The Global, Regional, and National Burden of Endometriosis in 204 Countries and Territories, 1990–2021: Results from the Global Burden of Disease Study 2021

The Global, Regional, and National Burden of Endometriosis in 204 Countries and Territories, 1990–2021: Results from the Global Burden of Disease Study 2021 | 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 Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article The Global, Regional, and National Burden of Endometriosis in 204 Countries and Territories, 1990–2021: Results from the Global Burden of Disease Study 2021 Linzi Lei, Qingchen Cui, Xiaolei Ji, Hong Gao, Yuzhen Zhang, Jiankang Zhang, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6763472/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract Background :To analyze the prevalence and burden of disease (Disability-Adjusted Life Years) of endometriosis in 204 countries and regions from 1990 to 2021, and evaluate its global trends, regional differences and association with Socio-Demographic Index (SDI) and age distribution. Methods ：Data on the prevalence and Disability-Adjusted Life Years（DALYs）of endometriosis in 204 countries and regions from 1990 to 2021 were extracted using the the Global Burden of Disease（GBD）results tool (https://vizhub.healthdata.org/gbd-results/). Age-standardized rates, percentage changes in prevalence and DALYs, and 95% uncertainty intervals were calculated to quantify the overall disease burden. SDI was used to assess each country's development level. All statistical analyses were performed using R software (version 4.2.1). Result (s)：The global age standardised point prevalence and DALY rates for endometriosis were 26.2% and 26.1% lower than in 1990,respectively,with regional differences were significant.Oceania and Eastern Europe had the highest burden, while Western Europe and high-income Asia-Pacific regions had the lowest burden. The SDI exhibited a significant negative correlation with DALYs (R=-0.66, p<0.001). Countries with lower SDI(e.g., Niger and Chad)experienced a higher disease burden, whereas countries with higher SDI (e.g., Singapore and Switzerland)demonstrated a lower disease burden. Endometriosis is most prevalent among women aged 20-40 years, with the peak prevalence occurring in the 25-29 age group,and approaching zero prevalence in individuals over 55 years. Conclusion (s):Despite the decreasing burden of endometriosis from 1990 to 2021,significant differences remain across regions, countries, and age groups.Higher SDI are closely associated with lower disease burden, while reproductive age is a key factor influencing the prevalence of endometriosis.Future public health policies should focus more on the impact of endometriosis on reproductivehealth.Early detection and treatment should be prioritized to alleviate the effects of endometriosis on fertility and population structure, thus supporting the improvement of global women's health and social development. Health sciences/Diseases/Reproductive disorders Health sciences/Medical research/Epidemiology Endometriosis Global Burden of Disease prevalence Disability-Adjusted Life Years Socio-Demographic Index Figures Figure 1 Figure 2 Figure 3 Figure 4 1. Introduction Endometriosis is a common and complex chronic inflammatory gynecological disease characterized by the abnormal growth of endometrial-like tissue outside the uterus[1][2] .It is often accompanied by pelvic pain, infertility and other symptoms, severely affecting the quality of life of affected individuals[3]. Global studies indicate that the prevalence of endometriosis among women of reproductive age is approximately 6%-10%, and it is observed in 50-80% of women with pelvic pain and up to 50% of women with infertility[4][5] .Currently, Sampson's retrograde menstruation theory is the most widely accepted pathological mechanism for endometriosis , proposing that endometrial tissues are shed through the fallopian tubes into the pelvic cavity during menstruation, resulting in ectopic endometrial lesions[6] .Despite the high prevalence of endometriosis, diagnosis is often delayed due to insufficient disease recognition, with the average diagnostic delay ranging from 7 to 9 years[7].This results in a lack of timely and effective treatment, affecting the patients' quality of life and increasing the difficulty and cost of treatment[8]. In addition to its significant health impacts, endometriosis imposes a considerable socioeconomic burden[9] .Existing studies show that the annual medical costs and economic losses due to work absenteeism caused by endometriosis in the United States are approximately $22 billion, and in the Canada, the cost is $30 million[10][11].The average annual total cost of per women with endometriosis and treated in referral centres was €9579[12].These figures underscore the significant impact of endometriosis on both public health systems and the broader socioeconomic landscape,which warrants urgent attention. This study aims to analyze the global prevalence and disease burden (DALYs) of endometriosis in 204 countries and regions from 1990 to 2021, using data from the GBD database. It examines three key factors: geographic location, age distribution, and Socio-Demographic Index (SDI), with the objective of identifying global patterns and the health burden of endometriosis. The findings of this study will contribute to greater attention to endometriosis and provide insights for resource allocation for endometriosis patients. 2. Materials and Methods 2.1Ethical declaration No ethical approval was required as data were publicly available and anonymized. 2.2 Study population and data collection The data in this study comes from the GBD project, an extensive international initiative designed to provide global epidemiological analyses of different diseases, injuries, and risk factors[13][14]. The GBD database includes data from 204 countries and regions, covering 371 diseases and injuries. In this study, we used the GBD Results Tool (https://vizhub.healthdata.org/gbd-results/) to extract data on the prevalence and DALYs of endometriosis from 204 countries and regions from 1990 to 2021[15][16]. We also utilized the SDI to assess the development levels of each country, which is calculated based on indicators like per capita income, average years of schooling, and fertility rate[17][18]. 2.3 Definitions In the GBD study, the code used to identify endometriosis follows the International Classification of Diseases (ICD) system[19]. According to ICD-10, the classification code for endometriosis is N80. In the GBD study, endometriosis is defined as the growth of endometrial tissue (which normally only exists within the uterus) outside of the uterus, such as on the ovaries, fallopian tubes, or other pelvic organs. In the GBD study, endometriosis cases are defined according to the guidelines of the American College of Obstetricians and Gynecologists (ACOG), diagnosed by pelvic examination and confirmed via laparoscopy or histopathological examination[20]. DALYs (Disability-adjusted life-years) is a summary measure of disease burden, calculating the total number of years of healthy life lost due to a disease from onset to death. It includes years lost due to premature death (YLLs) and years lived with disability (YLDs)[21]. ASR (Age-standardized rate) is a ratio adjusted according to a standard population structure, used to eliminate the influence of age structure differences across populations, making comparisons across different time periods or regions possible[22]. SDI( Socio-Demographic Index) is a comprehensive indicator of the development status of geographical regions, measuring the Socioeconomic development levels of countries and regions based on indicators such as per capita income, average years of education, and fertility rates. SDI values range from 0 to 1, with higher values indicating higher Socioeconomic development[23]. 2.4 Statistical analysis To ensure the comparability and reliability of statistical indicators while comparing the differences among multiple age structures, age-standardization is indispensable.We calculated the ASR of endometriosis globally using the following formula: To reveal the changes of absolute counts in endometriosis from 1990 to 2021, the increase rates of prevalence were used, and the formula could be expressed as: the prevalence rates = (endometriosis cases in 2021 – endometriosis cases in 1990) / endometriosis cases in 1990[25]. To assess the relationship between the burden of endometriosis and SDI across different regions and countries, we used a local regression smoothing model (loess) and Spearman correlation analysis. All statistical analyses and graphical representations were performed using R software (version 4.2.1). 3. Results 3.1 Global and regional level In 2021, the Global Burden of Disease Study 2021 estimated a total of 22.3 million cases of endometriosis worldwide, accompanied by an age-standardized point prevalence of 275.6 per 100,000 population, which marks a 26.2% decrease from 1990. In 2021, the total number of DALYs attributable to endometriosis was 2,049.5 thousands, with an age-standardized rate of 25.4 DALYs per 100,000 population, representing a 26.1% decline from 1990 (Table 1). Within the 21 GBD regions and 204 countries and territories, the highest age-standardized prevalence were observed in Oceania (491.9) and Eastern Europe (431.6), while the highest DALY rates occurred in Oceania (45.2) and Eastern Europe (39.8). From 1990 to 2021, age-standardized DALY rates declined across all regions, with the largest reductions seen in South Asia (-39.4%) and Central Sub-Saharan Africa (-38.3%) (Table 1). 95% UI=95% uncertainty intervals. 3.2 National level In 2021, the age-standardized prevalence of endometriosis at the national level was estimated to ranged from 150.3 to 669.5 per 100,000 population. The highest prevalence rates were found in Niger (669.5), Chad (568.6), and the Solomon Islands (541.7), while s the lowest estimates were seen in Portugal (150.3), Malta (162.9), and the United Arab Emirates (164.1) (Figure 1).Similarly,the age-standardized DALY rates for endometrioswere estimated to vary between 13.8 and 61.4 per 100,000 individuals. The highest DALY rates were found in Niger (61.4), Chad (51.8), and the Solomon Islands (49.8), while the lowest rates were found in Portugal (13.8), Malta (15), and the United States of America (15). (Figure 1) 3.3 Association with the SDI 3.3.1 Regional Level The correlation coefficient (R) between the SDI and the DALYs ASR of endometriosis from 1990 to 2021 was -0.66 (95% CI: [-0.70, -0.62], p < 0.001), indicating a statistically significant negative association.This suggests that regions with higher SDI levels generally tended to have lower DALYs ASR during the study period. Notably, the DALYs ASR in Oceania, North Africa and the Middle East, Eastern Europe, High-income Asia Pacific, Southern Sub-Saharan Africa, and Southeast Asia were positioned above the overall trend line (Figure 2), suggesting relatively higher burden levels than the global SDI-adjusted trend would predict. The DALYs ASR for Western Europe, East Asia, Central Latin America, Tropical Latin America, Andean Latin America, High−income North America, and the Caribbean were below the trend line, indicating that the DALYs ASR was lower than expected.（ Figure 2） 3.3.2 At the National Level In 2021, the burden of endometriosis decreased with increased Socioeconomic development, suggesting that improvements in Socioeconomic development may be associated with a reduction in disease burden. Somalia, Chad, and Niger showed lower SDI values and higher DALYs ASR. In contrast, Singapore, Switzerland, and Iceland showed higher SDI values and lower DALYs ASR. （ Figure 3） 3.4 Age Pattern In 2021, the number of individuals affected by endometriosis increased notably in the 20–24 age group, reaching 3.48 million, and peaked in the 25–29 age group at 4.23 million. Subsequently, the number of cases progressively declined with advancing age, with a more noticeable reduction observed after age 40. Specifically, the number of affected individuals decreased to 3.02 million in the 40–44 age group and 2.52 million in the 45–49 age group. In the older age groups, case numbers further dropped significantly, with 1.23 million in the 50–54 age group and approaching zero in the 55+ age group.（Figure 4） 4. Discussion 4.1 Principal findings Our analysis revealed a global decline in both the prevalence and DALY rates of endometriosis from 1990 to 2021. While the reasons for this trend are not directly assessed in this study, it may coincide with improvements in diagnostic capabilities, disease awareness, and treatment accessibility[26]. Despite this overall reduction, substantial variation in disease burden persists across regions, countries, and age groups. For instance, based on our estimates, several countries in Oceania, Eastern Europe, and Sub-Saharan Africa exhibit higher burden levels, whereas Western Europe and high-income Asia Pacific show comparatively lower figures. Our findings demonstrate a statistically significant negative correlation between the Socio-demographic Index (SDI) and the age-standardized DALY rate for endometriosis (R = -0.66, p < 0.001), suggesting that countries with higher levels of socioeconomic development tend to have lower disease burdens[19]. However, the substantial variation observed across regions and countries points to persistent disparities in healthcare infrastructure and access to health education.Previous studies have highlighted that in low-income settings, underdiagnosis and limited medical resources may lead to underestimation of disease burden, whereas high-income regions often report lower burdens, potentially due to earlier diagnosis and better treatment options[27][28]. By quantifying the association between SDI and disease burden, this study underscores the importance of socioeconomic factors in global endometriosis management and provides a comprehensive basis for further epidemiological research[29]. Moreover, this study provides a global analysis that contributes a broader perspective to related research. In high-income countries, lower disease burdens are often associated with well-established public health systems and greater awareness of endometriosis. Conversely, in low-income countries, limited healthcare resources, reduced disease knowledge, and cultural barriers may contribute to relatively higher disease burdens[28][30]. Finally, age-specific findings in this study indicate that the prevalence of endometriosis is notably higher among women aged 20–40 years, peaking specifically in the 25–29 age group. This age range aligns closely with the primary reproductive period for women, underscoring a clinically important association between endometriosis and fertility[31][32][33]. Current estimates indicate that approximately 30%–50% of individuals with endometriosis experience varying degrees of infertility[3]. The infertility associated with endometriosis presents important medical challenges and constitutes a significant public health issue within global reproductive health[34][35]. Particularly in regions experiencing low birth rates and aging populations, timely diagnosis and effective management of endometriosis could help address broader demographic and reproductive health challenges. In addition, in low and middle income countries, factors such as inadequate medical resources, lack of health awareness, and menstrual stigma contribute to lower diagnostic rates and a widespread lack of reproductive health knowledge[36]. As a result, the link between endometriosis and infertility may be underestimated, leaving many patients without timely diagnosis and intervention[34][37]. The normalization of symptoms such as menstrual pain and the social taboos surrounding them further deepen the disease’s concealment[36]. 4.2 Strengths and Limitations This study is based on data from the GBD project, covering 204 countries and regions from 1990 to 2021. By analyzing more than 30 years of data, it reveals the global trends and changes of endometriosis, offering a global perspective for epidemiological research on the disease[38]. Additionally, this study explores the epidemiological characteristics of endometriosis from multiple dimensions such as geographic location, age distribution, and socioeconomic development levels[39]. It reveals significant regional and national differences, particularly the high risk in the 20-40 reproductive age group, providing data to understand the threat of the disease to fertility and global population reproduction. The findings of this study provide important evidence to optimize global health resource allocation, develop early screening, infertility interventions, and health education strategies, thereby promoting the improvement of global women’s health and sustainable population development[40]. Although this study provides a comprehensive epidemiological analysis, there are some limitations.First, variations in data quality and reporting across countries may contribute to underestimation or overestimation of disease burden particularly in low and middle income countries where diagnostic infrastructure is limited.Second,the GBD estimates rely on modeling techniques and indirect data inputs in some regions, which may introduce uncertainty. Third, this analysis does not account for individual-level risk factors such as environmental exposures, genetic predisposition, or lifestyle, which may influence disease distribution but are beyond the scope of this study[41][42]. 5. Conclusions Between 1990 to 2021, the global prevalence and DALYs of endometriosis have shown a declining trend, but substantial disparities in disease burden remain across regions, countries, and age groups. Improvements in socioeconomic development appear to be associated with a reduction in the disease burden of endometriosis, with the reproductive age being an critical factor influencing its prevalence.The intersection of these factors highlights a notable association between endometriosis and infertility. Endometriosis represents both a medical concern and a public health issue that warrants attention in social and health policy frameworks. Future public health policies should place greater emphasis on the impact of endometriosis on reproductive health, particularly by incorporating it into the global reproductive health priority agenda[43]. Implementing targeted public health measures, promoting empirical diagnoses, and supporting early detection and treatment may help reduce the disease burden, thereby mitigating the impact on fertility and broader demographic structures, ultimately contributing to the advancement of global women's health and societal development[43]. Abbreviations SDI：Socio-Demographic Index DALYs：Disability-Adjusted Life Years GBD：Global Burden of Disease ASR:Age-standardized rate Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable . Availability of data and materials All data supporting the findings of this study are openly available through the Global Burden of Disease Study 2021 (GBD 2021). The datasets can be accessed via the IHME GBD Results Tool:https://vizhub.healthdata.org/gbd-results/. Competing interests The authors declare that they have no competing interests. Funding Statement This study was funded by the Xiamen City Natural Science Foundation, grant number 3502Z20227342. The project is entitled "Analysis of the Mechanism of Endometrial Carcinogenesis Using Single-Cell Sequencing." The total budget for the project is 50,000 RMB, and the project is funded for the period from July 2022 to June 2025. Authors' contributions LL: Conceptualization, Formal Analysis, Software, Visualization, Writing – Original Draft, Writing – Review & Editing. QC: Data Curation, Software, Writing – Review & Editing. XJ: Resources, Software, Visualization. HG: Supervision, Writing – Review & Editing. YZ: Project Administration, Supervision. JZ: Data Curation, Visualization, Investigation. YG: Data Curation, Methodology, Validation. FZ: Funding Acquisition, Supervision, Validation. YL: Funding Acquisition, Supervision, Writing – Review & Editing. Acknowledgements We thank the Institute for Health Metrics and Evaluation (IHME) for providing access tothe GBD 2021 database. We also acknowledge the contributions of clinical and research assistants at collaborating centers. Clinical trial number not applicable Data availability All data supporting the findings of this study are openly accessible via the Global Burden of Disease Study 2021 (GBD 2021). Specifically, aggregated data used for analysis can be obtained through the IHME GBD Results Tool (https://vizhub.healthdata.org/gbd-results/). Users may download the data by selecting specific indicators (e.g., prevalence, DALYs, age-standardized rates) and relevant regions or countries directly from the provided online tool. References Horne A W, Missmer S A. Pathophysiology, diagnosis, and management of endometriosis. BMJ 2022; 379 :e070750. Marquardt RM, Tran DN, Lessey BA, Rahman MS, Jeong J-W. Epigenetic Dysregulation in Endometriosis: Implications for Pathophysiology and Therapeutics. Endocrine Reviews 2023;44(6):1074–95. Zondervan KT, Becker CM, Missmer SA. Endometriosis. N Engl J Med [Internet] 2020;382(13). Taylor HS, Kotlyar AM, Flores VA. Endometriosis is a chronic systemic disease: clinical challenges and novel innovations. Lancet 2021;397(10276):839–52. Skorupskaite K, Hardy M, Bhandari H, Yasmin E, Saab W, Seshadri S. Evidence based management of patients with endometriosis undergoing assisted conception: British fertility society policy and practice recommendations. Human Fertility 2024;27(1):2288634. Li Y, Liu H, Ye S, Zhang B, Li X, Yuan J, et al. The effects of coagulation factors on the risk of endometriosis: a Mendelian randomization study. BMC Med 2023;21(1):195. Saunders PTK, Whitaker LHR, Horne AW. Endometriosis: Improvements and challenges in diagnosis and symptom management. Cell Rep Med 2024;5(6):101596.Zippl AL, Reiser E, Seeber B. Endometriosis and mental health disorders: identification and treatment as part of a multimodal approach. Fertil Steril 2024;121(3):370–8.doi:10.1016/j.fertnstert.2023.12.033 Sivajohan B, Elgendi M, Menon C, Allaire C, Yong P, Bedaiwy MA. Clinical use of artificial intelligence in endometriosis: a scoping review. npj Digit Med 2022;5(1):1–17. Ahn SH, Singh V, Tayade C. Biomarkers in endometriosis: challenges and opportunities. Fertil Steril 2017;107(3):523–32. Chen I, Thavorn K, Yong PJ, Choudhry AJ, Allaire C. Hospital-Associated Cost of Endometriosis in Canada: A Population-Based Study. J Minim Invasive Gynecol 2020;27(5):1178–87. Simoens S, Dunselman G, Dirksen C, Hummelshoj L, Bokor A, Brandes I, et al. The burden of endometriosis: costs and quality of life of women with endometriosis and treated in referral centres. Hum Reprod 2012;27(5):1292–9. Safiri S, Carson-Chahhoud K, Noori M, Nejadghaderi SA, Sullman MJM, Ahmadian Heris J, et al. Burden of chronic obstructive pulmonary disease and its attributable risk factors in 204 countries and territories, 1990-2019: results from the Global Burden of Disease Study 2019. BMJ 2022;378:e069679. Sun P, Yu C, Yin L, Chen Y, Sun Z, Zhang T, et al. Global, regional, and national burden of female cancers in women of child-bearing age, 1990-2021: analysis of data from the global burden of disease study 2021. EClinicalMedicine 2024;74:102713. Liang X, Lyu Y, Li J, Li Y, Chi C. Global, regional, and national burden of preterm birth, 1990-2021: a systematic analysis from the global burden of disease study 2021. EClinicalMedicine 2024;76:102840. Li N, Deng Y, Zhou L, Tian T, Yang S, Wu Y, et al. Global burden of breast cancer and attributable risk factors in 195 countries and territories, from 1990 to 2017: results from the Global Burden of Disease Study 2017. J Hematol Oncol 2019;12(1):140. Xie Y, Bowe B, Mokdad AH, Xian H, Yan Y, Li T, et al. Analysis of the Global Burden of Disease study highlights the global, regional, and national trends of chronic kidney disease epidemiology from 1990 to 2016. Kidney Int 2018;94(3):567–81. Rudd KE, Johnson SC, Agesa KM, Shackelford KA, Tsoi D, Kievlan DR, et al. Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study. Lancet 2020;395(10219):200–11. Cen J, Wang Q, Cheng L, Gao Q, Wang H, Sun F. Global, regional, and national burden and trends of migraine among women of childbearing age from 1990 to 2021: insights from the Global Burden of Disease Study 2021. J Headache Pain 2024;25(1):96. ACOG Committee Opinion No. 760 Summary: Dysmenorrhea and Endometriosis in the Adolescent. Obstet Gynecol 2018;132(6):1517–8. GBD 2017 Risk Factor Collaborators. Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 2018;392(10159):1923–94. Dai H, Alsalhe TA, Chalghaf N, Riccò M, Bragazzi NL, Wu J. The global burden of disease attributable to high body mass index in 195 countries and territories, 1990-2017: An analysis of the Global Burden of Disease Study. PLoS Med 2020;17(7):e1003198. Zhang K, Kan C, Han F, Zhang J, Ding C, Guo Z, et al. Global, Regional, and National Epidemiology of Diabetes in Children From 1990 to 2019. JAMA Pediatr 2023;177(8):837–46. Huang Y, Li Y, Pan H, Han L. Global, regional, and national burden of neurological disorders in 204 countries and territories worldwide. J Glob Health. 2023;13:04160.Medline:38018250. Zhou X, Zhang Z, Ruan C, Wu Y, Zeng B, Su X, et al. Trends in the global, regional, and national burden of testicular cancer from 1990 to 2019: an observational study with 30-year global data. Int J Surg 2024;110(8):4633–47. Wang Y, Wang X, Liao K, Luo B, Luo J. The burden of endometriosis in China from 1990 to 2019. Front Endocrinol (Lausanne) 2022;13:935931. GBD 2017 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 2018;392(10159):1789–858. GBD 2016 Healthcare Access and Quality Collaborators. Measuring performance on the Healthcare Access and Quality Index for 195 countries and territories and selected subnational locations: a systematic analysis from the Global Burden of Disease Study 2016. Lancet 2018;391(10136):2236–71. Lou Z, Huang Y, Li S, Luo Z, Li C, Chu K, et al. Global, regional,and national time trends in incidence, prevalence, years lived with disability for uterine fibroids, 1990-2019: an age-period-cohort analysis for the global burden of disease 2019 study. BMC Public Health 2023;23(1):916. GBD 2019 Risk Factors Collaborators. Global burden of 87 risk factors in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet 2020;396(10258):1223–49. Liang Y, Huang J, Zhao Q, Mo H, Su Z, Feng S, et al. Global, regional, and national prevalence and trends of infertility among individuals of reproductive age (15-49 years) from 1990 to 2021, with projections to 2040. Hum Reprod [Internet] 2025. Vercellini P, Viganò P, Bandini V, Buggio L, Berlanda N, Somigliana E. Association of endometriosis and adenomyosis with pregnancy and infertility. Fertil Steril 2023;119(5):727–40. Pirtea P, Vulliemoz N, de Ziegler D, Ayoubi JM. Infertility workup: identifying endometriosis. Fertil Steril 2022;118(1):29–33. Horton J, Sterrenburg M, Lane S, Maheshwari A, Li TC, Cheong Y. Reproductive, obstetric, and perinatal outcomes of women with adenomyosis and endometriosis: a systematic review and meta-analysis. Hum Reprod Update 2019;25(5):592–632. Kvaskoff M, Mahamat-Saleh Y, Farland LV, Shigesi N, Terry KL, Harris HR, et al. Endometriosis and cancer: a systematic review and meta-analysis. Hum Reprod Update 2021;27(2):393–420. As-Sanie S, Black R, Giudice LC, Gray Valbrun T, Gupta J, Jones B, et al. Assessing research gaps and unmet needs in endometriosis. Am J Obstet Gynecol 2019;221(2):86–94. Nnoaham KE, Hummelshoj L, Webster P, d’Hooghe T, Nardone F de C, Nardone C de C, et al. Impact of endometriosis on quality of life and work productivity: a multicenter study across ten countries. Fertility and Sterility 2011;96(2):366-373.e8. Roman H. Endometriosis in studies based on nationwide databases. Fertil Steril 2022;117(2):454–5. Zhou T, Wang X, Zhang J, Zhou E, Xu C, Shen Y, et al. Global burden of thyroid cancer from 1990 to 2021: a systematic analysis from the Global Burden of Disease Study 2021. J Hematol Oncol 2024;17(1):74. Smolarz B, Szyłło K, Romanowicz H. Endometriosis: Epidemiology, Classification, Pathogenesis, Treatment and Genetics (Review of Literature). Int J Mol Sci 2021;22(19):10554. Yang K, Yang X, Jin C, Ding S, Liu T, Ma B, et al. Global burden of type 1 diabetes in adults aged 65 years and older, 1990-2019: population based study. BMJ 2024;385:e078432. Prevalence, years lived with disability, and trends in anaemia burden by severity and cause, 1990-2021: findings from the Global Burden of Disease Study 2021. Lancet Haematol 2023;10(9):e713–34. Becker CM, Bokor A, Heikinheimo O, Horne A, Jansen F, Kiesel L, et al. ESHRE guideline: endometriosis. Hum Reprod Open 2022;2022(2):hoac009. Table Table 1 is available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Table1.xlsx Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 27 Dec, 2025 Reviewers agreed at journal 02 Aug, 2025 Reviewers invited by journal 21 Jul, 2025 Editor assigned by journal 21 Jul, 2025 Editor invited by journal 27 Jun, 2025 Submission checks completed at journal 26 Jun, 2025 First submitted to journal 26 Jun, 2025 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. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board 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-6763472","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":488827623,"identity":"fcc73f57-4bb4-4472-93ed-ff174daca581","order_by":0,"name":"Linzi Lei","email":"","orcid":"","institution":"Xiamen University","correspondingAuthor":false,"prefix":"","firstName":"Linzi","middleName":"","lastName":"Lei","suffix":""},{"id":488827625,"identity":"d5308e59-335d-4b2f-bc5c-07bc7de47811","order_by":1,"name":"Qingchen Cui","email":"","orcid":"","institution":"Xiamen University","correspondingAuthor":false,"prefix":"","firstName":"Qingchen","middleName":"","lastName":"Cui","suffix":""},{"id":488827627,"identity":"23b95d77-09bb-4b74-8865-23c54fa0cf77","order_by":2,"name":"Xiaolei Ji","email":"","orcid":"","institution":"Xiamen University","correspondingAuthor":false,"prefix":"","firstName":"Xiaolei","middleName":"","lastName":"Ji","suffix":""},{"id":488827628,"identity":"e2adec52-e13e-4153-8119-8cc40e4c957b","order_by":3,"name":"Hong Gao","email":"","orcid":"","institution":"The First Affiliated Hospital of Xiamen University","correspondingAuthor":false,"prefix":"","firstName":"Hong","middleName":"","lastName":"Gao","suffix":""},{"id":488827629,"identity":"23b5ef1a-6718-4f64-a0dd-f9e8fe27f14b","order_by":4,"name":"Yuzhen Zhang","email":"","orcid":"","institution":"The First Affiliated Hospital of Xiamen University","correspondingAuthor":false,"prefix":"","firstName":"Yuzhen","middleName":"","lastName":"Zhang","suffix":""},{"id":488827630,"identity":"f1588388-de90-4df3-907a-45e6266224ab","order_by":5,"name":"Jiankang Zhang","email":"","orcid":"","institution":"Xiamen University","correspondingAuthor":false,"prefix":"","firstName":"Jiankang","middleName":"","lastName":"Zhang","suffix":""},{"id":488827631,"identity":"f4ad032b-f385-4fad-8bdc-192c0ecfd553","order_by":6,"name":"Yu Gao","email":"","orcid":"","institution":"China Agricultural University","correspondingAuthor":false,"prefix":"","firstName":"Yu","middleName":"","lastName":"Gao","suffix":""},{"id":488827632,"identity":"04f55677-2f80-4c48-8a55-5ee7a2c15798","order_by":7,"name":"Fuxing Zhang","email":"","orcid":"","institution":"The First Affiliated Hospital of Xiamen University","correspondingAuthor":false,"prefix":"","firstName":"Fuxing","middleName":"","lastName":"Zhang","suffix":""},{"id":488827633,"identity":"b4d55cc6-0749-437f-9970-09cf0302e223","order_by":8,"name":"Youzhu Li","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAvklEQVRIiWNgGAWjYBACA4n8B4d//rOB8HiI05KQ+JjHII0ULTwHko15DA6TooW94Zg0j8H5xA3XDjA+eNvGIG9OUAszY5v0D4Pbxga3E5gN57YxGO5sIKiFmU36gcFtOaAWNmneNoYEgwMEtbCx/zYwOMcD1ML+m0gtPGzSEgYHwLYwE6+FxyDZWPJ2YrPknHMShhsIabFv5n8G1GKX2Hc7+eCHN2U28gRtQQKMDUBCgnj1o2AUjIJRMApwAwA6XDoj+IkK+gAAAABJRU5ErkJggg==","orcid":"","institution":"The First Affiliated Hospital of Xiamen University","correspondingAuthor":true,"prefix":"","firstName":"Youzhu","middleName":"","lastName":"Li","suffix":""}],"badges":[],"createdAt":"2025-05-28 02:38:32","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6763472/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6763472/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":87495182,"identity":"51ee5938-cd4a-4368-afc2-d29ca544398f","added_by":"auto","created_at":"2025-07-24 12:41:10","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":342243,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eGlobal Prevalence and Disease Burden of Endometriosis (2021)\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-6763472/v1/6fb090aa7b94a88767cd0f59.png"},{"id":87494196,"identity":"1033e4e0-4340-4a1b-9b69-04ab917004a3","added_by":"auto","created_at":"2025-07-24 12:33:10","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":378741,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eAge-standardized DALY rates attributable to endometriosis across 21 GBD regions by Socio-demographic Index for both sexes combined, 1990–2021.\u003c/strong\u003e \u003cstrong\u003eExpected values,based on sociodemographic index and disease rates in all locations, are shown as a solid line. Regions above the solid line represent a higher than expected burden and regions below the line show a lower than expected burden.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-6763472/v1/4317a3c689f8303ad6918433.png"},{"id":87494198,"identity":"aae48452-0924-4ad9-a329-b2c548b897c5","added_by":"auto","created_at":"2025-07-24 12:33:10","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":254887,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eAge-standardized DALY rates attributable to high body mass index across 204 countries and territories by Socio-demographic Index for both sexes combined in 2021.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-6763472/v1/2198379b938c4ea140ad73bc.png"},{"id":87494199,"identity":"4a2c5ec2-9e04-4157-b5f5-191d83c295bd","added_by":"auto","created_at":"2025-07-24 12:33:10","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":137875,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eThe global prevalence of endometriosis cases and the prevalent per 100,000 people by age in 2021. The lines represent the prevalence in female, with the uncertainty interval at 95%.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-6763472/v1/c927ab9561f4fe3678108b2a.png"},{"id":87496753,"identity":"5cb4ebe9-f616-480e-b067-c93db672da2d","added_by":"auto","created_at":"2025-07-24 13:05:10","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1828364,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6763472/v1/59ea59e0-688d-48ee-8250-e30289bab046.pdf"},{"id":87494227,"identity":"b120d8b8-9f6c-4204-a1af-75f8c21fe619","added_by":"auto","created_at":"2025-07-24 12:33:19","extension":"xlsx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":12226,"visible":true,"origin":"","legend":"","description":"","filename":"Table1.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-6763472/v1/5961b6e6cf42af2f245e51a7.xlsx"}],"financialInterests":"No competing interests reported.","formattedTitle":"The Global, Regional, and National Burden of Endometriosis in 204 Countries and Territories, 1990–2021: Results from the Global Burden of Disease Study 2021","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eEndometriosis is a common and complex chronic inflammatory gynecological disease characterized by the abnormal growth of endometrial-like tissue outside the uterus[1][2] .It is often accompanied by pelvic pain, infertility and other symptoms, severely affecting the quality of life of affected individuals[3]. Global studies indicate that the prevalence of endometriosis among women of reproductive age is approximately 6%-10%, and it is observed in 50-80% of women with pelvic pain and up to 50% of women with infertility[4][5] .Currently, Sampson\u0026apos;s retrograde menstruation theory is the most widely accepted pathological mechanism for endometriosis , proposing that endometrial tissues are shed through the fallopian tubes into the pelvic cavity during menstruation, resulting in ectopic endometrial lesions[6] .Despite the high prevalence of endometriosis, diagnosis is often delayed due to insufficient disease recognition, with the average diagnostic delay ranging from 7 to 9 years[7].This results in a lack of timely and effective treatment, affecting the patients\u0026apos; quality of life and increasing the difficulty and cost of treatment[8].\u003c/p\u003e\n\u003cp\u003eIn addition to its significant health impacts, endometriosis imposes a considerable socioeconomic burden[9] .Existing studies show that the annual medical costs and economic losses due to work absenteeism caused by endometriosis in the United States are approximately $22 billion,\u0026nbsp;\u0026nbsp;and in the Canada, the cost is $30 million[10][11].The average annual total cost of per women with endometriosis and treated in referral centres was\u0026nbsp;\u0026euro;9579[12].These figures underscore the significant impact of endometriosis on both public health systems and the broader socioeconomic landscape,which warrants urgent attention.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis study aims to analyze the global prevalence and disease burden (DALYs) of endometriosis in 204 countries and regions from 1990 to 2021, using data from the GBD database. It examines three key factors: geographic location, age distribution, and Socio-Demographic Index (SDI), with the objective of identifying global patterns and the health burden of endometriosis. The findings of this study will contribute to greater attention to endometriosis and provide insights for resource allocation for endometriosis patients.\u003c/p\u003e"},{"header":"2. Materials and Methods","content":"\u003cp\u003e\u003cstrong\u003e2.1Ethical declaration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo ethical approval was required as data were publicly available and anonymized.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.2\u003c/strong\u003e \u003cstrong\u003eStudy population and data collection\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data in this study comes from the GBD project, an extensive international initiative designed to provide global epidemiological analyses of different diseases, injuries, and risk factors[13][14]. The GBD database includes data from 204 countries and regions, covering 371 diseases and injuries. In this study, we used the GBD Results Tool (https://vizhub.healthdata.org/gbd-results/) to extract data on the prevalence and DALYs of endometriosis from 204 countries and regions from 1990 to 2021[15][16]. We also utilized the SDI to assess the development levels of each country, which is calculated based on indicators like per capita income, average years of schooling, and fertility rate[17][18].\u003c/p\u003e\n\u003cp\u003e2.3 \u003cstrong\u003eDefinitions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn the GBD study, the code used to identify endometriosis follows the International Classification of Diseases (ICD) system[19]. According to ICD-10, the classification code for endometriosis is N80. In the GBD study, endometriosis is defined as the growth of endometrial tissue (which normally only exists within the uterus) outside of the uterus, such as on the ovaries, fallopian tubes, or other pelvic organs. In the GBD study, endometriosis cases are defined according to the guidelines of the American College of Obstetricians and Gynecologists (ACOG), diagnosed by pelvic examination and confirmed via laparoscopy or histopathological examination[20].\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;DALYs (Disability-adjusted life-years) is a summary measure of disease burden, calculating the total number of years of healthy life lost due to a disease from onset to death. It includes years lost due to premature death (YLLs) and years lived with disability (YLDs)[21].\u003c/p\u003e\n\u003cp\u003eASR (Age-standardized rate) is a ratio adjusted according to a standard population structure, used to eliminate the influence of age structure differences across populations, making comparisons across different time periods or regions possible[22].\u003c/p\u003e\n\u003cp\u003eSDI(\u003cstrong\u003eSocio-Demographic Index)\u003c/strong\u003e is a comprehensive indicator of the development status of geographical regions, measuring the Socioeconomic development levels of countries and regions based on indicators such as per capita income, average years of education, and fertility rates. SDI values range from 0 to 1, with higher values indicating higher Socioeconomic development[23].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.4\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo ensure the comparability and reliability of statistical indicators while comparing the differences among multiple age structures, age-standardization is indispensable.We calculated the ASR of endometriosis globally using the following formula:\u003c/p\u003e\n\u003cp\u003e\u003cimg src=\"https://myfiles.space/user_files/58895_8739fc6c57c1c19a/58895_custom_files/img1753359654.png\" width=\"1000\" height=\"254\"\u003e\u003c/p\u003e\n\u003cp\u003eTo reveal the changes of absolute counts in endometriosis from 1990 to 2021, the increase rates of prevalence were used, and the formula could be expressed as: the prevalence rates = (endometriosis cases in 2021 \u0026ndash; endometriosis cases in 1990) / endometriosis cases in 1990[25].\u003c/p\u003e\n\u003cp\u003eTo assess the relationship between the burden of endometriosis and SDI across different regions and countries, we used a local regression smoothing model (loess) and Spearman correlation analysis. All statistical analyses and graphical representations were performed using R software (version 4.2.1).\u003c/p\u003e"},{"header":"3. Results","content":"\u003cp\u003e\u003cstrong\u003e3.1\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eGlobal and regional level\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn 2021,\u0026nbsp;the Global Burden of Disease Study 2021 estimated\u0026nbsp;a total of 22.3 million cases of endometriosis\u0026nbsp;worldwide, accompanied by an age-standardized point prevalence of 275.6 per 100,000 population, which marks a 26.2% decrease from 1990.\u0026nbsp;In 2021, the total number of DALYs attributable to endometriosis was\u0026nbsp;2,049.5 thousands, with an age-standardized rate of 25.4 DALYs per 100,000 population, representing a 26.1%\u0026nbsp;decline from 1990 (Table 1). Within the 21 GBD regions and 204 countries\u0026nbsp;and territories,\u0026nbsp;the highest age-standardized prevalence\u0026nbsp;were\u0026nbsp;observed\u0026nbsp;in Oceania (491.9) and Eastern Europe (431.6), while the highest DALY\u0026nbsp;rates occurred\u0026nbsp;in Oceania (45.2) and Eastern Europe (39.8).\u0026nbsp;From 1990 to 2021, age-standardized DALY rates declined across all regions, with the\u0026nbsp;largest\u0026nbsp;reductions seen in South Asia (-39.4%) and Central Sub-Saharan Africa (-38.3%) (Table 1).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;95% UI=95% uncertainty intervals.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.2 National level\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; In 2021, the age-standardized prevalence of endometriosis at the national level was estimated to ranged from 150.3 to 669.5 per 100,000 population. The highest prevalence rates were found in Niger (669.5), Chad (568.6), and the Solomon Islands (541.7), while s the lowest estimates were seen in Portugal (150.3), Malta (162.9), and the United Arab Emirates (164.1) (Figure 1).Similarly,the age-standardized DALY rates for endometrioswere estimated to vary between 13.8 and 61.4 per 100,000 individuals. The highest DALY rates were found in Niger (61.4), Chad (51.8), and the Solomon Islands (49.8), while the lowest rates were found in Portugal (13.8), Malta (15), and the United States of America (15). (Figure 1)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.3 Association with the SDI\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.3.1 Regional Level \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe correlation coefficient (R) between the SDI and the DALYs ASR of endometriosis from 1990 to 2021 was -0.66 (95% CI: [-0.70, -0.62], \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001), indicating a statistically significant negative association.This suggests that regions with higher SDI levels generally tended to have lower DALYs ASR during the study period. Notably, the DALYs ASR in Oceania, North Africa and the Middle East, Eastern Europe, High-income Asia Pacific, Southern Sub-Saharan Africa, and Southeast Asia were positioned above the overall trend line (Figure 2), suggesting relatively higher burden levels than the global SDI-adjusted trend would predict. The DALYs ASR for Western Europe, East Asia, Central Latin America, Tropical Latin America, Andean Latin America, High\u0026minus;income North America, and the Caribbean were below the trend line, indicating that the DALYs ASR was lower than expected.（ Figure 2）\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.3.2 At the National Level\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;In 2021, the burden of endometriosis decreased with increased Socioeconomic development, suggesting that improvements in Socioeconomic development may be associated with a reduction in disease burden. Somalia, Chad, and Niger showed lower SDI values and higher DALYs ASR. In contrast, Singapore, Switzerland, and Iceland showed higher SDI values and lower DALYs ASR. （ Figure 3）\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.4 Age Pattern\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn 2021, the number of individuals affected by endometriosis increased notably in the 20\u0026ndash;24 age group, reaching 3.48 million, and peaked in the 25\u0026ndash;29 age group at 4.23 million. Subsequently, the number of cases progressively declined with advancing age, with a more noticeable reduction observed after age 40. Specifically, the number of affected individuals decreased to 3.02 million in the 40\u0026ndash;44 age group and 2.52 million in the 45\u0026ndash;49 age group. In the older age groups, case numbers further dropped significantly, with 1.23 million in the 50\u0026ndash;54 age group and approaching zero in the 55+ age group.（Figure 4）\u003c/p\u003e"},{"header":"4. Discussion","content":"\u003cp\u003e\u003cstrong\u003e4.1 Principal findings\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOur analysis revealed a global decline in both the prevalence and DALY rates of endometriosis from 1990 to 2021. While the reasons for this trend are not directly assessed in this study, it may coincide with improvements in diagnostic capabilities, disease awareness, and treatment accessibility[26].\u0026nbsp;Despite this overall reduction, substantial variation in disease burden persists across regions, countries, and age groups. For instance, based on our estimates, several countries in Oceania, Eastern Europe, and Sub-Saharan Africa exhibit higher burden levels, whereas Western Europe and high-income Asia Pacific show comparatively lower figures.\u003c/p\u003e\n\u003cp\u003eOur findings demonstrate a statistically significant negative correlation between the Socio-demographic Index (SDI) and the age-standardized DALY rate for endometriosis (R = -0.66, p \u0026lt; 0.001), suggesting that countries with higher levels of socioeconomic development tend to have lower disease burdens[19]. However, the substantial variation observed across regions and countries points to persistent disparities in healthcare infrastructure and access to health education.Previous studies\u0026nbsp;have highlighted that in low-income settings, underdiagnosis and limited medical resources may lead to underestimation of disease burden, whereas high-income regions often report lower burdens, potentially due to earlier diagnosis and better treatment options[27][28]. By quantifying the association between SDI and disease burden, this study underscores the importance of socioeconomic factors in global endometriosis management and provides a comprehensive basis for further epidemiological research[29]. Moreover, this study provides a global analysis that contributes a broader perspective to related research. In high-income countries, lower disease burdens are often associated with well-established public health systems and greater awareness of endometriosis. Conversely, in low-income countries, limited healthcare resources, reduced disease knowledge, and cultural barriers may contribute to relatively higher disease burdens[28][30].\u003c/p\u003e\n\u003cp\u003eFinally, age-specific findings in this study indicate that the prevalence of endometriosis is notably higher among women aged 20\u0026ndash;40 years, peaking specifically in the 25\u0026ndash;29 age group. This age range aligns closely with the primary reproductive period for women, underscoring a clinically important association between endometriosis and fertility[31][32][33]. Current estimates indicate that approximately 30%\u0026ndash;50% of individuals with endometriosis experience varying degrees of infertility[3]. The infertility associated with endometriosis presents important medical challenges and constitutes a significant public health issue within global reproductive health[34][35].\u0026nbsp;Particularly in regions experiencing low birth rates and aging populations, timely diagnosis and effective management of endometriosis could help address broader demographic and reproductive health challenges.\u003c/p\u003e\n\u003cp\u003eIn addition, in low and middle income countries, factors such as inadequate medical resources, lack of health awareness, and menstrual stigma contribute to lower diagnostic rates and a widespread lack of reproductive health knowledge[36]. As a result, the link between endometriosis and infertility may be underestimated, leaving many patients without timely diagnosis and intervention[34][37]. The normalization of symptoms such as menstrual pain and the social taboos surrounding them further deepen the disease\u0026rsquo;s concealment[36].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e4.2 Strengths and Limitations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study is based on data from the GBD project, covering 204 countries and regions from 1990 to 2021. By analyzing more than 30 years of data, it reveals the global trends and changes of endometriosis, offering a global perspective for epidemiological research on the disease[38]. Additionally, this study explores the epidemiological characteristics of endometriosis from multiple dimensions such as geographic location, age distribution, and socioeconomic development levels[39]. It reveals significant regional and national differences, particularly the high risk in the 20-40 reproductive age group, providing data to understand the threat of the disease to fertility and global population reproduction.\u0026nbsp;The findings of this study provide important evidence to optimize global health resource allocation, develop early screening, infertility interventions, and health education strategies, thereby promoting the improvement of global women\u0026rsquo;s health and sustainable population development[40].\u003c/p\u003e\n\u003cp\u003eAlthough this study provides a comprehensive epidemiological analysis, there are some limitations.First, variations in data quality and reporting across countries may contribute to underestimation or overestimation of disease burden particularly in low and middle income countries where diagnostic infrastructure is limited.Second,the GBD estimates rely on modeling techniques and indirect data inputs in some regions, which may introduce uncertainty. \u0026nbsp;Third, this analysis does not account for individual-level risk factors such as environmental exposures, genetic predisposition, or lifestyle, which may influence disease distribution but are beyond the scope of this study[41][42].\u003c/p\u003e"},{"header":"5. Conclusions","content":"\u003cp\u003eBetween 1990 to 2021, the global prevalence and DALYs of endometriosis have shown a declining trend, but substantial disparities in disease burden remain across regions, countries, and age groups. Improvements in socioeconomic development appear to be associated with a reduction in the disease burden of endometriosis, with the reproductive age being an critical factor influencing its prevalence.The intersection of these factors highlights a notable association between endometriosis and infertility. Endometriosis represents both a medical concern and a public health issue that warrants attention in social and health policy frameworks. Future public health policies should place greater emphasis on the impact of endometriosis on reproductive health, particularly by incorporating it into the global reproductive health priority agenda[43]. Implementing targeted public health measures, promoting empirical diagnoses, and supporting early detection and treatment may help reduce the disease burden, thereby mitigating the impact on fertility and broader demographic structures, ultimately contributing to the advancement of global women\u0026apos;s health and societal development[43].\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eSDI：Socio-Demographic Index\u003c/p\u003e\n\u003cp\u003eDALYs：Disability-Adjusted Life Years\u003c/p\u003e\n\u003cp\u003eGBD：Global Burden of Disease\u003c/p\u003e\n\u003cp\u003eASR:Age-standardized rate\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003cstrong\u003e.\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data supporting the findings of this study are openly available through the Global Burden of Disease Study 2021 (GBD 2021). The datasets can be accessed via the IHME GBD Results Tool:https://vizhub.healthdata.org/gbd-results/.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was funded by the Xiamen City Natural Science Foundation, grant number 3502Z20227342. The project is entitled \u0026quot;Analysis of the Mechanism of Endometrial Carcinogenesis Using Single-Cell Sequencing.\u0026quot; The total budget for the project is 50,000 RMB, and the project is funded for the period from July 2022 to June 2025.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLL: Conceptualization, Formal Analysis, Software, Visualization, Writing \u0026ndash; Original Draft, Writing \u0026ndash; Review \u0026amp; Editing.\u003c/p\u003e\n\u003cp\u003eQC: Data Curation, Software, Writing \u0026ndash; Review \u0026amp; Editing.\u003c/p\u003e\n\u003cp\u003eXJ: Resources, Software, Visualization.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHG:\u0026nbsp;\u003c/strong\u003eSupervision, Writing \u0026ndash; Review \u0026amp; Editing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eYZ:\u0026nbsp;\u003c/strong\u003eProject Administration, Supervision.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eJZ:\u0026nbsp;\u003c/strong\u003eData Curation, Visualization, Investigation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eYG:\u0026nbsp;\u003c/strong\u003eData Curation, Methodology, Validation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFZ:\u0026nbsp;\u003c/strong\u003eFunding Acquisition, Supervision, Validation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eYL:\u0026nbsp;\u003c/strong\u003eFunding Acquisition, Supervision, Writing \u0026ndash; Review \u0026amp; Editing.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank the Institute for Health Metrics and Evaluation (IHME) for providing access tothe GBD 2021 database. We also acknowledge the contributions of clinical and research assistants at collaborating centers.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003enot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data supporting the findings of this study are openly accessible via the Global Burden of Disease Study 2021 (GBD 2021). Specifically, aggregated data used for analysis can be obtained through the IHME GBD Results Tool (https://vizhub.healthdata.org/gbd-results/). Users may download the data by selecting specific indicators (e.g., prevalence, DALYs, age-standardized rates) and relevant regions or countries directly from the provided online tool.\u003c/p\u003e"},{"header":"References","content":"\u003col class=\"decimal_type\"\u003e\n \u003cli\u003eHorne A W, Missmer S A. Pathophysiology, diagnosis, and management of endometriosis. BMJ 2022; 379 :e070750.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eMarquardt RM, Tran DN, Lessey BA, Rahman MS, Jeong J-W. Epigenetic Dysregulation in Endometriosis: Implications for Pathophysiology and Therapeutics. Endocrine Reviews 2023;44(6):1074\u0026ndash;95.\u003c/li\u003e\n \u003cli\u003eZondervan KT, Becker CM, Missmer SA. Endometriosis. N Engl J Med [Internet] 2020;382(13).\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eTaylor HS, Kotlyar AM, Flores VA. Endometriosis is a chronic systemic disease: clinical challenges and novel innovations. Lancet 2021;397(10276):839\u0026ndash;52.\u003c/li\u003e\n \u003cli\u003eSkorupskaite K, Hardy M, Bhandari H, Yasmin E, Saab W, Seshadri S. Evidence based management of patients with endometriosis undergoing assisted conception: British fertility society policy and practice recommendations. Human Fertility 2024;27(1):2288634.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eLi Y, Liu H, Ye S, Zhang B, Li X, Yuan J, et al. The effects of coagulation factors on the risk of endometriosis: a Mendelian randomization study. BMC Med 2023;21(1):195.\u003c/li\u003e\n \u003cli\u003eSaunders PTK, Whitaker LHR, Horne AW. Endometriosis: Improvements and challenges in diagnosis and symptom management. Cell Rep Med 2024;5(6):101596.Zippl AL, Reiser E, Seeber B. Endometriosis and mental health disorders: identification and treatment as part of a multimodal approach. Fertil Steril 2024;121(3):370\u0026ndash;8.doi:10.1016/j.fertnstert.2023.12.033\u003c/li\u003e\n \u003cli\u003eSivajohan B, Elgendi M, Menon C, Allaire C, Yong P, Bedaiwy MA. Clinical use of artificial intelligence in endometriosis: a scoping review. npj Digit Med 2022;5(1):1\u0026ndash;17.\u003c/li\u003e\n \u003cli\u003eAhn SH, Singh V, Tayade C. Biomarkers in endometriosis: challenges and opportunities. Fertil Steril 2017;107(3):523\u0026ndash;32.\u003c/li\u003e\n \u003cli\u003eChen I, Thavorn K, Yong PJ, Choudhry AJ, Allaire C. Hospital-Associated Cost of Endometriosis in Canada: A Population-Based Study. J Minim Invasive Gynecol 2020;27(5):1178\u0026ndash;87.\u003c/li\u003e\n \u003cli\u003eSimoens S, Dunselman G, Dirksen C, Hummelshoj L, Bokor A, Brandes I, et al. The burden of endometriosis: costs and quality of life of women with endometriosis and treated in referral centres. Hum Reprod 2012;27(5):1292\u0026ndash;9.\u003c/li\u003e\n \u003cli\u003eSafiri S, Carson-Chahhoud K, Noori M, Nejadghaderi SA, Sullman MJM, Ahmadian Heris J, et al. Burden of chronic obstructive pulmonary disease and its attributable risk factors in 204 countries and territories, 1990-2019: results from the Global Burden of Disease Study 2019. BMJ 2022;378:e069679.\u003c/li\u003e\n \u003cli\u003eSun P, Yu C, Yin L, Chen Y, Sun Z, Zhang T, et al. Global, regional, and national burden of female cancers in women of child-bearing age, 1990-2021: analysis of data from the global burden of disease study 2021. EClinicalMedicine 2024;74:102713.\u003c/li\u003e\n \u003cli\u003eLiang X, Lyu Y, Li J, Li Y, Chi C. Global, regional, and national burden of preterm birth, 1990-2021: a systematic analysis from the global burden of disease study 2021. EClinicalMedicine 2024;76:102840.\u003c/li\u003e\n \u003cli\u003eLi N, Deng Y, Zhou L, Tian T, Yang S, Wu Y, et al. Global burden of breast cancer and attributable risk factors in 195 countries and territories, from 1990 to 2017: results from the Global Burden of Disease Study 2017. J Hematol Oncol 2019;12(1):140.\u003c/li\u003e\n \u003cli\u003eXie Y, Bowe B, Mokdad AH, Xian H, Yan Y, Li T, et al. Analysis of the Global Burden of Disease study highlights the global, regional, and national trends\u0026nbsp;of chronic kidney disease epidemiology from 1990 to 2016. Kidney Int 2018;94(3):567\u0026ndash;81.\u003c/li\u003e\n \u003cli\u003eRudd KE, Johnson SC, Agesa KM, Shackelford KA, Tsoi D, Kievlan DR, et al. Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study. Lancet 2020;395(10219):200\u0026ndash;11.\u003c/li\u003e\n \u003cli\u003eCen J, Wang Q, Cheng L, Gao Q, Wang H, Sun F. Global, regional, and national burden and trends of migraine among women of childbearing age from 1990 to 2021: insights from the Global Burden of Disease Study 2021. J Headache Pain 2024;25(1):96.\u003c/li\u003e\n \u003cli\u003eACOG Committee Opinion No. 760 Summary: Dysmenorrhea and Endometriosis in the Adolescent. Obstet Gynecol 2018;132(6):1517\u0026ndash;8.\u003c/li\u003e\n \u003cli\u003eGBD 2017 Risk Factor Collaborators. Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 2018;392(10159):1923\u0026ndash;94.\u003c/li\u003e\n \u003cli\u003eDai H, Alsalhe TA, Chalghaf N, Ricc\u0026ograve; M, Bragazzi NL, Wu J. The global burden of disease attributable to high body mass index in 195 countries and territories, 1990-2017: An analysis of the Global Burden of Disease Study. PLoS Med 2020;17(7):e1003198.\u003c/li\u003e\n \u003cli\u003eZhang K, Kan C, Han F, Zhang J, Ding C, Guo Z, et al. Global, Regional, and National Epidemiology of Diabetes in Children From 1990 to 2019. JAMA Pediatr 2023;177(8):837\u0026ndash;46.\u003c/li\u003e\n \u003cli\u003eHuang Y, Li Y, Pan H, Han L. Global, regional, and national burden of neurological disorders in 204 countries and territories worldwide. J Glob Health. 2023;13:04160.Medline:38018250.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eZhou X, Zhang Z, Ruan C, Wu Y, Zeng B, Su X, et al. Trends in the global, regional, and national burden of testicular cancer from 1990 to 2019: an observational study with 30-year global data. Int J Surg 2024;110(8):4633\u0026ndash;47.\u003c/li\u003e\n \u003cli\u003eWang Y, Wang X, Liao K, Luo B, Luo J. The burden of endometriosis in China from 1990 to 2019. Front Endocrinol (Lausanne) 2022;13:935931.\u003c/li\u003e\n \u003cli\u003eGBD 2017 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 2018;392(10159):1789\u0026ndash;858.\u003c/li\u003e\n \u003cli\u003eGBD 2016 Healthcare Access and Quality Collaborators. Measuring performance on the Healthcare Access and Quality Index for 195 countries and territories and selected subnational locations: a systematic analysis from the Global Burden of Disease Study 2016. Lancet 2018;391(10136):2236\u0026ndash;71.\u003c/li\u003e\n \u003cli\u003eLou Z, Huang Y, Li S, Luo Z, Li C, Chu K, et al. Global, regional,and national time trends in incidence, prevalence, years lived with disability for uterine fibroids, 1990-2019: an age-period-cohort analysis for the global burden of disease 2019 study. BMC Public Health 2023;23(1):916.\u003c/li\u003e\n \u003cli\u003eGBD 2019 Risk Factors Collaborators. Global burden of 87 risk factors in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet 2020;396(10258):1223\u0026ndash;49.\u003c/li\u003e\n \u003cli\u003eLiang Y, Huang J, Zhao Q, Mo H, Su Z, Feng S, et al. Global, regional, and national prevalence and trends of infertility among individuals of reproductive age (15-49 years) from 1990 to 2021, with projections to 2040. Hum Reprod [Internet] 2025.\u003c/li\u003e\n \u003cli\u003eVercellini P, Vigan\u0026ograve; P, Bandini V, Buggio L, Berlanda N, Somigliana E. Association of endometriosis and adenomyosis with pregnancy and infertility. Fertil Steril 2023;119(5):727\u0026ndash;40.\u003c/li\u003e\n \u003cli\u003ePirtea P, Vulliemoz N, de Ziegler D, Ayoubi JM. Infertility workup: identifying endometriosis. Fertil Steril 2022;118(1):29\u0026ndash;33.\u003c/li\u003e\n \u003cli\u003eHorton J, Sterrenburg M, Lane S, Maheshwari A, Li TC, Cheong Y. Reproductive, obstetric, and perinatal outcomes of women with adenomyosis and endometriosis: a systematic review and meta-analysis. Hum Reprod Update 2019;25(5):592\u0026ndash;632.\u003c/li\u003e\n \u003cli\u003eKvaskoff M, Mahamat-Saleh Y, Farland LV, Shigesi N, Terry KL, Harris HR, et al. Endometriosis and cancer: a systematic review and meta-analysis. Hum Reprod Update 2021;27(2):393\u0026ndash;420.\u003c/li\u003e\n \u003cli\u003eAs-Sanie S, Black R, Giudice LC, Gray Valbrun T, Gupta J, Jones B, et al. Assessing research gaps and unmet needs in endometriosis. Am J Obstet Gynecol 2019;221(2):86\u0026ndash;94.\u003c/li\u003e\n \u003cli\u003eNnoaham KE, Hummelshoj L, Webster P, d\u0026rsquo;Hooghe T, Nardone F de C, Nardone C de C, et al. Impact of endometriosis on quality of life and work productivity: a multicenter study across ten countries. Fertility and Sterility 2011;96(2):366-373.e8.\u003c/li\u003e\n \u003cli\u003eRoman H. Endometriosis in studies based on nationwide databases. Fertil Steril 2022;117(2):454\u0026ndash;5.\u003c/li\u003e\n \u003cli\u003eZhou T, Wang X, Zhang J, Zhou E, Xu C, Shen Y, et al. Global burden of thyroid cancer from 1990 to 2021: a systematic analysis from the Global Burden of Disease Study 2021. J Hematol Oncol 2024;17(1):74.\u003c/li\u003e\n \u003cli\u003eSmolarz B, Szyłło K, Romanowicz H. Endometriosis: Epidemiology, Classification, Pathogenesis, Treatment and Genetics (Review of Literature). Int J Mol Sci 2021;22(19):10554.\u003c/li\u003e\n \u003cli\u003eYang K, Yang X, Jin C, Ding S, Liu T, Ma B, et al. Global burden of type 1 diabetes in adults aged 65 years and older, 1990-2019: population based study. BMJ 2024;385:e078432.\u003c/li\u003e\n \u003cli\u003ePrevalence, years lived with disability, and trends in anaemia burden by severity and cause, 1990-2021: findings from the Global Burden of Disease Study 2021. Lancet Haematol 2023;10(9):e713\u0026ndash;34.\u003c/li\u003e\n \u003cli\u003eBecker CM, Bokor A, Heikinheimo O, Horne A, Jansen F, Kiesel L, et al. ESHRE guideline: endometriosis. Hum Reprod Open 2022;2022(2):hoac009.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Table","content":"\u003cp\u003eTable 1 is available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Endometriosis, Global Burden of Disease, prevalence, Disability-Adjusted Life Years, Socio-Demographic Index","lastPublishedDoi":"10.21203/rs.3.rs-6763472/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6763472/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e:To analyze the prevalence and burden of disease (Disability-Adjusted Life Years) of endometriosis in 204 countries and regions from 1990 to 2021, and evaluate its global trends, regional differences and association with Socio-Demographic Index (SDI) and age distribution.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e：Data on the prevalence and Disability-Adjusted Life Years（DALYs）of endometriosis in 204 countries and regions from 1990 to 2021 were extracted using the the Global Burden of Disease（GBD）results tool (https://vizhub.healthdata.org/gbd-results/). Age-standardized rates, percentage changes in prevalence and DALYs, and 95% uncertainty intervals were calculated to quantify the overall disease burden. SDI was used to assess each country's development level. All statistical analyses were performed using R software (version 4.2.1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResult\u003c/strong\u003e(s)：The global age standardised point prevalence and DALY rates for endometriosis were 26.2% and 26.1% lower than in 1990,respectively,with regional differences were significant.Oceania and Eastern Europe had the highest burden, while Western Europe and high-income Asia-Pacific regions had the lowest burden.\u003c/p\u003e\n\u003cp\u003eThe SDI exhibited a significant negative correlation with DALYs (R=-0.66, p\u0026lt;0.001). Countries with lower SDI(e.g., Niger and Chad)experienced a higher disease burden, whereas countries with higher SDI (e.g., Singapore and Switzerland)demonstrated a lower disease burden.\u003c/p\u003e\n\u003cp\u003eEndometriosis is most prevalent among women aged 20-40 years, with the peak prevalence occurring in the 25-29 age group,and approaching zero prevalence in individuals over 55 years.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e(s):Despite the decreasing burden of endometriosis from 1990 to 2021,significant differences remain across regions, countries, and age groups.Higher SDI are closely associated with lower disease burden, while reproductive age is a key factor influencing the prevalence of endometriosis.Future public health policies should focus more on the impact of endometriosis on reproductivehealth.Early detection and treatment should be prioritized to alleviate the effects of endometriosis on fertility and population structure, thus supporting the improvement of global women's health and social development.\u003c/p\u003e","manuscriptTitle":"The Global, Regional, and National Burden of Endometriosis in 204 Countries and Territories, 1990–2021: Results from the Global Burden of Disease Study 2021","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-24 12:33:05","doi":"10.21203/rs.3.rs-6763472/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"259893060710757159364056355881677817013","date":"2025-12-27T10:03:01+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"319798307750675734851361987826127063148","date":"2025-08-02T18:13:03+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-07-21T23:29:29+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-07-21T23:25:52+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-06-27T06:19:05+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-06-27T03:11:16+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2025-06-27T03:08:13+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"66f7be15-339f-4098-bd99-c7f93f940f8d","owner":[],"postedDate":"July 24th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":51891082,"name":"Health sciences/Diseases/Reproductive disorders"},{"id":51891083,"name":"Health sciences/Medical research/Epidemiology"}],"tags":[],"updatedAt":"2025-07-24T12:33:05+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-24 12:33:05","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6763472","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6763472","identity":"rs-6763472","version":["v1"]},"buildId":"WvIrzKhiLBfengagbw6Ux","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}