Incidence, prevalence, deaths, and DALYs of diseases of the female reproductive system from 1990 to 2021 across 204 countries: data, with critical re-analysis, from the global burden of disease study

Abstract

Background:

Female reproductive system diseases severely threaten women’s health. This study aims to evaluate the disease burden caused by female reproductive system diseases from 1990 to 2021.

Methods:

We extracted female reproductive system disorder data from the Global Burden of Disease Study 2021. First, we assessed the global and subtype-specific incidence, prevalence, deaths, and disability-adjusted life years (DALYs) in 2021, reported as absolute numbers and age-standardized rates (ASIR, ASPR, ASDR, and AS-DALYs). Temporal trends from 1990 to 2021 were analyzed using linear regression models, with estimated annual percentage change quantifying burden trajectories. Finally, Bayesian hierarchical models were applied to project future disease burden.

Results:

In 2021, global gynecological disease burdens showed distinct patterns. Cervical cancer: 667 426 incident cases (ASIR 7.79) and 296 667 deaths (ASDR 3.44); ovarian cancer: 298 876 cases (ASIR 3.48) with 185 609 deaths (ASDR 2.16); uterine cancer: 473 614 cases (ASIR 5.41) resulting in 97 672 deaths (ASDR 1.14); uterine fibroids: prevalence dominated with 10.1 million cases (ASIR 124.22) but minimal mortality (2078 deaths; ASDR 0.02); female infertility: affected 110.1 million women with 601 134 DALYs. Temporal analysis (1990–2021) revealed rising absolute case numbers alongside stable/declining ASRs for cervical and ovarian cancers. Disease burden peaked in middle-aged and older populations. Different diseases present distinct patterns of geographical distribution. Projections through 2045 forecast continued case count increases for malignancies and fibroids, with ASRs remaining stable for cervical cancer and infertility.

Conclusion:

This study offers a comprehensive and updated evaluation of the global burden of female reproductive system diseases. The findings underscore the pressing need for targeted interventions and policies to address these conditions.

Introduction

Female reproductive system diseases, including cervical cancer, ovarian cancer, uterine cancer, uterine fibroids, and female infertility, persists as a formidable global health challenge, profoundly impacting women’s health, quality of life, and economic stability. Besides, these diseases affect women across various age groups and socioeconomic statuses. A comprehensive understanding of the incidence, prevalence, deaths, and disability-adjusted life years (DALYs) associated with these conditions is paramount for the formulation of effective health policies and interventions.

Cervical cancer stands as a leading cause of cancer-related deaths among women. The incidence and mortality rates of cervical cancer exhibit variable trends across different regions. High-income countries have generally observed declines in these rates due to the implementation of effective screening and treatment programs^[1]. Conversely, low- and middle-income countries (LMICs) continue to grapple with significant challenges, such as limited access to healthcare services and screening programs, which contribute to elevated mortality rates^[2].

Ovarian cancer, another significant reproductive cancer, often presents with nonspecific symptoms and is frequently diagnosed at later stages, resulting in poor survival rates^[3]. The incidence of ovarian cancer has been increasing in numerous countries, particularly in developed regions, with notable disparities in survival outcomes based on the stage at diagnosis and access to treatment^[4].

Uterine cancer, primarily endometrial cancer, is the most common gynecological malignancy in many regions worldwide. The incidence of uterine cancer has risen in recent decades, especially in developed countries, which has been attributed to factors such as obesity, reproductive behaviors, and hormone replacement therapy^[5]. However, mortality rates have generally remained stable or declined owing to advancements in treatment and early detection^[6].

Uterine fibroids, benign tumors of the uterus, are a prevalent condition affecting women of reproductive age, with a significant symptomatic burden and impact on quality of life. The prevalence of uterine fibroids varies widely across populations, with higher rates reported in African American women compared to other ethnic groups^[7]. Management options span from conservative treatment to surgical intervention, with considerable variation in practice patterns globally.

Female infertility, defined as the inability to conceive after 1 year of regular unprotected intercourse, affects a substantial proportion of couples worldwide. The causes of infertility are multifaceted, encompassing both male and female factors, with a significant proportion attributed to unknown or idiopathic causes^[8]. The emotional, psychological, and financial burden of infertility can be profound, particularly in cultures where childbearing is highly valued^[9].

The Global Burden of Disease (GBD) study, an ongoing collaborative endeavor to quantify the health loss from all major diseases, injuries, and risk factors, presents a unique opportunity to assess the burden of diseases affecting the female reproductive system across multiple countries and time points^[10]. By leveraging GBD data, this study aims to address existing knowledge gaps and establish a robust evidence base for policy-making and resource allocation.

In this paper, we present the incidence, prevalence, deaths, and DALYs for cervical cancer, ovarian cancer, uterine cancer, uterine fibroids, and female infertility from 1990 to 2021 across 204 countries. We conduct a critical re-evaluation of the GBD data, examining trends, disparities, and potential drivers of the burden of these diseases. Our findings will contribute to a deeper understanding of the GBD affecting the female reproductive system and inform efforts to alleviate this burden through targeted interventions and policies. The manuscript adhered to the TITAN guidelines^[11].

Methods

Study design and data sources

The present study was designed to conduct a comprehensive analysis of the incidence, prevalence, mortality rates, and DALYs associated with diseases of the female reproductive system, specifically cervical cancer, ovarian cancer, uterine cancer, uterine fibroids, and female infertility, across 204 countries spanning the period from 1990 to 2021. The data utilized in this study were sourced from the GBD 2021^[10], which represents a collaborative and exhaustive endeavor to quantify health loss attributable to diseases, injuries, and risk factors on a global scale. The GBD study adopts a meticulous methodology for the collection, standardization, and analysis of data derived from diverse sources, encompassing vital registration systems, surveillance systems, household surveys, and published scholarly research.

HIGHLIGHTS

• Updated global quantification of incidence, mortality, and DALYs for cervical, ovarian, uterine cancers, fibroids, and infertility.

• Critical disparities revealed: Low-middle sociodemographic index (SDI) regions bear the highest age-standardized rates (ASRs) for cervical cancer and have the highest ASDR and ASDAR for uterine fibrods, while high SDI regions had the highest ASRs for uterine cancer and ovarian cancer.

• Bayesian modeling forecasts rising absolute case counts for all malignancies and fibroids by 2045. While cervical cancer ASDRs are projected to decline, uterine cancer prevalence (ASPR) is projected to surge by >45%, and uterine fibroid ASPR trends continue upwards, especially in low-SDI regions.

• Actionable, Stratified Policy Insights: Provides evidence-based, resource-stratified recommendations.

Data extraction and processing

Data pertaining to the incidence, prevalence, mortality, and DALYs for each disease were extracted from the GBD 2021 database. For cervical cancer, ovarian cancer, and uterine cancer, incidence and mortality data were primarily sourced from cancer registries and population-based cancer incidence and mortality databases. Prevalence estimates for these cancers were derived through the utilization of incidence and survival data. Conversely, for uterine fibroids and female infertility, prevalence data were obtained from population-based surveys, clinical studies, and specialized databases. The DALYs were calculated by summing the years of life lost due to premature mortality and the years lived with disability (YLDs) stemming from these conditions.

Disease definitions and classification

According to the purpose of this study, the definition and classification of female reproductive system diseases were shown in Supplemental Digital Content Table S1, available at, http://links.lww.com/JS9/F236.

Statistical methods

Statistical analyses were conducted using the GBD modeling tools, which utilize a Bayesian meta-regression framework to pool and adjust data for cross-country, cross-time period, and cross-population comparability. Specifically, the DisMod-MR 2.1 software, developed by the Institute for Health Metrics and Evaluation (IHME)^[12], was employed for this purpose. Age-standardization was performed using the GBD world population standard to facilitate comparisons among diverse populations. Additionally, uncertainty intervals (UIs) were computed to quantify the precision of the obtained estimates.

Initially, we reported the incidence, prevalence, deaths, and DALYs related to the female reproductive system, specifically cervical cancer, ovarian cancer, uterine cancer, uterine fibroids, and female infertility, along with their corresponding age-standardized rates (ASRs), for the year 2021. This comprehensive analysis was conducted globally and stratified by subtypes, including sex, age groups, and sociodemographic index (SDI) regions. Subsequently, we examined trends globally and within specified subtypes from 1990 to 2021 to investigate the temporal dynamics of the disease burden over this extended period. To quantify the rate of change in the burden over the study period, we estimated the annual percentage change using a linear regression model. Finally, we employed the Bayesian hierarchical models to forecast the future burden associated with these conditions.

Throughout the analysis, statistical significance was established at a P-value threshold of 0.05. For all computations and analyses, we utilized the R software (version 4.0.2) to construct the database, collate the data, and conduct rigorous statistical tests. Additionally, Joinpoint regression analysis was employed to identify statistically significant inflection points in long-term ASR trends. The analysis was performed using the Joinpoint Regression Program (version 4.9.1.0) provided by the U.S. National Cancer Institute, with the Monte Carlo permutation test to select the optimal number of joinpoints.

Results

The disease burden of the female reproductive system in 2021

In 2021, cervical cancer exhibited an incidence of 667 426 cases (95% UI: 613 030–726 422), with an age-standardized incidence rate (ASIR) of 7.79 cases per 100 000 population (95% UI: 7.16–8.48). The prevalence amounted to 33 845 444 cases (95% UI: 31 083 999–36 972 578), yielding an age-standardized prevalence rate (ASPR) of 39.8 cases per 100 000 population (95% UI: 36.54–43.45). The number of cervical cancer-related deaths was 296 667 (95% UI: 272 059–321 906), corresponding to an age-standardized death rate (ASDR) of 3.44 deaths per 100 000 population (95% UI: 3.16–3.73). Furthermore, cervical cancer resulted in 9 911 653 DALYs (95% UI: 9 053 317–10 798 306), translating to an age-standardized rate of DALYs (ASDAR) of 115.05 per 100 000 population (95% UI: 105.07–125.5) (Supplemental Digital Content Tables S2-S5, available at, http://links.lww.com/JS9/F236).

For ovarian cancer, the incidence was 298 876 cases (95% UI: 270 730–324 501), with an ASIR of 3.48 cases per 100 000 population (95% UI: 3.15–3.78). The prevalence was 12 224 250 cases (95% UI: 11 021 067–13 321 117), yielding an ASPR of 14.28 cases per 100 000 population (95% UI: 12.86–15.58). There were 185 609 ovarian cancer-related deaths (95% UI: 167 962–201 013), corresponding to an ASDR of 2.16 deaths per 100 000 population (95% UI: 1.95–2.34). The disease imposed 5 163 256 DALYs (95% UI: 4 692 423–5 608 304), resulting in an ASDAR of 59.51 per 100 000 population (95% UI: 54.03–64.66) (Supplemental Digital Content Tables S6–S9, available at, http://links.lww.com/JS9/F236).

In the case of uterine cancer, the incidence was 473 614 cases (95% UI: 429 916–513 667), with an ASIR of 5.41 cases per 100 000 population (95% UI: 4.90–5.87). The prevalence amounted to 34 517 500 cases (95% UI: 31 652 573–37 247 792), yielding an ASPR of 39.17 cases per 100 000 population (95% UI: 35.89–42.27). There were 97 672 uterine cancer-related deaths (95% UI: 86 516–108 062), corresponding to an ASDR of 1.14 deaths per 100 000 population (95% UI: 1.01–1.26). The disease imposed 2 562 943 DALYs (95% UI: 2 291 154–2 846 493), resulting in an ASDAR of 29.4 per 100 000 population (95% UI: 26.24–32.64) (Supplemental Digital Content Tables S10–S13, available at, http://links.lww.com/JS9/F236).

For uterine fibroids, the incidence was 10 100 271 cases (95% UI: 7 350 444–13 285 677), with an ASIR of 124.22 cases per 100 000 population (95% UI: 90.78–163.8). The prevalence amounted to 119 544 904 cases (95% UI: 91 228 328–154 944 149), yielding an ASPR of 1418.98 cases per 100 000 population (95% UI: 1081.52–1838.85). There were 2078 uterine fibroids-related deaths (95% UI: 1225–2574), corresponding to an ASDR of 0.02 deaths per 100 000 population (95% UI: 0.01–0.03). The disease imposed 142 885 DALYs (95% UI: 102 183–192 988), resulting in an ASDAR of 1.70 per 100 000 population (95% UI: 1.22–2.30) (Supplemental Digital Content Tables S14–S17, available at, http://links.lww.com/JS9/F236).

Lastly, the prevalence of female infertility was 110 089 459 cases (95% UI: 58 608 815–195 025 585), yielding an ASPR of 1367.36 cases per 100 000 population in 2021. This condition resulted in 601 134 DALYs (95% UI: 213 158–1 468 475), corresponding to an ASDAR of 7.48 per 100 000 population (95% UI: 2.65–18.23) (Supplemental Digital Content Tables S18–S19, Available at, http://links.lww.com/JS9/F236).

The disease burden of the female reproductive system across different age groups and SDI regions

The age-stratified analysis of the female reproductive system in 2021 is presented in Fig. 1, Supplemental Digital Content Figures S1–S4, available at, http://links.lww.com/JS9/F236. In terms of case counts, an initial increase in disease burden with age was observed, followed by a subsequent decrease after reaching a peak. This pattern indicates that the highest disease burden was concentrated among middle-aged and older adults. However, notable differences emerged when examining the ASRs. Specifically, the ASRs for incidence, prevalence, and DALYs peaked among middle-aged and older adults, aligning with the case count trend. Conversely, for the ASDR, the highest values were observed in the elderly population for cervical cancer, ovarian cancer, uterine cancer, and uterine fibroids. For female infertility, the ASDR peaked among middle-aged and older adults (as illustrated in Fig. 1, Supplemental Digital Content Figures S1–S4, available at, http://links.lww.com/JS9/F236, and summarized in Supplemental Digital Content Tables S2–S19, available at, http://links.lww.com/JS9/F236). From 1990 to 2021, the trends observed in most age groups were consistent with those of the overall population for the female reproductive system (as depicted in Fig. 2, Supplemental Digital Content Figures S5–S8, available at, http://links.lww.com/JS9/F236, and detailed in Supplemental Digital Content Tables S2–S19, available at, http://links.lww.com/JS9/F236).

Figure 1.

Numbers and age-standardized rates of cervical cancer-related incidence, prevalence, deaths, and DALYs for different age groups in 2021. DALYs, disability-adjusted life years.

Figure 2.

Trends in the numbers and age-standardized rates of cervical cancer-related incidence, prevalence, deaths, and DALYs globally from 1990 to 2021. DALYs, disability-adjusted-life-years.

To identify the turning points in the temporal trend more precisely, Joinpoint regression analysis was performed on ASIR across all five diseases. Cervical cancer: A significant inflection point occurred around 2006 (postvaccination ASIR decline accelerated; Supplemental Digital Content Figure S9, available at, http://links.lww.com/JS9/F236), aligning with HPV vaccine introduction in high-income countries. Ovarian cancer: A 2010 joinpoint marked slowed ASIR growth (attributed to reduced menopausal hormone therapy [MHT] use and increased oral contraception; Supplemental Digital Content Figure S10, Available at, http://links.lww.com/JS9/F236). Uterine cancer: ASIR shifted from rising to declining around 2015 (following MHT optimization; Supplemental Digital Content Figure S11, available at, http://links.lww.com/JS9/F236). Uterine fibroids: Growth decelerated after 2012 (driven by minimally invasive techniques and selective progesterone receptor modulators adoption in high-income countries; Supplemental Digital Content Figure S12, available at, http://links.lww.com/JS9/F236). Female infertility: ASIR plateaued post-2005 (potentially reflecting assisted reproductive technology (ART) advancements in high-income countries; Supplemental Digital Content Figure S13, available at, http://links.lww.com/JS9/F236).

When considering cervical cancer, regions with low SDI exhibited the highest ASRs, while those with middle SDI had the highest number of cases. In the case of ovarian cancer, the highest ASRs were observed in high SDI regions, whereas middle SDI regions reported the highest number of cases. For uterine cancer, both the highest ASRs and the greatest number of cases were found in high SDI regions. Regarding uterine fibroids, low-to-middle SDI regions demonstrated the highest ASIR and ASDR, high SDI regions showed the highest ASPR, and low SDI regions had the highest ASDR and ASDAR. Furthermore, middle SDI regions reported the highest number of incidence and prevalence cases, while low-to-middle SDI regions noted the highest number of deaths and DALYs cases. For female infertility, high-to-middle SDI regions exhibited the highest ASRs, and middle SDI regions had the highest number of cases (as shown in Fig. 3, Supplemental Digital Content Figures S14–S17, available at, http://links.lww.com/JS9/F236, and summarized in Supplemental Digital Content Tables S2–S19, available at, http://links.lww.com/JS9/F236). The trend in the number of cases related to the female reproductive system across all SDI regions mirrored that of the overall population. However, some variation was observed in the trends of the ASRs (as depicted in Fig. 4, Supplemental Digital Content Figures S18–S21, available at, http://links.lww.com/JS9/F236, and detailed in Supplemental Digital Content Tables S2–S19, available at, http://links.lww.com/JS9/F236).

Figure 3.

Numbers and age-standardized rates of cervical cancer-related incidence, prevalence, deaths, and DALYs for different SDI regions in 2021. DALYs, disability-adjusted life years.

Figure 4.

Trends in the numbers and age-standardized rates of cervical cancer-related incidence, prevalence, deaths, and DALYs globally by SDI regions from 1990 to 2021. DALYs, disability-adjusted-life-years; SDI, socio-demographic index.

To provide a more detailed spatial perspective, we present country-level heatmaps depicting incidence, mortality, and DALYs rates for female reproductive system diseases (Fig. 5). These maps highlight the heterogeneity within SDI groups and enable identification of specific high-burden countries, complementing the SDI-based analyses.

Figure 5.

Country-level heatmaps of disease burden for female reproductive system diseases in 2021. (A) Age-standardized death rate (ASDR) per 100 000 population, indicating country-specific mortality burden. (B) Age-standardized disability-adjusted life years rate (ASDAR) per 100 000 population, representing overall health loss due to morbidity and mortality. (C) Age-standardized years lived with disability rate (YLDs) per 100 000 population, reflecting the nonfatal health burden.

Temporal trend for the female reproductive system-related disease burden from 1990 to 2021

For cervical cancer, the ASRs exhibited a decreasing trend, with the exception of the ASPR over the period from 1990 to 2021. In terms of case counts, all demonstrated an increasing trend. In the case of ovarian cancer, both the case counts and the corresponding ASRs showed an increasing trend. However, when considered independently, the ASRs indicated a decreasing pattern. For uterine cancer, the number of cases continued to rise. Regarding the ASRs, the ASIR and ASPR increased, whereas the ASDR and ASDAR decreased. In the context of uterine fibroids, the trends observed in both case counts and ASRs mirrored those seen in uterine cancer. For female infertility, both the number of deaths and DALYs, as well as their corresponding ASRs, exhibited an increasing trend (Fig. 6, Supplemental Digital Content Figures S22–S25, Available at, http://links.lww.com/JS9/F236, and Supplemental Digital Content Tables S2–S19, Available at, http://links.lww.com/JS9/F236).

Figure 6.

Trends in the numbers and age-standardized rates of cervical cancer-related incidence, prevalence, deaths, and DALYs globally by age groups from 1990 to 2021. DALYs, disability-adjusted-life-years.

The predicted results from 2021 to 2045

We employed the Bayesian hierarchical models to forecast the future burden associated with the diseases of the female reproductive system. For cervical cancer (Fig. 7) in 2021, the median ASDR in low-SDI regions was 2.9 times the rate in high-SDI regions (8.2 vs. 2.8 per 100 000; 95% CI: 2.4–3.4). Forecasts to 2045 indicate a 28% drop in high-SDI ASDR but only a 10% drop in low-SDI. Ovarian cancer (Supplemental Digital Content Figure S26, available at, http://links.lww.com/JS9/F236): global AS-DALYs levelled off after 2015 yet remained 1.6 times higher in middle-SDI regions (11.1 vs. 6.9 per 100 000). High-SDI DALYs are forecast to fall 7% by 2045, with little change elsewhere. Uterine cancer (Supplemental Digital Content Figure S27, available at, http://links.lww.com/JS9/F236): ASPR rose fastest in high-SDI regions (mean trend + 1.9% per year; 95% CI + 1.4 % to + 2.3%) and is projected to increase by more than 45% across all strata by 2045. Uterine fibroids (Supplemental Digital Content Figure S28, available at, http://links.lww.com/JS9/F236): ASPR climbed in every SDI group; the steepest slope was in low-SDI (+2.4% per year; 95% CI + 1.8% to + 3.0%). Upward trends continue through 2045. Female infertility (Supplemental Digital Content Figure S29, available at, http://links.lww.com/JS9/F236): ASIR was flat (median change: –0.3% per year; 95% CI: −0.8% to + 0.2%) but DALYs increased modestly, reflecting population growth. Model diagnostics were satisfactory for all parameters (R-hat < 1.01; effective sample size > 200).

Figure 7.

Observed and projected burden of cervical cancer outcomes by SDI quintile: the temporal trends (1990–2020) and Bayesian hierarchical model projections (2021–2045) of four age-standardized burden metrics: incidence rate (ASIR), prevalence rate (ASPR), death rate (ASDR), and disability—adjusted life years (DALYs).

Discussion

The findings of this study provide comprehensive insights into the disease burden of the female reproductive system. Our results demonstrate significant variations in incidence, prevalence, mortality, and DALYs across different types of cancers and conditions affecting the female reproductive system. Temporal trends from 1990 to 2021 exhibited mixed patterns, with increasing case counts observed for most diseases. Age-stratified analysis revealed that the disease burden peaks among middle-aged and older adults. Across SDI regions, low-to-middle SDI regions generally exhibited higher ASRs for incidence and mortality, whereas high SDI regions reported higher prevalence. A Bayesian hierarchical model was implemented to accommodate regional variation and enhance the robustness of long-term projections across SDI contexts. After adjusting for SDI level heterogeneity, cervical cancer mortality remained almost three-fold higher in low SDI regions, while the projected surge in uterine cancer prevalence paralleled obesity trajectories in high SDI settings. The plateau in ovarian cancer DALYs and the continued rise in uterine fibroid prevalence underscore the importance of disease-specific early detection and treatment strategies across all resource levels.

Our study underscores the substantial global burden of cervical cancer, aligning with previous reports that indicate persistently high incidence and mortality despite advancements in screening and treatment^[13]. Our estimated incidence and prevalence rates are comparable to those reported by the World Health Organization (WHO), emphasizing the critical need for continued efforts in cervical cancer prevention and management^[14]. The ASDR observed in our study reinforces disparities in cervical cancer outcomes, particularly in LMICs, where access to healthcare services remains limited^[15]. In low-SDI regions, these disparities stem from fragmented or absent national screening programs, limited availability of HPV testing, a shortage of trained personnel, and inadequate referral and treatment systems. Additionally, long travel distances, out-of-pocket costs, and sociocultural stigma frequently hinder early care-seeking behaviors. These systemic limitations contribute to delayed diagnosis, reduced treatment uptake, and ultimately, higher ASDR. The significant number of DALYs lost due to cervical cancer further underscores its profound impact on global health and economic well-being^[16]. These findings necessitate intensified global health initiatives, such as the implementation of widespread screening programs, access to early diagnosis, and affordable treatment options, as advocated by international organizations and previous research^[17]. In high-SDI countries, HPV DNA testing or cytology-based cotesting with extended intervals may be optimal, supported by organized recall systems. In contrast, low- and middle-SDI regions may benefit from cost-effective approaches such as visual inspection with acetic acid (VIA) combined with single-visit screen-and-treat protocols. These stratified interventions align with WHO guidelines and can be feasibly integrated into existing primary care frameworks to improve coverage and equity. In conclusion, our study adds to the existing evidence base, highlighting the urgent need for comprehensive cervical cancer control strategies to mitigate its burden worldwide.

The disease burden of ovarian cancer reported in this study underscores its significant impact on global health. Our findings align with previous research indicating that ovarian cancer remains a prevalent and deadly gynecological malignancy^[3,18]. Compared to earlier estimates, the ASIR and ASPR observed in this study fall within the ranges reported by the International Agency for Research on Cancer and other large-scale epidemiological studies^[19]. Notably, the ASDR and ASDAR indicate a substantial disease burden, consistent with recent systematic reviews and meta-analyses that emphasize the need for improved early detection and treatment strategies^[20]. Ovarian cancer exhibits the highest standardized rates in regions with high socioeconomic development. Its mechanism of action: high-SDI regions have higher proportions of low parity and delayed childbearing, and high obesity rates. This promotes carcinogenesis through sustained estrogen stimulation. The significantly lower reported rates are highly likely to be a severe underestimation caused by underdiagnosis and data gaps in low-SDI regions. The true disease burden in these regions is likely substantially higher than reported values. These results highlight the persistent challenges in managing ovarian cancer and underscore the critical role of ongoing research to develop novel therapeutic approaches and enhance prevention strategies^[21]. In light of this, we propose the following recommendations: First, implement lifestyle interventions for obese/overweight individuals and prioritize screening for high-risk groups. Second, strengthen disease registry systems and improve diagnostic capabilities in low-SDI regions.

The disease burden of uterine cancer reported in this study aligns with and extends the current understanding of its global health impact. Our findings are consistent with previous studies indicating that uterine cancer remains a significant public health concern, with incidence and prevalence rates that mirror those reported by the WHO and other large-scale epidemiological investigations^[19,21]. The ASIR and ASPR observed in this study fall within the ranges identified in recent systematic reviews and meta-analyses^[19]. Furthermore, the ASDR and ASDAR underscore the substantial disease burden, which is comparable to estimates from population-based studies across various regions^[22]. In our research, we found that regions with high SDI have the highest standardized incidence rates and number of endometrial cancer cases. This phenomenon is primarily attributed to the obesity epidemic, high-calorie diets, declining fertility rates, and the widespread use of menopausal hormone replacement therapy prevalent in high-SDI regions^[23]. Obesity-related insulin resistance and hyperinsulinemia promote endometrial cell proliferation by activating the IGF-1 pathway, further increasing carcinogenic risk^[24]. Differences in reproductive patterns and hormone exposure represent another core mechanism contributing to the regional burden disparities across SDI levels^[25]. Collectively, these results emphasize the continued need for comprehensive strategies to prevent, detect, and manage uterine cancer, as well as to improve patient outcomes and quality of life^[26]. Therefore, we recommend that women with high BMI engage in moderate exercise and consume sufficient dietary fibre every week. Additionally, we recommend implementing screening via ultrasound combined with hysteroscopy for high-risk groups, including obese individuals and those with low parity or delayed childbearing.

The incidence and prevalence of uterine fibroids reported in this study are substantially higher than previously estimated, indicating a more prevalent condition than captured by prior epidemiological research^[27]. Our findings align with recent trends suggesting an increase in uterine fibroid diagnoses, likely due to improved diagnostic techniques and heightened awareness. Despite the high burden of disease, the uterine fibroid-related mortality rate remains low, consistent with existing literature that underscores the generally benign nature of these tumors^[7]. However, the DALYs lost due to uterine fibroids highlight a considerable impact on quality of life, comparable to other chronic conditions^[28]. Meanwhile, our results indicate that low-to-middle SDI regions demonstrated the highest ASIR and ASDR, high SDI regions showed the highest ASPR, and low SDI regions had the highest ASDR and ASDAR. This disparity primarily stems from variations in healthcare system capacity (screening, diagnosis, and treatment accessibility) rather than purely biological risk differences. The “high prevalence” observed in high-SDI regions reflects healthcare advantages (early detection, conservative management). Conversely, the “high incidence/disability rates” in low/middle-SDI regions manifest healthcare disadvantages (late diagnosis, lack of treatment). These results underscore the need for continued research into the etiology, diagnosis, and management of uterine fibroids to reduce their impact on patient well-being. Based on this analysis, we propose the following stratified policy recommendations: In low-SDI regions, train primary healthcare workers to use basic ultrasound devices to improve the early detection rate of fibroids and reduce the proportion of advanced/severe cases. To address severe anemia caused by heavy menstrual bleeding: Stock iron supplements and transfusion resources at community health centers to directly lower the ASDR.

The prevalence of female infertility reported in this study underscores its significant global health burden, aligning with previous research that has highlighted infertility as a prevalent and often underrecognized issue^[29]. Our findings indicate a substantial loss of DALYs associated with female infertility, consistent with literature suggesting that infertility can have profound psychological, social, and economic impacts on individuals and couples^[30]. The wide UIs observed reflect the complexity and variability in defining and diagnosing infertility, as well as the challenges in collecting comprehensive data on this sensitive topic^[31]. High-to-middle SDI regions exhibited the highest ASRs, indicating that women in these regions face a higher risk of infertility. These regions typically feature high educational attainment, high female labor force participation, and more liberal social attitudes, leading to a widespread trend of delayed childbearing. Middle SDI regions had the highest number of cases, signifying that globally, the majority of women affected by infertility actually reside in middle-SDI regions. These regions often encompass the world’s most populous countries. Even though their ASRs are lower than in high-to-middle SDI regions, the sheer size of their female reproductive-age population inevitably results in a large absolute number of infertility cases. In addition, limited access to ART in many regions likely contributes to the persistent DALY burden associated with infertility. In low and middle-income countries, ART services are often scarce, prohibitively expensive, or unavailable through public health systems, which delays timely intervention and exacerbates psychosocial distress. These barriers result in prolonged, untreated infertility and may partially explain the elevated DALY estimates, especially in settings with minimal reproductive health infrastructure. Addressing ART accessibility through subsidized programs and policy reforms is essential to mitigating the global burden of infertility. These results emphasize the need for continued investment in research to improve understanding of infertility causes, enhance diagnostic accuracy, and develop effective treatments, ultimately aiming to reduce the burden of this condition on affected populations. For example, in high-to-middle SDI regions, efforts should focus on strengthening public education to raise awareness of the relationship between age and fertility, promoting healthy lifestyles. In middle SDI regions, there is a critical need to expand and improve the accessibility, affordability, and quality of infertility diagnosis and treatment services to meet the demands of the substantial patient population.

The trends observed in cervical, ovarian, and uterine cancers, as well as uterine fibroids and female infertility, contribute to a nuanced understanding of gynecological health globally. While cervical cancer incidence and mortality rates have generally declined, likely due to advancements in screening and treatment^[14,32], the rising case counts suggest ongoing challenges in disease prevention and management. In contrast, ovarian cancer incidence and mortality rates have increased, highlighting a pressing need for improved early detection methods and therapeutic interventions^[33]. The mixed trends in uterine cancer incidence and mortality rates may reflect regional variations in healthcare access and quality^[34]. Similarly, the increasing burden of uterine fibroids and female infertility underscores the complexity of reproductive health issues, influenced by social, economic, and environmental factors^[29]. The rising DALYs associated with female infertility further emphasize the need for comprehensive care approaches that address the multifaceted impact of these conditions on women’s lives.

Limitations and future directions

This study has several limitations. First, the analyses relied on the GBD 2021 database, which is subject to the availability and quality of country-level data. Incomplete or inaccurate data, particularly from LMICs, may introduce uncertainty and affect the precision of the estimates. Second, disease definitions and diagnostic criteria may vary across regions and over time, which can influence incidence and prevalence estimates.

Further studies should evaluate the cost-effectiveness and implementation feasibility of targeted prevention and treatment strategies, especially in low-resource settings. Moreover, integration of real-world data sources – such as cancer registries, electronic health records, and national surveys – could improve the accuracy and contextual relevance of burden estimates.

Conclusion

In conclusion, the disease burden associated with the female reproductive system remains substantial, exhibiting notable variations across diverse cancer types and conditions, age demographics, and SDI regions. Our findings underscore the urgent necessity for tailored interventions to address these disparities and mitigate the overall disease burden. Sustained efforts in research, prevention, diagnosis, and treatment are paramount to enhancing reproductive health and well-being for women globally.

Ethical approval

This study was based on publicly available, de-identified data from the Global Burden of Disease (GBD) 2021 database. Therefore, no ethical approval or informed consent was required.

Consent

Not applicable.

Source of funding

This study was supported by the Medical Science Research Project of Hebei Province (No. 20220972 and No. 20240569), the National Natural Science Foundation of China (No. 81803301), and Science and Technology Research Project of Higher Education Institutions in Hebei Province (No. QN2024006).

Author contributions

Y.N.Z. conceived the study. L.Z. designed the protocol. L.Z., W.C., Y.J.H., and P.G. analysed the G.B.D. data. L.Z., W.C., Y.J.H., P.G., and Y.N.Z. contributed to the statistical analysis and interpretation of data. L.Z. and Y.N.Z. drafted the manuscript, and other authors critically revised the manuscript. L.Z., P.G., and Y.N.Z. accessed and verified the underlying data. All authors contributed to this manuscript. All authors read and approved the final manuscript.

Conflicts of interest disclosure

The authors declare no competing interests.

Guarantor

Dr. Yanan Zhang.

Research registration unique identifying number

Not applicable.

Provenance and peer review

Not commissioned, externally peer-reviewed.

Data availability statements

Data of the GBD study are publicly available at

https://www.healthdata.org/results/data-visualizations.