Population-Level Co-Distribution and Spatiotemporal Burden Trends of Endometriosis and Polycystic Ovary Syndrome Among Reproductive-Age Women in Europe, 1990–2023: An Analysis of the Global Burden of Disease 2023

Endometriosis (EM) and polycystic ovary syndrome (PCOS) are two prevalent endocrine-related gynecological conditions with shared pathophysiological pathways, yet their population-level burden patterns and socioeconomic correlates across Europe remain unclear. This study examines the geographic overlap in population-level disease burden patterns of EM and PCOS (hereafter referred to as ecological co-distribution), which does not represent individual-level comorbidity.

Using the Global Burden of Disease (GBD) 2023 dataset, we retrieved incident cases and disability-adjusted life years (DALYs) data for EM and PCOS among women aged 15– 49 years covering 44 European countries (1990– 2023). Countries were classified into three population-level burden phenotypes (consistent pattern, EM-predominant pattern, PCOS-predominant pattern) by cross-tabulating quartiles of age-standardized incidence rates (ASIR). Temporal trajectories were quantified via the estimated annual percentage change (EAPC) method combined with Joinpoint regression modeling. Additional analyses included age-stratified burden distribution, correlation with the Socio-demographic Index (SDI), and decomposition analysis of burden drivers.

EM and PCOS exhibited diametrically opposite spatial gradients: EM burden concentrated in Central and Eastern Europe, while PCOS burden predominated in Western Europe. Only 7 countries showed consistent dual-disease burden levels, with 19 EM-dominant and 18 PCOS-dominant countries. From 1990 to 2023, ASIR of both diseases declined across most subregions. The age-standardized DALY rate (ASDR) of EM declined in Western Europe but showed a non-monotonic trajectory in Eastern Europe, whereas PCOS ASDR increased substantially across all regions. EM incidence was weakly but significantly negatively correlated with SDI, whereas both incidence and disability burden of PCOS showed significant positive associations with SDI. Decomposition analysis indicated that epidemiological shifts drove rising PCOS disability, while demographic changes mainly contributed to EM burden reduction.

EM and PCOS exhibit geographically divergent burden patterns with differing socioeconomic gradients across Europe, underscoring the need for regionally differentiated reproductive health strategies.

Endometriosis, Polycystic ovary syndrome, GBD 2023, Geographic disparity, SDI

Endocrine gynecological disorders exert persistent adverse impacts on women’s long-term physical and mental health.1 While global attention to women’s reproductive health has grown steadily, a 2022 WHO report indicated that global progress toward equitable women’s health goals has stalled.2 EM and PCOS are two widespread benign gynecological disorders defined by disruptions to endocrine and metabolic homeostasis, and they may share common underlying pathophysiological pathways.3,4 Given the wide disparities in national income, healthcare access, dietary patterns, and public health policies across 44 European countries, this region provides an ideal setting to explore how socioeconomic and geographic factors shape the burden of reproductive diseases. EM and PCOS rank among the most common benign gynecological conditions affecting reproductive-age women, and both are linked to considerable long-term health deterioration.5 Globally, EM affects approximately 5–10% of women of reproductive age, with symptoms including chronic pelvic pain, dysmenorrhea, and subfertility that substantially impair quality of life.6,7 PCOS is recognized as the most common endocrine disorder in women of childbearing age, characterized by ovulatory dysfunction, hyperandrogenism, inflammatory response, and long-term metabolic comorbidities such as insulin resistance.8–10 The prevalence of both disorders varies markedly across regions, shaped by differences in diagnostic practices, dietary patterns, and socioeconomic environments. EM and PCOS are both characterized by high prevalence and cumulative long-term health impairment, disrupting reproductive and metabolic homeostasis across women’s reproductive lifespan.11 For endometriosis, standard therapeutic regimens comprise estrogen-suppressive hormonal medication and laparoscopic lesion excision, with assisted reproductive technology reserved for patients with infertility.12,13 With regard to polycystic ovary syndrome, available interventions extend from lifestyle modification and insulin-sensitizing agents to anti-androgen pharmacotherapy and ovulation induction, though the overall therapeutic efficacy remains restricted.14 High post-treatment recurrence and refractory chronic metabolic comorbidities remain prominent challenges for both conditions. Driven by growing female populations and shifting modern dietary and lifestyle patterns, EM and PCOS impair patients’ quality of life while imposing significant clinical and economic burdens on global healthcare systems.15 At the individual level, the biological links between endometriosis and polycystic ovary syndrome have been explored in prior mechanistic research. For instance, ceramides have been proposed as potential mediators connecting the two disorders via the metabolic-inflammation-hormone-reproductive axis,16 and luteolin has been shown to exert synergistic therapeutic effects against both conditions through shared core targets.17 However, individual-level mechanistic findings do not necessarily imply that the two conditions co-distribute at the population level or that they share common pathogenic mechanisms across populations. Large-scale epidemiological evidence quantifying their population-level burden patterns across European countries remains scarce. Most existing studies are limited to single-country cohorts or specific demographic subgroups, lacking standardized cross-regional comparisons across diverse geographic and socioeconomic contexts. To date, most GBD-based epidemiological studies have profiled the burden of EM and PCOS independently. Few studies have systematically examined their spatial co-distribution patterns, temporal trajectory alignment, and socioeconomic gradients at the continental level, leaving the population-level burden characteristics of these two shared-pathway disorders insufficiently characterized in Europe. Given the remarkable epidemiological heterogeneity across Europe, this region provides an ideal context to explore population-level correlations between EM and PCOS. To address this gap, we leveraged the GBD 2023 dataset to conduct a systematic evaluation of spatiotemporal dynamics and population co-distribution of EM and PCOS across 44 European countries from 1990 to 2023. We classified countries into three population-level burden subtypes based on incidence quartiles,18,19 quantified temporal trajectories using Joinpoint regression, explored age-stratified patterns, examined correlations with SDI, and decomposed the drivers of burden change. Describing the geographic co-distribution of EM and PCOS burden and its temporal and socioeconomic patterns may reflect considerations for reproductive health planning across Europe. Given the heterogeneity in healthcare infrastructure and surveillance capacity across the continent, such population-level evidence is perhaps associated with regional variation in prevention priorities and resource allocation. This study may provide descriptive evidence pertinent to regional reproductive health governance and early screening in Europe.

Data Sources In this study, we performed a comprehensive spatiotemporal analysis of the co-occurring disease burden of EM and PCOS across the European region. We extracted burden data for EM and PCOS from GBD 2023 Results Tool (https://vizhub.healthdata.org/gbd-results/), a standardized epidemiological surveillance framework built on uniform analytical protocols.20 Covering 204 countries and territories from 1990 to 2023 across 21 super-regions, the GBD 2023 database also provides exposure data for 88 individual risk factors. In line with standard research conventions, we retrieved publicly available estimates of incident cases, prevalent cases, and disability-adjusted life years (DALYs) for each disorder. All estimates were reported with 95% uncertainty intervals (UIs) and could be stratified by age group, geographical location, sex, and disease cause.21 To characterize national socioeconomic development, we adopted the SDI developed by the Institute for Health Metrics and Evaluation (IHME), a composite indicator integrating per capita income, educational attainment, and fertility rate. The precision of GBD estimates is subject to the availability of primary source data: regions with diagnostic underreporting and incomplete disease registries, such as parts of Eastern Europe and low-SDI areas, tend to have wider estimation uncertainty.22 GBD provides point estimates and marginal 95% uncertainty intervals (UIs) for all burden indicators, but does not release the full joint distribution at the country-year-cause level, precluding formal uncertainty propagation into downstream analyses. All downstream secondary analyses (country classification, SDI correlation, Joinpoint regression, and decomposition) were performed using the point estimates downloaded from the GBD Results Tool. As GBD datasets only offer population-based aggregated estimates across national and regional scales, individual patients’ simultaneous diagnoses of EM and PCOS cannot be confirmed in the current analysis. For this reason, the present study defines “co-occurrence” as population-level overlaps in disease burden, geographical distribution, and long-term temporal patterns between EM and PCOS. Although this macro-epidemiological method helps uncover common environmental and metabolic risk factors linking the two diseases, its findings are not equivalent to individual comorbidity prevalence derived from clinical cohort investigations. To assess temporal trends in age-standardized incidence and DALY rates, we calculated the estimated annual percentage change (EAPC) for each indicator. Temporal trends in age-standardized rates were quantified using the estimated annual percentage change (EAPC). Briefly, a log-linear regression model was fitted with calendar year as the independent variable and the natural logarithm of the age-standardized rate as the dependent variable. EAPC was then derived as 100×[exp(β)–1], where β denotes the regression coefficient, and its 95% confidence interval (CI) was obtained from the regression model.23 We also plotted annual ASIR and ASDR values against corresponding annual SDI levels for each European subregion (subregion-year observations, n = 34 per subregion, pooled across Eastern, Central, and Western Europe) to visualize the longitudinal association between socioeconomic development and disease burden. Spearman’s rank correlation coefficient was used to quantify associations between SDI and ASIR/ASDR, with scatter plots overlaid with LOESS smooth curves to capture nonlinear trends. Because both SDI and disease burden change systematically over time, the pooled Spearman correlation may partly reflect shared secular trends; we therefore interpret these associations primarily as cross-sectional socioeconomic gradients across European subregions rather than as within-subregion temporal causal effects. Definition and Regional Distribution Patterns of EM-PCOS Co-Occurrence To explore the spatial heterogeneity underlying EM and PCOS co-occurrence across European regions, the incidence levels of the two disorders were separately categorized into four quartile-based grades, including low (75th percentile).18,19 Countries and territories were classified into three mutually exclusive patterns based on their relative incidence rates of EM and PCOS: “consistent” units—where the two diseases shared the same incidence level;“EM-dominant” units—where EM incidence outranked that of PCOS; and“PCOS-dominant” units—where PCOS incidence outranked that of EM. Together, these patterns divided the study area into three spatially distinct zones, enabling systematic mapping of geographic co-occurrence and comparative analysis of disease burden profiles. Joinpoint Analysis Joinpoint regression was employed to identify inflection points in long-term temporal trends and calculate phase-specific annual percentage changes (APCs), which can capture nonlinear trajectories that cannot be detected by linear EAPC estimation.24 For each region, we fitted log-linear Joinpoint models to the ASIR and ASDR of both disorders, with a maximum of 5 joinpoints allowed. Model selection was based on Monte Carlo permutation tests with 10,000 permutations. The average annual percent change (AAPC), a weighted summary of segment-specific APCs, was used to reflect the overall trend across the entire study period. All analyses were implemented in Joinpoint software (version 5.1.0.0, National Cancer Institute) and R software (version 4.5.1), with a two-sided P < 0.05 set as the threshold for statistical significance. Decomposition Analysis The Das Gupta decomposition method was applied to disentangle the drivers of changes in incident cases and DALYs between 1990 and 2023.25 This approach decomposes the total temporal change into three independent components: population growth (variation in total population size), population aging (shifts in age structure), and epidemiological change (the residual change in age-specific incidence rates after accounting for demographic factors).26 The epidemiological change component is a statistical construct that may reflect shifts in underlying risk factors, diagnostic practices, or healthcare access, but it does not directly measure any specific determinant. Both absolute contributions and relative proportional contributions of each component were calculated to compare driving patterns across subregions.

Spatial Distribution and Population-Level Co-Occurrence Patterns of EM and PCOS in Europe Among the 44 European countries included in the analysis, EM ASIR among reproductive-age women demonstrated substantial geographic heterogeneity, with a median value of 139.80 per 100,000 population. The lowest EM ASIR was observed in Iceland (95.37 per 100,000 population), while the highest rate was recorded in the Russian Federation (229.40 per 100,000 population). In comparison, PCOS ASIR displayed even greater cross-national variation, with a median of 64.66 per 100,000 population, ranging from 5.70 per 100,000 in Bosnia and Herzegovina to 144.25 per 100,000 in Italy. Overall incidence levels of both conditions remained high across Europe, posing a notable public health challenge for female reproductive health in the region. The spatial distribution of EM and PCOS ASIR revealed distinct and divergent geographical patterns across Europe. For EM, the highest incidence rates were predominantly concentrated in Eastern and Central Europe, including the Russian Federation, Belarus, Estonia, Latvia, and Lithuania, with incidence rates exceeding 180 per 100,000 population. Overall, EM incidence followed an east‑high, west‑low geographic gradient, with the highest rates concentrated in Central and Eastern Europe. For PCOS, the highest incidence rates were primarily distributed in Western Europe, including Italy, Spain, Portugal and France, with incidence rates above 100 per 100,000 population, while the lowest PCOS incidence rates were clustered in Central and Eastern Europe, including Bosnia and Herzegovina, Czechia, Bulgaria, Croatia, and Albania. We further explored the population-level co-distribution profiles of EM and PCOS across Europe, which revealed marked spatial heterogeneity. By cross-tabulating incidence quartiles of the two disorders, we defined three distinct population-level burden patterns: the consistent pattern (both disorders falling within the same incidence quartile), the EM-dominant pattern (EM incidence in a higher quartile than PCOS), and the PCOS-dominant pattern (PCOS incidence in a higher quartile than EM). The consistent pattern included the smallest number of countries, only 7 out of 44 nations (15.91%) were assigned to this category. The EM-dominant pattern (19 countries, 43.18%) and PCOS-dominant pattern (18 countries, 40.91%) included comparable numbers of nations, collectively representing more than 84% of all included European countries. Specifically, countries with matched high incidence rates for both disorders were predominantly located in the Consistent pattern area, including Austria, Belgium, Poland, Serbia, Sweden, Switzerland and United Kingdom. Conversely, countries with the most divergent incidence rates were mainly distributed in the two dominant pattern areas. The EM-dominant pattern area was primarily located in Eastern and Central Europe, with the Russian Federation representing the most prominent case: its EM incidence rate (229.40/100,000) was the highest in Europe, while its PCOS incidence rate was among the lowest in the region. The PCOS-dominant pattern area was mainly concentrated in Southern and Western Europe, with Italy as the most typical example: its PCOS incidence rate (144.25/100,000) ranked first in Europe, whereas its EM incidence rate was below the European median level (Figure 1, Supplementary Data 1). Overall Temporal Trends Estimated by EAPC of EM and PCOS in Europe We calculated EAPC values to quantify temporal trends in ASIR and ASDR for EM and PCOS across Eastern, Central, and Western Europe over the 1990–2023 period (Figure 2, Supplementary Data 2). For EM, ASIR showed a general decreasing trend across subregions, whereas ASDR patterns varied by geographic area. Specifically, EM ASIR declined significantly in Central Europe (EAPC = −0.39, 95% CI: −0.45 to −0.32) and Western Europe (EAPC = −0.18, 95% CI: −0.25 to −0.11), while no statistically significant change was observed in Eastern Europe (EAPC = 0.02, 95% CI: −0.13 to 0.17). Regarding EM ASDR, Eastern Europe saw a statistically significant increase (EAPC = 0.31, 95% CI: 0.12 to 0.51), and Western Europe experienced a significant decrease (EAPC = −0.19, 95% CI: −0.31 to −0.07). No significant change in EM ASDR was detected in Central Europe (EAPC = −0.04, 95% CI: −0.16 to 0.07) (Figure 2A). For PCOS, incidence rates declined across all three European subregions, while DALY rates showed a consistent and significant upward trend throughout the study period. Significant decreases in the ASIR of PCOS were recorded in Central Europe (EAPC = −0.91, 95% CI: −1.13 to −0.69) and Eastern Europe (EAPC = −0.25, 95% CI: −0.41 to −0.08), with Western Europe showing no statistically significant change (EAPC = −0.06, 95% CI: −0.17 to 0.04). In stark contrast to incidence trends, the ASDR of PCOS increased significantly in all three subregions: Eastern Europe had the largest annual increase (EAPC = 0.98, 95% CI: 0.90 to 1.07), followed by Central Europe (EAPC = 0.61, 95% CI: 0.57 to 0.66) and Western Europe (EAPC = 0.19, 95% CI: 0.13 to 0.25) (Figure 2B). Joinpoint Regression Analysis of the Burden of EM and PCOS in Europe This study used the Joinpoint regression model to assess the changing phases of disease burden for EM and PCOS among reproductive-age women in the three major regions of Europe from 1990 to 2023, revealing the dynamic trends of these diseases (Figure 3, Supplementary Data 3). Joinpoint regression further revealed nonlinear dynamic trajectories that were not captured by linear EAPC estimation. Overall, the ASIR of both EM and PCOS showed a consistent downward trend across all three European regions, while the ASDR exhibited divergent patterns: the ASDR of EM decreased in all subregions, whereas the ASDR of PCOS rose significantly throughout Europe. However, prominent regional disparities in trend magnitude were detected. Specifically, Central and Eastern Europe experienced steeper declines in the ASIR of EM and PCOS, while Western Europe had milder reductions; for the ASDR of PCOS, Eastern Europe presented the fastest annual growth, followed by Central Europe, with Western Europe showing the slowest increase. For EM, both the ASIR and the ASDR displayed downward trends in Central, Eastern, and Western Europe. In terms of the ASIR (Figure 3A), Central Europe had the largest average annual percentage change (AAPC = −0.46, 95% CI: −0.48 to −0.46), followed by Eastern Europe (AAPC = −0.38, 95% CI: −0.41 to −0.35), and Western Europe had the slightest drop (AAPC = −0.19, 95% CI: −0.23 to −0.17). Regarding the ASDR (Figure 3C), Central Europe also saw the most remarkable annual reduction (AAPC = −0.25, 95% CI: −0.27 to −0.24), Eastern Europe ranked second (AAPC = −0.22, 95% CI: −0.25 to −0.19), and Western Europe had the smallest decline (AAPC = −0.14, 95% CI: −0.17 to −0.12). For Eastern Europe’s EM ASDR, Joinpoint regression detected multiple inflection points. Notably, EAPC detected a slight overall increase in EM ASDR in Eastern Europe (EAPC = 0.31), while Joinpoint regression yielded an overall AAPC of −0.22. This discrepancy arises because linear EAPC cannot capture the non-monotonic trajectory, which features a mid-period increase followed by a marked recent decline. For PCOS, the ASIR declined in all three European subregions, while the ASDR maintained a significant upward trend over the whole period. For the ASIR (Figure 3B), Central Europe had the sharpest annual fall (AAPC = −0.31, 95% CI: −0.35 to −0.28), Eastern Europe came next (AAPC = −0.17, 95% CI: −0.19 to −0.14), and Western Europe showed a marginal decrease (AAPC = −0.06, 95% CI: −0.08 to −0.04). Contrary to trends in the ASIR, the ASDR of PCOS increased significantly in all regions (Figure 3D): Eastern Europe recorded the highest AAPC of 0.71 (95% CI: 0.70 to 0.73), followed by Central Europe (AAPC = 0.61, 95% CI: 0.60 to 0.62), and Western Europe had the lowest growth rate (AAPC = 0.27, 95% CI: 0.26 to 0.28). Age-Specific Disease Burden Distribution of EM and PCOS in Europe Age-stratified analyses were performed on the number of incident cases, total DALYs, the ASIR and the ASDR of EM and PCOS among reproductive-age women in Central, Eastern and Western Europe (Figure 4, Supplementary Data 4). For EM (Figure 4A,C): The number of incident cases and the ASIR of EM rose with age in all three regions and peaked at 20–24 years, and then gradually decreased in older age brackets. Across all age groups, Western Europe recorded the largest number of EM incident cases, followed by Eastern Europe, while Central Europe had the smallest case counts. For the ASIR of EM, Eastern Europe held the highest values in most age groups, followed by Central Europe, with Western Europe showing the lowest rates. The number of DALYs and the ASDR of EM increased steadily from the 15–19 age group to the 35–39 age group and remained relatively high in subsequent older groups. Western Europe had the largest DALY counts of EM in every age group, Eastern Europe ranked second, and Central Europe had the lowest DALY numbers. The ASDR of EM was consistently higher in Eastern Europe than in Central and Western Europe across all age ranges. For PCOS (Figure 4B,D): The number of incident cases and the ASIR of PCOS peaked at 15–19 years in all three regions and declined sharply with advancing age. Western Europe had vastly larger incident case numbers of PCOS than Central and Eastern Europe in all age groups; Eastern Europe maintained the smallest case counts. For the ASIR of PCOS, Western Europe showed far higher values across all ages, while Eastern Europe exhibited the lowest rates. The number of DALYs and the ASDR of PCOS grew continuously from 15–19 to 35–39 years and stayed elevated in older age groups. Western Europe produced substantially higher DALY numbers and the ASDR of PCOS than the other two subregions in every age bracket, whereas Eastern Europe recorded the lowest DALY counts and the ASDR of PCOS across all age groups. Correlation Between SDI and Disease Burden To further investigate the impact of the Socio-demographic Index (SDI) on the burden of EM and PCOS, we quantified their associations using Spearman rank correlation analysis. Figure 5 presents the distribution patterns of the ASIR and ASDR across Eastern, Central, and Western Europe along the SDI gradient (Supplementary Data 5). For EM, the overall ASIR showed a weak but statistically significant negative correlation with SDI (r = −0.2829, p < 0.001), with incidence rates generally declining as SDI increased, and Eastern Europe consistently recorded the highest values across the SDI range, followed by Central Europe and Western Europe (Figure 5A); in contrast, the ASDR of EM showed a statistically significant but extremely weak positive correlation with SDI (r = 0.0542, p = 0.001) with negligible public health significance, and Eastern Europe still maintained higher disability burden than the other two subregions (Figure 5C). For PCOS, the overall ASIR exhibited a moderate significant positive correlation with SDI (r = 0.3782, p < 0.001), with rates rising markedly alongside elevated SDI, and Western Europe sustained the highest incidence and the steepest growth trend, followed by Central Europe and Eastern Europe (Figure 5B); the ASDR of PCOS showed an even stronger significant positive correlation with SDI (r = 0.8626, p < 0.001), with disability burden rising sharply along the SDI gradient, and the geographic ranking of subregions remained consistent with the incidence pattern (Figure 5D). Decomposition Analysis of EM and PCOS The number of EM-related incident cases declined across Eastern, Central and Western Europe, with the largest reduction detected in Eastern Europe. Population aging accounted for 34.51%, 51.69% and −24.53% of total EM incidence change, whereas population growth accounted for 30.65%, 19.29% and 91.55% of EM incident shifts across the three subregions respectively. Epidemiological change accounted for 34.85%, 29.02% and 32.98% of the total EM incidence reduction (Figure 6A). The number of PCOS-related incident cases decreased in all three European subregions, with the most remarkable decline observed in Western Europe. Population aging accounted for 165.81%, 117.62% and 135.75% of total PCOS incidence reduction, whereas population growth accounted for 48.96%, 22.46% and 182.47% of PCOS incident shifts across the three subregions respectively. Epidemiological change exerted a burden-increasing effect, accounting for −114.78%, −40.08% and −218.22% of PCOS incidence shifts (Figure 6B). The number of EM-related DALYs decreased across Eastern, Central and Western Europe, with the largest DALY reduction detected in Eastern Europe. Population aging accounted for 14.13%, 42.49% and −150.69% of total EM DALY change, whereas population growth accounted for 40.74%, 24.22% and 158.36% of EM DALY shifts across the three subregions respectively. Epidemiological change accounted for 45.13%, 33.29% and 92.33% of the total EM DALY reduction (Figure 6C). The number of PCOS-related DALYs presented divergent trends across subregions: Eastern Europe saw a mild DALY rise, Central Europe had negligible DALY fluctuation, and Western Europe exhibited a prominent DALY increase. Population aging accounted for −22.69%, 1935.84% and 67.68% of total PCOS DALY variation, whereas population growth accounted for −51.34%, 932.63% and −89.53% of PCOS DALY shifts across the three subregions respectively. Epidemiological change consistently raised disability burden, accounting for 174.02%, −2768.47% and 121.85% of PCOS DALY shifts (Figure 6D). In the figure, positive values on the abscissa represent promoting factors, while negative values represent mitigating factors. The percentage of each factor is calculated as (the number of effect cases of each factor divided by the total difference effect) × 100% (Supplementary Data 6). Note that these proportional contributions are derived by dividing each component’s effect by the net change. In cases with near-zero net change and large opposing component effects, such as PCOS DALYs in Central Europe, the percentage estimates can be mathematically inflated.

Using the most up-to-date GBD 2023 dataset, our work provides a systematic spatiotemporal depiction of population-level co-occurrence patterns of endometriosis and polycystic ovary syndrome across the European continent. A key contribution of this continental-scale analysis is the delineation of three distinct national burden phenotypes and the systematic comparison of socioeconomic gradients across the two disorders, an aspect that remains under-investigated in existing European epidemiological literature. Since the GBD study generates aggregated estimates at national and regional scales, we acknowledge that ecological study designs carry inherent limitations in directly verifying individual-level comorbidity.27 For this reason, “co-occurrence” in the present study is operationally defined as the parallelism of disease burden, spatial congruence, and temporal trend consistency of EM and PCOS at the population level. This macro-epidemiological framework can help generate hypotheses regarding shared environmental and metabolic risk factors, and its results are not interchangeable with clinical comorbidity rates obtained from patient-level cohort studies.28,29 Contrary to the assumption of uniform continental disease distribution, our findings reveal stratified heterogeneous co-occurrence patterns shaped by geography and the Socio-demographic Index (SDI). We identified three distinct geographical phenotypes across Europe: Consistent, EM-dominant, and PCOS-dominant national burden areas. EM and PCOS exhibited highly heterogeneous geographic distributions across Europe. We categorized 44 European countries into three burden subtypes: consistent dual burden (7 nations, 15.91%), EM-dominant (19 nations, 43.18%) and PCOS-dominant (18 nations, 40.91%). EM concentrated in Central and Eastern Europe (Russia had the highest ASIR), whereas high PCOS burden clustered in Southern and Western Europe, with Italy recording the peak incidence but submedian EM rates. This mutually exclusive spatial pattern indicates divergent regional risk factors, including differences in contraceptive usage, gynecological diagnostic access, and dietary metabolic exposures. Existing single-disease GBD studies have separately noted EM’s negative SDI correlation and PCOS’s positive association, yet few cross-disease European comparisons have identified this tripartite national burden classification.30,31 The three distinct burden subtypes identified herein provide straightforward population-level evidence to support regionally differentiated reproductive health screening frameworks. EAPC and Joinpoint regression jointly depicted the divergent temporal trajectories of disability burden for the two diseases, with prominent nonlinear inflection points detected in Eastern Europe. The ASIR of EM and PCOS declined across all European subregions, with steeper reductions observed in Central and Eastern Europe. However, EM’s ASDR declined overall across Europe, while PCOS-related disability burden rose substantially, with Eastern Europe showing the fastest annual growth. This decoupling trend of falling incidence yet rising DALYs for PCOS deserves in-depth interpretation: although new PCOS incident cases gradually reduced over the decades, cumulative long-term metabolic complications including type 2 diabetes and cardiovascular risk persistently elevate population-wide disability weight; additionally, decomposition results suggest that population-wide unfavorable metabolic shifts increase per-case disease severity, fully offsetting the benefits of reduced new-onset cases. In Western Europe with advanced healthcare resources, improved laparoscopic diagnosis and standardized hormonal management have effectively reduced EM-related disability; whereas delayed diagnosis and insufficient access to long-term gynecological care in Eastern Europe may have contributed to its fluctuating high EM disability burden. Age-stratified analyses identified clear age-specific incidence patterns: PCOS incidence peaked at 15–19 years, possibly reflecting adolescent hyperandrogenism, while EM peaked at 20–24 years, potentially related to cumulative menstrual irritation and delayed clinical detection. The DALY burden of both disorders peaked at 35–39 years, representing the highest cumulative reproductive impairment in middle-aged women. Our observations are in line with multiple prior published investigations.32 Western Europe bore the largest absolute case numbers of both diseases across all age groups, while Eastern Europe maintained elevated EM but low PCOS age-standardized rates, delivering clear evidence for age-stratified, region-tailored screening strategies. Correlation analysis confirmed divergent SDI gradients for EM and PCOS across Europe. EM incidence was weakly negatively associated with SDI, but its disability burden did not show a parallel declining trend; in contrast, both incidence and disability burden of PCOS increased consistently with socioeconomic development. The higher PCOS burden in high-SDI Western regions may reflect the higher prevalence of obesogenic lifestyles in these settings, although their mature laparoscopic care may help alleviate EM symptoms, improved diagnostic coverage and longer disease duration offset the benefit of reduced incidence;consequently, population-level disability burden does not fall with SDI. Low- and middle-SDI Eastern populations have lower overall obesity risk, but limited routine reproductive screening may contribute to delayed EM diagnosis and accumulated severe pelvic lesions, resulting in higher baseline EM disability. This pattern of differentiated socioeconomic associations may partly explain the geographically separated hotspots of EM and PCOS across Europe. Decomposition analysis further disentangled the distinct driving forces underlying EM and PCOS burden changes. Population aging, population growth and epidemiological shifts jointly alleviated EM burden across Central and Eastern Europe. For PCOS, demographic factors suppressed incident case numbers, yet the epidemiological change component (which may reflect metabolic and lifestyle-related shifts) served as the dominant driver of rising DALYs, particularly in Western Europe. Overall, demographic shifts exerted protective effects for both disorders, while the epidemiological change component generated opposing impacts on EM vs PCOS burden. These decomposition findings, interpreted with caution as ecological rather than causal evidence, suggest that reproductive public health strategies may benefit from prioritizing metabolic risk management in Western Europe and strengthening early EM detection and care capacity in Central/Eastern Europe. The geographic divergence and socioeconomic gradients identified here may reflect policy-relevant patterns across Europe. First, distinct hotspots of EM (Central/Eastern Europe, lower SDI) and PCOS (Western Europe, higher SDI) are perhaps associated with limited utility of uniform resource allocation. Eastern regions may strengthen early EM diagnostic services, while Western regions could prioritize PCOS metabolic risk management. Second, decoupled trends of falling PCOS incidence and rising DALYs may reflect a potential need for chronic care alongside acute management. Third, divergent peak age-specific incidence (adolescence for PCOS, early adulthood for EM) may inform age-tailored prevention. One possible interpretation is that cross-national heterogeneity and limited GBD comparability support harmonized diagnostic criteria and standardized reporting. Collectively, these observations may favor regionally differentiated, age-specific responses over a one-size-fits-all framework. Although this study provides a systematic multi-dimensional assessment of the co-occurring burden of EM and PCOS across Europe, several important inherent limitations should be recognized. First, as an ecological study using national-level aggregated data, our findings are susceptible to the ecological fallacy, meaning we cannot directly infer individual-level co-morbidity of EM and PCOS from population-level patterns. Second, all estimates were derived from GBD 2023 modeling outputs, which are subject to inherent limitations related to variable raw data quality and diagnostic heterogeneity across countries.33 Specifically, the lack of harmonized diagnostic criteria and standardized reporting systems for EM and PCOS across regions tends to underestimate the actual disease burden and undermine cross-national comparability of the estimates.34 Furthermore, regions with scarce primary data sources (eg, parts of Eastern Europe) are subject to wider uncertainty intervals in estimation, which may further bias cross-country comparative analyses.35 Third, while we have mapped overall continental trends and regional burden hotspots, our analysis did not quantitatively adjust for contextual confounding factors such as cross-national differences in dietary patterns, cultural reproductive practices, and variations in national reproductive health policies and healthcare resource distribution, all of which likely contribute substantially to inter-country burden differences. Future macro-level research could integrate policy intensity and health inequality indicators to better explain geographic variation in EM and PCOS burden. Crucially, the “co-occurrence burden” described in this macro-analysis only refers to parallel national disease prevalence and temporal trend correlation, rather than true individual patient co-diagnosis rates. Without linked individual electronic medical records or disease registries, we cannot calculate the proportion of women simultaneously suffering from both disorders or quantify mutual disease interaction effects at the individual level. Future cohort or registry-based real-world studies are required to assess individual-level EM-PCOS comorbidity risk and joint pathogenic mechanisms, further improving the clinical translational value of population-level epidemiological findings. Importantly, while these limitations may affect the absolute magnitude of burden estimates, they are less likely to alter the relative geographic patterns and temporal trends identified in this study. The consistent East–West divergence, divergent SDI gradients, and contrasting temporal trajectories of EM and PCOS were robust across multiple analytical approaches (EAPC, Joinpoint regression, and decomposition analysis), suggesting that the observed population-level patterns are unlikely to be driven solely by data quality or modeling artifacts.

In summary, this study uses GBD 2023 data to characterize population-level burden patterns of EM and PCOS across Europe. The two disorders display diametrically opposed geographic distributions and distinct associations with SDI: EM incidence is elevated in low-to-middle SDI countries of Central and Eastern Europe, while PCOS burden is concentrated in high-SDI Western European nations. Only a small proportion of countries show comparable incidence levels for both disorders. Although incidence rates for both conditions declined over the 33-year study period, PCOS-related disability burden increased notably, with the epidemiological change component contributing most substantially. The differing peak age-specific incidence of the two disorders highlights the need for age-specific preventive strategies. As this is an ecological, population-level analysis, these findings are hypothesis-generating for policy design rather than direct evidence of intervention effectiveness. Implementing region-specific reproductive health policies may help reduce the uneven distribution of disease burden across Europe, and our findings provide supporting evidence for optimizing the allocation of regional reproductive healthcare resources. Abbreviations EM, Endometriosis; PCOS, Polycystic ovary syndrome; GBD, Global Burden of Disease; ASR, age-standardized rate; ASIR, age-standardized incidence rate; DALYs, disability-adjusted life years; ASDR, age-standardized DALYs rate; EAPC, estimated annual percentage change; AAPC, the average annual percentage change; SDI, Socio-demographic Index; Data Sharing Statement All data were extracted from the publicly accessible GBD 2023 dataset via the GBD Results Tool (https://vizhub.healthdata.org/gbd-results/). Access rules are available at https://ghdx.healthdata.org/gbd-2023. Ethics Approval and Informed Consent This study was a secondary analysis of publicly available aggregated data from the Global Burden of Disease (GBD) study, which had obtained ethical approval and a waiver of informed consent from the Institutional Review Board at the University of Washington. This secondary analysis was exempted by the Ethics Committee of Peking University People’s Hospital, which determined that, given the fully de-identified and aggregated nature of the data, the study posed no more than minimal risk to human subjects. Therefore, no additional ethical approval or individual participant consent was required. Acknowledgments We acknowledge the support from the Global Burden of Disease Collaborative Network and the Institute for Health Metrics and Evaluation (IHME). Special thanks go to the editor and reviewers, whose valuable remarks substantially improved the clarity of our findings. Author Contributions All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work. Funding This work was supported by the Research and Development Fund of Peking University People’s Hospital (RDL2024-25) and the commissioned research project from Beijing Juxi Technology Co., Ltd. (2026-Z-55). The funders had no role in study design, data collection and analysis, interpretation of data, or manuscript writing. Disclosure No conflicts of interest exist among the authors.

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