Global, regional, and national prevalence and disability-adjusted life-years for endometriosis in 204 countries and territories, 1990– 2019: findings from a global burden of disease study

Global, regional, and national prevalence and disability-adjusted life-years for endometriosis in 204 countries and territories, 1990– 2019: findings from a global burden of disease 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 Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Global, regional, and national prevalence and disability-adjusted life-years for endometriosis in 204 countries and territories, 1990– 2019: findings from a global burden of disease study Dongyi Shen, Jing Li, PanWei Hu, Cong Qi, Hong Yang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3857347/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Introduction: This study aimed to analyze the worldwide, regional, and intra-country burden of heteropathy and its trends from 1990 to 2019, utilizing the latest data and improved methodologies from GBD 2019. Methods: We utilized the Global Health Data Exchange Query tool, Global Burden of Disease (GBD), to analyze endometriosis in prevalence numbers, age-standardized prevalence rates (ASPR), and disability-adjusted life-years (DALYs) from 1990 to 2019 in 204 countries and regions. Additionally, this study investigated the impacts of period, age, and cohort on the prevalence and DALYs of endometriosis from the global perspective and in the five sociodemographic index (SDI) regions. Results: Among the 21 regions, the most significant reduction in the prevalence of heterosis between 1990 and 2019 occurred in Central Latin America. In 204 countries, the most pronounced decline was observed in Guatemala. At the SDI level, with the increase of SDI, the ASPR of endometriosis in all regions worldwide showed an overall decreasing trend. The prevalence of endometriosis peaked between the ages of 25 and 29. Discussion: The findings of this study reflect the temporal and spatial tendency of the burden of endometriosis during the study period and provide an epidemiological basis for reducing endometriosis. disability-adjusted life-years endometriosis global burden of disease age–period–cohort model prevalence Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Introduction Endometriosis is a common, chronic, non-fatal gynecological condition that affects approximately 5–10% of women of reproductive age worldwide, with clinical symptoms including infertility, dysmenorrhea, and non-menstrual pelvic pain ( 1 ) ( 2 ). Pelvic pain is prevalent in 50–80% of women with endometriosis, and female infertility is present in 50% of affected women. Endometriosis affects more than 176 million women globally ( 3 ). Pelvic endometriosis is primarily classified as superficial peritoneal endometriosis, deep endometriosis, and ovarian endometrioma ( 4 ). Despite the high prevalence of endometriosis, diagnosing the condition remains challenging, with 65% of women being initially misdiagnosed ( 5 ). Endometriosis is now recognized not only as a pelvic disease but also considered a systemic condition, endometriosis with a role in liver and fat tissue metabolism. It induces inflammation throughout the body and changes the expression of genes in the brain that cause pain sensitivity and disorders involving mood. The full impact of endometriosis is uncertain, and its effects extend beyond the pelvic cavity ( 1 ). Global Burden of Disease (GBD) 2019 is a global database tool for comprehensive analysis and an important result of long-term collaboration among governments worldwide. The GBD 2019 provides an opportunity to explore the global burden of endo diseases by systematically assessing and updating disease burdens and influencing factors in 204 territories and countries. Previous researchers have employed GBD tools to analyze the burden of endometriosis from global, regional, and national perspectives between 1990 and 2017 ( 6 ). For instance, the researchers focused on assessing the burden of endometriosis ( 7 ), long-term changes in the prevalence of endometriosis ( 8 ), and spatiotemporal changes, as well as age-period-cohort analysis of the global burden of endometriosis associated with infertility in China between 1990 to 2019 ( 9 ). This study aimed to analyze the worldwide, regional, and intra-country burden of heteropathy and its trends from 1990 to 2019, utilizing the latest data and improved methodologies from GBD 2019. Materials and Methods 3. Data sources This study used data on the annual prevalence numbers, age-standardized prevalence rates (ASPR), and DALYs of endometriosis in 204 countries and regions from 1990 to 2019 collected from the Global Health Data Exchange Query tool ( http://ghdx.healthdata.org/gbd-results-tool ) and SDI data ( http://ghdx.healthdata.org/data-type/estimate ). The GBD 2019 database encompasses population health and demographic data worldwide, sourced from census data, surveys, registries, indicators and estimates, administrative health data, and health-related financial data. Previous studies have detailed methods of data selection and entry ( 10 , 11 ). 4. Data definition The GBD 2019 study utilizes the SDI as a composite indicator to summarize the sociodemographic development of an area ( 12 ). The SDI, with a scale of 0 to 1, provides a comprehensive indicator of geographical development based on national per capita income, total fertility, and average educational attainment ( 13 ). Five SDI quartiles, namely low, medium-low, medium, medium-high, and high SDI regions, were derived from 204 countries and regions as per the SDI ( 10 ). 5. Statistical analysis GBD was determined utilizing the Bayesian meta-regression tool, disMOd-MR 2.1, to model the burden of non-fatal diseases ( 14 ). Truncated age-standardized rate (ASR), as a weighted average of a specific age ratio, was calculated by aggregating measures of the ratio that a population would have if it had a standard age structure. The assignment of weights was derived from the distribution of the standard population using the following equation: \(\text{A}\text{S}\text{R}=\frac{{\sum }_{i=1}^{A}{\alpha }iwi}{{\sum }_{i=1}^{A}wi}\times \text{100,000}\) , αi is a specific age ratio. The number (or weight) of the chosen standard population was 100,000 (per 100,000 people). The estimated annual percentage change (EAPC) was derived by fitting the linear regression line to the natural logarithm of the ASR: \(\text{E}\text{A}\text{P}\text{C}=\text{l}\text{n}\left(\text{A}\text{S}\text{R}\right)={\alpha }+\beta x+{\epsilon }\) , the x denotes the calendar year, and the ε denotes the error term, whose 95% confidence interval (CI) is established utilizing the formula 100×(exp (β) −1) ( 15 ). A positive value of EAPC, alongside a 95%CI, denotes an upward trend. Conversely, a negative value for both suggests a downward trend. Alternatively, we assume the trend to be relatively stable. This study employed the R language-based network APC analysis tool developed by the National Cancer Institute of the United States to ascertain the independent estimates of the impacts of period, age, and birth cohort on the burden of endometriosis globally and in five SDI-level regions. Period factors pertain to alterations in the load of anthropogenic factors in a particular epoch. Age factors contribute to the establishment of the aging factor. The changes in the cohort factor were associated with the various population exposure conditions at distinct birth periods. In this case, there was a 5-year interval between the age, period, and birth cohort. The net drift and a p -value < 0.05 indicate the overall time trend and statistical difference, respectively. The longitudinal age curve was used to assess changes in disease burden attributed to age effects. Period rate ratios (RR) and cohort RR showcase the influence of period and birth cohort, whereby RR exceeding 1 denotes a greater relative risk of disease in comparison to the reference cohort, while RR below 1 signifies a lower risk. This study used a smoothed spline model to evaluate the association between SDI and the burden of endometriosis in women. The Spearman rank correlation method was utilized for correlation analysis, and statistical significance was considered at p < 0.05. R version 4.3.1 (R Foundation, Vienna, Austria, https://www.r-project.org/ ) was used in this study. In this study, each step utilized to analyze the GBD database adhered to the cross-sectional study guidelines described in the Guidelines for Accurate and Transparent Health Estimates Reporting ( 16 ). Results 7. The endometriosis burden at the global level Globally, the prevalence change (PC) in ASR of endometriosis prevalence declined by 20.47% (95% CI: −22.82% to − 18.32%) from 1990 to 2019 (Tables S1; Fig. 1 A). The ASPR of endometriosis changed from 767.75 (95% uncertainty interval [UI]: 540.26–1060.37 per 100,000 population) in 1990 to 610.57 (95% UI: 436.15–842.30) per 100,000 population in 2019 (Tables S1; Fig. 2 A). The ASR in DALYs due to endometriosis was 71.08 (95% UI:42.52–112.47) worldwide in 1990, decreasing to 56.61 (95% UI: 34.05–89.66) per 100,000 population in 2019 (Tables S1; Fig. 3 A). 8. Endometriosis burden at the SDI quintile level When stratified by SDI levels, a downward trend was observed for ASPR in endometriosis in all SDI quintiles from 1990 to 2019 (Tables S1; Fig. 1 A). The most substantial downward trend was consistently observed in the low-middle SDI quintiles, accounting for − 31.03% (95% CI: −33.14% to − 28.77%) of the overall downward trend for PC in ASPR during this period (Tables S1; Fig. 1 A). In 2019, the highest ASPR of endometriosis among SDI levels was observed in low SDI countries (718.35 (95% UI: 502.46-1001.61) per 100,000 population), while the lowest ASPR was in high SDI countries (538.61 (95% UI: 394.87–719.64) per 100,000 population) (Tables S1; Fig. 2 A). Similarly, low SDI countries exhibited the highest age-standardized DALYs rate (66.22 (95% UI: 39.35-106.15) per 100,000 population) in 2019, whereas high SDI countries (49.72 (95% UI: 30.46–76.75) per 100,000 population) had the lowest rate (Tables S1; Fig. 3 A). 9. Endometriosis burden at the regional level From 1990 to 2019, all 21 regional levels demonstrated a decline in PC for ASPR of endometriosis (Table S2 ). Three areas where the decline was most pronounced were Central Latin America (-36.44% (95% CI: -41.75 to -31.04%)), South Asia (-31.56% (95% CI: -33.97 to -28.91%)), and high-income North America (-29.58% (95% CI: -42.23 to -15.47%)) from 1990 to 2019 (Table S2 ). Eastern Europe (-2.06% (95% CI: -4.50 to 0.26%)), Western Europe (-5.41% (95% CI: -8.94 to -1.30%)), and Central Europe (-8.18% (95% CI: -10.69 to -5.36%)) showed the least decline in PC for ASPR of endometriosis from 1990 to 2019 (Table S1 ). The three regions with the highest ASPR in 2019 for endometriosis were Oceania (915.28 (95% UI: 644.53–1266.00) per 100,000 population), Eastern Europe (833.83 (95% UI: 589.84–1143.83) per 100,000 population), and North Africa and Middle East (798.85 (95% UI: 568.90–1104.77) per 100,000 population) (Table S1 ; Fig. 2 B). Moreover, three regions with the lowest ASPR were high-income North America (377.99 (95% UI:282.88–497.81) per 100,000 population), East Asia (459.19 (95% UI: 327.72–614.23) per 100,000 population), and Central Europe (483.31(95% UI: 340.10–675.63) per 100,000 population) in 2019 (Table S1 ; Fig. 2 B). The three regions with the highest age-standardized DALYs rate in endometriosis were Oceania (84.48 (95% UI:49.95–134.33) per 100,000 population), Eastern Europe (77.74 (95% UI:46.30–122.85) per 100,000 population), and North Africa and Middle East (73.71 (95% UI: 44.14–117.62) per 100,000 population) in 2019 (Table S1 ; Fig. 3 B). Additionally, the three regions with the lowest age-standardized DALYs rate were high-income North America (34.56 (95% UI: 21.57–53.12) per 100,000 population), East Asia (43.03 (95% UI: 26.03–67.67) per 100,000 population), and Central Europe (45.07 (95% UI: 26.70–72.05) per 100,000 population) in 2019 (Table S1 ; Fig. 3 B). 10. Endometriosis burden at countries' level Except for the Russian Federation, Austria, Iceland, and Sweden, the PC of ASPR in endometriosis showed a downward trend in the other 200 countries included in the GBD database from 1990 to 2019. The five countries with the greatest decline in the PC of ASPR in this period were Guatemala (-48.81% (95% CI: -55.31 to -41.49%)), Oman (-46.89% (95% CI: -53.34 to -38.39%)), Equatorial Guinea (-41.80% (95% CI: -48.44 to -33.57%)), Yemen (-39.82% (95% CI: -46.18 to -31.23%)), and Nepal (-39.82% (95% CI: -46.18 to -31.23%)) (Table S2 ). Only Sweden (45.14% (95% CI:13.26 to 84.01%)), Iceland (12.30% (95% CI: -19.62 to 59.06%)), Austria (7.33% (95% CI: -9.14 to 24.19%)), and Russian Federation (0.22% (95% CI: -1.51 to 1.66%)) experienced an increase in PC of ASPR in endometriosis, and Greece (-0.76% (95% CI: -10.64 to 10.45%)) had the least decline during the same period (Table S2 ). The five countries with the highest ASPR of endometriosis in 2019 were New Zealand (1172.91 (95% UI:866.04–1566.59) per 100,000 population), Taiwan (Province of China) (1030.90 (95% UI:776.16–1314.40) per 100,000 population), Afghanistan (1017.18 (95% UI: 705.67–1448.47) per 100,000 population), Solomon Islands (953.85 (95% UI:670.81–1315.52) per 100,000 population) and Papua New Guinea (943.91 (95% UI:667.93–1318.78) per 100,000 population). Conversely, Iceland (301.96 (95% UI:207.63–445.17) per 100,000 population), United States of America (374.15 (95% UI: 282.40–491.91) per 100 000 population), Denmark (378.56 (95% UI:261.33–541.77) per 100,000 population), Malta (381.85 (95% UI:262.48–559.86) per 100,000 population) and Canada (412.75 (95% UI:286.88–572.81) per 100,000 population) had the lowest ASPR in 2019 (Table S2 ; Fig. 4 A). The five countries with the highest age-standardized DALYs rates of endometriosis per 100,000 population in 2019 were New Zealand (107.65 (95% UI: 65.60–169.33)), Taiwan (Province of China) (96.02 (95% UI: 59.77–146.03)), Afghanistan (92.50 (95% UI: 54.13–149.79)), Solomon Islands (88.45 (95% UI: 51.75–140.54)), and Papua New Guinea (87.02 (95% UI: 50.88–139.04)). Contrastingly, the lowest age-standardized DALYs rates per 100,000 population were recorded for Iceland (27.89 (95% UI: 16.02–45.88)), United States of America (34.15 (95% UI: 21.56–52.09)), Denmark (34.80 (95% UI: 19.88–55.20)), Malta (35.22 (95% UI: 20.47–56.84)) and Canada (38.27 (95% UI: 22.33–61.68)) in 2019 (Table S2 ). The three countries with the highest EAPC in endometriosis ASPR from 1990 to 2019 value were Sweden (154.02% (95% UI: 118.46–189.69%)), Iceland (59.07% (95% UI: 39.27–78.90%)), and Austria (49.54% (95% UI: 36.43–62.67%)). Conversely, the three countries with the lowest EAPC values were Guatemala (-243.71% (95% UI: -260.76% to -226.64%)), Oman (-225.05% (95% UI: -247.14% to -202.92%)), and Equatorial Guinea (-196.36% (95% UI: -202.97% to -189.74%)). (Table S3 ; Fig. 4 B). 11. Effect of sociodemographic transition on the burden of endometriosis We observed an overall downward trend in endometriosis ASPR in all regions of the world as SDI increased, as shown in Fig. 5 A. In regions where 0.4 < SDI 0.8, ASPR declined significantly again. There was a U-shaped correlation between ASPR and SDI levels in Central Asia, Australasia, and Eastern Europe. ASPR in high-income North America decreased significantly with SDI. When SDI exceeded 0.8, its ASPR showed a small increase (Table S4 ; Fig. 5 A). Figure 5 B illustrates the association between endometriosis and SDI levels in 204 countries worldwide for the year 2019. As SDI increased, the ASPR of endometriosis in all countries in the world exhibited a decreasing trend, and the decline was obvious when SDI > 0.8. When 0.3 < SDI 0.8, the decreasing trend is significant. Afghanistan, Solomon Islands, Papua New Guinea, Yeman, and New Zealand's ASPR were much higher than expected, while Iceland's APSR was much lower than expected (Table S5; Fig. 5 B). 12. Age–period–cohort impact of endometriosis burden We used an age-period-cohort model to further understand changes in the prevalence burden of endometriosis, and the APC model results showed that for global, middle SDI, low-middle SDI, high-middle SDI, and low SDI categories, NetDrift, all age deviations, 1990–2019 all period deviations, all cohort deviations, all period RR, all cohort RR, all local drifts demonstrated statistical significance ( P < 0.05). The NetDrift, all age deviations, all period deviations, All period RR, and all cohort RR of high SDI had statistical significance ( P < 0.05). However, all period deviations and all local drifts were not statistically significant (Table S6; Fig. 6 A). After adjusting for period and cohort effects, the prevalence of endometriosis exhibited an inverted V-shaped trend globally and in all five SDI regions, with the peak prevalence of endometriosis observed at 25–29 years of age per 100,000 population (global: (1672.01(95% UI:1059.47–2618.12)), high SDI (1310.47 (95% UI:825.23–2078.97)); high-middle SDI (1486.75(95%UI:943.06–2318.10)); middle SDI (1586.40 (95% UI:999.39–2492.78)); low-middle SDI (1842.95 (95% UI:1163.97–2875.41)); low SDI (2068.13 (95% UI:1295.21–3282.97))), and the prevalence decreased after the peak. The global prevalence of endometriosis remained high between the ages of 30 and 39, while the prevalence dropped rapidly when the age exceeded 40 years or between the ages of 15 and 24 years (Table S6, Table S2 ; Fig. 6 B). The time-varying RR values of endometriosis prevalence globally and in any SDI region decreased monotonously throughout the study period. Using the 2000–2004 period group as the reference value (RR = 1), the risk of disease gradually decreased globally and in all SDI regions since that period. Moreover, we observed that in the low-middle SDI and the low SDI areas, the prevalence decreased rapidly after the 2000–2004 period group, while the high SDI and high-middle SDI started from the 2005–2009 period group and the 2010–2014 period group, respectively, demonstrating a relatively slow downward trend. After considering the influence of the correction period and age factors using the 1970–1974 birth cohort as the reference value (RR = 1), the risk of disease in the global and SDI regions basically decreased with the passage of the birth cohort. The global decline in disease risk slowed after the 1990–1994 birth cohort, and the high SDI, high-middle SDI, and middle SDI regions had a slight increase in disease risk after the 1995–1999 birth cohort. Conversely, low-middle SDI and low SDI regions consistently maintained a faster rate of decline (Table S6, Table S2 ; Fig. 6 C). Discussion Endometriosis can affect several organ systems, and the condition is chronic. Hence, it has an impact on work productivity, intimate relationships, mental health, and social life ( 17 ). Additionally, endometriosis influences fertility by disrupting the pelvic integrity and modifying the peritoneal environment ( 18 ). Approximately 30% of people with endometriosis experience fertility issues ( 19 ). Researchers have also studied the association between endometriosis and mental illness, and approximately 87% of women with endometriosis reported some type of mental illness ( 20 ) ( 21 ). Despite endometriosis being a non-malignant disease, there is substantial evidence that endometriosis is associated with an elevated risk of cancer, especially ovarian and breast cancer ( 22 ) ( 23 ). Current methods for diagnosing endometriosis include transvaginal ultrasound, laparoscopy, and magnetic resonance imaging ( 4 ). However, these diagnostic tests prove inadequate due to varied locations and the appearance of endometriosis lesions, thus delaying diagnosis and increasing the possibility of misdiagnosis ( 24 ). Other factors contributing to delayed diagnosis include variability of symptoms, suboptimal health care providers and awareness of endometriosis by the patient, stigma toward discussions regarding gynecological symptoms, and the social normalization of pain among women ( 25 ). Existing treatments, including medications and surgical methods, can relieve symptoms but do not lead to a permanent cure for endometriosis ( 26 , 27 ). Several studies have used nanotechnology to locate and remove painful and dangerous lesions in the ovaries, fallopian tubes, and pelvis in animal models of endometriosis and have made progress in the diagnosis as well as management of endometriosis ( 28 ). Moreover, some researchers have explored the use of microRNA to diagnose endometriosis and have confirmed the feasibility of this method ( 29 ). From 1990 to 2019, this study demonstrated a downward trend in ASPR and DALYs in all regions and countries worldwide. Among the 21 regions, the most remarkable reduction in the prevalence of heterosis between 1990 and 2019 was in Central Latin America, followed by South Asia, and the least in Eastern Europe, followed by Western Europe. In 204 countries, the decline was most pronounced in Guatemala, Oman, and Equatorial Guinea. Only Sweden, Iceland, Austria, and the Russian Federation experienced an increase in PC of ASPR in endometriosis. At the SDI level, as SDI increased, the ASPR of endometriosis in all regions worldwide showed an overall decreasing trend, and the most obvious decreasing trend was in low-middle SDI quintiles. These results indicate some success in the global efforts to combat endometriosis. The endometriosis awareness campaign might have had a huge impact on transforming the knowledge and attitudes of healthcare providers about endometriosis and the importance of early diagnosis of the condition ( 30 ). There is a U-shaped correlation between ASPR and SDI levels in Central Asia, Australasia, and Eastern Europe. ASPR in high-income North America decreased significantly with SDI. When SDI was greater than 0.8, its ASPR showed a small increase. This finding suggests that while the burden is generally lower in areas with higher SDI, it is likely to increase again if interventions remain suboptimal. Furthermore, initiatives aimed at reducing the prevalence of endometriosis should be aligned with genuine health needs and social determinants. This entails considering the disease context, age composition, and regional culture to reduce the disease burden effectively. Differences in the diagnosed prevalence have been observed across various ethnic and racial groups. A systematic review determined that Asian women have a higher risk of endometriosis, while black women have a lower risk compared to white women; however, these estimates may be influenced by biases associated with access to care ( 31 ). The prevalence of endometriosis differs among various continents, with Asia, America, Europe, Africa, and Australia exhibiting the highest to lowest prevalence, respectively ( 32 ). However, the prevalence rate is not necessarily comparable between countries and regions due to significant structural differences in their respective healthcare systems. The diagnosis and treatment of female endometriosis patients are influenced by various conditions, including views, society, economy, education, medical conditions, and security systems, and there may be delays in the diagnosis of female endometriosis patients in some economically underdeveloped regions. Cultural and social differences may also affect how individuals conceptualize pain ( 33 ). In one study, 82% of French patients reported that dysmenorrhea affected their lives, compared to only 44% of Chinese patients. Additionally, endometriosis is more common in French women without endometriosis than in Chinese women. This suggests that there may be different healthcare experiences and/or expectations between patients from different regions ( 34 ). A lower body mass index and a high intake of trans fats and red meat were listed as risk factors for the onset of endometriosis ( 35 ). The risk of endometriosis has been shown to be reduced by physical activity, oral contraceptives, and a diet rich in fruits, vegetables, and omega-3 long-chain fatty acids ( 36 ). Birth cohort effects revealed various risk factors that affect different birth cohorts early in life, encompassing behavioral, environmental, and socioeconomic factors. The prevalence of endometriosis peaked between the ages of 25 and 29, maintained a high global prevalence of endometriosis between the ages of 30 and 39, and dropped rapidly when the age was over 40 or between the ages of 15 and 24, which may also be related to the diagnosis of endometriosis. Normalization of menstrual pain in women acts as an obstacle to the exploration and diagnosis of health issues, and the extensive utilization of hormonal contraceptives suppresses and conceals symptoms associated with endometriosis. Typically, undiagnosed women with endometriosis are identified after discovering infertility problems, deciding to stop using hormonal contraceptives, or seeking counseling related to endometriosis for 6–10 years. However, our findings are inconsistent with those of Christ et al., who suggested that women aged 36 to 45 had the highest prevalence of endometriosis (2006–2015)( 37 ). After adjusting for the effects of time and age, using the 1970–1974 birth cohort as the reference value (RR = 1), the risk of disease in the global and SDI regions basically decreased with the passage of the birth cohort. The global decline in disease risk slowed after the 1990–1994 birth cohort, and the high-middle SDI, high SDI, and middle SDI regions exhibited a slight increase in disease risk after the 1995–1999 birth cohort. Conversely, the low-middle SDI, in conjunction with the low SDI regions, consistently maintained a remarkable rate of decline. This observation may be attributed to the economic development and social progress, as the recent birth cohort has a greater awareness of disease prevention compared to the earlier birth cohort, and with the improvement of laparoscopic surgery, there is an improvement in the diagnosis and therapeutic management of endometriosis ( 38 ). The GBD 2019 study provides a comprehensive and high-quality assessment of the disease burden of endometriosis. However, this study has some limitations. First, the data pertaining to endometriosis from some regions and countries require improvement to generate estimates that are reasonable and relatively more accurate on the disease burden. Second, this study lacked data on factors that impact endometriosis, including diet, environment, and lifestyle. There are differences in social security systems, medical conditions, economies, and cultures in distinct regions and countries, and women have different needs when seeking treatment for endometriosis, which also affects the accuracy of this study. Finally, the 2019 GBD lacks a classification of endometriosis to account for the disease burden of different types of endometriosis separately. However, this study also has unique advantages as it is the latest comprehensive epidemiological study on the trends of the burden of endometriosis worldwide from 1990 to 2019. Conclusively, this study demonstrates a downward trend in ASPR and DALYs in all regions and countries globally from 1990 to 2019. Among the 21 regions, the most substantial reduction in the prevalence of heterosis between 1990 and 2019 was in Central Latin America, followed by South Asia, and the least in Eastern Europe, followed by Western Europe. In 204 countries, the decline was most pronounced in Guatemala, Oman, and Equatorial Guinea. Notably, only Sweden, Iceland, Austria, and the Russian Federation exhibited an increase in PC of ASPR in endometriosis. This study indicates that at different SDI levels, with the increase of SDI, the ASPR of endometriosis in all regions of the world showed an overall decreasing trend, and the most obvious decreasing trend was low-middle SDI quintiles. Furthermore, the prevalence of endometriosis peaks between the ages of 25 and 29, maintains a high global prevalence between the ages of 30 and 39 and declines rapidly when the age is over 40 or between the ages of 15 and 24. This study presents a comprehensive survey of the global burden of endometriosis among women that can inform decision-makers about healthcare priorities related to endometriosis, strengthen education, raise public awareness of female endometriosis, safeguard women's legitimate rights, reduce the stigma associated with women's pain visits and reduce delays in endometriosis diagnosis. The findings underscore the importance of maintaining the status and safety of women and implementing necessary preventive and management interventions to reduce the prevalence of female endometriosis and protect women's health. Abbreviations GBD, Global Burden of Disease; DALY, disability-adjusted life-year; SDI, sociodemographic index; ASPR, age-standardized prevalence rates; ASR, age-standardized rate; EAPC, estimated annual percentage change; UI, uncertainty interval. Declarations Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Declarations The data in this study were sourced from a publicly available database and do not require ethical review. All authors agreed to the study's publication in Reproductive Health and were willing to pay a page fee. Funding This study was supported by the National Nature Science Foundation of China (NO. 82274571), the National Nature Science Foundation of China (NO. 82305284), the Shanghai Medical Innovation and Development Foundation (WL-HBMS-2021004K), the Siming Research Project in Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (SGKY-202306), Author Contribution D.Y. Shen wrote the original manuscript and conceived the study; J. L performed the data analysis; P.W. Hu revised the final manuscript; C. Qi and H. Yang supervised the study process. All authors reviewed the manuscript. Acknowledgments We highly appreciate the works of the Global Burden of Disease Study 2019 collaborators. We thank Bullet Edits Limited for the linguistic editing and proofreading of the manuscript. Data Availability Statement The data underlying this article are available in the Global Health Data Exchange at http://ghdx.healthdata.org/gbd-results-tool . References Taylor HS, Kotlyar AM, Flores VA. Endometriosis is a chronic systemic disease: clinical challenge and novel innovations. Lancet. 2021;397(10276):839–52. 10.1016/S0140-6736(21)00389-5 . Taylor HS, Adamson GD, Diamond MP, Goldstein SR, Horne AW, Missmer SA, et al. An evidence-based approach to assessing surgical versus clinical diagnosis of symptomatic endometriosis. Int J Gynaecol Obstet. 2018;142(2):131–42. 10.1002/ijgo.12521 . Zondervan KT, Becker CM, Koga K, Missmer SA, Taylor RN, Viganò P. Endometriosis. 2018;4(1):9. 10.1038/s41572-018-0008-5 . 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Culley L, Law C, Hudson N, Denny E, Mitchell H, Baumgarten M, et al. The social and psychological impact of endometriosis on women's lives: a critical narrative review. Hum Reprod Update. 2013;19(6):625–39. 10.1093/humupd/dmt027 . Levy AR, Osenenko KM, Lozano-Ortega G, Sambrook R, Jeddi M, Belisle S, et al. Economic burden of surgically confirmed endometriosis in Canada. J Obstet Gynaecol Can. 2011;33(8):830–7. 10.1016/S1701-2163(16)34986-6 . Prescott J, Farland LV, Tobias DK, Gaskins AJ, Spiegelman D, Chavarro JE, et al. A prospective cohort study of endometriosis and subsequent risk of infertility. Hum Reprod. 2016;31(7):1475–82. 10.1093/humrep/dew085 . As-Sanie S, Black R, Giudice LC, Gray Valbrun T, Gupta J, Jones B et al. Assessing research gaps and unmet needs in endometriosis. (2019),221(2):86–94. 10.1016/j.ajog.2019.02.033 . Vercellini P, Fedele L, Aimi G, Pietropaolo G, Consonni D, Crosignani PG. Association between endometriosis stage, lesion type, patient characteristics and severity of pelvic pain symptoms: a multivariate analysis of over 1000 patients. Hum Reprod. 2007;22(1):266–71. 10.1093/humrep/del339 . Shafrir AL, Farland LV, Shah DK, Harris HR, Kvaskoff M, Zondervan K, et al. Risk for and consequences of endometriosis: A critical epidemiologic review. Best Pract Res Clin Obstet Gynaecol. 2018;51:1–15. 10.1016/j.bpobgyn.2018.06.001 . Kvaskoff M, Mu F, Terry KL, Harris HR, Poole EM, Farland L, et al. Endometriosis: a high-risk population for major chronic diseases? Hum Reprod Update. 2015;21(4):500–16. 10.1093/humupd/dmv013 . Koninckx PR, Fernandes R, Ussia A, Schindler L, Wattiez A, Al-Suwaidi S et al. Pathogenesis Based Diagnosis and Treatment of Endometriosis. (2021),12:745548. 10.3389/fendo.2021.745548 . Wahl KJ, Yong PJ, Bridge-Cook P, Allaire C. Endometriosis in Canada: It Is Time for Collaboration to Advance Patient-Oriented, Evidence-Based Policy, Care, and Research. (2021),43(1):88–90. 10.1016/j.jogc.2020.05.009 . Hudelist G, Fritzer N, Fau - Thomas A, Thomas A, Fau - Niehues C, Niehues C, Fau - Oppelt P, Oppelt P, Fau - Haas D, Haas D, Fau - Tammaa A et al. Diagnostic delay for endometriosis in Austria and Germany: causes and possible consequences. (2012),27(12):3412–6. 10.1093/humrep/des316 . Singh S, Soliman AM, Rahal Y, Robert C, Defoy I, Nisbet P et al. Prevalence, Symptomatic Burden, and Diagnosis of Endometriosis in Canada: Cross-Sectional Survey of 30 000 Women. (2020),42(7):829–38. 10.1016/j.jogc.2019.10.038 . Volpini C, Bloise N, Dominoni M, Barra F, Vellone VG, Minzioni P, et al. The nano-revolution in the diagnosis and treatment of endometriosis. Nanoscale. 2023;15(43):17313–25. 10.1039/d3nr03527a . Moustafa S, Burn M, Mamillapalli R, Nematian S, Flores V, Taylor HS. Accurate diagnosis of endometriosis using serum microRNAs. Am J Obstet Gynecol. (2020),223(4):557 e1- e11. 10.1016/j.ajog.2020.02.050 . Sims OA-O, Gupta J, Missmer SA, Aninye IA-O. Stigma and Endometriosis: A Brief Overview and Recommendations to Improve Psychosocial Well-Being and Diagnostic Delay. (2021),18(15):8210. 10.3390/ijerph18158210 . Bougie O, Yap MI, Sikora L, Flaxman TA-O, Singh S. Influence of race/ethnicity on prevalence and presentation of endometriosis: a systematic review and meta-analysis. (2019),(1471 – 0528 (Electronic)):126(9):1104–15. 10.1111/1471-0528.15692 . Ghiasi M, Kulkarni MT, Missmer SA. Is Endometriosis More Common and More Severe Than It Was 30 Years Ago? (2020),27(2):452–61. 10.1016/j.jmig.2019.11.018 . Kwok W, Bhuvanakrishna T. The relationship between ethnicity and the pain experience of cancer patients: a systematic review. (2014),20(3):194–200. 10.4103/0973-1075.138391 . Chapron C, Lang JH, Leng JH, Zhou Y, Zhang X, Xue M, et al. Factors and Regional Differences Associated with Endometriosis: A Multi-Country, Case-Control Study. Adv Ther. 2016;33(8):1385–407. 10.1007/s12325-016-0366-x . Parasar P, Ozcan P, Terry KL. Endometriosis: Epidemiology, Diagnosis and Clinical Management. Curr Obstet Gynecol Rep. 2017;6(1):34–41. 10.1007/s13669-017-0187-1 . Vercellini P, Somigliana SDEM, Buggio E, Frattaruolo L, Fedele MP. Long-term adjuvant therapy for the prevention of postoperative endometrioma recurrence: a systematic review and meta-analysis. Acta Obstet Gynecol Scand. 2013;92(1):8–16. 10.1111/j.1600-0412.2012.01470.x . Christ JP, Yu O, Schulze-Rath R, Grafton J, Hansen K, Reed SD. Incidence, prevalence, and trends in endometriosis diagnosis: a United States population-based study from 2006 to 2015. Am J Obstet Gynecol. (2021),225(5):500 e1- e9. 10.1016/j.ajog.2021.06.067 . Tavcar J, Loring M, Movilla PR, Clark NV. Diagnosing endometriosis before laparoscopy: radiologic tools to evaluate the disease. Curr Opin Obst Gynecol. 2020;32(4):292–7. 10.1097/Gco.0000000000000638 . Additional Declarations No competing interests reported. Supplementary Files SupplementaryTable1.pdf SupplementaryTable2.pdf SupplementaryTable3.pdf SupplementaryTable4.pdf SupplementaryTable5.pdf SupplementaryTable6.pdf data1.csv data2.csv data3.csv data4.csv Cite Share Download PDF Status: Posted Version 1 posted 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-3857347","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":267291125,"identity":"370c5f7c-8723-495c-b0e7-eab133a509f1","order_by":0,"name":"Dongyi Shen","email":"","orcid":"","institution":"Shuguang Hospital, Shanghai University of Traditional Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Dongyi","middleName":"","lastName":"Shen","suffix":""},{"id":267291126,"identity":"e82371b4-8987-4baf-828b-ea972d51832b","order_by":1,"name":"Jing Li","email":"","orcid":"","institution":"Shuguang Hospital, Shanghai University of Traditional Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Jing","middleName":"","lastName":"Li","suffix":""},{"id":267291127,"identity":"4575a3bb-3311-4d45-8268-748386f57c01","order_by":2,"name":"PanWei Hu","email":"","orcid":"","institution":"Shuguang Hospital, Shanghai University of Traditional Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"PanWei","middleName":"","lastName":"Hu","suffix":""},{"id":267291128,"identity":"d9603a82-2b7c-4d61-ad8b-6ac95f2cee1d","order_by":3,"name":"Cong Qi","email":"","orcid":"","institution":"Shuguang Hospital, Shanghai University of Traditional Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Cong","middleName":"","lastName":"Qi","suffix":""},{"id":267291129,"identity":"53754bb3-4a5c-4a0e-b8ac-346cb0474018","order_by":4,"name":"Hong Yang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAuklEQVRIiWNgGAWjYBACxvkHGw5+qJDg4SdaC/MM5sbDEmcs5CQbiNXCPoO9+QBvS4WxwQFitfDObmw4INkgkbj5ePIGhh8V2whrkZxzsOFA4Q6JxG1nnhUw9py5TViLYUMi0JYzQC03cgyYGduI0GJ/AKiFtw3osBnEamGcAdFibCBBtJaegw3AQJaQkwD65SBRfmFsb3/88UNFHQ9/e/LGBz8qiNCCBBKIjxqEFlJ1jIJRMApGwQgBAEDiRZXxLDNlAAAAAElFTkSuQmCC","orcid":"","institution":"Shanghai municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine","correspondingAuthor":true,"prefix":"","firstName":"Hong","middleName":"","lastName":"Yang","suffix":""}],"badges":[],"createdAt":"2024-01-12 14:59:18","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3857347/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3857347/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":49745961,"identity":"c5f2c9af-c79e-44b6-a7a7-421a47600d43","added_by":"auto","created_at":"2024-01-17 10:48:28","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":940711,"visible":true,"origin":"","legend":"\u003cp\u003eSDI-specific counts in 2019 and percentage change counts of endometriosis, 1990–2019 of prevalence and DALYs across various age groups ranging from 15 years to more than 54 years old. (A) Age-SDI-specific prevalence counts in 2019 and their percentage change counts of endometriosis during 1990–2019. (B) Age-SDI-specific DALYs count in 2019 and their percentage change counts of endometriosis during 1990–2019.\u003c/p\u003e","description":"","filename":"Fig1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3857347/v1/4527e5fbd7953406c26bc01e.jpg"},{"id":49746256,"identity":"4312d4ff-2fc7-4e95-b52b-a3883da8743d","added_by":"auto","created_at":"2024-01-17 10:56:28","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1923813,"visible":true,"origin":"","legend":"\u003cp\u003eTrends in global disease burden of endometriosis prevalence from 1990 to 2019. (A) Trends in global disease burden of endometriosis prevalence based on sociodemographic index from 1990 to 2019; (B) Trends in global disease burden of endometriosis prevalence by region from 1990 to 2019.\u003c/p\u003e","description":"","filename":"Fig2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3857347/v1/a3240419af5b64f3ce27e996.jpg"},{"id":49746257,"identity":"4be710df-c930-4366-8e29-ee1e535ee5fc","added_by":"auto","created_at":"2024-01-17 10:56:28","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1889855,"visible":true,"origin":"","legend":"\u003cp\u003eTrends in global disease burden of endometriosis DALYs from 1990 to 2019. (A) Trends in global disease burden of endometriosis DALYs by sociodemographic index from 1990 to 2019; (B) Trends in global disease burden of endometriosis DALYs by region from 1990 to 2019.\u003c/p\u003e","description":"","filename":"Fig3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3857347/v1/69593283bc48df6cf25267a2.jpg"},{"id":49745970,"identity":"b6a8e96b-bf64-424d-aa7f-b7faf07514f6","added_by":"auto","created_at":"2024-01-17 10:48:28","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":4030483,"visible":true,"origin":"","legend":"\u003cp\u003eGlobal disease burden of endometriosis prevalence in 204 countries and territories. (A) The percent change in age-standardized prevalence of endometriosis between 1990 and 2019; (B) The estimated annual percentage change of endometriosis age-standardized prevalence from 1990 to 2019.\u003c/p\u003e","description":"","filename":"Fig4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3857347/v1/3565897832df678690deac2b.jpg"},{"id":49745964,"identity":"026dc253-bedd-4300-9c4e-9f79f287d67f","added_by":"auto","created_at":"2024-01-17 10:48:28","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":2796585,"visible":true,"origin":"","legend":"\u003cp\u003eAge-standardized rate of prevalence due to endometriosis. (A) Data across 21 GBD regions by SDI during 1990–2019. The points in each region, progressing from left to right, display estimates for every year from 1990 to 2019. (B) Data across 204 countries and territories by SDI in 2019.\u003c/p\u003e","description":"","filename":"Fig5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3857347/v1/d1f1d7dad317fc25dfc83ba8.jpg"},{"id":49746258,"identity":"9bc1c00c-7ecc-4aae-b01d-5a987e190c94","added_by":"auto","created_at":"2024-01-17 10:56:28","extension":"jpg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":884970,"visible":true,"origin":"","legend":"\u003cp\u003eAge–period–cohort impact of burden for ASPR of endometriosis. 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study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eEndometriosis is a common, chronic, non-fatal gynecological condition that affects approximately 5\u0026ndash;10% of women of reproductive age worldwide, with clinical symptoms including infertility, dysmenorrhea, and non-menstrual pelvic pain (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Pelvic pain is prevalent in 50\u0026ndash;80% of women with endometriosis, and female infertility is present in 50% of affected women. Endometriosis affects more than 176\u0026nbsp;million women globally (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Pelvic endometriosis is primarily classified as superficial peritoneal endometriosis, deep endometriosis, and ovarian endometrioma (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Despite the high prevalence of endometriosis, diagnosing the condition remains challenging, with 65% of women being initially misdiagnosed (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eEndometriosis is now recognized not only as a pelvic disease but also considered a systemic condition, endometriosis with a role in liver and fat tissue metabolism. It induces inflammation throughout the body and changes the expression of genes in the brain that cause pain sensitivity and disorders involving mood. The full impact of endometriosis is uncertain, and its effects extend beyond the pelvic cavity (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eGlobal Burden of Disease (GBD) 2019 is a global database tool for comprehensive analysis and an important result of long-term collaboration among governments worldwide. The GBD 2019 provides an opportunity to explore the global burden of endo diseases by systematically assessing and updating disease burdens and influencing factors in 204 territories and countries. Previous researchers have employed GBD tools to analyze the burden of endometriosis from global, regional, and national perspectives between 1990 and 2017 (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). For instance, the researchers focused on assessing the burden of endometriosis (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e), long-term changes in the prevalence of endometriosis (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e), and spatiotemporal changes, as well as age-period-cohort analysis of the global burden of endometriosis associated with infertility in China between 1990 to 2019 (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). This study aimed to analyze the worldwide, regional, and intra-country burden of heteropathy and its trends from 1990 to 2019, utilizing the latest data and improved methodologies from GBD 2019.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\n\u003ch3\u003e3. Data sources\u003c/h3\u003e\n\u003cp\u003eThis study used data on the annual prevalence numbers, age-standardized prevalence rates (ASPR), and DALYs of endometriosis in 204 countries and regions from 1990 to 2019 collected from the Global Health Data Exchange Query tool (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://ghdx.healthdata.org/gbd-results-tool\u003c/span\u003e\u003cspan address=\"http://ghdx.healthdata.org/gbd-results-tool\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) and SDI data (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://ghdx.healthdata.org/data-type/estimate\u003c/span\u003e\u003cspan address=\"http://ghdx.healthdata.org/data-type/estimate\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e). The GBD 2019 database encompasses population health and demographic data worldwide, sourced from census data, surveys, registries, indicators and estimates, administrative health data, and health-related financial data. Previous studies have detailed methods of data selection and entry (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e\n\u003ch3\u003e4. Data definition\u003c/h3\u003e\n\u003cp\u003eThe GBD 2019 study utilizes the SDI as a composite indicator to summarize the sociodemographic development of an area (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). The SDI, with a scale of 0 to 1, provides a comprehensive indicator of geographical development based on national per capita income, total fertility, and average educational attainment (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Five SDI quartiles, namely low, medium-low, medium, medium-high, and high SDI regions, were derived from 204 countries and regions as per the SDI (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e).\u003c/p\u003e\n\u003ch3\u003e5. Statistical analysis\u003c/h3\u003e\n\u003cp\u003eGBD was determined utilizing the Bayesian meta-regression tool, disMOd-MR 2.1, to model the burden of non-fatal diseases (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). Truncated age-standardized rate (ASR), as a weighted average of a specific age ratio, was calculated by aggregating measures of the ratio that a population would have if it had a standard age structure. The assignment of weights was derived from the distribution of the standard population using the following equation: \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\text{A}\\text{S}\\text{R}=\\frac{{\\sum }_{i=1}^{A}{\\alpha }iwi}{{\\sum }_{i=1}^{A}wi}\\times \\text{100,000}\\)\u003c/span\u003e\u003c/span\u003e, \u003cem\u003eαi\u003c/em\u003e is \u003cem\u003ea\u003c/em\u003e specific age ratio. The number (or weight) of the chosen standard population was 100,000 (per 100,000 people).\u003c/p\u003e \u003cp\u003eThe estimated annual percentage change (EAPC) was derived by fitting the linear regression line to the natural logarithm of the ASR: \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\text{E}\\text{A}\\text{P}\\text{C}=\\text{l}\\text{n}\\left(\\text{A}\\text{S}\\text{R}\\right)={\\alpha }+\\beta x+{\\epsilon }\\)\u003c/span\u003e\u003c/span\u003e, the \u003cem\u003ex\u003c/em\u003e denotes the calendar year, and the ε denotes the error term, whose 95% confidence interval (CI) is established utilizing the formula 100\u0026times;(exp (β) \u0026minus;1) (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). A positive value of EAPC, alongside a 95%CI, denotes an upward trend. Conversely, a negative value for both suggests a downward trend. Alternatively, we assume the trend to be relatively stable.\u003c/p\u003e \u003cp\u003eThis study employed the R language-based network APC analysis tool developed by the National Cancer Institute of the United States to ascertain the independent estimates of the impacts of period, age, and birth cohort on the burden of endometriosis globally and in five SDI-level regions. Period factors pertain to alterations in the load of anthropogenic factors in a particular epoch. Age factors contribute to the establishment of the aging factor. The changes in the cohort factor were associated with the various population exposure conditions at distinct birth periods. In this case, there was a 5-year interval between the age, period, and birth cohort. The net drift and a \u003cem\u003ep\u003c/em\u003e-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 indicate the overall time trend and statistical difference, respectively. The longitudinal age curve was used to assess changes in disease burden attributed to age effects. Period rate ratios (RR) and cohort RR showcase the influence of period and birth cohort, whereby RR exceeding 1 denotes a greater relative risk of disease in comparison to the reference cohort, while RR below 1 signifies a lower risk.\u003c/p\u003e \u003cp\u003eThis study used a smoothed spline model to evaluate the association between SDI and the burden of endometriosis in women. The Spearman rank correlation method was utilized for correlation analysis, and statistical significance was considered at \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05. R version 4.3.1 (R Foundation, Vienna, Austria, \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.r-project.org/\u003c/span\u003e\u003cspan address=\"https://www.r-project.org/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) was used in this study.\u003c/p\u003e \u003cp\u003eIn this study, each step utilized to analyze the GBD database adhered to the cross-sectional study guidelines described in the Guidelines for Accurate and Transparent Health Estimates Reporting (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e).\u003c/p\u003e"},{"header":"Results","content":"\n\u003ch3\u003e7. The endometriosis burden at the global level\u003c/h3\u003e\n\u003cp\u003eGlobally, the prevalence change (PC) in ASR of endometriosis prevalence declined by 20.47% (95% CI: \u0026minus;22.82% to \u0026minus;\u0026thinsp;18.32%) from 1990 to 2019 (Tables S1; Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA). The ASPR of endometriosis changed from 767.75 (95% uncertainty interval [UI]: 540.26\u0026ndash;1060.37 per 100,000 population) in 1990 to 610.57 (95% UI: 436.15\u0026ndash;842.30) per 100,000 population in 2019 (Tables S1; Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA). The ASR in DALYs due to endometriosis was 71.08 (95% UI:42.52\u0026ndash;112.47) worldwide in 1990, decreasing to 56.61 (95% UI: 34.05\u0026ndash;89.66) per 100,000 population in 2019 (Tables S1; Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e\n\u003ch3\u003e8. Endometriosis burden at the SDI quintile level\u003c/h3\u003e\n\u003cp\u003eWhen stratified by SDI levels, a downward trend was observed for ASPR in endometriosis in all SDI quintiles from 1990 to 2019 (Tables S1; Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA). The most substantial downward trend was consistently observed in the low-middle SDI quintiles, accounting for \u0026minus;\u0026thinsp;31.03% (95% CI: \u0026minus;33.14% to \u0026minus;\u0026thinsp;28.77%) of the overall downward trend for PC in ASPR during this period (Tables S1; Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA).\u003c/p\u003e \u003cp\u003eIn 2019, the highest ASPR of endometriosis among SDI levels was observed in low SDI countries (718.35 (95% UI: 502.46-1001.61) per 100,000 population), while the lowest ASPR was in high SDI countries (538.61 (95% UI: 394.87\u0026ndash;719.64) per 100,000 population) (Tables S1; Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA). Similarly, low SDI countries exhibited the highest age-standardized DALYs rate (66.22 (95% UI: 39.35-106.15) per 100,000 population) in 2019, whereas high SDI countries (49.72 (95% UI: 30.46\u0026ndash;76.75) per 100,000 population) had the lowest rate (Tables S1; Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA).\u003c/p\u003e\n\u003ch3\u003e9. Endometriosis burden at the regional level\u003c/h3\u003e\n\u003cp\u003eFrom 1990 to 2019, all 21 regional levels demonstrated a decline in PC for ASPR of endometriosis (Table \u003cspan refid=\"MOESM2\" class=\"InternalRef\"\u003eS2\u003c/span\u003e). Three areas where the decline was most pronounced were Central Latin America (-36.44% (95% CI: -41.75 to -31.04%)), South Asia (-31.56% (95% CI: -33.97 to -28.91%)), and high-income North America (-29.58% (95% CI: -42.23 to -15.47%)) from 1990 to 2019 (Table \u003cspan refid=\"MOESM2\" class=\"InternalRef\"\u003eS2\u003c/span\u003e). Eastern Europe (-2.06% (95% CI: -4.50 to 0.26%)), Western Europe (-5.41% (95% CI: -8.94 to -1.30%)), and Central Europe (-8.18% (95% CI: -10.69 to -5.36%)) showed the least decline in PC for ASPR of endometriosis from 1990 to 2019 (Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe three regions with the highest ASPR in 2019 for endometriosis were Oceania (915.28 (95% UI: 644.53\u0026ndash;1266.00) per 100,000 population), Eastern Europe (833.83 (95% UI: 589.84\u0026ndash;1143.83) per 100,000 population), and North Africa and Middle East (798.85 (95% UI: 568.90\u0026ndash;1104.77) per 100,000 population) (Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e; Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB). Moreover, three regions with the lowest ASPR were high-income North America (377.99 (95% UI:282.88\u0026ndash;497.81) per 100,000 population), East Asia (459.19 (95% UI: 327.72\u0026ndash;614.23) per 100,000 population), and Central Europe (483.31(95% UI: 340.10\u0026ndash;675.63) per 100,000 population) in 2019 (Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e; Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB).\u003c/p\u003e \u003cp\u003eThe three regions with the highest age-standardized DALYs rate in endometriosis were Oceania (84.48 (95% UI:49.95\u0026ndash;134.33) per 100,000 population), Eastern Europe (77.74 (95% UI:46.30\u0026ndash;122.85) per 100,000 population), and North Africa and Middle East (73.71 (95% UI: 44.14\u0026ndash;117.62) per 100,000 population) in 2019 (Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e; Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eB). Additionally, the three regions with the lowest age-standardized DALYs rate were high-income North America (34.56 (95% UI: 21.57\u0026ndash;53.12) per 100,000 population), East Asia (43.03 (95% UI: 26.03\u0026ndash;67.67) per 100,000 population), and Central Europe (45.07 (95% UI: 26.70\u0026ndash;72.05) per 100,000 population) in 2019 (Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e; Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eB).\u003c/p\u003e\n\u003ch3\u003e10. Endometriosis burden at countries' level\u003c/h3\u003e\n\u003cp\u003eExcept for the Russian Federation, Austria, Iceland, and Sweden, the PC of ASPR in endometriosis showed a downward trend in the other 200 countries included in the GBD database from 1990 to 2019. The five countries with the greatest decline in the PC of ASPR in this period were Guatemala (-48.81% (95% CI: -55.31 to -41.49%)), Oman (-46.89% (95% CI: -53.34 to -38.39%)), Equatorial Guinea (-41.80% (95% CI: -48.44 to -33.57%)), Yemen (-39.82% (95% CI: -46.18 to -31.23%)), and Nepal (-39.82% (95% CI: -46.18 to -31.23%)) (Table \u003cspan refid=\"MOESM2\" class=\"InternalRef\"\u003eS2\u003c/span\u003e). Only Sweden (45.14% (95% CI:13.26 to 84.01%)), Iceland (12.30% (95% CI: -19.62 to 59.06%)), Austria (7.33% (95% CI: -9.14 to 24.19%)), and Russian Federation (0.22% (95% CI: -1.51 to 1.66%)) experienced an increase in PC of ASPR in endometriosis, and Greece (-0.76% (95% CI: -10.64 to 10.45%)) had the least decline during the same period (Table \u003cspan refid=\"MOESM2\" class=\"InternalRef\"\u003eS2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe five countries with the highest ASPR of endometriosis in 2019 were New Zealand (1172.91 (95% UI:866.04\u0026ndash;1566.59) per 100,000 population), Taiwan (Province of China) (1030.90 (95% UI:776.16\u0026ndash;1314.40) per 100,000 population), Afghanistan (1017.18 (95% UI: 705.67\u0026ndash;1448.47) per 100,000 population), Solomon Islands (953.85 (95% UI:670.81\u0026ndash;1315.52) per 100,000 population) and Papua New Guinea (943.91 (95% UI:667.93\u0026ndash;1318.78) per 100,000 population). Conversely, Iceland (301.96 (95% UI:207.63\u0026ndash;445.17) per 100,000 population), United States of America (374.15 (95% UI: 282.40\u0026ndash;491.91) per 100 000 population), Denmark (378.56 (95% UI:261.33\u0026ndash;541.77) per 100,000 population), Malta (381.85 (95% UI:262.48\u0026ndash;559.86) per 100,000 population) and Canada (412.75 (95% UI:286.88\u0026ndash;572.81) per 100,000 population) had the lowest ASPR in 2019 (Table \u003cspan refid=\"MOESM2\" class=\"InternalRef\"\u003eS2\u003c/span\u003e; Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eA).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe five countries with the highest age-standardized DALYs rates of endometriosis per 100,000 population in 2019 were New Zealand (107.65 (95% UI: 65.60\u0026ndash;169.33)), Taiwan (Province of China) (96.02 (95% UI: 59.77\u0026ndash;146.03)), Afghanistan (92.50 (95% UI: 54.13\u0026ndash;149.79)), Solomon Islands (88.45 (95% UI: 51.75\u0026ndash;140.54)), and Papua New Guinea (87.02 (95% UI: 50.88\u0026ndash;139.04)). Contrastingly, the lowest age-standardized DALYs rates per 100,000 population were recorded for Iceland (27.89 (95% UI: 16.02\u0026ndash;45.88)), United States of America (34.15 (95% UI: 21.56\u0026ndash;52.09)), Denmark (34.80 (95% UI: 19.88\u0026ndash;55.20)), Malta (35.22 (95% UI: 20.47\u0026ndash;56.84)) and Canada (38.27 (95% UI: 22.33\u0026ndash;61.68)) in 2019 (Table \u003cspan refid=\"MOESM2\" class=\"InternalRef\"\u003eS2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe three countries with the highest EAPC in endometriosis ASPR from 1990 to 2019 value were Sweden (154.02% (95% UI: 118.46\u0026ndash;189.69%)), Iceland (59.07% (95% UI: 39.27\u0026ndash;78.90%)), and Austria (49.54% (95% UI: 36.43\u0026ndash;62.67%)). Conversely, the three countries with the lowest EAPC values were Guatemala (-243.71% (95% UI: -260.76% to -226.64%)), Oman (-225.05% (95% UI: -247.14% to -202.92%)), and Equatorial Guinea (-196.36% (95% UI: -202.97% to -189.74%)). (Table \u003cspan refid=\"MOESM3\" class=\"InternalRef\"\u003eS3\u003c/span\u003e; Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eB).\u003c/p\u003e\n\u003ch3\u003e11. Effect of sociodemographic transition on the burden of endometriosis\u003c/h3\u003e\n\u003cp\u003eWe observed an overall downward trend in endometriosis ASPR in all regions of the world as SDI increased, as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eA. In regions where 0.4\u0026thinsp;\u0026lt;\u0026thinsp;SDI\u0026thinsp;\u0026lt;\u0026thinsp;0.6, ASPR showed a significant decrease. When SDI was between 0.65 and 0.8, the decline trend tended to be flat, and when SDI\u0026thinsp;\u0026gt;\u0026thinsp;0.8, ASPR declined significantly again. There was a U-shaped correlation between ASPR and SDI levels in Central Asia, Australasia, and Eastern Europe. ASPR in high-income North America decreased significantly with SDI. When SDI exceeded 0.8, its ASPR showed a small increase (Table \u003cspan refid=\"MOESM4\" class=\"InternalRef\"\u003eS4\u003c/span\u003e; Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eA).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFigure\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eB illustrates the association between endometriosis and SDI levels in 204 countries worldwide for the year 2019. As SDI increased, the ASPR of endometriosis in all countries in the world exhibited a decreasing trend, and the decline was obvious when SDI\u0026thinsp;\u0026gt;\u0026thinsp;0.8. When 0.3\u0026thinsp;\u0026lt;\u0026thinsp;SDI\u0026thinsp;\u0026lt;\u0026thinsp;0.7, the ASPR trend of endoheterogeneity is relatively flat, and when SDI\u0026thinsp;\u0026gt;\u0026thinsp;0.8, the decreasing trend is significant. Afghanistan, Solomon Islands, Papua New Guinea, Yeman, and New Zealand's ASPR were much higher than expected, while Iceland's APSR was much lower than expected (Table S5; Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eB).\u003c/p\u003e\n\u003ch3\u003e12. Age–period–cohort impact of endometriosis burden\u003c/h3\u003e\n\u003cp\u003eWe used an age-period-cohort model to further understand changes in the prevalence burden of endometriosis, and the APC model results showed that for global, middle SDI, low-middle SDI, high-middle SDI, and low SDI categories, NetDrift, all age deviations, 1990\u0026ndash;2019 all period deviations, all cohort deviations, all period RR, all cohort RR, all local drifts demonstrated statistical significance (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). The NetDrift, all age deviations, all period deviations, All period RR, and all cohort RR of high SDI had statistical significance (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). However, all period deviations and all local drifts were not statistically significant (Table S6; Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003eA).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAfter adjusting for period and cohort effects, the prevalence of endometriosis exhibited an inverted V-shaped trend globally and in all five SDI regions, with the peak prevalence of endometriosis observed at 25\u0026ndash;29 years of age per 100,000 population (global: (1672.01(95% UI:1059.47\u0026ndash;2618.12)), high SDI (1310.47 (95% UI:825.23\u0026ndash;2078.97)); high-middle SDI (1486.75(95%UI:943.06\u0026ndash;2318.10)); middle SDI (1586.40 (95% UI:999.39\u0026ndash;2492.78)); low-middle SDI (1842.95 (95% UI:1163.97\u0026ndash;2875.41)); low SDI (2068.13 (95% UI:1295.21\u0026ndash;3282.97))), and the prevalence decreased after the peak. The global prevalence of endometriosis remained high between the ages of 30 and 39, while the prevalence dropped rapidly when the age exceeded 40 years or between the ages of 15 and 24 years (Table S6, Table \u003cspan refid=\"MOESM2\" class=\"InternalRef\"\u003eS2\u003c/span\u003e; Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003eB). The time-varying RR values of endometriosis prevalence globally and in any SDI region decreased monotonously throughout the study period. Using the 2000\u0026ndash;2004 period group as the reference value (RR\u0026thinsp;=\u0026thinsp;1), the risk of disease gradually decreased globally and in all SDI regions since that period. Moreover, we observed that in the low-middle SDI and the low SDI areas, the prevalence decreased rapidly after the 2000\u0026ndash;2004 period group, while the high SDI and high-middle SDI started from the 2005\u0026ndash;2009 period group and the 2010\u0026ndash;2014 period group, respectively, demonstrating a relatively slow downward trend. After considering the influence of the correction period and age factors using the 1970\u0026ndash;1974 birth cohort as the reference value (RR\u0026thinsp;=\u0026thinsp;1), the risk of disease in the global and SDI regions basically decreased with the passage of the birth cohort. The global decline in disease risk slowed after the 1990\u0026ndash;1994 birth cohort, and the high SDI, high-middle SDI, and middle SDI regions had a slight increase in disease risk after the 1995\u0026ndash;1999 birth cohort. Conversely, low-middle SDI and low SDI regions consistently maintained a faster rate of decline (Table S6, Table \u003cspan refid=\"MOESM2\" class=\"InternalRef\"\u003eS2\u003c/span\u003e; Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003eC).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eEndometriosis can affect several organ systems, and the condition is chronic. Hence, it has an impact on work productivity, intimate relationships, mental health, and social life (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). Additionally, endometriosis influences fertility by disrupting the pelvic integrity and modifying the peritoneal environment (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). Approximately 30% of people with endometriosis experience fertility issues (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). Researchers have also studied the association between endometriosis and mental illness, and approximately 87% of women with endometriosis reported some type of mental illness (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e) (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). Despite endometriosis being a non-malignant disease, there is substantial evidence that endometriosis is associated with an elevated risk of cancer, especially ovarian and breast cancer (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e) (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eCurrent methods for diagnosing endometriosis include transvaginal ultrasound, laparoscopy, and magnetic resonance imaging (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). However, these diagnostic tests prove inadequate due to varied locations and the appearance of endometriosis lesions, thus delaying diagnosis and increasing the possibility of misdiagnosis (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). Other factors contributing to delayed diagnosis include variability of symptoms, suboptimal health care providers and awareness of endometriosis by the patient, stigma toward discussions regarding gynecological symptoms, and the social normalization of pain among women (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). Existing treatments, including medications and surgical methods, can relieve symptoms but do not lead to a permanent cure for endometriosis (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). Several studies have used nanotechnology to locate and remove painful and dangerous lesions in the ovaries, fallopian tubes, and pelvis in animal models of endometriosis and have made progress in the diagnosis as well as management of endometriosis (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). Moreover, some researchers have explored the use of microRNA to diagnose endometriosis and have confirmed the feasibility of this method (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eFrom 1990 to 2019, this study demonstrated a downward trend in ASPR and DALYs in all regions and countries worldwide. Among the 21 regions, the most remarkable reduction in the prevalence of heterosis between 1990 and 2019 was in Central Latin America, followed by South Asia, and the least in Eastern Europe, followed by Western Europe. In 204 countries, the decline was most pronounced in Guatemala, Oman, and Equatorial Guinea. Only Sweden, Iceland, Austria, and the Russian Federation experienced an increase in PC of ASPR in endometriosis. At the SDI level, as SDI increased, the ASPR of endometriosis in all regions worldwide showed an overall decreasing trend, and the most obvious decreasing trend was in low-middle SDI quintiles. These results indicate some success in the global efforts to combat endometriosis. The endometriosis awareness campaign might have had a huge impact on transforming the knowledge and attitudes of healthcare providers about endometriosis and the importance of early diagnosis of the condition (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). There is a U-shaped correlation between ASPR and SDI levels in Central Asia, Australasia, and Eastern Europe. ASPR in high-income North America decreased significantly with SDI. When SDI was greater than 0.8, its ASPR showed a small increase. This finding suggests that while the burden is generally lower in areas with higher SDI, it is likely to increase again if interventions remain suboptimal. Furthermore, initiatives aimed at reducing the prevalence of endometriosis should be aligned with genuine health needs and social determinants. This entails considering the disease context, age composition, and regional culture to reduce the disease burden effectively.\u003c/p\u003e \u003cp\u003eDifferences in the diagnosed prevalence have been observed across various ethnic and racial groups. A systematic review determined that Asian women have a higher risk of endometriosis, while black women have a lower risk compared to white women; however, these estimates may be influenced by biases associated with access to care (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e). The prevalence of endometriosis differs among various continents, with Asia, America, Europe, Africa, and Australia exhibiting the highest to lowest prevalence, respectively (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e). However, the prevalence rate is not necessarily comparable between countries and regions due to significant structural differences in their respective healthcare systems. The diagnosis and treatment of female endometriosis patients are influenced by various conditions, including views, society, economy, education, medical conditions, and security systems, and there may be delays in the diagnosis of female endometriosis patients in some economically underdeveloped regions. Cultural and social differences may also affect how individuals conceptualize pain (\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e). In one study, 82% of French patients reported that dysmenorrhea affected their lives, compared to only 44% of Chinese patients. Additionally, endometriosis is more common in French women without endometriosis than in Chinese women. This suggests that there may be different healthcare experiences and/or expectations between patients from different regions (\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e). A lower body mass index and a high intake of trans fats and red meat were listed as risk factors for the onset of endometriosis (\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e). The risk of endometriosis has been shown to be reduced by physical activity, oral contraceptives, and a diet rich in fruits, vegetables, and omega-3 long-chain fatty acids (\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eBirth cohort effects revealed various risk factors that affect different birth cohorts early in life, encompassing behavioral, environmental, and socioeconomic factors. The prevalence of endometriosis peaked between the ages of 25 and 29, maintained a high global prevalence of endometriosis between the ages of 30 and 39, and dropped rapidly when the age was over 40 or between the ages of 15 and 24, which may also be related to the diagnosis of endometriosis. Normalization of menstrual pain in women acts as an obstacle to the exploration and diagnosis of health issues, and the extensive utilization of hormonal contraceptives suppresses and conceals symptoms associated with endometriosis. Typically, undiagnosed women with endometriosis are identified after discovering infertility problems, deciding to stop using hormonal contraceptives, or seeking counseling related to endometriosis for 6\u0026ndash;10 years. However, our findings are inconsistent with those of Christ et al., who suggested that women aged 36 to 45 had the highest prevalence of endometriosis (2006\u0026ndash;2015)(\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAfter adjusting for the effects of time and age, using the 1970\u0026ndash;1974 birth cohort as the reference value (RR\u0026thinsp;=\u0026thinsp;1), the risk of disease in the global and SDI regions basically decreased with the passage of the birth cohort. The global decline in disease risk slowed after the 1990\u0026ndash;1994 birth cohort, and the high-middle SDI, high SDI, and middle SDI regions exhibited a slight increase in disease risk after the 1995\u0026ndash;1999 birth cohort. Conversely, the low-middle SDI, in conjunction with the low SDI regions, consistently maintained a remarkable rate of decline. This observation may be attributed to the economic development and social progress, as the recent birth cohort has a greater awareness of disease prevention compared to the earlier birth cohort, and with the improvement of laparoscopic surgery, there is an improvement in the diagnosis and therapeutic management of endometriosis (\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe GBD 2019 study provides a comprehensive and high-quality assessment of the disease burden of endometriosis. However, this study has some limitations. First, the data pertaining to endometriosis from some regions and countries require improvement to generate estimates that are reasonable and relatively more accurate on the disease burden. Second, this study lacked data on factors that impact endometriosis, including diet, environment, and lifestyle. There are differences in social security systems, medical conditions, economies, and cultures in distinct regions and countries, and women have different needs when seeking treatment for endometriosis, which also affects the accuracy of this study. Finally, the 2019 GBD lacks a classification of endometriosis to account for the disease burden of different types of endometriosis separately.\u003c/p\u003e \u003cp\u003eHowever, this study also has unique advantages as it is the latest comprehensive epidemiological study on the trends of the burden of endometriosis worldwide from 1990 to 2019.\u003c/p\u003e \u003cp\u003eConclusively, this study demonstrates a downward trend in ASPR and DALYs in all regions and countries globally from 1990 to 2019. Among the 21 regions, the most substantial reduction in the prevalence of heterosis between 1990 and 2019 was in Central Latin America, followed by South Asia, and the least in Eastern Europe, followed by Western Europe. In 204 countries, the decline was most pronounced in Guatemala, Oman, and Equatorial Guinea. Notably, only Sweden, Iceland, Austria, and the Russian Federation exhibited an increase in PC of ASPR in endometriosis. This study indicates that at different SDI levels, with the increase of SDI, the ASPR of endometriosis in all regions of the world showed an overall decreasing trend, and the most obvious decreasing trend was low-middle SDI quintiles. Furthermore, the prevalence of endometriosis peaks between the ages of 25 and 29, maintains a high global prevalence between the ages of 30 and 39 and declines rapidly when the age is over 40 or between the ages of 15 and 24.\u003c/p\u003e \u003cp\u003eThis study presents a comprehensive survey of the global burden of endometriosis among women that can inform decision-makers about healthcare priorities related to endometriosis, strengthen education, raise public awareness of female endometriosis, safeguard women's legitimate rights, reduce the stigma associated with women's pain visits and reduce delays in endometriosis diagnosis. The findings underscore the importance of maintaining the status and safety of women and implementing necessary preventive and management interventions to reduce the prevalence of female endometriosis and protect women's health.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eGBD, Global Burden of Disease; DALY, disability-adjusted life-year; SDI, sociodemographic index; ASPR, age-standardized prevalence rates; ASR, age-standardized rate; EAPC, estimated annual percentage change; UI, uncertainty interval.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eConflict of interest\u003c/h2\u003e \u003cp\u003eThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eDeclarations\u003c/h2\u003e \u003cp\u003eThe data in this study were sourced from a publicly available database and do not require ethical review. All authors agreed to the study's publication in \u003cem\u003eReproductive Health\u003c/em\u003e and were willing to pay a page fee.\u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThis study was supported by the National Nature Science Foundation of China (NO. 82274571), the National Nature Science Foundation of China (NO. 82305284), the Shanghai Medical Innovation and Development Foundation (WL-HBMS-2021004K), the Siming Research Project in Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (SGKY-202306),\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eD.Y. Shen wrote the original manuscript and conceived the study; J. L performed the data analysis; P.W. Hu revised the final manuscript; C. Qi and H. Yang supervised the study process. All authors reviewed the manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgments\u003c/h2\u003e \u003cp\u003eWe highly appreciate the works of the Global Burden of Disease Study 2019 collaborators. We thank Bullet Edits Limited for the linguistic editing and proofreading of the manuscript.\u003c/p\u003e\u003ch2\u003eData Availability Statement\u003c/h2\u003e \u003cp\u003eThe data underlying this article are available in the Global Health Data Exchange at \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://ghdx.healthdata.org/gbd-results-tool\u003c/span\u003e\u003cspan address=\"http://ghdx.healthdata.org/gbd-results-tool\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eTaylor HS, Kotlyar AM, Flores VA. Endometriosis is a chronic systemic disease: clinical challenge and novel innovations. 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Curr Opin Obst Gynecol. 2020;32(4):292\u0026ndash;7. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/Gco.0000000000000638\u003c/span\u003e\u003cspan address=\"10.1097/Gco.0000000000000638\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"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":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"disability-adjusted life-years, endometriosis, global burden of disease, age–period–cohort model, prevalence","lastPublishedDoi":"10.21203/rs.3.rs-3857347/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3857347/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eIntroduction: \u003c/strong\u003eThis study aimed to analyze the worldwide, regional, and intra-country burden of heteropathy and its trends from 1990 to 2019, utilizing the latest data and improved methodologies from GBD 2019.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eWe utilized the Global Health Data Exchange Query tool, Global Burden of Disease (GBD), to analyze endometriosis in prevalence numbers, age-standardized prevalence rates (ASPR), and disability-adjusted life-years (DALYs) from 1990 to 2019 in 204 countries and regions. Additionally, this study investigated the impacts of period, age, and cohort on the prevalence and DALYs of endometriosis from the global perspective and in the five sociodemographic index (SDI) regions.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eAmong the 21 regions, the most significant reduction in the prevalence of heterosis between 1990 and 2019 occurred in Central Latin America. In 204 countries, the most pronounced decline was observed in Guatemala. At the SDI level, with the increase of SDI, the ASPR of endometriosis in all regions worldwide showed an overall decreasing trend. The prevalence of endometriosis peaked between the ages of 25 and 29.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDiscussion: \u003c/strong\u003eThe findings of this study reflect the temporal and spatial tendency of the burden of endometriosis during the study period and provide an epidemiological basis for reducing endometriosis.\u003c/p\u003e","manuscriptTitle":"Global, regional, and national prevalence and disability-adjusted life-years for endometriosis in 204 countries and territories, 1990– 2019: findings from a global burden of disease study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-17 10:48:23","doi":"10.21203/rs.3.rs-3857347/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"7615d2b2-8792-4279-b050-8e83041e8d89","owner":[],"postedDate":"January 17th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-08-22T10:57:50+00:00","versionOfRecord":[],"versionCreatedAt":"2024-01-17 10:48:23","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3857347","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3857347","identity":"rs-3857347","version":["v1"]},"buildId":"_2-kVJe1T_tPrBINL-cwx","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}