Global, regional, and national burden and trends of endometriosis, 1990-2021: an analysis of the global burden of disease study 2021 and forecast to 2050

A notable global rise was observed in the absolute numbers of endometriosis-related prevalence, incidence, and DALY cases over the past three decades. Generally, the number of prevalent cases increased from 19.87 million in 1990 to 22.28 million in 2021, the incident cases increased from 3.33 million in 1990 to 3.45 million in 2021, and the DALY cases escalated from 1.83 million in 1990 to 2.05 million in 2021 (Fig.  1 , Table S1-S3). Despite these increases in case counts, the ASPR, ASIR and age-standardized DALY rates of endometriosis globally exhibited a declining trend from 1990 to 2021, with AAPC of −0.9832 (95% CI: −0.9951, −0.9731), −0.9564 (95% CI: −0.9709, −0.9459) and − 0.9811 (95% CI: −0.9923, −0.9706), respectively. And they all sharply declined from 2006 to 2009 (Figs.  2 and 3 , Table S1-S6). Fig. 1 All ages number of ( A ) prevalence, ( B ) incidence and ( C ) DALYs in the world, various SDI regions, and 21 GBD regions in 1990 and 2021. DALYs, disability-adjusted life-years; SDI, sociodemographic index All ages number of ( A ) prevalence, ( B ) incidence and ( C ) DALYs in the world, various SDI regions, and 21 GBD regions in 1990 and 2021. DALYs, disability-adjusted life-years; SDI, sociodemographic index Fig. 2 Age-standardized rates of ( A ) prevalence, ( B ) incidence and ( C ) DALYs in the world, various SDI regions, and 21 GBD regions in 1990 and 2021. DALYs, disability-adjusted life-years; SDI, sociodemographic index Age-standardized rates of ( A ) prevalence, ( B ) incidence and ( C ) DALYs in the world, various SDI regions, and 21 GBD regions in 1990 and 2021. DALYs, disability-adjusted life-years; SDI, sociodemographic index Fig. 3 Joinpoint regression analysis of the endometriosis disease burden temporal trends in the world and various SDI regions from 1990 to 2021. A  ASPR, age-standardized prevalence rates; ( B ) ASIR, age-standardized incidence rates; ( C ) ASR-DALY, age-standardized DALY rates. DALYs, disability-adjusted life-years Joinpoint regression analysis of the endometriosis disease burden temporal trends in the world and various SDI regions from 1990 to 2021. A  ASPR, age-standardized prevalence rates; ( B ) ASIR, age-standardized incidence rates; ( C ) ASR-DALY, age-standardized DALY rates. DALYs, disability-adjusted life-years From 1990 to 2021, the number of endometriosis-related prevalence, incidence, and DALY cases declined in both high-middle and high SDI regions, while in the low SDI, low-middle SDI, and middle SDI regions almost all increased with the exception of the incidence cases of middle SDI region, where there was a very slight decrease from 1.05 million (95% UI: 0.72, 1.44) to 1.00 million (95% UI: 0.71, 1.35) (Fig.  1 A-C, Table S1-S3). Among all SDI regions, the middle SDI region reported the highest numbers of prevalence, incidence, and DALYs. As for the majority of GBD regions, the absolute number of prevalence, incidence, and DALYs of endometriosis increased over time. Only six GBD regions, specifically East Asia, Eastern Europe, Central Europe, Western Europe, high-income North America and high-income Asia Pacific exhibited a decrease, all of which are from high SDI or high-middle SDI regions. Meanwhile, the ASPR, ASIR and age-standardized DALY rates reduced from 1990 to 2021 in all regions. These rates were inversely associated with SDI levels, increasing progressively as SDI decreased (Fig.  2 A-C). Joinpoint analysis shows that the low SDI and low-middle SDI regions demonstrated a rapid decrease from 1990 to 2021 (Fig.  3 A-C). Notably, the high-middle SDI region exhibited an increasing trend of the ASPR, ASIR and age-standardized DALY rates from 2010 to 2015, with APC of 0.6659 (95% CI: 0.5237, 0.8098), 0.8090 (95% CI: 0.6549, 0.9876) and 0.6888 (95% CI: 0.5377, 0.8417), respectively. In 204 countries and territories, more than 50% exhibited an increasing trend in the number of prevalence, incidence, and DALYs of endometriosis from 1990 to 2021 (Fig.  4 A-B, Fig. S1A-B, Fig. S2A-B, Table S7-S9). China and India had the highest values of the three measures in 1990 and 2021, probably due to the large population. However, China experienced a decelerating trajectory, whereas India underwent an ascending trajectory, which may be related to the overall development level in terms of social, economic, and demographic aspects. From 1990 to 2021, the SDI index of China, high-middle SDI region, changed from 0.46 to 0.72, while India, low-middle SDI region, changed just from 0.33 to 0.58. During the past 32 Years, declines in ASPR, ASIR, and age-standardized DALYs were documented in nearly all countries and territories, accounting for 97.06%, 98.04%, and 97.06% respectively (Fig.  4 C-D, Fig. S1C-D, Fig. S2C-D, Table S7-S9). Only six countries, Niger, Iceland, Sweden, Austria, Israel and Russian Federation exhibited upward trends in ASPR and age-standardized DALY rates. And Iceland, Sweden, Austria and Israel also exhibited upward trends in ASIR. Except for Niger, all other countries belong to the high-middle or high SDI regions. Fig. 4 Global distribution of the prevalence of endometriosis. A All ages number of prevalence in 1990; ( B ) All ages number of prevalence in 2021; ( C ) ASPR, age-standardized prevalence rates in 1990; ( D ) ASPR, age-standardized prevalence rates in 2021 Global distribution of the prevalence of endometriosis. A All ages number of prevalence in 1990; ( B ) All ages number of prevalence in 2021; ( C ) ASPR, age-standardized prevalence rates in 1990; ( D ) ASPR, age-standardized prevalence rates in 2021 By Joinpoint regression model, the temporal trend of endometriosis burden in 15–19, 20–24, 25–29, 30–34, 35–39, 40–44, 45–49, 50–54 age groups are analyzed. From 1990 to 2021, the global rates of prevalence, incidence, and DALYs of endometriosis demonstrated a consistent declining trend across all age groups, and the largest declines in these three measures occurred between 2005 and 2010 for most age groups, except for the 15–19 age group, which saw the sharpest decrease between 1996 and 2004 (Fig.  5 A-C, Table S10-S12). Overall, the most pronounced decrease was observed in the 30–34 age group, with AAPC values of −1.0850 (95% CI: −1.0928, −1.0781) for prevalence rates, −1.1689 (95% CI: −1.1827, −1.1589) for incidence rates, and − 1.0784 (95% CI: −1.0866, −1.0711) for DALY rates. The lowest disease burden was recorded in the 15–19 and 50–54 age groups. However, the incidence rates in the 15–19 age group remained relatively high. In addition, the highest incidence rates were recorded in the 20–24 age group, which may reflect increased awareness, screening, and diagnosis efforts. Subsequently, the disease burden peaked in the 25–29 age group, likely representing the progression and manifestation of more pronounced symptoms following initial diagnosis. Fig. 5 Joinpoint regression analysis of the endometriosis disease burden temporal trends in the various age groups from 1990 to 2021. A  Prevalence rates; ( B ) Incidence rates; ( C ) DALY rates. DALYs, disability-adjusted life-years Joinpoint regression analysis of the endometriosis disease burden temporal trends in the various age groups from 1990 to 2021. A  Prevalence rates; ( B ) Incidence rates; ( C ) DALY rates. DALYs, disability-adjusted life-years Utilizing the BAPC model, projections indicate that although the age-specific rates of prevalence, incidence, and DALYs for endometriosis are expected to decline from 2022 to 2050 -- potentially reflecting advances in medical care, earlier diagnosis, and increased awareness -- the total number of cases may still rise slightly due to continued population growth (Figs.  6 and 7 , Fig. S3-S6, Table S13). For instance, the 25–29 age group is projected to maintain the highest prevalence, with rates declining from 1465.33 (95% CI: 1425.15, 1505.51) cases per 100,000 in 2022 to 1255.27 (95% CI: 208.08, 2302.46) per 100,000 by 2050, Yet the absolute number of cases remains substantial. Similarly, the highest incidence rate in 2022 is expected in the 20–24 age group at 305.94 (95% CI: 292.51, 319.37) per 100,000, declining to 270.75 (95% CI: − 1.11, 542.61) per 100,000 in 2050. The DALY rates are also projected to decrease, with the 25–29 age group peaking at 135.52 (95% CI: 131.83,139.22) per 100,000 in 2022 and falling to 112.90 (95% CI: 18.18, 207.63) per 100,000 by 2050. Despite these downward trends in rates, the overall disease burden may not significantly diminish due to demographic changes. Women over 45 continue to exhibit lower rates, reaffirming that endometriosis primarily affects those of reproductive age. These findings, consistent with Joinpoint regression analysis from 1990 to 2021, highlight the necessity of sustained public health attention to endometriosis, especially targeted toward high-risk age groups, to mitigate its long-term impact. Fig. 6 Forecast of prevalence cases for endometriosis from 1990 to 2050 by BAPC model, grouped by ages Forecast of prevalence cases for endometriosis from 1990 to 2050 by BAPC model, grouped by ages Fig. 7 Forecast of prevalence rates for endometriosis from 1990 to 2050 by BAPC model, grouped by ages Forecast of prevalence rates for endometriosis from 1990 to 2050 by BAPC model, grouped by ages In 1990 and 2021, there were significant absolute inequalities and slight relative inequalities in relation to the SDI, with a heavier burden observed in countries and territories with lower SDI levels (Fig.  8 , Table S14). Analysis using SII revealed a notable reduction in the ASPR gap between high- and low-SDI regions (Fig.  8 A, Table S14). Specifically, the gap decreased from − 558.82 (95% CI: −642.82, −474.81) in 1990 to −241.36 (95% CI: −306.57, −176.15) in 2021. In parallel, the concentration index demonstrated a downward trend, albeit without statistical significance, shifting from − 0.12 (95% CI: −0.31, 0.12) in 1990 to −0.07 (95% CI: −0.26, 0.12) in 2021(Fig.  8 B, Table S14). The ASIR and ASR-DALY followed similar trends (Fig.  8 C-F, Table S14). The slope index gap for ASIR decreased from − 73.51 (95% CI: −84.6, −62.43) in 1990 to −29.43 (95% CI: −38.58, −20.28) in 2021, while the gap for ASR-DALY decreased from − 49.82 (95% CI: −57.45, −42.20) in 1990 to −21.41 (95% CI: −27.39, −15.44) in 2021. The concentration index for ASIR and ASR-DALY also decreased, from 0.10 (95% CI: −0.29, 0.14) to −0.06 (95% CI: −0.25, 0.14) and from − 0.12 (95% CI: −0.31, 0.12) to −0.07 (95% CI: −0.26, 0.13), respectively. Collectively, these results indicate a progressive narrowing of health inequalities in endometriosis burden during the past three decades. Fig. 8 Health inequality regression curves and concentration curves for the endometriosis disease burden worldwide in 1990 and 2021. The slope index of inequality, depicting the relationship between SDI and ( A ) ASPR, ( C ) ASIR (E) ASR-DALY, with points representing individual countries and territories sized by population. The concentration index, which quantifies relative inequalities by integrating the area under the Lorenz curve, aligning ( B ) prevalence, ( D ) incidence and ( F ) DALYs distribution with population distribution by SDI. ASPR, age-standardized prevalence rates; ASIR, age-standardized incidence rates; ASR-DALY, age-standardized DALY rates; DALYs, disability-adjusted life-years; SDI, sociodemographic index Health inequality regression curves and concentration curves for the endometriosis disease burden worldwide in 1990 and 2021. The slope index of inequality, depicting the relationship between SDI and ( A ) ASPR, ( C ) ASIR (E) ASR-DALY, with points representing individual countries and territories sized by population. The concentration index, which quantifies relative inequalities by integrating the area under the Lorenz curve, aligning ( B ) prevalence, ( D ) incidence and ( F ) DALYs distribution with population distribution by SDI. ASPR, age-standardized prevalence rates; ASIR, age-standardized incidence rates; ASR-DALY, age-standardized DALY rates; DALYs, disability-adjusted life-years; SDI, sociodemographic index To evaluate the potential for reducing the burden of endometriosis, a frontier analysis was conducted, incorporating variations in national and regional development levels. This approach assessed the improvement space for ASPR, ASIR, and ASR-DALY indicators. For ASPR, the 15 countries and territories with the greatest potential for advancement (effective difference range: 735.56-522.61) are Tokelau, Taiwan (Province of China), Lithuania, Russian Federation, Nauru, Guam, Solomon Islands, Belarus, Tonga, Estonia, Kiribati, Papua New Guinea, Latvia, Ukraine, American Samoa (Fig.  9 A-B, Table S15). Among countries and territories with an SDI below 0.5, Somalia, Mozambique, Liberia, Malawi, and Eritrea exhibit the smallest gaps from the frontier. Conversely, five countries and territories with an SDI exceeding 0.85 -- Austria, Japan, South Korea, Lithuania, and Taiwan (Province of China) -- demonstrate relatively high potential for improvement. Fig. 9 Frontier analysis assessing the relationship between SDI and the endometriosis disease burden in 204 countries and territories. A , C , E  The color gradient from light green (1990) to dark green (2021) illustrates temporal progression. B , D , F  Each dot represents a specific country or territory in 2021, with the frontier line depicted in black. The dot colors indicate the trend from 1990 to 2021: orange for decreases, green for increases. The names of top 15 countries and territories with the largest differences from the frontier are highlighted in black. Blue names represent the smallest differences from the frontier when SDI below 0.5, while red names represent the largest differences from the frontier when SDI exceeding 0.85. ASPR, age-standardized prevalence rates; ASIR, age-standardized incidence rates; ASR-DALY, age-standardized DALY rates; DALYs, disability-adjusted life-years; SDI, sociodemographic index Frontier analysis assessing the relationship between SDI and the endometriosis disease burden in 204 countries and territories. A , C , E  The color gradient from light green (1990) to dark green (2021) illustrates temporal progression. B , D , F  Each dot represents a specific country or territory in 2021, with the frontier line depicted in black. The dot colors indicate the trend from 1990 to 2021: orange for decreases, green for increases. The names of top 15 countries and territories with the largest differences from the frontier are highlighted in black. Blue names represent the smallest differences from the frontier when SDI below 0.5, while red names represent the largest differences from the frontier when SDI exceeding 0.85. ASPR, age-standardized prevalence rates; ASIR, age-standardized incidence rates; ASR-DALY, age-standardized DALY rates; DALYs, disability-adjusted life-years; SDI, sociodemographic index A similar pattern was observed for ASIR and ASR-DALY, where the top 15 countries and territories with the widest gaps between observed and optimal values showed effective differences of 111.83–80.21 and 67.84–48.03, respectively (Fig.  9 C-F, Table S16-S17). Frontier analysis highlighted the potential for reducing disease burden across various countries and territories. Notably, despite facing resource constraints, some lower SDI nations and territories -- such as Somalia, Liberia, and Malawi -- have performed efficiently in managing disease burden. Meanwhile, many higher SDI countries, including South Korea, Lithuania, and Taiwan (Province of China), still present notable potential for further health system enhancements. A decomposition analysis was conducted to examine how demographic and epidemiological factors -- including population aging, population growth, and changes in disease frequency -- contributed to trends in endometriosis prevalence, incidence, and DALYs globally and across the five SDI categories from 1990 to 2021 (Fig.  10 , Table S18). The overall change of prevalence, incidence and DALYs during the past three decades have seen a slight increase in global and lower SDI regions, with the most prominent increase occurring in low SDI regions. These regions faced greater challenges due to a combination of factors, including population growth and aging, which are exacerbating health burdens. Fig. 10 Population-level determinant changes in aging, population growth, and disease frequency for ( A ) prevalence, ( B ) incidence and ( C ) DALYs globally and in various SDI regions from 1990 to 2021. Black dots represent the total change contributed by all three components Population-level determinant changes in aging, population growth, and disease frequency for ( A ) prevalence, ( B ) incidence and ( C ) DALYs globally and in various SDI regions from 1990 to 2021. Black dots represent the total change contributed by all three components In terms of prevalence, the global prevalence of endometriosis increased by 2,405,819.57 cases, with aging contributing 22.28%, and population growth leading to 352.16% (Fig.  10 A, Table S18). However, disease frequency resulted in a substantial reduction of 6,602,583.68 cases (−274.44%), highlighting their role in mitigating the disease burden. In lower SDI regions, population growth remained a key factor driving prevalence increases. In higher SDI regions, prevalence declined, largely attributed to disease frequency, indicating advancements in healthcare and diagnostic capacity. A similar pattern was observed in incidence trends, where a global increase of 116,925.82 cases was driven by population growth (1169.15%) (Fig.  10 B, Table S18). However, disease frequency significantly counteracted this increase, leading to a reduction of 1,042,201.23 cases (−891.34%). Despite the decrease in disease frequency in all SDI regions, the incidence had increased in lower SDI regions due to large population growth and aging trend, particularly in low-SDI (181.99%/20.38%) and low-middle-SDI (415.34%/60.03%) regions. In higher SDI regions, population growth was also a dominant factor driving incidence increases, though the overall incidence trend is downward. For DALYs, a global increase of 220,130.48 was observed, with population growth contributing 354.21% and aging 20.61% (Fig.  10 C, Table S18). However, disease frequency played a crucial role in mitigating the disease burden, leading to a decrease (−274.82%). Lower SDI regions followed the same trend, with population growth continuing to drive increases in DALYs, while higher SDI regions saw an overall reduction, mainly attributed to disease frequency, reflecting advancements in medical interventions and healthcare access. This decomposition analysis highlights that disease frequency is the primary factor reducing the global burden of endometriosis, particularly in high-middle SDI and middle SDI regions. However, population growth continues to hinder further reductions, especially in lower SDI regions, where healthcare access and disease awareness may still be limited.

The data of endometriosis analyzed in this study is available in GBD 2021, which provides the epidemiological data on the burden of 371 diseases from 1990 to 2021 for the globe, seven super-regions, 21 regions, 204 countries and territories (including 21 countries with subnational locations), and 811 subnational locations ( https://vizhub.healthdata.org/gbd-results/)(8) . For GBD 2021, endometriosis is defined as cases of endometrial tissue outside the uterine cavity diagnosed by pelvic exam confirmed by laparoscopy or pathology, based on the International Classification of Diseases (ICD)−10 codes N80-N80.9. We selected counts and age-standardized rates of prevalence, incidence and DALYs to analyzed the disease burden globally and across five SDI regions, 21 GBD regions, and 204 countries and territories. And we selected the age groups “15–19 years”, “20–24 years”, “25–29 years”, “30–34 years”, “35–39 years”, “40–44 years”, “45–49 years”, and “50–54 years” for analysis, by counts and rates of prevalence, incidence and DALYs. SDI is an integrated indicator developed by the GBD research team to assess development status strongly related to health outcomes, including three standardized indices -- total fertility for women under age 25 (TFU25), the average educational Years for those aged 15 and over (EDU15+), and lag-distributed income per capita (LDI). By calculating the geometric mean of these indices after normalizing them to values between 0 and 1, the SDI value is obtained. An SDI value of 0 corresponds to the lowest theoretical level of socio-demographic development relevant for health, while 1 represents the highest theoretical standard. In GBD 2021, this index divides all countries into five groups: low SDI, low-middle SDI, middle SDI, high-middle SDI and high SDI, with cutoff values of 0.47, 0.62, 0.71 and 0.81, respectively ( https://ghdx.healthdata.org/data-type/estimate ). We evaluated the burden of endometriosis using prevalence, incidence, and DALYs, presented both as number and as rate per 100,000 population. Absolute number represent the total burden, whereas rates are standardized estimates allowing population-level comparisons. Each estimate is accompanied by a 95% uncertainty interval (UI). Statistical significance was defined as a p-value of less than 0.05, and appropriate statistical methods were employed throughout. Specific analytical approaches -- including Joinpoint regression, the Bayesian Age-Period-Cohort (BAPC) model, slope index of inequality (SII), concentration index, frontier analysis, and decomposition analysis -- are thoroughly described in later sections. All analyses and visualizations were completed using Joinpoint Trend Analysis Software (version 5.3.0.0) and R Software (version 4.3.1). This study used the Joinpoint model to evaluate the age-standardized prevalence rates (ASPR), age-standardized incidence rates (ASIR) and age-standardized DALY rates (ASR-DALY) for global, regional, and national trends and the rates of prevalence, incidence and DALYs for different age groups. In the Joinpoint regression model, the primary outcome measures include the annual percent change (APC), average annual percent change (AAPC), and their corresponding 95% confidence intervals (CIs). The APC represents the average yearly percentage change in the dependent variable and is used to assess the trend within each segment of the piecewise model, or the overall trend when no joinpoints are present. In contrast, the AAPC provides a summary measure of the average trend across all segments, offering a more comprehensive view of long-term changes ( https://surveillance.cancer.gov/joinpoint/ ). In this study, we used the BAPC model by the “BAPC” package in R to forecast future trends of disease burden for different age groups. Compared to other forecasting approaches, the BAPC model has been shown in previous studies to provide greater precision and more comprehensive coverage [ 14 ]. The BAPC model dynamically integrates age, period, and cohort effects by treating these variables as continuously evolving processes. A significant advantage of this modeling approach lies in its incorporation of Integrated Nested Laplace Approximation (INLA), which efficiently approximates marginal posterior distributions. It proves effective in projecting long-term disease trends, notably in studies that analyze age-specific populations and complex cohort effects. SII and concentration index are widely used metrics for assessing health inequalities. The SII quantifies absolute disparities in disease burden across countries and territories by measuring the linear association between the ASPR, ASIR, or age-standardized DALY rates and the rank by SDI. Specifically, it represents the estimated absolute difference in burden between the highest SDI and lowest SDI populations. In contrast, the concentration index is a relative measure that assesses the degree to which disease burden are distributed unequally. Values of the concentration index range from − 1 to + 1: negative values indicate greater concentration among lower SDI, positive values imply greater concentration among higher SDI, and zero denotes perfect equality. Together, these indices offer complementary perspectives for understanding and quantifying health disparities. Frontier analysis is an analytical technique to quantify the potential for health improvement by measuring the gap between the existing burden of a country or territory and its lowest achievable burden. It enables policymakers and researchers to determine achievable targets, recognize performance gaps, and understand how resource allocation and health policies might be optimized to minimize disease burden given available resources. We employed Locally Estimated Scatterplot Smoothing (LOESS) to smooth frontier lines to account for the nonlinear relationship between SDI and ASPR, ASIR, or age-standardized DALY rates in 204 countries and territories. A decomposition analysis, for the change of prevalence, incidence and DALYs from 1990 to 2021, was performed to quantify the respective contributions of population growth, ageing, and changes in disease frequency. Decomposition analysis differs from conventional approaches like linear regression, which mainly emphasize identifying relationships among variables; instead, it provides an in-depth evaluation of how each factor independently contributes to the overall variation in disease burden. Therefore, this analytical approach helps to identify the main driving factors that lead to increases or decreases in the burden, and provides a scientific basis for public health decision makers and researchers to optimize health policies and resource allocation [ 15 ].

Endometriosis is a prevalent yet significantly understudied global health concern, that significantly impacts patients’ quality of life [ 5 , 16 ]. Using the most recent data from GBD 2021 study, our research provides a comprehensive and up-to-date assessment of the global, regional, and national burden of endometriosis in prevalence, incidence, and DALYs. We also explored associations with the SDI and key drivers through decomposition analysis. In addition, we examined trends for different age groups from 1990 to 2021 and projected future trends through 2050. These results may guide public health authorities in developing effective strategies to confront this challenge. Our study indicates that while the absolute number of prevalence, incidence and DALYs due to endometriosis have increased globally, the ASPR, ASIR and age-standardized DALY rates reduced, which may be related to the population growth. Notably, a sharp decline of rates was observed between 2006 and 2009, possibly due to the reduction in laparoscopic invasive operations for diagnosing endometriosis. This trend may reflect doctors’ increased tendency to diagnose pelvic pain without invasive procedures [ 17 ], as well as the influence of the global financial crisis resulting in the delay of elective surgeries. Regionally, high and high-middle SDI regions experienced reductions in absolute case number, whereas lower SDI regions saw increases. In higher SDI regions, the pace of population growth is relatively slow and the extensive utilization of hormonal contraceptives may be associated with lower cases [ 10 , 18 ], though, high-SDI regions may have better access to care and therefore would be more likely to be diagnosed [ 19 ]. Lower SDI countries usually have faster population growth, and the social security system and medical security level are relatively low. It is difficult for patients to obtain early diagnosis. Also, in the process of disease treatment and rehabilitation, they may face greater economic pressure, which affects the treatment effect and the return of the disease [ 20 ]. As for ASPR, ASIR and age-standardized DALY rates, five SDI regions all reduced from 1990 to 2021. However, Jionpoint analysis shows that the high-middle SDI region exhibited an increasing trend from 2010 to 2015. This trend may be influenced by recommendations from The World Endometriosis Society (WES) in 2011, which increased relevance and awareness of endometriosis, Increased case detection rate [ 21 ]. And high-middle SDI region had sufficient funding sources to implement WES-led consensus [ 22 ]. Among 204 countries and territories, China and India had the highest case number; however, China showed a decelerating trend, while India exhibited an ascending trajectory, which confirms the impact of social development on disease burden, again. Besides, while most countries exhibited a declining trend, six exceptions (Niger, Iceland, Sweden, Austria, Israel, and the Russian Federation) showed increasing rates. In Niger, a low-SDI country, this rise likely reflects improvements in diagnostic and treatment capabilities and demographic changes [ 23 ]. By contrast, in high-SDI countries (Iceland, Sweden, Austria, and Israel), the apparent rise may represent a “false increase” driven by greater healthcare investment, policy improvements, and heightened awareness, which enhance detection and reporting rather than actual disease prevalence [ 10 , 24 ]. The situation in Russia reflects the complex impact of the transitional society on women’s health. After the Soviet Union collapsed in the 1990 s, the healthcare system underwent dramatic disruption, with sharp cuts in public spending and declining service quality. Since the 2000 s, however, government investment has increased, leading to gradual improvements. Changes in the ASPR, ASIR, and DALY rates of endometriosis across countries are shaped by multiple factors, including healthcare investment, public policy, women’s awareness, diagnostic advances, and environmental conditions [ 24 , 25 ]. Understanding these factors is critical to developing targeted intervention strategies. In lower-SDI countries, efforts should focus on strengthening gynecological diagnostic and treatment capacity to reduce missed diagnoses and disease burden. In higher-SDI countries, the priority is to improve diagnostic standards to shorten delays while avoiding resource waste from overdiagnosis and overtreatment. Although laparoscopy remains the gold standard for diagnosing endometriosis, it is invasive and may miss certain cases. With advances in imaging, particularly transvaginal ultrasound (TVUS) and magnetic resonance imaging (MRI), noninvasive approaches are increasingly advocated for comprehensive pelvic evaluation, improved detection of deep infiltrating lesions, and more accurate preoperative mapping [ 1 , 26 ]. In this context, higher-SDI countries should leverage their medical resources to advance TVUS and MRI technologies and work toward establishing a standardized noninvasive diagnostic pathway for endometriosis, reducing reliance on invasive laparoscopy. Beyond diagnostic strategies, broader public health measures are also essential. Efforts should be made to improve women’s health awareness, reduce the stigma and cognitive blind spots related to the disease, and advocate healthy weight and appropriate birth planning [ 21 ]. In addition, more research is needed on the impact of environmental endocrine disruptors, with the goal of reducing the risk of endometriosis at the population level [ 27 , 28 ]. To elucidate age-specific patterns, our analysis highlights several critical findings. Adolescence (15–19 years) is the peak onset period for endometriosis [ 29 ]. Compared to other age groups, the burden in 15–19 age group may be underestimated due to the later onset of symptomatic endometriosis, underdiagnosis, or delayed healthcare-seeking behavior in adolescents [ 30 , 31 ]. This underscores the need for early detection and timely intervention, as delayed diagnosis in younger individuals can contribute to disease progression and long-term complications [ 32 ]. Women of reproductive age, particularly those aged 25–29 years, bear the highest burden, consistent with previous evidence identifying this age range as a key risk factor [ 33 ]. And Comptour et al. found that the percentage of patients with severe dysmenorrhea were more in younger age groups [ 32 , 34 ]. In contrast, the lowest burden was observed in 50–54 age group may be attributed to menopausal transition, declining estrogen levels, and cumulative surgical interventions such as hysterectomy or oophorectomy [ 35 , 36 ]. Projections of BAPC model suggest the age-specific disease burden still rise slightly, though the rates of prevalence, incidence, and DALYs may decline from 2022 to 2050. These findings emphasize the importance of targeted interventions for younger women, particularly in reproductive age groups, to reduce the long-term disease burden. Over the past three decades, treatment of endometriosis has shifted from non-specific hormonal suppression to individualized regimens, including combined oral contraceptives, progestins, GnRH agonists and antagonists, and selective modulators. Minimally invasive laparoscopy remains central, though surgical practice increasingly favors fertility-sparing, symptom-directed interventions [ 1 , 7 , 33 , 37 – 39 ]. Current management combines pharmacological and surgical strategies. Hormonal agents are considered first-line therapy for symptomatic premenopausal women not seeking pregnancy, but some patients experience limited benefit or recurrence after discontinuation. Laparoscopic excision is recommended when medical therapy is ineffective or contraindicated, with GnRH analogues and aromatase inhibitors as second- and third-line options [ 1 ]. Fertility preservation is another key consideration. Women with endometriosis and adenomyosis often face impaired oocyte quality and diminished ovarian reserve. On this basis, assisted reproductive technologies (ART) offer both opportunities and challenges, providing potential options for improving fertility outcomes while raising important questions regarding efficacy, accessibility, and long-term safety [ 37 , 40 – 44 ]. Furthermore, recent studies have refined our understanding of the oncologic implications associated with endometriosis. In particular, emerging evidence highlights strong links between endometriosis and rare yet aggressive ovarian neoplasms, such as mesonephric-like adenocarcinoma [ 45 ]. Another line of investigation delves into whether endometriosis-associated ovarian cancers represent correlated pathogenic entities or incidental findings, shedding light on whether malignant transformation arises from shared etiological origins or coincidental coexistence [ 46 ]. Together, these insights underscore the dual priorities of preserving fertility while remaining vigilant about oncologic risks. They further emphasize the need for individualized counseling, judicious use of ART, and continued research into the molecular underpinnings of endometriosis-associated malignancies. Beyond standard therapies, lifestyle and dietary modifications are being explored as adjuncts. Omega-3 fatty acids, antioxidant vitamins, and low fermentable oligo-, di-, and mono-saccharides and polyols diet have shown potential in reducing symptoms, particularly in patients with gastrointestinal comorbidities, though evidence remains limited [ 47 ]. A holistic approach integrating medical, surgical, and lifestyle interventions appears most promising, but more high-quality randomized studies are required. From a public health perspective, access to endometriosis interventions varies considerably across regions. Exploring the link between development status and disease burden is thus critical. Accordingly, we utilized SII and concentration index to assess the health inequalities across countries and territories, considering both population size and SDI. Our study results indicate that lower SDI countries and territories still bear a relatively high burden of disease [ 48 ]. However, compared to 1990, both the absolute and relative health inequalities in the burden of endometriosis have decreased by 2021, improvements in medical standards have contributed to an overall reduction in disease burden [ 5 , 49 – 54 ]. In particular, changes in the concentration index show that lower SDI countries and territories have already strived to reduce their disease burden. Further frontier analysis once again shows that despite limited resources, some low-SDI countries and territories have demonstrated a strong ability to control endometriosis, which may benefit from specific public health interventions, international assistance [ 55 , 56 ], while some high-SDI countries and territories still have room for improvement, possibly due to insufficient attention and investment to endometriosis. This demonstrates that even with limited resources, rational public health policies can still help reduce the disease burden. Policymakers should delve into the management models of countries with better disease burden control, exploring how to promote these approaches in other resource-limited countries, and remind all countries to increase attention to women’s health [ 57 , 58 ]. To explain the reasons for changes in disease burden of endometriosis from 1990 to 2021, we conducted a decomposition analysis of aging, population growth, and disease frequency. With the inevitability of demographic changes (aging and population growth), the burden showed a slight upward trend in lower SDI regions, owing to limited medical resources. In contrast, in high and high-middle SDI regions with better healthcare, the reduction of disease frequency offset the influence of population growth. Therefore, it is necessary for policymakers to consider the potential health impacts of aging and population growth and to implement effective measures of disease prevention and health promotion to reduce the adverse impacts brought about by demographic changes [ 59 ]. This study provides a comprehensive analysis of the latest global and regional burdens of endometriosis, while previous studies had data before 2019 or focused on the impact of infertility or were limited to China [ 9 – 13 ]. Notably, for the first time ever, the changes in the disease burden of endometriosis were explored through decomposition analysis. Furthermore, this study tries to explain the specific reasons for changes in the burden, hoping to provide a basis for public health policy formulation. However, there are some limitations. Firstly, the estimates based on available data sources in GBD may be inaccurate due to potential biases data between the differences in countries or regions. Secondly, the GBD data sources do not cover all countries or regions for endometriosis. Thirdly, the GBD 2021 case definition for endometriosis is relatively strict, requiring a pelvic examination and confirmation of the diagnosis by laparoscopy or laparotomy, which may lead to an underestimation of the burden. Fourthly, the preference of which doctors in different countries diagnose endometriosis by diagnostic criteria may lead to bias. Fifthly, the different classifications of endometriosis are not analyzed in this article. Lastly, it is important to analysis that the risk factors for endometriosis, but this article does not include this part due to the absence of data in the GBD 2021. In conclusion, despite the ASPR, ASIR and age-standardized DALY rates reduced -- likely due to medical progress and improved awareness -- the overall disease burden increased, mainly driven by demographic growth. Moreover, the disease burden is closely associated with the level of social development. To address this challenge, health policies should prioritize increasing investment in resources and education related to endometriosis, while actively working to reduce health inequalities. Particular attention should be given to early detection and timely intervention, especially among younger women, who remain the most affected group. Sustained efforts are essential to mitigate the long-term impact of endometriosis and improve outcomes for high-risk populations.

Endometriosis (EMs) is a chronic, estrogen-dependent disease characterized by the presence of endometrial tissue outside the uterine cavity. Ectopic endometrial tissues are often accompanied by an inflammatory response and cause a wide range of symptoms; notably, up to 90% of affected individuals experience pelvic pain -- including dysmenorrhea, nonmenstrual pelvic pain, and dyspareunia -- while approximately 26% report infertility [ 1 ]. Women with endometriosis have 1.7-fold higher endometrial cancer risk, 4.2-fold higher ovarian cancer risk and 1.1-fold higher breast cancer risk than those without endometriosis, though endometriosis being a non-malignant disease [ 2 , 3 ]. Besides, women with endometriosis frequently experience elevated rates of anxiety, depression, and various other mental health conditions [ 4 ]. It is estimated that around 190 million women globally are affected by endometriosis, representing roughly 10% of those of reproductive age [ 5 ]. Although endometriosis is highly prevalent and costly, it receives insufficient funding and research attention, and remains poorly understood by both healthcare providers and the public [ 6 , 7 ]. A recent comprehensive review published in JAMA further underscored the substantial global disease burden, diagnostic challenges, and unmet clinical needs associated with endometriosis, highlighting the importance of large-scale epidemiologic analyses to guide clinical and policy strategies [ 1 ]. The Global Burden of Disease (GBD) 2021 dataset offers a robust framework for assessing endometriosis-related disease burden across global, regional, and national levels, and enables the identification of health inequalities in relation to sociodemographic index (SDI) based on development levels. Counts and age-standardized rates were calculated globally, for seven super-regions, 21 regions, 204 countries and territories, from 1990 to 2021 [ 8 ]. In previous assessments, the burden of endometriosis, just utilizing data in GBD before 2019, often focused on the burden of endometriosis-related infertility or just limited to China [ 9 – 13 ]. However, there is a lack of study using the latest data to explore the burden of endometriosis, not just on infertility of endometriosis, on a global scale. Moreover, prior studies primarily focus on describing the epidemiological characteristics of endometriosis, without conducting predictions of the future of the disease burden. In this study, we utilize the GBD 2021 data from 1990 to 2021 to assess the disease burden of endometriosis, including its prevalence, incidence and disability-adjusted life-years (DALYs). Our study emphasizes regional patterns and associations with the SDI, age-specific distributions and temporal trends, and applies decomposition analysis to evaluate the contributions of aging, population growth and disease frequency. This analysis may enhance disease awareness among clinicians, health policymakers and the public, to formulate more effective policies to minimize the burden with limited health resources.

Additional file 1. Additional file 1. Additional file 2: Fig. S1. Global distribution of the incidence of endometriosis. (A) All ages number of incidence in 1990; (B) All ages number of incidence in 2021; (C) ASIR, age-standardized incidence rates in 1990; (D) ASIR, age-standardized incidence rates in 2021. Additional file 2: Fig. S1. Global distribution of the incidence of endometriosis. (A) All ages number of incidence in 1990; (B) All ages number of incidence in 2021; (C) ASIR, age-standardized incidence rates in 1990; (D) ASIR, age-standardized incidence rates in 2021. Additional file 3: Fig. S2. Global distribution of the DALYs of endometriosis. (A) All ages number of DALYs in 1990; (B) All ages number of DALYs in 2021; (C) ASR-DALY, age-standardized DALY rates in 1990; (D) ASR-DALY, age-standardized DALY rates in 2021. Additional file 3: Fig. S2. Global distribution of the DALYs of endometriosis. (A) All ages number of DALYs in 1990; (B) All ages number of DALYs in 2021; (C) ASR-DALY, age-standardized DALY rates in 1990; (D) ASR-DALY, age-standardized DALY rates in 2021. Additional file 4: Fig. S3. Forecast of incidence cases for endometriosis from 1990 to 2050 by BAPC model, grouped by ages. Additional file 4: Fig. S3. Forecast of incidence cases for endometriosis from 1990 to 2050 by BAPC model, grouped by ages. Additional file 5: Fig. S4. Forecast of DALY cases for endometriosis from 1990 to 2050 by BAPC model, grouped by ages. Additional file 5: Fig. S4. Forecast of DALY cases for endometriosis from 1990 to 2050 by BAPC model, grouped by ages. Additional file 6: Fig. S5. Forecast of incidence rates for endometriosis from 1990 to 2050 by BAPC model, grouped by ages. Additional file 6: Fig. S5. Forecast of incidence rates for endometriosis from 1990 to 2050 by BAPC model, grouped by ages. Additional file 7: Fig. S6. Forecast of DALY rates for endometriosis from 1990 to 2050 by BAPC model, grouped by ages. Additional file 7: Fig. S6. Forecast of DALY rates for endometriosis from 1990 to 2050 by BAPC model, grouped by ages.