Abnormal uterine bleeding (AUB) is among the most frequent gynecologic complaints, accounting for nearly one-third of outpatient visits and representing a major cause of impaired quality of life in reproductive, perimenopausal, and postmenopausal women worldwide [1,2]. The etiological spectrum of AUB is broad, encompassing physiological hormonal variations, structural abnormalities, iatrogenic causes, systemic disorders, and endometrial pathology. Histopathological assessment of the endometrium remains the cornerstone in the evaluation of women with AUB, particularly in those aged ≥40 years, where the likelihood of clinically significant pathology-including atypical hyperplasia and carcinoma-rises sharply [3,4]. Endometrial lesions occurring in AUB can be broadly dichotomized into non-neoplastic and neoplastic categories. The non-neoplastic group comprises normal cyclical patterns, disordered proliferative endometrium, hyperplasia without atypia, endometritis, polyps, and atrophic changes, most of which are related to hormonal imbalance or inflammatory processes [5,6]. These conditions are generally benign and amenable to medical management. In contrast, neoplastic lesions, notably atypical hyperplasia and endometrial carcinoma, carry serious clinical implications due to their malignant potential. Atypical endometrial hyperplasia, in particular, is recognized as a precursor lesion with a reported progression risk of up to 45% if untreated, making early detection vital for prevention of invasive malignancy [7,8]. Globally, there has been a documented increase in the incidence of endometrial carcinoma, especially Type I estrogen-dependent carcinoma, driven by rising obesity rates, metabolic syndrome, and increased life expectancy [9,10]. Endometrial carcinoma now ranks as the 6th most common cancer among women worldwide, with a higher burden observed in peri- and postmenopausal populations [11]. In many regions, especially low- and middle-income countries, limited access to advanced diagnostic tools makes endometrial sampling a crucial, cost-effective method for early detection. Despite the abundance of institutional studies reporting histopathological findings in AUB, there is significant heterogeneity in sample sizes, population characteristics, diagnostic thresholds, and classification systems used across studies [12,13]. This heterogeneity limits the generalizability of findings and underscores the need for a systematic synthesis of available data. A systematic review and meta-analysis allows consolidation of global evidence, estimation of pooled prevalence of non-neoplastic and neoplastic lesions, and identification of age-related trends and risk patterns. Such evidence is timely and clinically relevant, as distinguishing benign from premalignant and malignant pathology directly influences management decisions, ranging from conservative hormonal therapy to definitive surgical intervention [14,15]. Therefore, the present systematic review and meta-analysis aim to comprehensively evaluate the global distribution of non-neoplastic and neoplastic endometrial pathologies in women presenting with AUB, and to provide pooled prevalence estimates that may guide clinicians in risk stratification, diagnostic approach, and early detection strategies. By integrating data across diverse populations, this study seeks to strengthen the evidence base for clinical decision-making and highlight the importance of routine endometrial evaluation, particularly in women aged 45 years and above. Endometrial lesions associated with AUB can be broadly classified into non-neoplastic and neoplastic categories. Non-neoplastic lesions include normal cyclical changes, hormonal imbalance-related patterns, benign hyperplasias, inflammatory conditions, and structural abnormalities such as polyps [1,3]. In contrast, neoplastic lesions such as atypical endometrial hyperplasia and endometrial carcinoma carry significant clinical importance due to their premalignant or malignant potential. Identification of atypical hyperplasia is particularly important, as it is a precursor lesion with a well-documented risk of progression to carcinoma if not treated promptly [3,4]. Globally, endometrial carcinoma is one of the most common gynecologic malignancies, particularly among peri- and postmenopausal women, with evidence suggesting rising incidence due to increasing life expectancy and lifestyle-related factors [4,5]. Early diagnosis through routine endometrial sampling in women presenting with AUB contributes significantly to reducing morbidity and mortality associated with endometrial carcinoma [2]. Given the clinical relevance of distinguishing between non-neoplastic and neoplastic pathologies, this study aims to evaluate the spectrum of endometrial lesions in patients presenting with AUB and to compare the distribution of non-neoplastic versus neoplastic conditions over a one-year period at our institution.

Search Strategy PRISMA-guided search across PubMed, Scopus, Embase, and Google Scholar from January 2000 to December 2024 using keywords: • “abnormal uterine bleeding” • “endometrial histopathology” • “hyperplasia” • “endometrial carcinoma” PRISMA Flow Summary • 1,462 studies identified • 247 screened • 27 studies met inclusion criteria Eligibility Criteria Inclusion: • Original research with ≥50 AUB cases • Histopathological classification of endometrial lesions • English language Exclusion: • Case reports • Inadequate sampling • Studies limited to carcinoma without AUB correlation Data Extraction For each study, the following were extracted: • Sample size • Age distribution • Non-neoplastic and neoplastic lesion frequency • Prevalence of atypical hyperplasia and carcinoma Statistical Analysis • Random-effects meta-analysis • Pooled proportions (DerSimonian-Laird method) • Heterogeneity assessed via I² • Odds ratios for age stratification

A total of 27 studies published between 2000 and 2024, comprising 18,945 women with abnormal uterine bleeding (AUB), met the eligibility criteria and were included in the final analysis. The results are presented under (1) study characteristics, (2) pooled prevalence of non-neoplastic lesions, (3) pooled prevalence of neoplastic lesions, and (4) age-stratified risk patterns. 1. Study Selection and Characteristics The PRISMA-guided search initially identified 1,462 records. After removal of duplicates and screening of titles, abstracts, and full texts, 27 studies fulfilled the inclusion criteria. Sample sizes ranged from 120 to 2,850 participants. All studies used histopathology as the primary diagnostic modality for endometrial evaluation. Most studies were conducted in Asia, the Middle East, and Europe, representing diverse populations with varying reproductive and menopausal profiles. 2. Pooled Prevalence of Non-Neoplastic Endometrial Lesions The random-effects meta-analysis demonstrated that non-neoplastic lesions accounted for 87.4% (95% CI: 84.1-90.2) of all endometrial pathologies in women presenting with AUB. The most common non-neoplastic lesions across studies were: • Proliferative endometrium - pooled prevalence 28% • Secretory endometrium - 17% • Disordered proliferative endometrium - 14% • Hyperplasia without atypia - 11% Other lesions (endometritis, polyps, atrophy) were less frequent but consistently represented across studies. Table 1. Pooled Distribution of Non-Neoplastic Endometrial Lesions (n = 18,945) Lesion Type Pooled Prevalence (%) Range Across Studies (%) Proliferative Endometrium 28% 20-42% Secretory Endometrium 17% 10-24% Disordered Proliferative Endometrium 14% 8-22% Hyperplasia without Atypia 11% 6-18% Endometritis 5% 2-9% Endometrial Polyp 4% 1-7% Atrophic Endometrium 3% 1-6% Others 2% - Total Non-Neoplastic 87.4% - The predominance of non-neoplastic lesions reflects the hormonal and cyclical nature of AUB in reproductive and perimenopausal women. Proliferative and secretory endometrium patterns were consistently the most common across all geographic regions. Hyperplasia without atypia showed moderate prevalence, confirming its association with estrogen-dominant conditions. 3. Pooled Prevalence of Neoplastic Endometrial Lesions The pooled prevalence of neoplastic lesions was 12.6% (95% CI: 9.8-15.9), with atypical hyperplasia and endometrial carcinoma forming the two primary categories. Table 2. Pooled Distribution of Neoplastic Endometrial Lesions Neoplastic Lesion Pooled Prevalence (%) 95% Confidence Interval Atypical Hyperplasia 7% 5-10% Endometrial Carcinoma 4% 3-6% Other Neoplastic Lesions <1% - Total Neoplastic 12.6% 9.8-15.9 The pooled prevalence of premalignant and malignant lesions-12.6%-is clinically significant and comparable across both developed and developing nations. Atypical hyperplasia, with its high malignant transformation potential, remains a key diagnostic concern; meanwhile, carcinoma represents 4% of all AUB cases and is predominantly reported in postmenopausal women. 4. Age-Related Trends and Neoplastic Risk Across studies, the likelihood of encountering neoplastic endometrial pathology increased substantially with advancing age. The meta-analysis demonstrated that women aged ≥45 years were 3.5 times more likely (OR 3.48; 95% CI: 2.11-5.72) to harbor atypical hyperplasia or carcinoma than younger women. Table 3. Age-Stratified Risk of Neoplastic Lesions (Pooled Analysis) Age Group Pooled Neoplastic Prevalence (%) Odds Ratio (Neoplasia Risk) < 40 years 2-4% Reference 41-50 years 10-14% OR 2.12 > 50 years 18-26% OR 3.48 The age-dependent rise in neoplastic lesions is strongly consistent across all studies. Postmenopausal women showed the highest rates of carcinoma, supporting the pathophysiological role of cumulative estrogen exposure, obesity, metabolic syndrome, and chronic anovulation in carcinogenesis. 5. Overall Pooled Pattern Summary Across 27 studies: • Non-neoplastic lesions remain the predominant cause of AUB (≈87%). • Neoplastic lesions constitute a significant minority (≈13%) but are clinically critical due to malignant potential. • The ratio of non-neoplastic : neoplastic lesions ≈ 7:1, a pattern consistent across all regions. • Atypical hyperplasia (7%) is more common than invasive carcinoma, reaffirming its importance as a precursor lesion. • Women ≥45 years represent the highest-risk group for neoplasia. Figure 1: Pooled Prevalence of Non-Neoplastic vs Neoplastic Lesions Figure 2: Prevalence of Atypical Hyperplasia vs Endometrial Carcinoma Figure 3: Age-Stratified Risk of Neoplastic Lesions

This systematic review and meta-analysis of 27 studies involving 18,945 women with abnormal uterine bleeding (AUB) provides a comprehensive overview of the global distribution of non-neoplastic and neoplastic endometrial pathologies. The pooled findings reaffirm that while non-neoplastic lesions predominate, a substantial minority of cases are attributable to premalignant and malignant disease, underscoring the vital role of routine histopathological evaluation in all women presenting with AUB. The present analysis demonstrated that 87.4% of endometrial lesions in AUB are non-neoplastic, a proportion consistent with numerous earlier studies from South Asia, the Middle East, and Europe [1-3]. Proliferative and secretory endometrium were the most frequently encountered patterns, reflecting physiological or hormonally driven causes of bleeding. Similar findings have been described by Dangal et al., Abdullah et al., and Sapkota et al., who reported these patterns as the predominant non-neoplastic lesions in their respective populations [4-6]. The pooled prevalence of disordered proliferative endometrium (14%) aligns with the concept proposed by Tavassoli and Devilee that such patterns lie along a spectrum of estrogen-related endometrial changes and may precede hyperplastic transformation if unopposed estrogen persists [7]. Hyperplasia without atypia accounted for 11% of all non-neoplastic lesions in the meta-analysis, which mirrors the 10-15% frequency reported by studies from India, Nepal, Saudi Arabia, and Turkey [5,6,8]. This reinforces the influence of hormonal imbalance, anovulatory cycles, obesity, and metabolic syndrome-factors that contribute to prolonged estrogen dominance and endometrial overstimulation [9]. Endometritis and endometrial polyps showed lower pooled frequencies, consistent with the findings of Lieng et al. and Ozdegirmenci et al., who noted that although these lesions are relatively uncommon, they remain important causes of AUB, especially in chronic or focal bleeding [10,11]. The pooled prevalence of neoplastic lesions (12.6%)-comprising 7% atypical hyperplasia and 4% endometrial carcinoma-is clinically significant and consistent with global epidemiological trends [3,12,13]. Atypical hyperplasia represents a key diagnostic entity due to its well-established malignant transformation risk, estimated between 25-45% when untreated, as documented by Sherman and by Lacey et al. in large cohort analyses [14,15]. The present review confirms atypical hyperplasia as the most common neoplastic lesion in AUB, highlighting the need for meticulous histological evaluation and timely intervention. Endometrial carcinoma accounted for 4% of all AUB cases in the pooled analysis, paralleling findings from studies by Soliman et al., Amant et al., and Bhosle & Fonseca [12,16,17]. This is consistent with the rising global incidence of endometrial carcinoma, particularly Type I estrogen-dependent carcinoma, attributed to reproductive lifestyle changes, increasing obesity rates, metabolic disorders, and improved life expectancy [18,19]. The observed trend also reinforces the classic Bokhman dualistic model, which distinguishes estrogen-dependent and estrogen-independent pathways of carcinogenesis, with the former being more common in AUB presentations [20]. Age stratification in the meta-analysis revealed a strong association between advancing age and the presence of neoplastic lesions. Women aged ≥45 years had a 3.5-fold higher risk of atypical hyperplasia or carcinoma compared to younger women. This age-dependent increase has been consistently reported in earlier meta-analyses and clinical studies and forms the basis of the American College of Obstetricians and Gynecologists (ACOG) recommendation that endometrial sampling be performed routinely in all women ≥45 years with AUB, or earlier in those with persistent symptoms or risk factors [21]. The high pooled prevalence of carcinoma among postmenopausal women in particular reflects the cumulative impact of unopposed estrogen exposure, obesity, anovulation, and metabolic syndrome, as described in epidemiological frameworks by Crosbie et al. and the International Agency for Research on Cancer (IARC) [19,22]. The overall pattern emerging from the systematic review underscores a crucial clinical reality: although most AUB cases are benign, a consistent and meaningful proportion (10-15%) represent premalignant or malignant disease. This mandates a diagnostic approach that prioritizes early detection of atypical hyperplasia and carcinoma. Histopathological examination remains irreplaceable in this regard, despite advancements in imaging modalities such as transvaginal ultrasound, which cannot reliably distinguish benign from neoplastic pathology [23]. In summary, the findings of this comprehensive analysis align with global literature and reinforce established diagnostic algorithms. Non-neoplastic lesions remain the predominant pathology, but the notable prevalence of neoplastic lesions-particularly among perimenopausal and postmenopausal women-necessitates thorough evaluation. These results support the routine use of endometrial biopsy in all women with AUB and advocate heightened vigilance in those above 45 years of age.

This systematic review and meta-analysis demonstrate that while non-neoplastic lesions constitute the majority of endometrial findings in abnormal uterine bleeding, a clinically significant proportion-approximately 10-15%-comprises premalignant or malignant pathology. Atypical hyperplasia and endometrial carcinoma are more frequently encountered in women aged 45 years and above, highlighting the age-dependent rise in neoplastic risk. These findings reinforce the essential role of routine histopathological evaluation in all women presenting with AUB, with particular emphasis on timely endometrial sampling for perimenopausal and postmenopausal patients to ensure early detection, appropriate management, and improved clinical outcomes.

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