women with endometriosis have a three-to tenfold higher odds of fibroids compared with controls. Clinical awareness of this association is crucial to optimize both patient management and short- and long-term women's health outcomes. FUNDING: This study was funded by the Italian Ministry of Health-Current research IRCCS.