Changes in the global burden of polycystic ovary syndrome from 1990 to 2021

Changes in the global burden of polycystic ovary syndrome from 1990 to 2021 | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Changes in the global burden of polycystic ovary syndrome from 1990 to 2021 Tong Lin, Bingqin Xie, Juan Yang, Jinbang Xu, Fa Chen This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5823228/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 20 May, 2025 Read the published version in Reproductive Health → Version 1 posted 9 You are reading this latest preprint version Abstract BACKGROUND Polycystic ovary syndrome (PCOS) is a chronic, multifaceted condition influenced by epigenetic and environmental factors that is responsible for a significant proportion of anovulatory infertility cases. Here, we analyzed the global, regional, and national burdens of PCOS from 1990 to 2021 using data from the Global Burden of Disease 2021 (GBD 2021). METHODS Incidence, prevalence, and Disability-Adjusted Life Years(DALYs) data relevant to PCOS from 204 countries and 21 territories from 1990 to 2021 were obtained from the GBD 2021 study. Here, we considered age-standardized rates (per 100,000 individuals) with 95% uncertainty intervals (95% UIs) obtained from the aforementioned research and presented trends based on age and Socio-demographic Index (SDI) parameters. RESULTS Global age-standardized incidence and prevalence of PCOS in 2021 were reported at 30.7 and 867.7 per 100,000, respectively, revealing increases of 26.77% and 28.21%, respectively, since 1990. Additionally, age-standardized disability-adjusted life years stood at 7.6 per 100,000 globally in 2021, marking a 27.58% increase from 1990. Age-standardized prevalence of PCOS varied across countries, ranging from 93.1 to 3978.9 cases per 100,000 women, with Italy (3978.9), Japan (3104.7), and New Zealand (2789.7) having the highest rates. Notably, PCOS prevalence was noted to peak globally among females 15–19 years of age. Regions with a high SDI exhibited the highest age-standardized incidence (70.2), prevalence (1720.7), and death (15.2) rates of PCOS. Furthermore, a nonlinear correlation between PCOS burden and SDI was noted, with prevalence rates peaking around an SDI of approximately 0.9. CONCLUSION Our findings highlight the growing global impact of PCOS and underscore the need for concerted efforts to attenuate the increasing global prevalence of this condition. Significantly divergent PCOS disease burdens were observed across different age groups and SDI regions, with high SDI regions bearing heavier burdens. The increased disease burden among younger age groups and regional disparities underscore urgency for targeted intervention and formulation of policies to effectively address this public health issue. polycystic ovary syndrome global burden of disease disability-adjusted life years socio-demographic Index Figures Figure 1 Figure 2 Figure 3 Figure 4 1 Introduction Polycystic ovary syndrome (PCOS), a common hormonal condition affecting women of reproductive age, exhibits a prevalence range from 8–13%( 1 ). Increasing evidence has revealed PCOS to be a complex, heterogeneous, and lifelong condition that strongly associates with epigenetic and environmental variables( 2 – 4 ). Importantly, PCOS is the most common cause of anovulatory infertility( 3 ). Apart from adversely affecting female reproductive function, PCOS also increases the risk of various comorbidities, such as obesity, insulin resistance, diabetes, and cardiovascular disease, thus exacerbating global health and economic burdens( 2 , 3 ). Screening and health management needs of PCOS patients remain unmet. The reproductive-related effects of PCOS include an increased risk of irregular menstrual cycles, anovulatory infertility, pregnancy complications( 5 , 6 ), and endometrial cancer( 7 ). Furthermore, PCOS associates with anxiety, depression, eating disorders, psychosexual disorders, and negative body image perception( 8 , 9 ), all of which impact quality of life. Clinical management of PCOS is no longer limited to promotion of ovulatory regularity and pregnancy; increasing focus has been placed on the importance of glycolipid metabolism and complication management in this patient population( 1 ), highlighting a need for studies to accurately characterize PCOS disease burden. Importantly, a comprehensive understanding of PCOS disease burden would provide a more solid rationale for developing future women's health plans and better accommodating needs of PCOS patients, thereby assisting high-burden countries strengthen PCOS screening and management operations to achieve early detection, diagnosis, and treatment goals. The accuracy of PCOS global prevalence and incidence data previously reported has often been inconsistent due to discrepancies in research methodologies, regional differences and shifting diagnostic criteria( 1 , 3 , 10 ). The Global Burden of Disease (GBD) database is a comprehensive database organized by the Global Health Research Institute to assess and analyze the health impact of diseases, injuries, and risk factors globally and regionally. To facilitate comprehensive assessment, the GBD divides the world into 21 regions and 204 countries and territories. The Socio-demographic Index (SDI) is used to link developmental status to health outcomes, while disability-adjusted life years (DALYs), the sum of years lost due to premature death and years survived due to disability, are used to denote years of healthy life lost. Although recent GBD studies reviewed PCOS burden( 11 – 13 ), detailed quantitative estimates of PCOS incidence, prevalence, and associated DALYs in 2021 have not been published. Here, we explored the impact of the COVID-19 pandemic on global PCOS burden; this would not have been possible considering only pre-2020 data. We furthermore assessed global, regional and national PCOS burdens among women 15–49 years old in 21 regions and 204 countries and territories from 1990 to 2021 via analysis of GBD 2021 data to highlight incidence, prevalence, and DALYs relevant to this patient population and facilitate more effective future formulation of policy, resource allocation, and health system planning. 2 Materials and methods 2.1 Overview PCOS data were obtained from GBD 2021 using the Global Health Data Exchange website ( http://ghdx.healthdata.org ). The database systematically compiles the health burden of 369 conditions from 1990 to 2021 and includes samples obtained from 204 countries and territories. Relevant methods for estimating incidence, prevalence and DALY rates have been previously detailed( 14 ). This study was conducted in accordance with the 1975 Declaration of Helsinki. As this study evaluated publicly available datasets, ethical committee approval was not required. Informed consent was waived as GBD 2021 compiled de-identified pooled data. 2.2 Case definitions and data sources Collectively, PCOS is characterized by androgenesis, anovulation and polycystic ovarian morphology( 1 , 2 ). The reference definition of PCOS was standardized in GBD 2021 and is based on the definition set forth by the American College of Obstetricians and Gynecologists, where the diagnosis may be established using any of the three accepted methods (i.e. NIH, Rotterdam or AE-PCOS) ( 1 ). 2.3 Data processing and presentation Joint point regression was used to assess temporal trends and annual percentage changes for PCOS incidence, prevalence, and rates of DALYs from 1990 to 2021. Data were analyzed according to 204 countries, 5 SDI regions, 21 GBD regions, and different age groups. Correlation among SDI and incidence, prevalence, and rates of DALYs in 2021 was also determined. The SDI was assessed based on total fertility rate for females younger than 25 years of age, educational attainment of females aged 15 years and older, as well as per capita lagged distribution income. The 204 geographical regions were categorized into five groups based on SDI: low; medium-low; medium; medium-high; and high SDI. Based on GBD classification, women of childbearing age were categorized as 15–19, 20–24, 25–29, 30–34, 35–39, 40–44, or 45–49 years old. Each estimate was calculated 1000 times in GBD 2021; final data were presented as a mean of these estimates. A 95% uncertainty interval (95% UI) was calculated for each analysis, determined using 25th and 97.5th values of a set of ordered 1000 extractions. A two-sided P < 0.05 was considered statistically significant. Data were downloaded from the GBD website and Excel software (Microsoft, USA) was used for descriptive analysis. Other statistical analyses were performed using R version 4.4.1 (The R Foundation, Austria). 3 Results 3.1 Global burden In 2021, there were 2.3 million new cases of PCOS at an age-standardized rate of 30.7 per 100,000, an increase of 26.77% since 1990 (Table 1; Fig. 1 ). In 2021, there were 69.47 million prevalent cases of PCOS globally at an age-standardized rate of 867.7 per 100,000 women, an increase of 28.21% since 1990 (Table 1; Fig. 1 ). In 2021, the total number of PCOS-associated DALYs was 610,000 at an age-standardized rate of 7.6 cases per 100,000 women, an increase of 27.58% since 1990 (Table 1; Fig. 1 ). 3.2 Regional burdens In 2021, the high-income Asia Pacific [109.2 (95% UI: 77.9-153.9)], Australasia [98.2 (95% UI: 70.4-135.4)], and Western Europe [75.2 (95%UI: 53.1–105)] regions had the greatest age-standardized PCOS incidence rates. In contrast, the regions of Central Europe [4.3 (95% UI: 3-6.1)], Eastern Europe [5.3 (95% UI: 3.7–7.5)], and Central Asia [9.1 (95% UI: 6.3–12.7)] had the lowest age-standardized PCOS incidence rates (Table 1). In 2021, the age-standardized PCOS prevalence rates were greatest in the high-income Asia Pacific [2544.9 (95% UI: 1836.1-3551.3)], Australasia [2387 (95% UI: 1708.4-3297.5)], and Western Europe [1944.3 (95% UI: 1361.7-2726.7)] regions. Conversely, the regions of Central Europe [111.7 (95% UI: 77-159.2)], Eastern Europe [132.4 (95% UI: 91.2-190.5)], and Central Asia [240.5 (95% UI: 164.6-337.3)] exhibited the lowest age-standardized PCOS prevalence rates (Table 1). In 2021, the high-income Asia Pacific [22.2 (95% UI: 10.1–45.2)], Australasia [20.8 (95% UI: 9.3–43.0)] and Western Europe [17.3 (95% UI: 7.8–35.9)] regions had the greatest age-standardized DALYs rates for PCOS, while those of Central Europe [ 1 (95% UI: 0.4-2)], Eastern Europe [ 1.2 (95% UI: 0.5–2.5)], and Central Asia [2.1 (95% UI: 0.9–4.5)] had the lowest (Table 1). The greatest increases in the rates of age-standardized incidence and prevalence of PCOS from 1990 to 2021 were found in Southeast Asia [incidence: 82.8% (95% UI: 69.3-97.25); prevalence: 81.61% (95% UI: 68.92–94.86)], East Asia [incidence: 75.02% (95% UI: 62.37–86.34); prevalence: 81.5% (95% UI: 70.23–93.05)], and South Asia [incidence: 66.10% (95% UI: 56.5-77.13); prevalence: 80.44% (95% UI: 69.61–94.73)], with no regional declines through this time period (Table 1). In addition, the regions with the largest increases in age-standardized DALY rates for PCOS from 1990 to 2021 were East Asia [82.86% (95% UI: 71.06–94.3)], Southeast Asia [80.53% (95% UI: 68.47–93.64)], and South Asia [78.54% (95% UI: 67.27–91.55)], with no regional declines through this time period (Table 1). 3.3 National burden At the national level, the countries with the greatest age-standardized incidence rates for PCOS in 2021 were Italy [158 (95% UI: 110.1-222.2)], Japan [129.5 (95% UI: 92.2-182.4)], and New Zealand [114.6 (95% UI: 81.2-158.4 )]; those with the lowest rates were Albania [3.7 (95% UI: 2.5–5.4)], Serbia [3.7 (95% UI: 2.5–5.3)], and Bosnia and Herzegovina [3.7 (95% UI: 2.5–5.4)]. The percentage change for age-standardized PCOS incidence rates from 1990 to 2021 varied widely between countries, with the Maldives [125.23% (95% UI: 94.68-161.28)], Myanmar [104.11% (95% UI: 78.02-133.16)], and Vietnam [95.03% (95% UI: 70.01-118.06)] exhibiting the largest increases; Italy [− 10.53% (95% UI: −17.1-−5.29)], Mexico [− 1.93% (95% UI: −7.84–2.72)], and New Zealand [− 1.39% (95% UI: −14.34–10.98)] exhibited negative trends (Fig. 2 ; Supplementary Table S1 ). In 2021, the age-standardized prevalence rates of PCOS ranged from 93.1 to 3978.9 cases per 100,000 women among different countries. Countries with the greatest prevalence rates were Italy [3978.9 (95% UI: 2823.1-5523.3)], Japan [3104.7 (95% UI: 2244.2-4312.7)], and New Zealand [2789.7 (95% UI: 2008.7-3805.9)]; those with the lowest were Albania [93.1 (95% UI: 61.5-141.7)], Bosnia and Herzegovina [94 (95% UI: 61.5-144.2)], and North Macedonia [94.6 (95% UI: 61.6-144.2)]. The variance in age-standardized PCOS prevalence exhibited a notable contrast from 1990 to 2021. The largest increases were in Myanmar [108.01% (95% UI: 80.46-137.42)], Equatorial Guinea [97.11% (95% UI: 73.89-133.94)] and Thailand [96.44% (95% UI: 73.39–123)]; negative trends were noted in Italy [− 6.52% (95% UI: −13.08-−1.05)] and New Zealand [− 0.82% (95% UI: −13.79-−10.35)] (Fig. 2 ; Supplementary Table S1 ). In 2021, the greatest age-standardized PCOS DALYs rates were in Italy [35.1 (95% UI: 15.8–74.9)], Japan [27 (95% UI: 12.3–54.9)], and New Zealand [24.3 (95% UI: 11.1–50.6)]; Bosnia and Herzegovina [0.8 (95% UI: 0.3–1.8)], North Macedonia [0.8 (95% UI: 0.4–1.7)], and Albania [0.8 (95% UI: 0.3–1.8)] had the lowest rates. The percentage change for age-standardized PCOS DALY rates from 1990 to 2021 similarly varied by country. The largest increases were in Myanmar [108.27% (95% UI: 81.45-138.62)], Equatorial Guinea [97.49% (95% UI: 70.58-141.74)], and Thailand [92.4% (95% UI: 68.81-121.15)]; Italy [− 5.69% (95% UI: −12.63 − 0.36)], New Zealand [− 0.74% (95% UI: −12.75–10.31)], and Mexico [− 0.73% (95% UI: −6.76–5.12)] exhibited negative trends (Fig. 2 ; Supplementary Table S1 ). 3.4 PCOS burden by SDI In 2021, high SDI regions exhibited the greatest age-standardized incidence [70.2 (95% UI: 52-95.3)], prevalence [1720.7 (95% UI: 1270.5-2331.7)], and mortality [15.2 (95% UI: 7–31)] rates for PCOS, while low SDI regions exhibited the lowest age-standardized incidence [13.8 (95% UI: 9.8–19.3)], prevalence [361.6 (95% UI: 255.3-509.8)], and mortality [3.1 (95% UI: 1.4–6.6)] rates for PCOS. Increasing trends were noted in all regions (Table 1). At the district level, a nonlinear association between SDI and age-standardized incidence, prevalence, and DALY rates for PCOS from 1990 to 2021 were noted, with age-standardized rates greatest at an SDI of approximately 0.9, indicating that a higher SDI associated with greater age-standardized incidence, prevalence, and DALY rates for PCOS (Fig. 3 ). 3.5 Age patterns In 2021, the greatest rate of age-standardized incidence for PCOS was observed in the 15–19 age group [169.3 (95% UI: 105.6-263.2)]; the lowest was observed in the 45–49 age group [0.7 (95% UI: 0.1–1.4)]. In 2021, the 40–44 age group [1828.5 (95% UI: 1308.3-2540.1)] had the highest age-standardized prevalence, while the 15–19 age group [1228.1 (95% UI: 830.7-1758.4)] had the lowest. In 2021, the highest rate of age-standardized DALYs was in the 25–29 age group [15.9 (95% UI: 7-32.6)], while the lowest was in the 15–19 age group [11 (95% UI: 4.9–23.4)] (Table 1, Fig. 4 ). The greatest increase in PCOS age-standardized incidence from 1990 to 2021 was in the 15–19 age group [25.63% (95% UI: 20.76–30.03)]; the smallest increase was in the 20–24 age group [− 0.99% (95% UI: −6.32–4.79)]. In addition, the age group with the largest increase in rates of age-standardized prevalence and DALYs for PCOS from 1990 to 2021 was the 20–24 age group [prevalence: 31.7% (95% UI: 28.1–35.5); DALYs: 31.07% (95% UI: 26.69–35.33)]; the 40–44 age group exhibited the smallest increase [prevalence: 22.82% (95% UI: 19.43–26.14); DALYs: 22.31% (95% UI: 18.59–25.58)] (Table 1, Fig. 4 ). 4 Discussion This study presents a thorough and updated analysis of PCOS prevalence on global, regional, and national scales spanning more than three decades. In 2021, the worldwide incidence, prevalence, and associated DALY rates for PCOS stood at 2.3 million, 69.47 million, and 610,000, respectively. The global age-standardized incidence, prevalence, and DALY rates exhibited an increase from 1990 to 2021 by 26.77%, 28.21%, and 27.58%, respectively. Our findings underscore the increasing prevalence of PCOS on global, regional, and national scales, revealing notable variations across different age groups and SDI regions. The highest prevalence of PCOS was observed in high SDI regions, contrasting with lower rates in regions with low SDI. The high-income Asia Pacific exhibited the greatest age-standardized prevalence rates, whereas Central Europe exhibited the lowest. Italy exhibited the greatest disease burden for PCOS in 2021, and there has indeed been a concerning upward trend in disease burden in Italy over the past 32 years. Importantly, from 1990 to 2021, the incidence, prevalence, and DALY rates for PCOS exhibited a marked increase across most age brackets, but particularly among the younger population. The marked increase in global PCOS prevalence from 1990 to 2021 is a concerning trend that necessitates further study. Various factors likely contributed to this increase, including changes in the diagnostic criteria for this condition. The 1990 National Institutes of Health (NIH) criteria established the initial formal diagnostic guidelines for clinically identifying PCOS, mandating the presence of oligoovulation and hyperandrogenism. The introduction of the 2003 Rotterdam criteria( 15 ) broadened diagnostic possibilities by incorporating polycystic ovarian morphology (PCOM) as a necessary characteristic while requiring the presence of 2 out of 3 criteria for PCOS diagnosis (i.e. irregular or absent ovulation; clinical or biochemical signs of hyperandrogenism; evidence of PCOM on ultrasound exam). As of 2018, collaboration among an Australian academic group, the American Society for Reproductive Medicine (ASRM), and the European Society of Human Reproduction and Embryology (ESHRE)( 1 ) has advocated for continued clinical use of the 2003 Rotterdam criteria for diagnosis of adult patients, emphasizing a progressive approach based on clinical symptoms. Expanded diagnostic criteria and enhanced imaging capabilities have led to a substantial increase in PCOS diagnosis among women of reproductive age, rising from a range of 4%-8–21%( 16 ). Importantly, PCOS is recognized as a heritable condition, yet also multifactorial in etiology( 17 ). Emerging evidence suggests that susceptibility to PCOS is influenced not solely by genetic factors but also epigenetic modifications and developmental influences( 18 , 19 ); such variables have likely contributed to the escalating prevalence of PCOS. Furthermore, environmental factors are understood to have contributed to the increase in PCOS incidence. Environmental exposure to perfluoroalkyl substances (PFAS), polyfluoroalkyl substances (PFAS)( 20 , 21 ), and toxic metals (Pb, Hg, As, Ba, and Cd)( 22 ) was reported to increase risk of developing PCOS. The SDI of a region closely associates with population social development status and health outcomes for a given population. This parameter also serves as a composite measure, reflecting a delayed distribution of per capita income, average years of schooling, and total fertility rate among individuals less than 25 years old. Our findings reveal significant regional variations in the prevalence of PCOS, with the greatest standardized incidence, prevalence, and DALY rates noted in high SDI regions and lowest in low SDI regions, consistent with prior studies( 11 ). Within ethnically homogeneous PCOS patient groups, a correlation was noted between higher socioeconomic status and an increased prevalence of PCOS characterized by altered ovulatory patterns. Furthermore, differences in insulin levels and fat distribution across social strata were linked to ovulatory status( 23 ). The 2021 PCOS burden exhibited significant variation across geographic regions evaluated in the GBD 2021 study. The high-income Asia Pacific region exhibited the greatest age-standardized rates of PCOS, whereas Central Europe exhibited the lowest. An earlier meta-analysis( 24 ) revealed varying accuracy in ultrasound diagnosis of PCOS among Asian, European, and North American studies, suggesting differences in age, BMI, and diagnostic criteria clinically utilized in these regions. Although Italy carried the greatest PCOS disease burden in 2021, the disease burden decreased in the country over the past 32 years. The risk of diabetes for women with PCOS was found to resemble that of individuals otherwise at high risk for diabetes( 25 , 26 ). A study in Sicily( 27 ) revealed the prevalence rates of obesity, metabolic syndrome, diabetes mellitus, dysglycemia, and dyslipidemia to be 6.6%, 6.6%, 2.1%, 13.1%, and 60%, respectively. Furthermore, certain intronic variants of the NR3C1 gene (rs10482672 and rs11749561)( 28 ) as well as a history of growth hormone deficiency( 29 ) have been linked to increased PCOS prevalence. Interestingly, our findings noted a marked decline in PCOS disease burden in Italy. Italy's health system, ranked second in the World Health Report 2000, as well as its efficiency ( 30 ) and greater adherence to the Mediterranean diet among the populace( 31 , 32 ), likely play crucial roles in mitigating Italy’s national PCOS disease burden. Here, we found increases in incidence, prevalence, and DALY rates for PCOS from 1990 to 2021 across various patient age groups, with the greatest increase among individuals aged 15–19 years. These findings align with those recently reported in an American study( 33 ). The challenges associated with diagnosing PCOS during adolescence stem from the overlap of diagnostic criteria with physiological changes seen in young individuals( 34 ). The updated International Evidence-Based Guidelines for PCOS Evaluation and Management have been instrumental in enhancing diagnostic precision and reducing instances of erroneous diagnosis( 35 , 36 ). Importantly, obesity is prevalent among PCOS patients, with over 21.9% of adolescent PCOS cases also exhibiting dysglycemia( 37 ). Research has indicated that childhood obesity and adipose tissue dysfunction serve as early indicators of PCOS risk in later life( 38 ). Furthermore, the increased prevalence of obesity and abnormal glucose metabolism contribute to a diagnosis of early onset PCOS. In this study, we analyzed a comprehensive dataset spanning 32 years as well as various facets of relevant to global, regional, and national impact of PCOS on patient groups. Nevertheless, this study was not without limitations. Firstly, data on PCOS risk factors were unavailable, and our analysis predominantly focused on describing trends relevant to PCOS burden rather than elucidation of potential causative factors for the condition. Secondly, discrepancies in data quality and accessibility related to PCOS burden were likely due to economic disparities, health expenditure variations, care standards, and health policies, potentially impacting the accuracy of our findings. Thirdly, the dynamic nature of PCOS diagnostic criteria may have introduced inconsistencies in determining PCOS prevalence rates( 16 ). Finally, in developed nations with robust healthcare infrastructures and higher healthcare-seeking tendencies among patients, detection bias may have inflated PCOS incidence and prevalence rates. As such, future research should concentrate on pinpointing more specific risk factors and elucidating pathophysiological mechanisms contributing to observed variances in PCOS burden across diverse populations and age groups. 5 Conclusion Our findings highlight the growing impact of PCOS on a worldwide scale, underscoring an urgent need for concerted efforts to alleviate the global prevalence of this condition. Varying disease burdens of PCOS were observed across different age groups and SDI regions, with high SDI regions bearing heavier disease burdens. The increased burdens in younger patients as well as wide regional disparities highlight the need for effective interventions and policies to combat this burgeoning public health challenge. Declarations AUTHOR CONTRIBUTIONS TL conceptualised and supervised the study, and drafted the article. BX contributed data curation and formal analysis, and drafted the article. JY reviewed and revised the article. FC and JX conceptualised and supervised the study, and reviewed and revised the article. ACKNOWLEDGEMENTS We would like to thank the Institute for Health Metrics and Evaluation staff and its collaborators who prepared these publicly available data. Also, we would like to acknowledge the support of the Department of Epidemiology and Health Statistics at the Fujian Medical University, Fuzhou, China. FUNDING INFORMATION This work was supported by grants from Fujian Provincial Natural Science Foundation of China（Grant no.2022QNA054）, National Nature Science Foundation of China (Grant no. 82074542), Joint Funds for the innovation of Science and Technology, Fujian province (Grant no.2020Y94020265), and Fujian provincial health technology project (Grant no.2023ZQNZD01010013). 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Thong EP, Codner E, Laven JSE, Teede H. Diabetes: a metabolic and reproductive disorder in women. Lancet Diabetes & Endocrinology. 2020;8(2):134-49. Carmina E, Nasrallah MP, Guastella E, Lobo RA. Characterization of metabolic changes in the phenotypes of women with polycystic ovary syndrome in a large Mediterranean population from Sicily. Clinical endocrinology. 2019;91(4):553-60. Syed S, Gragnoli C. The glucocorticoid receptor gene (NR3C1) is linked to and associated with polycystic ovarian syndrome in Italian families. Journal of ovarian research. 2024;17(1):13. Ciresi A, Amato MC, Bianco J, Giordano C. Prevalence and clinical features of polycystic ovarian syndrome in adolescents with previous childhood growth hormone deficiency. Journal of pediatric endocrinology & metabolism. 2016;29(5):571-8. Bonora E, Monami M, Bruno G, Zoppini G, Mannucci E. Attending Diabetes Clinics is associated with a lower all-cause mortality. A meta-analysis of observational studies performed in Italy. Nutrition metabolism and cardiovascular diseases. 2018;28(5):431-5. Barrea L, Muscogiuri G, Pugliese G, de Alteriis G, Colao A, Savastano S. Metabolically Healthy Obesity (MHO) vs. Metabolically Unhealthy Obesity (MUO) Phenotypes in PCOS: Association with Endocrine-Metabolic Profile, Adherence to the Mediterranean Diet, and Body Composition. Nutrients. 2021;13(11):3925. Che X, Chen Z, Liu M, Mo Z. Dietary Interventions: A Promising Treatment for Polycystic Ovary Syndrome. Annals of nutrition and metabolism. 2021;77(6):313-23. Yu O, Christ JP, Schulze-Rath R, Covey J, Kelley A, Grafton J, et al. Incidence, prevalence, and trends in polycystic ovary syndrome diagnosis: a United States population-based study from 2006 to 2019. American journal of obstetrics and gynecology. 2023;229(1):39.e1-.e12. DiVall SA. Practical considerations for diagnosis and treatment of polycystic ovary syndrome in adolescence - distilling guidelines into clinical practice. Current opinion in pediatrics. 2023;35(4):494-9. Peña AS, Witchel SF, Hoeger KM, Oberfield SE, Vogiatzi MG, Misso M, et al. Adolescent polycystic ovary syndrome according to the international evidence-based guideline. BMC medicine. 2020;18(1):72. Tay CT, Hart RJ, Hickey M, Moran LJ, Earnest A, Doherty DA, et al. Updated adolescent diagnostic criteria for polycystic ovary syndrome: impact on prevalence and longitudinal body mass index trajectories from birth to adulthood. BMC medicine. 2020;18(1):389. Gupta J, Antal Z, Censani M. Prevalence of Impaired Glucose Tolerance in Adolescent Patients with Polycystic Ovary Syndrome in an Urban Health Care Center. Diabetes. 2018;67(Supple 1):722. Whooten RC, Rifas-Shiman SL, Perng W, Chavarro JE, Taveras E, Oken E, et al. Associations of Childhood Adiposity and Cardiometabolic Biomarkers With Adolescent PCOS. Pediatrics. 2024;153(5):e2023064894. Table Table 1 is available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Table.xlsx SupplementaryTable.xlsx Cite Share Download PDF Status: Published Journal Publication published 20 May, 2025 Read the published version in Reproductive Health → Version 1 posted Editorial decision: Revision requested 13 Mar, 2025 Reviews received at journal 01 Mar, 2025 Reviews received at journal 21 Feb, 2025 Reviewers agreed at journal 08 Feb, 2025 Reviewers agreed at journal 06 Feb, 2025 Reviewers invited by journal 20 Jan, 2025 Editor assigned by journal 14 Jan, 2025 Submission checks completed at journal 14 Jan, 2025 First submitted to journal 13 Jan, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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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-5823228","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":402247613,"identity":"6938a1af-09c6-46c5-bd85-ef66e0288e20","order_by":0,"name":"Tong Lin","email":"","orcid":"","institution":"Fujian Maternity and Child Health Hospital","correspondingAuthor":false,"prefix":"","firstName":"Tong","middleName":"","lastName":"Lin","suffix":""},{"id":402247615,"identity":"8b54788e-3bf1-4ee8-8aae-f29893786475","order_by":1,"name":"Bingqin Xie","email":"","orcid":"","institution":"Fujian Medical University","correspondingAuthor":false,"prefix":"","firstName":"Bingqin","middleName":"","lastName":"Xie","suffix":""},{"id":402247617,"identity":"95557cb5-91c8-433c-9540-dca1f53e5566","order_by":2,"name":"Juan Yang","email":"","orcid":"","institution":"Fujian Maternity and Child Health Hospital","correspondingAuthor":false,"prefix":"","firstName":"Juan","middleName":"","lastName":"Yang","suffix":""},{"id":402247618,"identity":"ae1cc021-cfd1-4972-9322-9899d446503c","order_by":3,"name":"Jinbang Xu","email":"","orcid":"","institution":"Fujian Maternity and Child Health Hospital","correspondingAuthor":false,"prefix":"","firstName":"Jinbang","middleName":"","lastName":"Xu","suffix":""},{"id":402247620,"identity":"9da4a325-566a-4ade-8d5b-d93c4c30a100","order_by":4,"name":"Fa Chen","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAsUlEQVRIiWNgGAWjYDACCSCuYLCBs4nUcoYhjXQth0nQwj+7+diDAzXnow0OMB+8zcNgl0fYkjvH0g0OHLudu+EAW7I1D0NyMUEtBhI5ZtIf2EBaeMykeRgOJDYQ1pL/TeLAv3NALfzfiNWSwyZxsO0AyBY24rRI3EgzkzjYl5w78zCbseUcg2TCWvhnJD+TOPDNLrfvePPDG28q7AhrQQBmsDuJVz8KRsEoGAWjAA8AAEkUPTQnjyKGAAAAAElFTkSuQmCC","orcid":"","institution":"Fujian Medical University","correspondingAuthor":true,"prefix":"","firstName":"Fa","middleName":"","lastName":"Chen","suffix":""}],"badges":[],"createdAt":"2025-01-14 01:53:26","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5823228/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5823228/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12978-025-02016-y","type":"published","date":"2025-05-20T15:57:02+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":74076514,"identity":"cbb7336c-3dcb-40a7-8aa0-45e0edc398a8","added_by":"auto","created_at":"2025-01-17 13:41:34","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":863183,"visible":true,"origin":"","legend":"\u003cp\u003eBurden of PCOS from 1990 to 2021.(A) Numbers from 1990 to 2021.(B) Age-standardized rate from 1990 to 2021(generated from data available from http://ghdx.healthdata.org/gbd-results-tool).DALYs, disability-adjusted life years.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-5823228/v1/73273e50a6ac8b505df8a96b.png"},{"id":74076520,"identity":"a2d15771-7472-4cec-a96a-86e9caca0c0b","added_by":"auto","created_at":"2025-01-17 13:41:35","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":12098259,"visible":true,"origin":"","legend":"\u003cp\u003eAge-standardized burden of PCOS in 2021, by 204 countries and territories.(A) World map of ASIR for PCOS.(B) World map of ASPR for PCOS.(C) World map of ASDR for PCOS (generated from data available from http://ghdx.healthdata.org/gbd-results-tool).DALYs, disability-adjusted life years; ASIR, age-standardized incidence rate; ASPR, age-standardized prevalence rate; ASDR, age-standardized rate of DALYs.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-5823228/v1/7d4ad98dd89f45254e60ad0d.png"},{"id":74076518,"identity":"6f37f968-aad7-4dbd-b868-84a5b09b7c84","added_by":"auto","created_at":"2025-01-17 13:41:34","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":4546858,"visible":true,"origin":"","legend":"\u003cp\u003eAge-standardized burden of PCOS for the 21 Global Burden of Disease regions by socio-demographic index, 1990-2021.(A) ASIR for 21 GBD regions.(B) ASPR for 21 GBD regions.(C) ASDR for 21 GBD regions (generated from data available from http://ghdx.healthdata.org/gbd-results-tool).DALYs, disability-adjusted life years; ASIR, age-standardized incidence rate; ASPR, age-standardized prevalence rate; ASDR, age-standardized rate of DALYs.\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-5823228/v1/70aa448d31a3094e12a6e668.png"},{"id":74076521,"identity":"938c767e-19aa-4895-aef7-1f2733163e0f","added_by":"auto","created_at":"2025-01-17 13:41:35","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":1235658,"visible":true,"origin":"","legend":"\u003cp\u003eAge-standardized burden of PCOS in 2021, by age pattern(generated from data available from http://ghdx.healthdata.org/gbd-results-tool).\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-5823228/v1/b4b0d9ddfd1c1bbc332bd908.png"},{"id":83459957,"identity":"b02ea99d-6d02-480f-bbaa-95d070687b3e","added_by":"auto","created_at":"2025-05-26 16:05:59","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":17375939,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5823228/v1/9d795518-aa81-49fa-9299-a08dcd4b1248.pdf"},{"id":74076513,"identity":"b8cc2ad5-01e6-4e60-b7a8-97d96573dedf","added_by":"auto","created_at":"2025-01-17 13:41:34","extension":"xlsx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":25410,"visible":true,"origin":"","legend":"","description":"","filename":"Table.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-5823228/v1/3afa06a9b5f9b062a0eeea34.xlsx"},{"id":74076512,"identity":"ddef6ae3-6443-4444-b012-e30a98294e48","added_by":"auto","created_at":"2025-01-17 13:41:34","extension":"xlsx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":105130,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryTable.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-5823228/v1/3c4e74b6b065349340d5e2a5.xlsx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Changes in the global burden of polycystic ovary syndrome from 1990 to 2021","fulltext":[{"header":"1 Introduction","content":"\u003cp\u003ePolycystic ovary syndrome (PCOS), a common hormonal condition affecting women of reproductive age, exhibits a prevalence range from 8\u0026ndash;13%(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Increasing evidence has revealed PCOS to be a complex, heterogeneous, and lifelong condition that strongly associates with epigenetic and environmental variables(\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Importantly, PCOS is the most common cause of anovulatory infertility(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Apart from adversely affecting female reproductive function, PCOS also increases the risk of various comorbidities, such as obesity, insulin resistance, diabetes, and cardiovascular disease, thus exacerbating global health and economic burdens(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eScreening and health management needs of PCOS patients remain unmet. The reproductive-related effects of PCOS include an increased risk of irregular menstrual cycles, anovulatory infertility, pregnancy complications(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e), and endometrial cancer(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Furthermore, PCOS associates with anxiety, depression, eating disorders, psychosexual disorders, and negative body image perception(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e), all of which impact quality of life. Clinical management of PCOS is no longer limited to promotion of ovulatory regularity and pregnancy; increasing focus has been placed on the importance of glycolipid metabolism and complication management in this patient population(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e), highlighting a need for studies to accurately characterize PCOS disease burden.\u003c/p\u003e \u003cp\u003eImportantly, a comprehensive understanding of PCOS disease burden would provide a more solid rationale for developing future women's health plans and better accommodating needs of PCOS patients, thereby assisting high-burden countries strengthen PCOS screening and management operations to achieve early detection, diagnosis, and treatment goals.\u003c/p\u003e \u003cp\u003eThe accuracy of PCOS global prevalence and incidence data previously reported has often been inconsistent due to discrepancies in research methodologies, regional differences and shifting diagnostic criteria(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). The Global Burden of Disease (GBD) database is a comprehensive database organized by the Global Health Research Institute to assess and analyze the health impact of diseases, injuries, and risk factors globally and regionally. To facilitate comprehensive assessment, the GBD divides the world into 21 regions and 204 countries and territories. The Socio-demographic Index (SDI) is used to link developmental status to health outcomes, while disability-adjusted life years (DALYs), the sum of years lost due to premature death and years survived due to disability, are used to denote years of healthy life lost. Although recent GBD studies reviewed PCOS burden(\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e), detailed quantitative estimates of PCOS incidence, prevalence, and associated DALYs in 2021 have not been published. Here, we explored the impact of the COVID-19 pandemic on global PCOS burden; this would not have been possible considering only pre-2020 data. We furthermore assessed global, regional and national PCOS burdens among women 15\u0026ndash;49 years old in 21 regions and 204 countries and territories from 1990 to 2021 via analysis of GBD 2021 data to highlight incidence, prevalence, and DALYs relevant to this patient population and facilitate more effective future formulation of policy, resource allocation, and health system planning.\u003c/p\u003e"},{"header":"2 Materials and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Overview\u003c/h2\u003e \u003cp\u003ePCOS data were obtained from GBD 2021 using the Global Health Data Exchange website (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://ghdx.healthdata.org\u003c/span\u003e\u003cspan address=\"http://ghdx.healthdata.org\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e). The database systematically compiles the health burden of 369 conditions from 1990 to 2021 and includes samples obtained from 204 countries and territories. Relevant methods for estimating incidence, prevalence and DALY rates have been previously detailed(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). This study was conducted in accordance with the 1975 Declaration of Helsinki. As this study evaluated publicly available datasets, ethical committee approval was not required. Informed consent was waived as GBD 2021 compiled de-identified pooled data.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Case definitions and data sources\u003c/h2\u003e \u003cp\u003eCollectively, PCOS is characterized by androgenesis, anovulation and polycystic ovarian morphology(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). The reference definition of PCOS was standardized in GBD 2021 and is based on the definition set forth by the American College of Obstetricians and Gynecologists, where the diagnosis may be established using any of the three accepted methods (i.e. NIH, Rotterdam or AE-PCOS) (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Data processing and presentation\u003c/h2\u003e \u003cp\u003eJoint point regression was used to assess temporal trends and annual percentage changes for PCOS incidence, prevalence, and rates of DALYs from 1990 to 2021. Data were analyzed according to 204 countries, 5 SDI regions, 21 GBD regions, and different age groups. Correlation among SDI and incidence, prevalence, and rates of DALYs in 2021 was also determined.\u003c/p\u003e \u003cp\u003eThe SDI was assessed based on total fertility rate for females younger than 25 years of age, educational attainment of females aged 15 years and older, as well as per capita lagged distribution income. The 204 geographical regions were categorized into five groups based on SDI: low; medium-low; medium; medium-high; and high SDI. Based on GBD classification, women of childbearing age were categorized as 15\u0026ndash;19, 20\u0026ndash;24, 25\u0026ndash;29, 30\u0026ndash;34, 35\u0026ndash;39, 40\u0026ndash;44, or 45\u0026ndash;49 years old.\u003c/p\u003e \u003cp\u003eEach estimate was calculated 1000 times in GBD 2021; final data were presented as a mean of these estimates. A 95% uncertainty interval (95% UI) was calculated for each analysis, determined using 25th and 97.5th values of a set of ordered 1000 extractions. A two-sided P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant. Data were downloaded from the GBD website and Excel software (Microsoft, USA) was used for descriptive analysis. Other statistical analyses were performed using R version 4.4.1 (The R Foundation, Austria).\u003c/p\u003e \u003c/div\u003e"},{"header":"3 Results","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e3.1 Global burden\u003c/h2\u003e \u003cp\u003eIn 2021, there were 2.3\u0026nbsp;million new cases of PCOS at an age-standardized rate of 30.7 per 100,000, an increase of 26.77% since 1990 (Table\u0026nbsp;1; Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). In 2021, there were 69.47\u0026nbsp;million prevalent cases of PCOS globally at an age-standardized rate of 867.7 per 100,000 women, an increase of 28.21% since 1990 (Table\u0026nbsp;1; Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). In 2021, the total number of PCOS-associated DALYs was 610,000 at an age-standardized rate of 7.6 cases per 100,000 women, an increase of 27.58% since 1990 (Table\u0026nbsp;1; Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e3.2 Regional burdens\u003c/h2\u003e \u003cp\u003eIn 2021, the high-income Asia Pacific [109.2 (95% UI: 77.9-153.9)], Australasia [98.2 (95% UI: 70.4-135.4)], and Western Europe [75.2 (95%UI: 53.1\u0026ndash;105)] regions had the greatest age-standardized PCOS incidence rates. In contrast, the regions of Central Europe [4.3 (95% UI: 3-6.1)], Eastern Europe [5.3 (95% UI: 3.7\u0026ndash;7.5)], and Central Asia [9.1 (95% UI: 6.3\u0026ndash;12.7)] had the lowest age-standardized PCOS incidence rates (Table\u0026nbsp;1). In 2021, the age-standardized PCOS prevalence rates were greatest in the high-income Asia Pacific [2544.9 (95% UI: 1836.1-3551.3)], Australasia [2387 (95% UI: 1708.4-3297.5)], and Western Europe [1944.3 (95% UI: 1361.7-2726.7)] regions. Conversely, the regions of Central Europe [111.7 (95% UI: 77-159.2)], Eastern Europe [132.4 (95% UI: 91.2-190.5)], and Central Asia [240.5 (95% UI: 164.6-337.3)] exhibited the lowest age-standardized PCOS prevalence rates (Table\u0026nbsp;1). In 2021, the high-income Asia Pacific [22.2 (95% UI: 10.1\u0026ndash;45.2)], Australasia [20.8 (95% UI: 9.3\u0026ndash;43.0)] and Western Europe [17.3 (95% UI: 7.8\u0026ndash;35.9)] regions had the greatest age-standardized DALYs rates for PCOS, while those of Central Europe [ 1 (95% UI: 0.4-2)], Eastern Europe [ 1.2 (95% UI: 0.5\u0026ndash;2.5)], and Central Asia [2.1 (95% UI: 0.9\u0026ndash;4.5)] had the lowest (Table\u0026nbsp;1).\u003c/p\u003e \u003cp\u003eThe greatest increases in the rates of age-standardized incidence and prevalence of PCOS from 1990 to 2021 were found in Southeast Asia [incidence: 82.8% (95% UI: 69.3-97.25); prevalence: 81.61% (95% UI: 68.92\u0026ndash;94.86)], East Asia [incidence: 75.02% (95% UI: 62.37\u0026ndash;86.34); prevalence: 81.5% (95% UI: 70.23\u0026ndash;93.05)], and South Asia [incidence: 66.10% (95% UI: 56.5-77.13); prevalence: 80.44% (95% UI: 69.61\u0026ndash;94.73)], with no regional declines through this time period (Table\u0026nbsp;1). In addition, the regions with the largest increases in age-standardized DALY rates for PCOS from 1990 to 2021 were East Asia [82.86% (95% UI: 71.06\u0026ndash;94.3)], Southeast Asia [80.53% (95% UI: 68.47\u0026ndash;93.64)], and South Asia [78.54% (95% UI: 67.27\u0026ndash;91.55)], with no regional declines through this time period (Table\u0026nbsp;1).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e3.3 National burden\u003c/h2\u003e \u003cp\u003eAt the national level, the countries with the greatest age-standardized incidence rates for PCOS in 2021 were Italy [158 (95% UI: 110.1-222.2)], Japan [129.5 (95% UI: 92.2-182.4)], and New Zealand [114.6 (95% UI: 81.2-158.4 )]; those with the lowest rates were Albania [3.7 (95% UI: 2.5\u0026ndash;5.4)], Serbia [3.7 (95% UI: 2.5\u0026ndash;5.3)], and Bosnia and Herzegovina [3.7 (95% UI: 2.5\u0026ndash;5.4)]. The percentage change for age-standardized PCOS incidence rates from 1990 to 2021 varied widely between countries, with the Maldives [125.23% (95% UI: 94.68-161.28)], Myanmar [104.11% (95% UI: 78.02-133.16)], and Vietnam [95.03% (95% UI: 70.01-118.06)] exhibiting the largest increases; Italy [\u0026minus;\u0026thinsp;10.53% (95% UI: \u0026minus;17.1-\u0026minus;5.29)], Mexico [\u0026minus;\u0026thinsp;1.93% (95% UI: \u0026minus;7.84\u0026ndash;2.72)], and New Zealand [\u0026minus;\u0026thinsp;1.39% (95% UI: \u0026minus;14.34\u0026ndash;10.98)] exhibited negative trends (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e; Supplementary Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eIn 2021, the age-standardized prevalence rates of PCOS ranged from 93.1 to 3978.9 cases per 100,000 women among different countries. Countries with the greatest prevalence rates were Italy [3978.9 (95% UI: 2823.1-5523.3)], Japan [3104.7 (95% UI: 2244.2-4312.7)], and New Zealand [2789.7 (95% UI: 2008.7-3805.9)]; those with the lowest were Albania [93.1 (95% UI: 61.5-141.7)], Bosnia and Herzegovina [94 (95% UI: 61.5-144.2)], and North Macedonia [94.6 (95% UI: 61.6-144.2)]. The variance in age-standardized PCOS prevalence exhibited a notable contrast from 1990 to 2021. The largest increases were in Myanmar [108.01% (95% UI: 80.46-137.42)], Equatorial Guinea [97.11% (95% UI: 73.89-133.94)] and Thailand [96.44% (95% UI: 73.39\u0026ndash;123)]; negative trends were noted in Italy [\u0026minus;\u0026thinsp;6.52% (95% UI: \u0026minus;13.08-\u0026minus;1.05)] and New Zealand [\u0026minus;\u0026thinsp;0.82% (95% UI: \u0026minus;13.79-\u0026minus;10.35)] (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e; Supplementary Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn 2021, the greatest age-standardized PCOS DALYs rates were in Italy [35.1 (95% UI: 15.8\u0026ndash;74.9)], Japan [27 (95% UI: 12.3\u0026ndash;54.9)], and New Zealand [24.3 (95% UI: 11.1\u0026ndash;50.6)]; Bosnia and Herzegovina [0.8 (95% UI: 0.3\u0026ndash;1.8)], North Macedonia [0.8 (95% UI: 0.4\u0026ndash;1.7)], and Albania [0.8 (95% UI: 0.3\u0026ndash;1.8)] had the lowest rates. The percentage change for age-standardized PCOS DALY rates from 1990 to 2021 similarly varied by country. The largest increases were in Myanmar [108.27% (95% UI: 81.45-138.62)], Equatorial Guinea [97.49% (95% UI: 70.58-141.74)], and Thailand [92.4% (95% UI: 68.81-121.15)]; Italy [\u0026minus;\u0026thinsp;5.69% (95% UI: \u0026minus;12.63\u0026thinsp;\u0026minus;\u0026thinsp;0.36)], New Zealand [\u0026minus;\u0026thinsp;0.74% (95% UI: \u0026minus;12.75\u0026ndash;10.31)], and Mexico [\u0026minus;\u0026thinsp;0.73% (95% UI: \u0026minus;6.76\u0026ndash;5.12)] exhibited negative trends (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e; Supplementary Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e3.4 PCOS burden by SDI\u003c/h2\u003e \u003cp\u003eIn 2021, high SDI regions exhibited the greatest age-standardized incidence [70.2 (95% UI: 52-95.3)], prevalence [1720.7 (95% UI: 1270.5-2331.7)], and mortality [15.2 (95% UI: 7\u0026ndash;31)] rates for PCOS, while low SDI regions exhibited the lowest age-standardized incidence [13.8 (95% UI: 9.8\u0026ndash;19.3)], prevalence [361.6 (95% UI: 255.3-509.8)], and mortality [3.1 (95% UI: 1.4\u0026ndash;6.6)] rates for PCOS. Increasing trends were noted in all regions (Table\u0026nbsp;1).\u003c/p\u003e \u003cp\u003eAt the district level, a nonlinear association between SDI and age-standardized incidence, prevalence, and DALY rates for PCOS from 1990 to 2021 were noted, with age-standardized rates greatest at an SDI of approximately 0.9, indicating that a higher SDI associated with greater age-standardized incidence, prevalence, and DALY rates for PCOS (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e3.5 Age patterns\u003c/h2\u003e \u003cp\u003eIn 2021, the greatest rate of age-standardized incidence for PCOS was observed in the 15\u0026ndash;19 age group [169.3 (95% UI: 105.6-263.2)]; the lowest was observed in the 45\u0026ndash;49 age group [0.7 (95% UI: 0.1\u0026ndash;1.4)]. In 2021, the 40\u0026ndash;44 age group [1828.5 (95% UI: 1308.3-2540.1)] had the highest age-standardized prevalence, while the 15\u0026ndash;19 age group [1228.1 (95% UI: 830.7-1758.4)] had the lowest. In 2021, the highest rate of age-standardized DALYs was in the 25\u0026ndash;29 age group [15.9 (95% UI: 7-32.6)], while the lowest was in the 15\u0026ndash;19 age group [11 (95% UI: 4.9\u0026ndash;23.4)] (Table\u0026nbsp;1, Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe greatest increase in PCOS age-standardized incidence from 1990 to 2021 was in the 15\u0026ndash;19 age group [25.63% (95% UI: 20.76\u0026ndash;30.03)]; the smallest increase was in the 20\u0026ndash;24 age group [\u0026minus;\u0026thinsp;0.99% (95% UI: \u0026minus;6.32\u0026ndash;4.79)]. In addition, the age group with the largest increase in rates of age-standardized prevalence and DALYs for PCOS from 1990 to 2021 was the 20\u0026ndash;24 age group [prevalence: 31.7% (95% UI: 28.1\u0026ndash;35.5); DALYs: 31.07% (95% UI: 26.69\u0026ndash;35.33)]; the 40\u0026ndash;44 age group exhibited the smallest increase [prevalence: 22.82% (95% UI: 19.43\u0026ndash;26.14); DALYs: 22.31% (95% UI: 18.59\u0026ndash;25.58)] (Table\u0026nbsp;1, Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e"},{"header":"4 Discussion","content":"\u003cp\u003eThis study presents a thorough and updated analysis of PCOS prevalence on global, regional, and national scales spanning more than three decades. In 2021, the worldwide incidence, prevalence, and associated DALY rates for PCOS stood at 2.3\u0026nbsp;million, 69.47\u0026nbsp;million, and 610,000, respectively. The global age-standardized incidence, prevalence, and DALY rates exhibited an increase from 1990 to 2021 by 26.77%, 28.21%, and 27.58%, respectively.\u003c/p\u003e \u003cp\u003eOur findings underscore the increasing prevalence of PCOS on global, regional, and national scales, revealing notable variations across different age groups and SDI regions. The highest prevalence of PCOS was observed in high SDI regions, contrasting with lower rates in regions with low SDI. The high-income Asia Pacific exhibited the greatest age-standardized prevalence rates, whereas Central Europe exhibited the lowest. Italy exhibited the greatest disease burden for PCOS in 2021, and there has indeed been a concerning upward trend in disease burden in Italy over the past 32 years. Importantly, from 1990 to 2021, the incidence, prevalence, and DALY rates for PCOS exhibited a marked increase across most age brackets, but particularly among the younger population.\u003c/p\u003e \u003cp\u003eThe marked increase in global PCOS prevalence from 1990 to 2021 is a concerning trend that necessitates further study. Various factors likely contributed to this increase, including changes in the diagnostic criteria for this condition. The 1990 National Institutes of Health (NIH) criteria established the initial formal diagnostic guidelines for clinically identifying PCOS, mandating the presence of oligoovulation and hyperandrogenism. The introduction of the 2003 Rotterdam criteria(\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e) broadened diagnostic possibilities by incorporating polycystic ovarian morphology (PCOM) as a necessary characteristic while requiring the presence of 2 out of 3 criteria for PCOS diagnosis (i.e. irregular or absent ovulation; clinical or biochemical signs of hyperandrogenism; evidence of PCOM on ultrasound exam). As of 2018, collaboration among an Australian academic group, the American Society for Reproductive Medicine (ASRM), and the European Society of Human Reproduction and Embryology (ESHRE)(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) has advocated for continued clinical use of the 2003 Rotterdam criteria for diagnosis of adult patients, emphasizing a progressive approach based on clinical symptoms. Expanded diagnostic criteria and enhanced imaging capabilities have led to a substantial increase in PCOS diagnosis among women of reproductive age, rising from a range of 4%-8\u0026ndash;21%(\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). Importantly, PCOS is recognized as a heritable condition, yet also multifactorial in etiology(\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). Emerging evidence suggests that susceptibility to PCOS is influenced not solely by genetic factors but also epigenetic modifications and developmental influences(\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e); such variables have likely contributed to the escalating prevalence of PCOS. Furthermore, environmental factors are understood to have contributed to the increase in PCOS incidence. Environmental exposure to perfluoroalkyl substances (PFAS), polyfluoroalkyl substances (PFAS)(\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e), and toxic metals (Pb, Hg, As, Ba, and Cd)(\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e) was reported to increase risk of developing PCOS.\u003c/p\u003e \u003cp\u003eThe SDI of a region closely associates with population social development status and health outcomes for a given population. This parameter also serves as a composite measure, reflecting a delayed distribution of per capita income, average years of schooling, and total fertility rate among individuals less than 25 years old. Our findings reveal significant regional variations in the prevalence of PCOS, with the greatest standardized incidence, prevalence, and DALY rates noted in high SDI regions and lowest in low SDI regions, consistent with prior studies(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Within ethnically homogeneous PCOS patient groups, a correlation was noted between higher socioeconomic status and an increased prevalence of PCOS characterized by altered ovulatory patterns. Furthermore, differences in insulin levels and fat distribution across social strata were linked to ovulatory status(\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe 2021 PCOS burden exhibited significant variation across geographic regions evaluated in the GBD 2021 study. The high-income Asia Pacific region exhibited the greatest age-standardized rates of PCOS, whereas Central Europe exhibited the lowest. An earlier meta-analysis(\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e) revealed varying accuracy in ultrasound diagnosis of PCOS among Asian, European, and North American studies, suggesting differences in age, BMI, and diagnostic criteria clinically utilized in these regions.\u003c/p\u003e \u003cp\u003eAlthough Italy carried the greatest PCOS disease burden in 2021, the disease burden decreased in the country over the past 32 years. The risk of diabetes for women with PCOS was found to resemble that of individuals otherwise at high risk for diabetes(\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). A study in Sicily(\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e) revealed the prevalence rates of obesity, metabolic syndrome, diabetes mellitus, dysglycemia, and dyslipidemia to be 6.6%, 6.6%, 2.1%, 13.1%, and 60%, respectively. Furthermore, certain intronic variants of the NR3C1 gene (rs10482672 and rs11749561)(\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e) as well as a history of growth hormone deficiency(\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e) have been linked to increased PCOS prevalence. Interestingly, our findings noted a marked decline in PCOS disease burden in Italy. Italy's health system, ranked second in the World Health Report 2000, as well as its efficiency (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e) and greater adherence to the Mediterranean diet among the populace(\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e), likely play crucial roles in mitigating Italy\u0026rsquo;s national PCOS disease burden.\u003c/p\u003e \u003cp\u003eHere, we found increases in incidence, prevalence, and DALY rates for PCOS from 1990 to 2021 across various patient age groups, with the greatest increase among individuals aged 15\u0026ndash;19 years. These findings align with those recently reported in an American study(\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e). The challenges associated with diagnosing PCOS during adolescence stem from the overlap of diagnostic criteria with physiological changes seen in young individuals(\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e). The updated International Evidence-Based Guidelines for PCOS Evaluation and Management have been instrumental in enhancing diagnostic precision and reducing instances of erroneous diagnosis(\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e). Importantly, obesity is prevalent among PCOS patients, with over 21.9% of adolescent PCOS cases also exhibiting dysglycemia(\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e). Research has indicated that childhood obesity and adipose tissue dysfunction serve as early indicators of PCOS risk in later life(\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e). Furthermore, the increased prevalence of obesity and abnormal glucose metabolism contribute to a diagnosis of early onset PCOS.\u003c/p\u003e \u003cp\u003eIn this study, we analyzed a comprehensive dataset spanning 32 years as well as various facets of relevant to global, regional, and national impact of PCOS on patient groups. Nevertheless, this study was not without limitations. Firstly, data on PCOS risk factors were unavailable, and our analysis predominantly focused on describing trends relevant to PCOS burden rather than elucidation of potential causative factors for the condition. Secondly, discrepancies in data quality and accessibility related to PCOS burden were likely due to economic disparities, health expenditure variations, care standards, and health policies, potentially impacting the accuracy of our findings. Thirdly, the dynamic nature of PCOS diagnostic criteria may have introduced inconsistencies in determining PCOS prevalence rates(\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). Finally, in developed nations with robust healthcare infrastructures and higher healthcare-seeking tendencies among patients, detection bias may have inflated PCOS incidence and prevalence rates. As such, future research should concentrate on pinpointing more specific risk factors and elucidating pathophysiological mechanisms contributing to observed variances in PCOS burden across diverse populations and age groups.\u003c/p\u003e"},{"header":"5 Conclusion","content":"\u003cp\u003eOur findings highlight the growing impact of PCOS on a worldwide scale, underscoring an urgent need for concerted efforts to alleviate the global prevalence of this condition. Varying disease burdens of PCOS were observed across different age groups and SDI regions, with high SDI regions bearing heavier disease burdens. The increased burdens in younger patients as well as wide regional disparities highlight the need for effective interventions and policies to combat this burgeoning public health challenge.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAUTHOR CONTRIBUTIONS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTL conceptualised and supervised the study, and drafted the article. BX contributed data curation and formal analysis, and drafted the article. JY reviewed and revised the article. FC and JX conceptualised and supervised the study, and reviewed and revised the article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eACKNOWLEDGEMENTS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to thank the Institute for Health Metrics and Evaluation staff and its collaborators who prepared these publicly available data. Also, we would like to acknowledge the support of the Department of Epidemiology and Health Statistics at the Fujian Medical University, Fuzhou, China.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFUNDING INFORMATION\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by grants from Fujian Provincial Natural Science Foundation of China（Grant no.2022QNA054）, National Nature Science Foundation of China (Grant no. 82074542), Joint Funds for the innovation of Science and Technology, Fujian province (Grant no.2020Y94020265), and Fujian provincial health technology project (Grant no.2023ZQNZD01010013).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCONFLICT OF INTEREST STATEMENT\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003c/strong\u003eThe authors report no conflicts of interest.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eTeede HJ, Misso ML, Costello MF, Dokras A, Laven J, Moran L, et al. 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Practical considerations for diagnosis and treatment of polycystic ovary syndrome in adolescence - distilling guidelines into clinical practice. Current opinion in pediatrics. 2023;35(4):494-9.\u003c/li\u003e\n\u003cli\u003ePe\u0026ntilde;a AS, Witchel SF, Hoeger KM, Oberfield SE, Vogiatzi MG, Misso M, et al. Adolescent polycystic ovary syndrome according to the international evidence-based guideline. BMC medicine. 2020;18(1):72.\u003c/li\u003e\n\u003cli\u003eTay CT, Hart RJ, Hickey M, Moran LJ, Earnest A, Doherty DA, et al. Updated adolescent diagnostic criteria for polycystic ovary syndrome: impact on prevalence and longitudinal body mass index trajectories from birth to adulthood. BMC medicine. 2020;18(1):389.\u003c/li\u003e\n\u003cli\u003eGupta J, Antal Z, Censani M. Prevalence of Impaired Glucose Tolerance in Adolescent Patients with Polycystic Ovary Syndrome in an Urban Health Care Center. Diabetes. 2018;67(Supple 1):722.\u003c/li\u003e\n\u003cli\u003eWhooten RC, Rifas-Shiman SL, Perng W, Chavarro JE, Taveras E, Oken E, et al. Associations of Childhood Adiposity and Cardiometabolic Biomarkers With Adolescent PCOS. Pediatrics. 2024;153(5):e2023064894.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Table","content":"\u003cp\u003eTable 1 is available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"reproductive-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"reph","sideBox":"Learn more about [Reproductive Health](http://reproductive-health-journal.biomedcentral.com)","snPcode":"12978","submissionUrl":"https://submission.nature.com/new-submission/12978/3","title":"Reproductive Health","twitterHandle":"@Reprod_Health","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"polycystic ovary syndrome, global burden of disease, disability-adjusted life years, socio-demographic Index","lastPublishedDoi":"10.21203/rs.3.rs-5823228/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5823228/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBACKGROUND\u003c/h2\u003e \u003cp\u003ePolycystic ovary syndrome (PCOS) is a chronic, multifaceted condition influenced by epigenetic and environmental factors that is responsible for a significant proportion of anovulatory infertility cases. Here, we analyzed the global, regional, and national burdens of PCOS from 1990 to 2021 using data from the Global Burden of Disease 2021 (GBD 2021).\u003c/p\u003e\u003ch2\u003eMETHODS\u003c/h2\u003e \u003cp\u003eIncidence, prevalence, and Disability-Adjusted Life Years(DALYs) data relevant to PCOS from 204 countries and 21 territories from 1990 to 2021 were obtained from the GBD 2021 study. Here, we considered age-standardized rates (per 100,000 individuals) with 95% uncertainty intervals (95% UIs) obtained from the aforementioned research and presented trends based on age and Socio-demographic Index (SDI) parameters.\u003c/p\u003e\u003ch2\u003eRESULTS\u003c/h2\u003e \u003cp\u003eGlobal age-standardized incidence and prevalence of PCOS in 2021 were reported at 30.7 and 867.7 per 100,000, respectively, revealing increases of 26.77% and 28.21%, respectively, since 1990. Additionally, age-standardized disability-adjusted life years stood at 7.6 per 100,000 globally in 2021, marking a 27.58% increase from 1990. Age-standardized prevalence of PCOS varied across countries, ranging from 93.1 to 3978.9 cases per 100,000 women, with Italy (3978.9), Japan (3104.7), and New Zealand (2789.7) having the highest rates. Notably, PCOS prevalence was noted to peak globally among females 15\u0026ndash;19 years of age. Regions with a high SDI exhibited the highest age-standardized incidence (70.2), prevalence (1720.7), and death (15.2) rates of PCOS. Furthermore, a nonlinear correlation between PCOS burden and SDI was noted, with prevalence rates peaking around an SDI of approximately 0.9.\u003c/p\u003e\u003ch2\u003eCONCLUSION\u003c/h2\u003e \u003cp\u003eOur findings highlight the growing global impact of PCOS and underscore the need for concerted efforts to attenuate the increasing global prevalence of this condition. Significantly divergent PCOS disease burdens were observed across different age groups and SDI regions, with high SDI regions bearing heavier burdens. The increased disease burden among younger age groups and regional disparities underscore urgency for targeted intervention and formulation of policies to effectively address this public health issue.\u003c/p\u003e","manuscriptTitle":"Changes in the global burden of polycystic ovary syndrome from 1990 to 2021","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-01-17 13:41:29","doi":"10.21203/rs.3.rs-5823228/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-03-13T07:13:55+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-03-01T12:14:28+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-02-21T15:10:49+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"276015520721370515448086127800712924990","date":"2025-02-09T04:53:21+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"167615249368271979704732210836002100302","date":"2025-02-06T06:58:11+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-01-20T11:17:28+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-01-14T22:11:20+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-01-14T22:10:32+00:00","index":"","fulltext":""},{"type":"submitted","content":"Reproductive Health","date":"2025-01-14T01:44:45+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"reproductive-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"reph","sideBox":"Learn more about [Reproductive Health](http://reproductive-health-journal.biomedcentral.com)","snPcode":"12978","submissionUrl":"https://submission.nature.com/new-submission/12978/3","title":"Reproductive Health","twitterHandle":"@Reprod_Health","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"557adb70-c09e-433e-beeb-cfa94b10027a","owner":[],"postedDate":"January 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-05-26T15:59:27+00:00","versionOfRecord":{"articleIdentity":"rs-5823228","link":"https://doi.org/10.1186/s12978-025-02016-y","journal":{"identity":"reproductive-health","isVorOnly":false,"title":"Reproductive Health"},"publishedOn":"2025-05-20 15:57:02","publishedOnDateReadable":"May 20th, 2025"},"versionCreatedAt":"2025-01-17 13:41:29","video":"","vorDoi":"10.1186/s12978-025-02016-y","vorDoiUrl":"https://doi.org/10.1186/s12978-025-02016-y","workflowStages":[]},"version":"v1","identity":"rs-5823228","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5823228","identity":"rs-5823228","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}