A Retrospective Cohort Study of Uterine Cancer Epidemiological Analysis and Age-Based Disparities in Saudi Arabian Population across 32 Years

The GBD database was used in the study; it offers an extensive and standardized collection of epidemiological data (covering healthcare impacts and mortality) sourced from up-to-date vital registration records of all nations that share data with the World Health Organization (WHO). Additionally, it incorporates data from WHO departments in partnership with United Nations organizations, expert advisory panels, and education partners. Statistics from the GBD were integrated for countries that lacked reliable vital registration data. The total number of sources and countries included varied according to the specific disease conditions analyzed. The main data source was the Institute for Health Metrics and Evaluation database. Uterine tumor data between 1990 and 2021 was retrieved from a database. In this study, we investigated the epidemiological incidence and prevalence of uterine cancer in Saudi Arabia presented in the analysis: i) disability-adjusted life years (DALYs), ii) years of life lost (YLLs), iii) deaths, iv) and years lived with disabilities (YLDs). It is important to note that the GBD 2021 dataset includes information only from the local population and does not capture expatriate health data. Age standardization was used as a controller for age structure, proportional rankings, and disease frequencies for cohorts of age to study the risk causes in different age groups. This study was approved by the Biomedical Research Ethics Committee at Umm Al-Qura University (Approval No. HAPO-02-K-012-2025-12-3081). The statistical uncertainty of each parameter was derived from 1,000 samples from the distribution, categorized by age and location data for each year were included in the 2021 analysis. The lower and upper uncertainty intervals (UIs) were defined as the 25 th and 95 th percentile draws of each estimate representing 95% UIs. These UIs capture the uncertainty from multiple modeling steps in the final estimates. For mortality and YLLs, the 95% UIs were constructed to reflect uncertainties in the regression models and levels of all-cause mortality for YLDs; 95% of UIs incorporated uncertainties in prevalence estimates, the distribution of severity across each cause, and the valuations assigned to disability weights. The study was accomplished in March 2025. The data was extracted and analyzed based on the prevalence of UC in past 31 years. The Global Health Data Exchange (GHDx) tool was used to visualize the causes of mortality in age categorization patterns in KSA. Changes in each parameter were determined by matching the corresponding data for 1990 and 2021. The data are expressed as 95% confidence intervals (95%CI). Finally, UC data were analyzed in terms of 5-year periods within the 1990–2021 study period and across age groups (ranging from 0 to 55+ years).

From 1990 to 2021, KSA recorded approximately 78,017 UC. In 2021, an estimated female population (6,365.507 [95% UI 4,353.77–9,001.35]) had UC in KSA, resultant to a rise of approximately 1,170% compared to the diagnosed population in 1990 (507.432 [95% UI 339.881–757.114]). The age-standardized prevalence rate of UC in 1990 was 18.03 (12.288–26.940) cases per 100,000 and 55.329 (38.643–76.558) cases per 100,000 in 2021, representing a surge of 206% in Fig. 1 . Demonstrates the trend in the age-standardized prevalence rate of uterine cancer from 1990 to 2021 in Saudi Arabia increased with increasing population age. Subcategorization by female age was conducted to determine whether we could recognize any age clusters with a higher risk of developing the disease. The prevalence rates remained consistently stable for the female population in their 20's (20–24 and 25–29 years). In contrast, a significant increase was observed in the older population, particularly in the 30–54 age group, where the prevalence rate escalated by 2021. Moreover, in this study, cases were classified according to female reproductive age (>39 years) to investigate the occurrence of UC in the Saudi female population. We found that women tend to suffer from UC earlier in their late reproductive age (34–39), compared to data from 1990 in Fig. 2 . The prevalence rate of uterine cancer in Saudi Arabia (1990 and 2021), stratified by reproductive age group <39 years. An overall of 10,170 new cases of UC were diagnosed in KSA from 1990 to 2021, which accounted for 5.13% (3.52–7.21) of the total incidence of all diseases in KSA. Figures among patients with newly developed UC in 2021 were anticipated to be (804.58 [95% UI 553.07–1129.98]), which rose dramatically compared to (72 [95% UI 49.31–107.99]) UC cases in 1990 that 11-time fold change than 2021 new cases. In 2021, the age-standardized incidence rate due to UC was 7.50 (1.861–4.0158) new cases per 100,000, and 2.701 (1.861–4.015) new cases per 100,000 in 1990, indicating a growth of almost 300% relative to the incidence of UC in 1990. According to the database, throughout these 32 years, a consistent rise in UC cases was observed among Saudi females across different age groups ( Fig. 3 ). In 2021, the data indicated that the incidence were highest in the 55 years group of age, while the incidence rates were almost zero in the 25 years group of age and under. Demonstrates the trend in the age-standardized incidence rate of uterine cancer from 1990 to 2021 in Saudi Arabia increased with increasing population age. By 2021, the in DALYs, reached 3,492.91 (95% UI: 2,401.05–4,998.92), reflecting a 500% increase from 1990 levels (668.29 DALYs [95% UI: 452.94–991.74]). In 2021, the total age-standardized DALYs were 33.75 (95% CI 23.875–46.676) per 100,000 people, which increased steadily compared to age-standardized DALYs 24.611 (95% CI 16.91 36.925) in 1990. In 2021, the age-standardized YLDs were 15.2 (95% UI 3.8–2.26) per 100,000 population, associated with 49.4% of the morbidity attributed to uterine cancer. Across age cohorts, DALYs exhibited growth from 1990 to 2021, displaying an age-dependent rise. Interestingly, in the last 2 years (2020 and 2021), the DALYs rate decreased compared to the former 7 years, which was approximately 34.55 DALYs. Between 1990 and 2021, approximately 1641 deaths attributed to UC in KSA. Over the study timeframe, the annual death rate increased noticeably from 22 deaths in 1990 to 93 deaths in 2021, an approximately fourfold increase. These deaths, altogether, represented 0.18% (1.39–1.88) of all-cause deaths in KSA. The age-standardized mortality rate attributed to UC reached 1.9 (95% UI 0.86–1.63) deaths per 100,000 in 2021, marking a 41.4% rise relative to 1990, when the rate was 0.9 (95% UI 0.69–1.41) deaths per 100, 000 in Fig. 4 . In 2021, the age-standardized YLLs were 29.92 (95% UI 21.26–41.26) per 100,000 population, which contributed to approximately 98% of DALYs due to UC. Demonstrates the trend in the age-standardized mortality rate of uterine cancer from 1990 to 2021 in Saudi Arabia increased with increasing population age. Subcategorization by female age was conducted to determine whether we could recognize any age cluster with an elevated risk of death from this disease. This analysis indicated that 50.9% of UC cases occurred in females aged 45 and 49 years old. Interestingly, women in the age group of 20–24 show a trend of increased mortality from 2004 to 2007, which reduces after that to similar values as before 2004 in Fig. 5 . Collectively, the death rates caused by UC increased across the entire age spectrum from 1990 to 2021, along with an increase in age. However, the mortality rate decreased in 2021 compared with that in the previous 14 years. Deaths caused by UC were calculated, which was responsible for the loss of 905 years of life as a result of mortality throughout the 31-year study timeframe. The age structures of the YLLs and YLDs in 2021 were analyzed to determine which age category was at a greater risk of UC, lost years of life, and disability. The results showed that peak UC disability was associated females aged 65–69 years. Age group 20–24 shows a trend of increase mortality rate from 2004 to 2007 in female in Saudi Arabia.

The authors declare that they have no conflicts of interest related to the research presented in this manuscript and this study was not funded by any institution.

Recently, KSA has shown an increased interest in developing epidemiological data on its patient population, especially for those diagnosed with cancer. However, despite the publication of some studies on UC in KSA, available data remain limited. Access to UC data is valuable for tailoring medical treatment because the disease has various subtypes, each with distinct prognosis and survival rates that vary based on ethnicity and environmental influences. Personalized treatment is one of the main goals of KSA's 2030 vision and is the primary domain of research interest in KSA. As far as we know, the current work is the 1 st study to examine the UC burden in females from KSA, which comprises the epidemiology, DALYs, YLDs, YLLs and death rates from 1990 to 2021. In this study, the data showed increased in the prevalence and incidence of UC in the KSA in older group of age from 1990 to 2021 by 206 and 300%. These results are consistent with earlier global studies [ 1 2 4 ]. These outcomes are similar with those of earlier investigations of global patterns of UC burden. The incidence of uterine tumor has increased in numerous developed countries [ 19 ]. This pattern is consistent with the results of regional studies in Egypt and the United Arab Emirates [ 20 21 ]. The global and regional rise in the incidence of UC may be attributed to several factors, including enhanced screening efforts, improved record-keeping, and advancements in diagnostic methods, such as the identification of Lynch Syndrome in Saudi patients with endometrial cancer through a widespread screening method [ 22 ]. Additionally, more frequent follow-ups of incidental findings likely have a role in the observed rise. The introduction of transvaginal ultrasound scanning and endometrial sampling, has improved the early detection of endometrial abnormalities. Consequently, the increased detection rate may have contributed to the apparent rise in morbidity [ 23 ]. The growing prevalence and incidence of UC in KSA can be associated with the rapid change in the socioeconomic for example lower fertility rates, increased rates of nulliparity, and fewer pregnancies. The high socio-demographic index which subsequently lead to aging populations and decreasing fecundity rates can eventually cause high mortality rate [ 24 ]. Moreover, a significant transformation in KSA's population structure due to the large-scale arrival of migrants has affected the incidence of reproductive cancer [ 25 ]. The increasing prevalence of cigarette smoking among Saudi women is another risk factor for UC [ 26 ]. Uterine cancer is strongly associated with obesity among all cancers [ 8 ]. As a result, weight reduction strategies including increased physical activity, dietary modifications, and bariatric surgery may represent some of the most cost-effective and efficient interventions for reducing the incidence of UC [ 9 10 11 12 26 ]. Many studies showed that significant levels of physical activity were associated with a reduction in the risk of UC compared to lower activity levels [ 10 11 ]. Additionally, metabolic syndrome showed a strong contribution to uterine tumor development. Insulin resistance, hyperinsulinemia, and polycystic ovary syndrome (PCOS) promote cellular growth and inhibit apoptosis, further elevating the risk of endometrial hyperplasia and malignant transformation [ 27 ]. Despite the strong correlation between obesity and UC, it is important to note that not all obese women develop UC and not all women with UC are obese. This suggests that other risk factors such as differences in genetic predisposition in such as germline pathogenic or likely pathogenic variants occurring in the deoxyribonucleic acid (DNA) mismatch repair genes (MutL homolog 1, MutS homolog 2, MutS homolog 6, and Postmeiotic Segregation Increased 2) or in the epithelial cell adhesion molecule gene, also contributes to the uterine tumor prevalence [ 22 ]. The increase rate of many reproductive disease globally including KSA such as endometriosis, polycystic ovary syndrome and hormonal imbalances contribute to the increase of the occurrence and the morbidity rate of UC [ 28 ]. With the advancement of industrialization, xenoestrogens have become widely distributed in the environment. These substances can disrupt the endocrine system, potentially leading to precocious puberty and early onset of menstruation [ 29 ]. In this study, over the past 32 years, all DALYs and mortality rates related to UC increased across different age cohorts in the Saudi population, in parallel with the growth in life expectancy. Despite this increasing trend, KSA currently registers lower DALY and mortality rates for UC than the global rates. This may be due to the relatively young demographics: over half of the population is under 35. This may be attributed to relatively young demographics, with population who are under 35 years are 50%. As part of the Saudi Vision 2030, one of the country's key objectives is to increase life expectancy. Projections indicate that the proportion of the Saudis aged 60 and above will raise from 5.5% in 2020 to 11% by 2030. To support this national target, it is essential to improve the efficacy and quality of healthcare service industries and promote preventive measures targeting C risk factors. The current work is the first report to examine the role of UC on female reproductive age in KSA. Age was the greatest contributor to the incidence, prevalence, morbidity, and the death of UC in females in KSA. Interestingly, we found that females (20–24) years between 2004 and 2007 had a higher mortality rate than men. The significantly higher mortality rate of endometrial cancer observed in young women (20–24) compared to older women in KSA could be attributed to two main factors: i) the rising rates of obesity among young women ii) and the reduced use of hormone replacement therapy (HRT). The interplay between HRT use and UC risk depends on the regimen. Estrogen-only therapy increases endometrial proliferation and carcinoma risk unless combined with progestin to counter stimulation. Combined estrogen–progestin therapy mitigates these effects and has been linked to lower UC risk than estrogen alone. After the Women's Health Initiative (WHI) trial in 2002, reduced HRT use may have removed protective benefits, increasing UC incidence. Studies indicate that post-treatment HRT does not raise recurrence risk and may prolong disease-free survival [ 30 ]. Combined therapy shows protective effect against recurrence, while estrogen-only regimens do not show similar effect, emphasizing the need for specific data to interpret such findings. The staging system for UC has been revised to include a new subcategorization within stage IB and refined grading criteria. This update enables a more precise assessment of patient conditions and may potentially shift reported incidence rates. Molecular analyses from recent research have identified four UC subtypes: i) polymerase epsilon (POLE)-ultra mutated, ii) microsatellite instability-high (MSI-H), iii) copy number (CN)-low, iv) and CN-high), with UC's most often linked to the CN-high subtype, known for its poor prognosis. Some studies have link between the endometrial types and the survival rates of women in KSA. Patients diagnosed at an early stage had a longer median survival (24 months) compared to those at a late stage (14 months), underscoring the importance of early detection and screening since represented 4.7% of endometrial cancer cases at Princess Noorah Oncology Center (2003–2023), aligning with both United States and global data [ 31 ]. Endometrioid carcinoma represented 70.5% (n = 86) of all cases. Among these, 24.4% (21/86) demonstrated coexistent complex atypical hyperplasia, and 1.64% (2/86) showed simple atypical hyperplasia, highlighting a strong correlation between atypical endometrial hyperplasia and the development of carcinoma and indict the timing of the sampling could affect the prognosis and the management plan [ 32 ]. This investigation confirmed that age is a significant factor influencing mortality in UC. Previous studies have demonstrated that younger patients generally have better survival outcomes than older patients [ 23 ]. Additionally, younger age has been linked to lower-risk clinicopathological prognostic factors, such as early-stage disease and more favorable tumor characteristics [ 33 ]. However, these findings in younger patients with UC, particularly those of reproductive age, have been challenged in recent studies [ 34 ]. Furthermore, because UC is relatively uncommon in women of reproductive age, research on younger patients is limited, often because of the small sample size within this demographic [ 34 ]. In our analysis, women exhibited higher epidemiological rates across all measured domains during the postmenopausal years. These findings align with those of recent studies examining trends in UC among postmenopausal women worldwide [ 34 ]. Although we found a massive increase in the incidence of diseases and disabilities in 2021 compared to 1990, most C cases occurred in females over the age of 50 years, with an average age at diagnosis of 60 years. In contrast, this disease is uncommon in women aged <45 years. In this analysis, older women faced a higher risk of mortality UC than their younger counterparts because of diagnoses did at more advanced stages or the presence of more aggressive tumor types [ 35 ]. This pattern of late-stage diagnosis in older women may be affected by many factors, such as educational barriers that delay access to health information, and the presence of multiple health conditions that may lead healthcare providers to hesitate in recommending surgical treatments. Moreover, older patients may experience more complications from invasive treatments such as surgery and chemotherapy [ 22 ]. To our knowledge, no recent studies have comprehensively assessed access to uterine cancer care and screening in KSA. It is provided free to citizen and non-citizen with insurances or health agreement. Over the past three decades, KSA has advanced oncology services by establishing modern treatment centers and improving care through national guidelines and collaborations [ 36 ]. Despite these achievements, challenges persist, due to the geographical concentration of specialized oncology services in Riyadh, Makkah, and the Eastern Province. As a result of the limits access for patients in remote regions. To address this, restructuring the healthcare system into regional health clusters, to ensure integrated cancer services. Ehalati help patient transfers between institutions, however, the Seha offer virtual oncology consultations. These platforms are helpful for UC patients, which require multidisciplinary treatment [ 36 ]. Current study had medical and public implications. The study highlights the increasing incidence of UC in KSA with tracking to its progression over the past 3 decades. Moreover, the result emphasis the need for targeted health policies and accessible community-level interventions, such as early screening programs. Specific age groups screening is vital especially with the different classifications of UC. The age-related incidence patterns in KSA are in line with the global trends, emphasizing the need of age-focused strategies in UC research and treatment. Raising public awareness through health campaigns can play a role in educating patients and their families. As any retrospective study possible missing data and inaccuracies are inherent. Although uncertainty was integrated at all stage of the analytical process, some uncertainties may exist. However, the study follows the Guidelines for Accurate and Transparent Health Estimates Reporting, which integrates data from a large scale of resource to produce reliable estimates. Absence of cancer staging data which is an important prognostic factor for evaluating the outcomes of patients with UC could considered a limitation of this result. Despite this restriction, current study proposes a large-scale, population-based analysis of the UC disease burden and age disparities, minimizing possible selection bias. In conclusion, this study uses the most recent data from the GBD 2021 database which offers a comprehensive analysis of the national burden of UC among females in KSA over 32 years (1990–2021). The key findings are as follows. First, both the absolute numbers and age-standardized rates of prevalence, incidence, morbidity, DALYs, YLDs, YLLs, and mortality related to US in females showed significant increases during this period. Second, the disease burden varied notably across different age groups in this demographic study. Third, women aged 35–39 years experienced the most rapid increase in disease burden, whereas those aged 50 years consistently exhibited the highest overall burden. Finally, predictions indicate that the global burden of US among women in KSA, especially those over the age of 50 years, is expected to continue to rise until 2030.

Uterine cancer (UC) is the 6 th most prevalent tumor in women worldwide. Its occurrence has increased in the latest 20 years [ 1 ]. Approximately 400,000 cases were diagnosed with uterine tumor in 2020, resulting in 97,000 fatalities associated to this disease [ 1 ]. According to the guidelines provided by the International Federation of Gynecology and Obstetrics (FIGO), this malignancy is categorized into stages I, II, III, and IV, representing different histological characteristics, tumor patterns, and molecular classifications [ 2 ]. Survival rates for UC have declined over the past 4 decades, making it one of the few cancers with worsening outcomes despite medical advances [ 3 4 ]. Since 2007, both the incidence and mortality rates have increased, with the death rate rising at higher rates [ 1 ]. In Saudi Arabia, over 13,000 cancer cases were reported among women in 2020, with corpus uteri cancer being the most prevalent gynecological malignancy, accounting for 7.5% of all female cancer diagnoses [ 1 ]. Uterine tumor can appear at any age, although it is very common seen in those aged 55 years and older, with an average age of 63 years [ 5 ]. The rise in aggressive high-risk subtypes could be the reason for the greater increase in mortality than in incidence [ 6 ]. Previous studies examining UC incidence trends by age, race, ethnicity, and histological subtype have yielded inconsistent results [ 6 7 ]. There are many reasons increase the chance of development of uterine tumor. After the age of 50, UC becomes more common. A study revealed that over 75% of females who were diagnosed with UC before the age of 25 were obese; their body mass index (BMI) was 30 or above [ 8 ]. Further risk factors for UC in females aged <50 years include the absence of combined hormonal contraceptive use and giving birth for the first time after 30 years of age [ 9 ]. Sedative lifestyle is 1 of the main causes of uterine cancer [ 10 ]. Various works have consistently demonstrated the preventive effect of physical exercise, irrespective of BMI and the effect of higher levels of sedentary behavior on the chance of uterine cancer incidence [ 10 11 ]. Diets with a high glycemic index, such processed and junk food may be linked to a higher chance of UC [ 12 ]. Multiple works have demonstrated a positive link between elevated caloric consumption and an elevation of the chance of uterine tumor, whereas a negative link has been noticed between a healthy diet consumption and the probability of UC [ 10 13 ]. Prolonged exposure to natural hormones is associated with increase in the chance of developing uterine tumor [ 14 ]. Moreover, early onset of menstruation at age or earlier and later onset of menopause [ 15 16 ]. Pregnancy appears to have a protective effect. Nulliparous women have a higher risk ratio for UC than parous women which shows that the level of risk diminishes as the number of occurrences increases [ 17 ]. Type of uterine cancer tend to have an effect of the mortality rate globally. The rising mortality rates of no endometrioid carcinomas correspond with the recent increase in the incidence of these more aggressive subtypes observed over the past 2 decades. In contrast, mortality rates for endometrioid carcinomas have remained relatively stable across all racial and ethnic group [ 18 ]. A dramatic development in of KSA has been noticed at different levels from the economy or to cultural changes over the past decades, potentially increasing the prevalence of key risk factors for UC: i) such as obesity; ii) sedentary lifestyle; iii) and marriage age shifts. This epidemiological transition makes it imperative to investigate the incidence of UC in different age groups in KSA. This retrospective cohort study aimed to analyze the incidence of UC cases in KSA over a 31-year period by investigative the influence of age disparities on UC trends. Current analysis will provide valuable insights into disease burden in the KSA and inform future strategies for prevention, screening, and management.

The authors would like to thank Editage ( www.editage.com ) for English language editing.