Intro
Endometriosis and menorrhagia represent two of the most prevalent gynecological conditions affecting women of reproductive age globally. Endometriosis affects approximately 10% of women of reproductive age worldwide, while menorrhagia affects 9% to 14%, with both conditions significantly impacting quality of life and healthcare utilization. [ 1 - 3 ] Despite their high prevalence, comparative studies examining the distinct characteristics of these conditions remain limited, particularly from Middle Eastern populations. While prevalence data from Saudi Arabia exist, [ 4 , 5 ] studies examining how regional factors might influence disease presentation remain scarce.
Endometriosis, characterized by the presence of endometrial-like tissue outside the uterine cavity, has complex pathophysiology involving retrograde menstruation, genetic predisposition, immune dysfunction, and hormonal factors. [ 6 , 7 ] The condition typically presents with chronic pelvic pain, dysmenorrhea, dyspareunia, and potential infertility, though symptom severity correlates poorly with disease extent. [ 8 ] Diagnosis often requires invasive procedures such as laparoscopy, contributing to diagnostic delays averaging 7 to 10 years from symptom onset, resulting in significant healthcare costs and reduced quality of life. [ 9 - 11 ]
Menorrhagia, clinically defined as excessive menstrual blood loss interfering with a woman’s physical, social, emotional, or material quality of life, represents a major public health concern. [ 12 ] The International Federation of Gynecology and Obstetrics (FIGO) classification system (polyp, adenomyosis, leiomyoma, malignancy-coagulopathy, ovulatory dysfunction, endometrial, iatrogenic, not yet classified [PALM-COEIN]) categorizes causes into structural and nonstructural etiologies, with the pathophysiology involving complex interactions between endometrial hemostasis, vascular function, and hormonal regulation. [ 13 , 14 ] Chronic blood loss frequently leads to iron deficiency anemia, affecting up to 63% of women with menorrhagia and significantly impacting work productivity and healthcare costs. [ 15 - 17 ]
The Saudi population presents unique characteristics that may influence gynecological disease presentation. Epidemiological studies have reported varying obesity prevalence among Saudi women, ranging from 44% in earlier studies to more recent estimates, [ 18 ] though current national data are needed, with metabolic syndrome affecting approximately 37% of the Saudi population. [ 19 ] These population-specific factors, combined with high rates of consanguinity and specific genetic polymorphisms prevalent in the region, [ 20 – 22 ] may affect disease presentation and progression in ways not captured by studies from other populations.
Red cell distribution width (RDW), a measure of red blood cell size variability routinely reported in complete blood counts, has emerged as a sensitive marker of iron deficiency, often becoming elevated before other indices change. [ 23 ] Mean platelet volume (MPV) has been proposed as a marker of platelet activation and inflammation. [ 24 ] However, no studies have systematically compared these readily available hematological parameters between endometriosis and menorrhagia in Middle Eastern populations.
This observational study aimed to characterize demographic and hematological differences between endometriosis and menorrhagia in Saudi women, providing essential baseline data for this understudied population and identifying patterns that may inform clinical management.
Author
Conceptualization: Abdulhadi M. Abdulwahed, Rawan Hussain Shahbaz.
Data curation: Meshal Marzoog Al-sharafa, Nada Tahan Alanazi, Masheal Alanazi.
Formal analysis: Abdulhadi M. Abdulwahed, Meshal Marzoog Al-sharafa.
Funding acquisition: Abdulhadi M. Abdulwahed
Investigation: Abdulhadi M. Abdulwahed, Mohammed Mahdi Alqahtani, Rawan Hussain Shahbaz.
Methodology: Abdulhadi M. Abdulwahed, Fuad Alanazi, Raed Farzan, Mohammed Mahdi Alqahtani, Meshal Marzoog Al-sharafa.
Project administration: Abdulhadi M. Abdulwahed.
Supervision: Abdulhadi M. Abdulwahed.
Writing – original draft: Abdulhadi M. Abdulwahed.
Writing – review & editing: Abdulhadi M. Abdulwahed, Fuad Alanazi, Raed Farzan, Turki F. Alselmi, Glowi Alasiri, Mamdouh Souleymane.
Methods
We conducted a retrospective observational study at King Khalid Medical City. We retrospectively identified 1087 patient records (438 with endometriosis and 649 with menorrhagia) from January 2020 to December 2024. After applying predefined inclusion and exclusion criteria, 946 patients with complete demographic and hematological data were included in the final analysis. The primary reason for exclusion was incomplete or insufficient medical records (n = 141). The study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines for cross-sectional studies (see Table, Supplemental Digital Content 1, Supplemental Digital Content, https://links.lww.com/MD/R574 ). [ 25 ]
The study included 946 female patients diagnosed with either endometriosis (n = 351, 37.1%) or menorrhagia (n = 595, 62.9%). Patient selection and inclusion are detailed in Figure, Supplemental Digital Content 6, Supplemental Digital Content, https://links.lww.com/MD/R574 , which shows the study flow diagram. Inclusion criteria were: female patients aged ≥12 years; confirmed diagnosis of either endometriosis or menorrhagia (not both); at least 1 documented clinical visit during the study period; and available complete blood count performed within 3 months of diagnosis.
Exclusion criteria included: incomplete medical records lacking basic demographic data or hematological parameters; concurrent diagnosis of both endometriosis and menorrhagia; pregnancy during the study period or within 6 months before diagnosis; active malignancy or primary hematological disorders; and current anticoagulant therapy or blood transfusion within 3 months.
Endometriosis diagnosis: All endometriosis cases (n = 351) were surgically-confirmed via laparoscopic visualization with histological confirmation, representing the gold standard for diagnosis. This rigorous diagnostic approach strengthens the validity of our comparisons.
Menorrhagia diagnosis was based on: clinical history of heavy menstrual bleeding interfering with quality of life; plus at least 1 objective criterion: pictorial blood loss assessment chart (PBAC) score > 100 when available (n = 342, 57.5%), [ 26 ] patient-reported bleeding lasting > 7 days or requiring > 5 pads/tampons daily, or hemoglobin < 120 g/L with no other identifiable cause; and exclusion of other causes through appropriate evaluation per PALM-COEIN criteria. [ 13 ] menorrhagia diagnostic criteria varied in objectivity, with 57.5% diagnosed using validated PBAC scores and 42.5% using subjective criteria (bleeding duration or pad/tampon frequency). This heterogeneity may have introduced variability in bleeding severity, potentially affecting the strength of observed hematological differences.
Data were systematically extracted from electronic medical records using a standardized form by 2 trained researchers (MMA and MMA-S), with 10% randomly audited for accuracy (>98% concordance). Variables collected included demographic characteristics (age at diagnosis, marital status), anthropometric measurements (height and weight measured within 6 months of diagnosis; Body mass index (BMI) calculated as weight (kg)/height (m) 2 and categorized per World Health Organization criteria), and hematological parameters from complete blood counts.
Hematological parameters were categorized using standard clinical cutoffs: anemia (hemoglobin < 120 g/L per World Health Organization criteria for nonpregnant women), low hematocrit (<36%), microcytosis (MCV 15%), and elevated MPV (>11 fL). These cutoffs represent clinical thresholds for abnormality rather than population-specific reference intervals. Lipid abnormalities were defined per standard criteria: high cholesterol ≥ 5.2 mmol/L, low HDL < 1.0 mmol/L, high LDL ≥ 3.4 mmol/L, and high triglycerides ≥ 1.7 mmol/L.
This observational study employed descriptive statistics to characterize differences between conditions. Categorical variables were compared using chi-square tests or Fisher’s exact test when expected cell counts were <5. Continuous variables were compared using independent t -tests. Odds ratios (OR) with 95% confidence intervals (CI) were calculated for categorical comparisons, with menorrhagia as the outcome. Complete case analysis was performed for each variable, with sample sizes reported for transparency. Exploratory discrimination metrics (sensitivity, specificity, predictive values, likelihood ratios) were calculated for descriptive purposes only and were not intended to support diagnostic use.
Given the exploratory nature, P values < .05 are reported to identify patterns warranting validation in future confirmatory studies.
The study protocol was approved by the Institutional Review Board of King Saud University (approval number: E-24-9010, date: August 21, 2024). The need for informed consent was waived due to the retrospective nature of the study using de-identified data, as approved by the Institutional Review Board (IRB). All procedures were conducted in accordance with the Declaration of Helsinki.
Results
A total of 1087 records were screened. After excluding 141 records (mostly due to incomplete data), 946 patients were included in the final analytic cohort, comprising 351 with endometriosis and 595 with menorrhagia (see diagram, Supplemental Digital Content 6, Supplemental Digital Content, https://links.lww.com/MD/R574 , which shows study flow diagram for participant selection). Complete demographic data were available for all included patients, BMI data for 701 (74.1%), and lipid profiles for 385 (40.7%). Comparison of patients with and without missing BMI data showed no significant differences in demographic or hematological parameters except for RDW (see Table, Supplemental Digital Content 2, Supplemental Digital Content, https://links.lww.com/MD/R574 , which shows comparison of patients with and without missing BMI data).
Women with endometriosis were significantly younger than those with menorrhagia (Table 1 ). Among endometriosis patients, 229/351 (65.2%) were aged < 40 years compared to 232/595 (39.0%) in the menorrhagia group (OR = 2.94, 95% CI: 2.26–3.84, P < .0001). The mean age was 35.2 ± 10.8 years for endometriosis versus 42.1 ± 11.2 years for menorrhagia patients. Detailed age distribution by decade is presented in Supplemental Digital Content 3, Supplemental Digital Content, https://links.lww.com/MD/R574 which age distribution by decade.
Baseline demographic and anthropometric characteristics.
Data are n (%) unless otherwise indicated. ORs (95% CI) compare menorrhagia with endometriosis (reference).
P values from chi-square tests unless otherwise noted.
BMI = body mass index, CI = confidence interval, OR = odds ratio, RDW = red cell distribution width.
BMI data available for 701 patients (251 endometriosis, 450 menorrhagia).
Marital status differed significantly between groups ( P < .0001; see Figure, Supplemental Digital Content 7, Supplemental Digital Content, https://links.lww.com/MD/R574 ,which shows marital status distribution). Single women comprised 187/351 (53.3%) of endometriosis cases versus 198/595 (33.3%) of menorrhagia cases. Married women had 2.41 times higher odds of having menorrhagia compared to single women (95% CI: 1.84–3.15, P < .0001).
Among patients with available BMI data (n = 701), significant differences in body weight categories were observed. Obesity (BMI ≥ 30 kg/m 2 ) was present in 221/450 (49.1%) menorrhagia patients compared to 69/251 (27.5%) endometriosis patients (OR = 2.55, 95% CI: 1.84–3.53, P < .0001). The mean BMI was 26.8 ± 6.2 kg/m 2 in endometriosis versus 30.9 ± 7.4 kg/m 2 in menorrhagia ( P < .0001). Detailed BMI distribution is shown in Supplemental Digital Content 4, Supplemental Digital Content, https://links.lww.com/MD/R574 , which shows Distribution of BMI Categories.
Comprehensive hematological analysis revealed a distinct pattern consistent with chronic iron deficiency in menorrhagia patients (Fig, 1 , Table 2 ). Menorrhagia patients demonstrated significantly higher prevalence of all iron deficiency markers. Low hemoglobin (<120 g/L) was present in 276/595 (46.4%) menorrhagia patients versus 125/351 (35.6%) endometriosis patients (OR = 1.57, 95% CI: 1.18–2.10, P = .004). Low hematocrit (<36%) showed similar patterns: 299/594 (50.3%) versus 138/351 (39.3%), respectively (OR = 1.56, 95% CI: 1.19–2.05, P = .001).
Hematological parameters comparison.
Cutoffs: hemoglobin < 120 g/L, hematocrit < 36%, MCV 15%, MPV > 11 fL.
ORs (95% CI) compare menorrhagia with endometriosis (reference). P values from chi-square tests unless otherwise noted.
CI = confidence interval, MCV = mean corpuscular volume, MPV = mean platelet volume, OR = odds ratio, RDW = red cell distribution width.
OR < 1 indicates lower odds in menorrhagia (equivalent to higher odds in endometriosis).
Comparative hematological profiles demonstrating iron deficiency pattern in menorrhagia patients. Four-panel bar graph showing the prevalence (%) of abnormal hematological parameters in women with endometriosis (n = 351, blue bars) versus menorrhagia (n = 595, pink bars). (A) Low hemoglobin (<120 g/L): 35.6% vs 46.4%, P = .004, OR = 1.57 (95% CI: 1.18–2.10). (B) Low hematocrit (<36%): 39.3% vs 50.3%, P = .001, OR = 1.56 (95% CI: 1.19–2.05). (C) Low MCV (15%): 41.0% vs 56.6%, P < .0001, OR = 1.88 (95% CI: 1.42–2.48). Error bars represent 95% confidence intervals. The comprehensive pattern of elevated RDW with microcytic anemia reflects classic chronic iron deficiency secondary to blood loss in menorrhagia patients. CI = confidence interval, MCV = mean corpuscular volume, OR = odds ratio, RDW = red cell distribution width.
Microcytosis (MCV < 80 fL) was significantly more prevalent in menorrhagia (249/595, 41.9%) compared to endometriosis (112/351, 31.9%) patients (OR = 1.54, 95% CI: 1.16–2.04, P = .003). The most striking difference was observed in RDW elevation (>15%), present in 337/595 (56.6%) menorrhagia patients versus 144/351 (41.0%) endometriosis patients (OR = 1.88, 95% CI: 1.42–2.48, P 11 fL) was more common in endometriosis (31/351, 8.8%) than menorrhagia (20/595, 3.4%) patients. Converting the OR for easier interpretation: endometriosis patients had 2.78 times higher odds of elevated MPV (95% CI: 1.56–4.95, P < .001).
No significant differences were found in RBC count ( P = .126), WBC count ( P = .366), MCH ( P = .102), MCHC ( P = .810), or platelet count ( P = .430) (see Figure, Supplemental Digital Content 8, Supplemental Digital Content, https://links.lww.com/MD/R574 , which shows normal hematological parameters).
Exploratory discrimination metrics for individual indices (RDW, hemoglobin, MCV, hematocrit) showed modest sensitivity and specificity and therefore limited clinical discrimination between conditions; full results are provided (see Table, Supplemental Digital Content 5, Supplemental Digital Content, https://links.lww.com/MD/R574 , which shows diagnostic performance metrics).
Among the subset with available lipid profiles (n = 385: 181 endometriosis, 204 menorrhagia), no significant differences were found between groups (see Figure, Supplemental Digital Content 9, Supplemental Digital Content, https://links.lww.com/MD/R574 , which shows lipid profile comparison). High total cholesterol was present in 27.6% versus 34.3% ( P = .178), low HDL in 13.8% versus 18.6% ( P = .087), high LDL in 21.5% versus 24.5% ( P = .547), and high triglycerides in 18.2% versus 23.5% ( P = .146) for endometriosis and menorrhagia, respectively.
Discussion
This observational study of 946 Saudi women demonstrates distinct demographic and hematological profiles between surgically-confirmed endometriosis and menorrhagia, providing the first comprehensive comparison of these conditions in a Middle Eastern population. The prominent iron deficiency pattern in menorrhagia characterized by elevated RDW (56.6%), microcytosis (41.9%), and anemia (46.4%) contrasts markedly with relatively preserved hematological parameters in endometriosis, offering important insights into disease phenotypes in this population with unique metabolic characteristics.
The marked age difference between groups, with endometriosis patients being predominantly younger (65.2% <40 years) compared to menorrhagia patients (39.0% <40 years), aligns with international epidemiological patterns and reflects the natural history of these conditions. [ 27 , 28 ] Endometriosis typically manifests during peak reproductive years when retrograde menstruation and hormonal factors are most active, while menorrhagia often develops later due to accumulated structural changes, uterine fibroids, and perimenopausal hormonal fluctuations. [ 29 , 30 ]
The obesity findings are particularly striking in the Saudi context, where national obesity prevalence has reached epidemic proportions. With 49.1% of menorrhagia patients being obese compared to 27.5% of endometriosis patients (OR = 2.55), our data suggest important metabolic differences between conditions. This aligns with the “adiposity paradox” in endometriosis, where several studies report inverse associations with BMI. [ 31 , 32 ] The high obesity prevalence in menorrhagia may reflect multiple mechanisms: adipose tissue aromatization leading to unopposed estrogen exposure, obesity-related anovulation causing irregular endometrial shedding, and inflammatory pathways affecting endometrial hemostasis. [ 33 , 34 ]
The comprehensive iron deficiency pattern observed in menorrhagia patients represents the most clinically relevant finding of our study. The combination of elevated RDW (56.6%), microcytosis (41.9%), and anemia (46.4%) reflects the classic progression of iron deficiency from chronic blood loss. [ 15 , 23 ] RDW elevation, showing the strongest association (OR = 1.88), deserves particular attention. As an early marker of iron deficiency, RDW increases before hemoglobin falls or MCV decreases, representing the heterogeneity in red cell size as the body produces both normal cells and smaller iron-deficient cells. [ 23 , 24 ] The 56.6% prevalence of elevated RDW in menorrhagia substantially exceeds the 10% to 15% expected in healthy Saudi populations, confirming significant iron depletion in this group. [ 35 ]
The preserved hematological parameters in endometriosis patients challenge assumptions about bleeding patterns in this condition. Despite potential irregular bleeding, our data suggest that endometriosis-associated bleeding rarely causes significant iron deficiency, possibly due to different bleeding patterns, volumes, or compensatory mechanisms. [ 36 ] This finding has important clinical implications, suggesting that significant anemia in endometriosis patients should prompt investigation for concurrent pathology rather than being attributed solely to the endometriosis. Although between-group differences were statistically robust, single indices provided limited discrimination (modest sensitivity/specificity), reinforcing that these parameters should be interpreted as supportive markers rather than diagnostic tests in isolation.
Elevated MPV was more common in endometriosis (8.8% vs 3.4%, OR = 2.78), potentially reflecting inflammatory pathways distinct from chronic blood loss. However, the small number of affected patients (n = 51) and wide confidence interval (1.56–4.95) preclude definitive conclusions. This exploratory finding warrants targeted investigation in larger cohorts. MPV reflects platelet size and activity, with larger platelets being more reactive and producing more prothrombotic factors. [ 37 ] This finding aligns with emerging evidence of endometriosis as a systemic inflammatory disorder with altered platelet function and coagulation cascades. [ 38 , 39 ] The elevated MPV might reflect chronic inflammation, oxidative stress, or altered thrombopoiesis in endometriosis, warranting further investigation as a potential biomarker for disease activity or severity.
Our findings must be interpreted within the Saudi context, where rapid epidemiological transitions have created unique health challenges. The 49.1% obesity prevalence in menorrhagia patients exceeds even the high national average of 44%, suggesting particular vulnerability in this group. [ 18 , 19 ] Cultural factors including limited physical activity due to cultural restrictions and dietary patterns characterized by low fruit and vegetable consumption may influence both disease presentation and metabolic profiles. [ 40 , 41 ]
The younger age and higher proportion of single women in the endometriosis group might reflect cultural factors affecting healthcare-seeking behavior. Marital status may influence healthcare-seeking behavior, with unmarried women facing greater stigma-related barriers to seeking reproductive health services in conservative societies, while married women might prioritize fertility concerns over pain management. [ 42 ] Additionally, the stigma associated with gynecological complaints in conservative societies may delay presentation, contributing to the diagnostic delays observed globally. [ 9 , 43 ]
This study provides several key contributions: it represents the first comparative analysis of endometriosis and menorrhagia in a Middle Eastern population, includes a large well-characterized cohort, employs systematic data collection with quality control measures, and importantly, all endometriosis cases were surgically-confirmed, eliminating diagnostic uncertainty for this group.
However, several limitations must be acknowledged. First, the cross-sectional design prevents causal inference; we cannot determine whether observed differences are causes or consequences of the conditions. Second, we present unadjusted analyses; observed associations may be confounded by age, BMI, or unmeasured factors such as dietary habits, menstrual flow volume, or medication use. Third, missing BMI data (26%) may introduce bias if missingness was related to body weight; however, sensitivity analysis showed demographic and hematological parameters were similar between patients with and without BMI data, except for slightly higher RDW in those missing BMI (see Table, Supplemental Digital Content 2, Supplemental Digital Content, https://links.lww.com/MD/R574 , which compares patients with missing BMI data). Fourth, while the hematological patterns showed P < .05, they lack sufficient discriminatory power for standalone diagnostic use. Finally, the small number of patients with elevated MPV (n = 51) limits the robustness of this finding. Fifth, menorrhagia diagnostic criteria varied in objectivity, with 57.5% diagnosed using validated PBAC scores and 42.5% using subjective criteria (bleeding duration or pad/tampon frequency). This heterogeneity may have introduced variability in bleeding severity, potentially affecting the strength of observed hematological differences. Future studies should employ standardized quantitative assessment of menstrual blood loss.
While these markers cannot be used for diagnosis, our findings have several important implications for clinical practice. The high prevalence of iron deficiency markers in menorrhagia emphasizes the need for systematic screening and treatment of iron deficiency in all women presenting with heavy menstrual bleeding, not just those with overt anemia. The distinct phenotypic patterns observed may help clinicians recognize these conditions earlier, particularly in resource-limited settings where advanced diagnostic modalities are unavailable.
Future research priorities include: prospective validation of these findings with standardized diagnostic criteria and quantitative assessment of menstrual blood loss; investigation of MPV and other platelet activation markers as potential biomarkers for endometriosis severity or treatment response; longitudinal studies to determine whether early RDW elevation predicts progression to clinical anemia and whether early intervention prevents morbidity; evaluation of culturally appropriate screening strategies for iron deficiency in at-risk populations; and multi-center Middle Eastern studies to determine whether findings extend beyond Saudi Arabia to other regional populations with similar genetic and environmental factors.
Conclusions
Women with menorrhagia demonstrated a prominent iron deficiency pattern characterized by elevated RDW (56.6%), low hemoglobin (46.4%), microcytosis (41.9%), and low hematocrit (50.3%), markedly different from the endometriosis group. Endometriosis showed preserved hematological parameters but higher MPV, suggesting distinct inflammatory pathways. These findings underscore the need for routine iron status evaluation in women with heavy menstrual bleeding and provide baseline data for Middle Eastern populations, warranting validation in prospective studies.
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