The etiology differs regards to the locations of the lesion: a clinical experience of 1350 patients with adenomyosis confirmed by postoperative pathology

In the present study we included 1350 patients with a diagnosis of adenomyosis based on histopathological results from uterine-sparing or non-uterine-sparing specimens. The mean age of patients was 46.67 ± 5.74(23, 81)years old (at the time of operation), 91 (6.7%)of them were post-menopausal, while the remaining 1259 (93.3%)patients were premenopausal. The main indications for operation were treatment-resistant menorrhagia, moderate to severe dysmenorrhea, abnormal endometrial or cervical pathology, and ovarian neoplasm. A group of 213(15.8%)patients had no typical symptoms and pathologically confirmed adenomyosis after surgery for other benign or malignant gynecological conditions. The characteristics of all patients are listed in Table  1 . Table 1 Characteristics of the 1350 patients with pathologically diagnosed adenomyosis Variables Results ( n  = 1350) Age(years) 46.67 ± 5.74(23, 81)  <30 7(0.52)  30–40 127(9.41)  40–50 821(60.81)  50–60 378(28)  ≥ 60 17(1.26) Gravidity(times) 3.29 ± 1.72(0, 12) Parity(times) 1.55 ± 0.80(0, 6) BMI(kg/m 2) 24.21 ± 3.27(15.82, 42.06) Menopause(n,%)  Yes 91(6.7)  No 1259(93.3) Sonographic Signs(n,%)  Yes 1074(79.6)  No 276(20.4) Asymptomatic(n,%) 213(15.8) History of Hormone Therapy(n,%) 259(19.2) Surgical Modality(n,%)  non-uterine-sparing 1127(83.5)  uterine-sparing 223(16.5) Combined Gynecological Conditions(n,%)  Uterine Leiomyomas 666(49.3)  Endometriosis 224(16.6)  Endometrial polyps 177(13.1)  Benign ovarian tumor 81(6.0)  Ovarian cancer 18(1.3)  CIN 52(3.9)  Cervical cancer 47(3.5)  Endometrial hyperplasia 60(4.4)  Endometrial cancer 37(2.7)  Other Malignant Gynecological conditions 6(0.4) Education status(n,%)  Primary 546(40.4)  Secondary 432(32.0)  High school 160(11.9)  University 212(15.7) For continuous variables, data are presented as means ± the standard deviation and (minimum, maximum) values; and for qualitative variables, the data are reported as number (percentage) BMI, body mass index; CIN, cervical intraepithelial neoplasia Characteristics of the 1350 patients with pathologically diagnosed adenomyosis For continuous variables, data are presented as means ± the standard deviation and (minimum, maximum) values; and for qualitative variables, the data are reported as number (percentage) BMI, body mass index; CIN, cervical intraepithelial neoplasia Of the patients ( n  = 1350) who underwent ultrasound scan before surgeries, 1074 (79.56%) with a definitive adenomyotic sonographic signs. Among them, 329 cases (30.63%) were focal adenomyosis, while 745 cases (69.37%) had diffuse adenomyosis. There is no statistically significant difference between the diffuse and focal adenomyosis groups regarding the age of first birth, uterine operation history, and other gynecological condition. Patients with diffuse adenomyosis tend to be older (46.80 ± 4.30 vs. 44.76 ± 6.56), heavier (24.41 ± 3.29 vs. 23.86 ± 3.18) and have more pregnancies (3.58 ± 1.75 vs. 2.86 ± 1.68) and births (1.58 ± 0.78 vs. 1.40 ± 0.72). On the comparison of clinical symptoms, the proportion of patients with moderate to severe dysmenorrhea (66.7% vs. 45.3%) and menorrhagia (65.2% vs. 52%) in the diffuse adenomyosis was higher than that in the focal group. About one-third of the patients in both groups had irregular menstruation. In the diffuse adenomyosis group, 8.3% of the patients had anemia manifestations such as dizziness, weakness, and palpitations, which were significantly higher than the 4.6% in the focal group. There is a higher proportion of patients in the focal adenomyosis group combined with lumbosacral pain rather than the diffused group (4.3% vs. 2.0%). Both groups had similar symptoms of bladder compression (4.7% vs. 4.0%) and rectal irritation (1.7% vs. 0.9%). The characteristics of the patients are listed in Table  2 . Table 2 Comparison between diffuse and focal adenomyosis features Variables Diffuse( n  = 745) Focal( n  = 329) P Age(year) 46.80 ± 4.30 44.74 ± 6.46 0.000 Age of First Birth(year) 24.16 ± 3.06 24.23 ± 3.17 0.723 Gravidity(times) 3.58 ± 1.75 2.86 ± 1.68 0.000 Parity(times) 1.58 ± 0.78 1.40 ± 0.73 0.000  Natural Labor 1.32 ± 0.91 1.12 ± 0.85 0.001  Cesarean Section 0.26 ± 0.52 0.28 ± 0.56 0.579 Abortion(times) 2.00 ± 1.62 1.46 ± 1.49 0.000 BMI(kg/m²) 24.41 ± 3.29 23.86 ± 3.18 0.012 Course of Disease(year) 4.94 ± 4.25 3.56 ± 3.56 0.000 History of Uterine Operation(n,%) 200(26.8) 92(28.0) 0.704 Clinical Symptom(n,%)  Moderate to Severe Dysmenorrhea 497(66.7) 149(45.3) 0.000  Menorrhagia 486(65.2) 171(52.0) 0.000  Irregular Menstrual Cycle 236(33.3) 94(32.8) 0.268  Symptoms of Anemia 62(8.3) 15(4.6) 0.028  Bladder Compression 35(4.7) 13(4.0) 0.597  Rectum Irritation 13(1.7) 3(0.9) 0.227  Lumbosacral Pain 15(2.0) 14(4.3) 0.037  Asymptomatic 40(5.4) 65(19.8) 0.000 Surgical Modality(n,%) 0.000  non-uterine-sparing 722(96.9) 192(58.4)  uterine-sparing 23(3.1) 137(41.6) Combined Gynecological Conditions(n,%)  Uterine Leiomyomas 269(36.1) 131(39.8) 0.246  Endometrial Polyps 96(12.9) 44(13.4) 0.827  Endometriosis 130(17.4) 74(22.5) 0.052  Benign Ovarian Tumor 37(5.0) 21(6.4) 0.344  Ovarian Cancer 6(0.8) 3(0.9) 1.000  CIN 17(2.3) 11(3.3) 0.314  Cervical Cancer 15(2.0) 6(1.8) 0.836  Endometrial Hyperplasia 38(5.1) 12(3.6) 0.297  Endometrial Cancer 16(2.1) 2(0.6) 0.070  Uterine Malformation 8(1.1) 4(1.2) 0.764 Data are presented as means ± the standard deviation values or n (%) as appropriate BMI, body mass index; CIN, cervical intraepithelial neoplasia Comparison between diffuse and focal adenomyosis features Data are presented as means ± the standard deviation values or n (%) as appropriate BMI, body mass index; CIN, cervical intraepithelial neoplasia The variables with statistically significant difference between the groups were included in multinomial logistic regression analysis for determining independent risk factors of diffuse adenomyosis, using the focal adenomyosis group as the reference category. After adjusting for confounding factors, the variables age, gravidity, BMI, course of disease, moderate to severe dysmenorrhea, and asymptomatic were included in the regression model. The results showed that patients in the diffuse adenomyosis group were older ( OR , 1.09; 95% CI : 1.06–1.12), had more pregnancies ( OR , 1.22; 95% CI : 1.11–1.33), higher BMI ( OR , 1.05; 95% CI : 1.00-1.09), long course of disease ( OR , 1.06; 95% CI : 1.02–1.11) and higher risk of moderate to severe dysmenorrhea ( OR , 1.88; 95% CI : 1.36–2.60) (Table  3 ). Table 3 Risk factors of diffuse and focal adenomyosis Variables Diffuse adenomyosis (versus Focal adenomyosis) OR 95%CI P Age(years) 1.09 1.06–1.12 0.000 Gravidity(times) 1.22 1.11–1.33 0.000 BMI(kg/m 2) 1.05 1.00-1.09 0.036 Course of Disease(year) 1.06 1.02–1.11 0.003 Moderate to Severe Dysmenorrhea 1.88 1.36–2.60 0.000 Asymptomatic 0.34 0.21–0.54 0.000 Risk factors of diffuse and focal adenomyosis Multinomial logistic regression with focal adenomyosis as the reference group, adjusted for natural labor, parity, abortion, the presence of menorrhagia, and symptoms of anemia. BMI: body mass index; CI: confidence interval; OR: odds ratio. Following the predefined exclusion criteria, 645 patients were eligible for subgroup analysis, including 227 cases in the anterior wall group and 418 cases in the posterior wall group. There was no difference in the comparison of age, BMI, uterine operation history, and course of disease between the two groups. The terms of gravidity (3.53 ± 1.82 vs. 3.12 ± 1.65) and abortion (2.00 ± 1.68 vs. 1.67 ± 1.47) were higher in the anterior group than in the posterior group. Still, there was no difference in delivery, either natural labor (1.25 ± 0.90 vs. 1.17 ± 0.84) or cesarean Sect. (0.26 ± 0.50 vs. 0.28 ± 0.56). Menorrhagia was significantly more common in the anterior group than the posterior group (67.0% vs. 54.8%, P  = 0.003). The rate of moderate to severe dysmenorrhea in the posterior group was higher than that in the anterior group (70.6% vs. 58%, P  = 0.002). The posterior group had a higher proportion of patients with endometriosis (9.3% vs. 27.8%, P  = 0.000) also more intraoperative blood loss (68.88 ± 75.53 vs. 95.08 ± 131.97, P  = 0.001). No significant difference was observed between the two groups regarding other combined gynecological conditions. SII、D-dimer, and uterine volume were not different between the two groups, and CA125 in the posterior group was significantly higher than in anterior group (Table  4 ). Table 4 Comparison between anterior and posterior adenomyosis features Variables Anterior ( n  = 227) Posterior ( n  = 418) P Age(year) 45.52 ± 4.98 45.38 ± 5.24 0.747 Age of First Birth(year) 24.11 ± 3.01 24.11 ± 3.12 0.986 Gravidity(times) 3.53 ± 1.82 3.12 ± 1.65 0.005 Parity(times) 1.52 ± 0.80 1.45 ± 0.72 0.304  Natural Labor 1.25 ± 0.90 1.17 ± 0.84 0.239  Cesarean Section 0.26 ± 0.50 0.28 ± 0.56 0.647 Abortion(times) 2.00 ± 1.68 1.67 ± 1.47 0.010 BMI(kg/m²) 24.20 ± 3.39 23.95 ± 3.07 0.353 Course of Disease(year) 5.45 ± 7.04 5.45 ± 6.48 0.994 History of Uterine Operation(n,%) 65(28.6) 117(28.0) 0.862 Clinical Symptom(n,%)  Moderate to Severe Dysmenorrhea 133(58.6) 295(70.6) 0.002  Menorrhagia 152(67.0) 229(54.8) 0.003  Irregular Menstrual Cycle 71(31.3) 149(35.6) 0.264  Symptoms of Anemia 33(14.5) 36(8.6) 0.020  Bladder Compression 12(5.3) 18(4.3) 0.572  Rectum Irritation 3(1.3) 8(1.9) 0.755  Lumbosacral Pain 2(0.9) 9(2.2) 0.344  Asymptomatic 12(5.3) 30(7.2) 0.353 Combined Gynecological Conditions(n,%)  Uterine Leiomyomas 80(35.2) 131(31.3) 0.313  Endometriosis 21(9.3) 116(27.8) 0.000  Endometrial polyps 32(14.1) 42(10.0) 0.123  Benign ovarian tumor 16(7.0) 23(5.5) 0.431  Endometrial hyperplasia 11(4.8) 13(3.1) 0.266  CIN 7(3.1) 11(2.6) 0.739 Type of adenomyosis(n,%) 0.637  Diffuse 146(64.3) 261(62.4)  Focal 81(35.7) 157(37.6) Surgical Modality(n,%) 0.877  non-uterine-sparing 182(80.2) 333(79.7)  uterine-sparing 45(19.8) 85(20.3) Intraoperative Blood Loss(ml) 68.88 ± 75.53 95.08 ± 131.97 0.001 SII 580.34 ± 342.27 580.10 ± 386.91 0.994 D-dimer(ug/ml) 0.29(0.11, 17.89) 0.27(0.10, 15.25) 0.197 CA125(U/ml) 87.96 ± 65.94(171) 112.83 ± 111.97(347) 0.002 Uterine Volume(cm 3 ) 266.18 ± 139.12(168) 265.82 ± 159.08(280) 0.981 Data are presented as means ± the standard deviation values or n (%) as appropriate BMI, body mass index; CIN, cervical intraepithelial neoplasia; SII, systemic immunoinflammatory index Comparison between anterior and posterior adenomyosis features Data are presented as means ± the standard deviation values or n (%) as appropriate BMI, body mass index; CIN, cervical intraepithelial neoplasia; SII, systemic immunoinflammatory index SII = platelet count × neutrophil count / lymphocyte count; Uterine Volume = vertical diameter × transverse diameter × anteroposterior diameter × π/6. The variables with statistically significant difference between the groups were included in further multinomial logistic regression analysis. Adjusting for gravidity, abortion, the presence of menorrhagia, symptoms of anemia, and CA125, the results showed that patients in the posterior adenomyosis group have higher risk of moderate to severe dysmenorrhea ( OR , 1.88; 95% CI : 1.36–2.60), more endometriosis combination ( OR , 3.24; 95% CI : 1.85–5.68) and intraoperative blood loss ( OR , 1.001; 95% CI : 1.001–1.003) (Table  5 ). Table 5 Risk factors of anterior and posterior adenomyosis Variables Posterior adenomyosis (versus anterior adenomyosis) OR 95%CI P Moderate to Severe Dysmenorrhea 1.58 1.06–2.36 0.026 Combined Endometriosis 3.24 1.85–5.68 0.000 Intraoperative Blood Loss(ml) 1.001 1.001–1.003 0.015 Multinomial logistic regression with anterior adenomyosis as the reference group, adjusted for gravidity, abortion, the presence of menorrhagia, symptoms of anemia, and CA125 CI: confidence interval; OR: odds ratio Risk factors of anterior and posterior adenomyosis Multinomial logistic regression with anterior adenomyosis as the reference group, adjusted for gravidity, abortion, the presence of menorrhagia, symptoms of anemia, and CA125 CI: confidence interval; OR: odds ratio

The patients who underwent partial or total hysterectomy for various gynecological diseases and diagnosed adenomyosis pathologically between January 2017 and December 2022 at the Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University were included retrospectively. In accordance with the Declaration of Helsinki, the study protocol was approved by the Ethics Committee of the First Affiliated Hospital of Anhui Medical University (Lot No.: FAH.AMU.EC-Fast-PJ 2023-09-15). The following data of all eligible patients were detailly collected and compiled from their medical records: (1) demographic characteristics, (2) symptoms presented, (3) the details of preoperative examination and surgical procedures, and (4) pathological reports. The pathologic diagnostic criteria of adenomyosis were the presence of endometrial glands at a distance of 3 mm from the endometrial-myometrial junction. Dysmenorrhea severity was classified using a 4-grade Verbal Descriptor Scale (None, Mild, Moderate, Severe) [ 11 , 12 ]. Full criteria are provided in Supplementary File S1 . “Abnormally heavy or prolonged menstruation (> 7 days) was considered to be menorrhagia, and irregular uterine bleeding interval time ( 35 days) was supposed to be irregular menstrual cycle. The course of disease namely the duration interval from the occurrence of adenomyosis-related symptoms to the uterine operation, also was recorded. Routine preoperative pelvic ultrasonography was recorded. The presence or absence of the following sonographic signs for adenomyosis was evaluated: The uterine shape (globular or normal); Symmetry of anterior and posterior wall; Presence of myometrial alterations. Adenomyosis is categorized as focal and diffused. Focal adenomyosis refers to a well-defined area in the myometrium that presents one or more of the above-mentioned typical adenomyosis ultrasound signs, while diffuse adenomyosis refers to adenomyosis signs that extend to the entire myometrium or less than 25% of the lesions are surrounded by the normal myometrium [ 13 ]. Patients were stratified into anterior or posterior wall cohorts according to ultrasound-localized primary adenomyotic lesions. Exclusion criteria comprised postmenopausal status, malignancy, acute abdominal pathology, and multifocal leiomyomatosis (≥ 1 lesion ≥ 5 cm in maximum diameter). Unclassifiable cases (e.g., circumferential lesions spanning both uterine walls) were systematically excluded to maintain phenotypic homogeneity. The uterus size was measured and calculated by the prolate ellipse equation: Uterine Volume = D1×D2×D3 × π/6(D1, D2, and D3 represent the vertical, transverse, and anteroposterior diameter of the uterus, respectively) [ 14 ]. Blood markers were recorded, such as systemic immunoinflammatory index (SII = platelet count × neutrophil count / lymphocyte count), D-dime and carbohydrate antigen 125(CA125). The surgery records and pathology reports from hysterectomies were also reviewed. Postoperative findings, such as leiomyomas, the presence of endometriosis, and other gynecological conditions, were recorded.

In summary, our data integrated anatomical (anterior/posterior), distributional (diffuse/focal), and etiological (intrinsic/extrinsic) classifications provides a multidimensional view of adenomyosis, providing a framework for subtype-driven management. By evaluating imaging, biomarker (e.g., CA125), and symptomatology data, clinicians can better stratify patients for personalized therapeutic strategies, ultimately improving outcomes in this complex patient population. Future studies should focus on molecular subtyping and longitudinal designs to unravel the mechanistic underpinnings of these differences.

To our knowledge, this is most significant number of cases to date to investigate clinical differences between diffuse and focal adenomyosis, and it is also a rare study to analyze lesions of the anterior and posterior walls of the uterus. Adenomyosis, characterized by the ectopic presence of endometrial tissue within the myometrium, manifests heterogeneously in terms of lesion distribution (diffuse vs. focal) and anatomical location (anterior vs. posterior uterine walls). While previous studies have highlighted differences in clinical and imaging features between subtypes, our study, encompassing 1,350 histologically confirmed cases, provides novel insights into the distinct pathophysiological and clinical profiles of these subtypes, bridging critical gaps in understanding their etiological and therapeutic implications. Based on histologically confirmed cases, we comprehensively evaluated patients’ medical histories, transvaginal ultrasound (TVUS) features, and intraoperative findings. Our results revealed that the “adenomyosis” was incidentally detected in approximately one in six cases during postoperative histopathological examination. Compared to endometriosis, which typically requires 6.7 to 11.7 years for diagnosis [ 15 ], adenomyosis exhibited a shorter symptom-to-diagnosis interval, averaging 4.3 years. Notably, 821 patients (60.81%) were aged 40 to 50 years at the time of surgery, and fewer than 10% were postmenopausal. Consistent with previous studies [ 16 , 17 ], adenomyosis was frequently diagnosed alongside other gynecological comorbidities. In our cohort, 49.3% of cases coexisted with uterine leiomyomas, followed by endometriosis (16.6%) and endometrial polyps (13.1%). The majority of patients presented with prominent symptoms, including moderate-to-severe dysmenorrhea, menorrhagia, and irregular menstrual cycles. However, approximately 20% of patients had not received hormone therapy, likely due to a prevalent belief among Chinese women that long-term hormonal management is “harmful.” This reluctance may contribute to accelerated disease progression, highlighting the urgent need for enhanced public education and primary care initiatives to improve early symptom recognition and timely medical intervention. While some studies suggest that adenomyosis may elevate the risk of gynecological malignancies, such as endometrial or ovarian cancer [ 18 ], our data did not support this association. Cervical cancer was observed in 3.5% of adenomyosis patients, followed by endometrial cancer (2.7%) and ovarian cancer (1.3%). These findings align with a prior study of 647 adenomyosis cases [ 19 ], which also found no significant increase in malignancy risk among affected women. About 80% of patients had at least one definitive adenomyotic sonographic signs, with 329 (30.63%) focal adenomyosis and 745 (69.37%) diffuse adenomyosis. A study comparing the ultrasound and clinical features of adenomyosis in early (18–35) and advanced (> 35) reproductive age found that the incidence of severe dysmenorrhea and focal adenomyosis was higher in younger patients, while older women present more frequently menorrhagia, diffuse and severe adenomyosis [ 20 ]. Our findings reinforce that diffuse adenomyosis is associated with more severe symptomatology, including higher rates of moderate-to-severe dysmenorrhea (66.7% vs. 45.3%, P  < 0.001) and menorrhagia (65.2% vs. 52.0%, P  < 0.001), compared to focal adenomyosis. Notably, our multivariate analysis identified older age, higher gravidity, and prolonged disease duration as independent risk factors for diffuse adenomyosis, suggesting a progressive nature of the disease, possibly evolving from focal lesions over time. As described by Byun et al. [ 21 ], diffuse adenomyosis typically presents as global junctional zone thickening on MRI, whereas focal lesions appear as circumscribed masses. Our data corroborate these patterns, with diffuse cases showing widespread myometrial involvement on preoperative ultrasound, while focal lesions exhibited localized hyperechoic islets. The absence of critical quantitative data—including lesion size, thickness of the affected uterine wall, and the number of direct/indirect sonographic signs—precluded standardized severity grading of adenomyosis based on established criteria (e.g., lesion volume, myometrial infiltration depth). However, studies have indicating that lesion distribution and anatomical location may serve as indirect proxies for disease severity in clinical practice [ 22 – 25 ]. Early diagnosis in young women suffering from focal adenomyosis may help to interrupt the mechanisms that drive the development of adenomyosis, starting immediately the right treatment. It has been observed that there was no difference in estrogen receptors (ER) /progesterone receptors (PR) expression in gland cells/stromal cells of adenomyotic lesions on the ipsilateral side of focal adenomyosis and the anterior/posterior walls of diffuse adenomyosis [ 26 ]. For diffuse adenomyosis, the severity of symptoms and responsiveness to hormonal therapies may necessitate early consideration of uterine-sparing interventions (e.g., gonadotropin-releasing hormone agonists) or hysterectomy in refractory cases. Conversely, focal adenomyosis, with its localized pathology, may benefit from targeted surgical excision, particularly in patients desiring fertility preservation. The pathogenesis of adenomyosis has not yet been definitively clarified. Two main theories dominate the literature; the widely accepted one involves tissue injury and repair (TIAR) at the endo-myometrial interface, triggered by physiological or iatrogenic tissue injury, which facilitates invasion of the endometrial basalis epithelial w/o stromal cells into the myometrium [ 27 ]. Another one is metaplasia, which means that displaced embryonic pluripotent Müllerian remnants or endometrial stem cells may behave aberrantly for some unknown reason and disintegrate into endometrial tissues [ 28 , 29 ]. When stratifying patients into anterior and posterior uterine wall lesion groups based on adenomyosis lesion indicated via ultrasonography, we observed that patients with anterior wall lesions exhibited significantly higher gravidity and abortion frequency compared to the posterior group. Conversely, the posterior wall group demonstrated a markedly higher incidence of coexisting endometriosis (27.8% vs. 9.3%, P  < 0.001). Furthermore, menorrhagia was more prevalent in the anterior group, whereas moderate-to-severe dysmenorrhea predominated in the posterior group. These distinct clinical profiles suggest potential etiopathogenetic differences between anterior and posterior lesions. Previous studies have demonstrated that adolescent adenomyosis without a history of pregnancy, is characterized by coexisting endometriosis, severe dysmenorrhea, and a predilection for the posterior uterine wall and extrinsic myometrial layer [ 22 ]. Khan et al. [ 30 ] proposed another classification of adenomyosis into intrinsic and extrinsic types, in which the extrinsic subtype is characterized by its strong association with deep infiltrating endometriosis (DIE), aligns closely with our observations of posterior wall adenomyosis. As a diagnostic parameter and follow-up tool for patients with adenomyosis, the preoperative CA125 levels is significantly correlated with pelvic adhesion [ 31 , 32 ]. Our data also found that, in the absence of differences in uterine volume, patients in the posterior wall group with higher CA125 values also experienced more intraoperative blood loss, possibly related to more severe pelvic adhesions. These findings reflect Khan et al. ‘s report that extrinsic adenomyosis has the same histopathological and molecular features as DIE, including stromal invasion and inflammatory cytokine overexpression, and also suggest that posterior wall adenomyosis, which is similar to extrinsic adenomyosis, may have the same metaplasia as endometriosis. In contrast, anterior wall lesions could be linked to physiological or iatrogenic tissue injury—potentially attributed to anterior uterine wall vulnerability during procedures like cesarean sections or curettage. It has already been experimentally confirmed that mechanical or heat-induced disruption of the endometrium-myometrium interface can cause adenomyosis in mice, perioperative protective measures can reduce the incidence of adenomyosis [ 33 ]. Such injury may disrupt endometrial integrity, leading to endometrial cell migration, while simultaneously triggering aberrant tissue repair processes that drive adenomyosis development. Our data show that patients with anterior lesions were predominantly associated with menorrhagia, possibly due to disrupt to endometrial integrity and function. In addition, consistent with observations by Khan et al., it rarely coexists with endometriosis, simplifying treatment options such as hormonal suppression or focal resection. This study elucidates distinct clinical and pathophysiological profiles of adenomyosis subtypes. Diffuse adenomyosis, characterized by older age, higher gravidity, prolonged disease duration, and severe dysmenorrhea, likely represents a progressive phenotype driven by tissue injury and repair mechanisms. In contrast, focal adenomyosis, while associated with milder symptoms and younger age, exhibited unique features such as higher rates of lumbosacral pain and asymptomatic presentation, suggesting early-stage or localized pathology. Regarding anatomical localization, posterior wall lesions demonstrated a 3.24-fold increased risk of coexisting endometriosis and elevated intraoperative blood loss, likely reflecting inflammatory complexity akin to deep infiltrating endometriosis. While these findings highlight the technical challenges of managing posterior lesions, we recommend enhance preoperative screening (CA125, endometriosis) (e.g., preoperative CA125 assessment, endometriosis screening). Conversely, anterior wall lesions, linked to menorrhagia and mechanical disruption, may benefit from uterine-sparing interventions targeting focal pathology. This study has several limitations. First, while our findings suggest potential etiopathogenetic distinctions between anterior and posterior adenomyosis subtypes—whether driven by TIAR (tissue injury and repair) mechanisms in anterior cases or metaplastic processes in posterior cases—remains speculative and require further validation through rigorously designed studies, ideally incorporating molecular profiling and longitudinal cohorts. Second, the retrospective inclusion of only surgically confirmed cases of adenomyosis introduced a bias in the selection of symptomatic or treatation-resistant populations, while a majority of cases were combined with uterine leiomyoma, which may confuse the cause of symptoms (e.g., menorrhagia and dysmenorrhea). Third, while we stratified lesions by anterior/posterior location, internal/external myometrial involvement was not systematically evaluated. This limits our ability to correlate symptom severity with specific myometrial layers, an area warranting prospective investigation.

Data were coded and entered into a statistical analysis software, Statistical Package for the Social Sciences(SPSS 25.0). Continuous variables were presented as means ± standard deviations, and intragroup differences were investigated using independent sample t-tests. Categorical variables were expressed as the number of cases and percentages. Differences between categorical data were evaluated using the Chi-squared test or Fisher exact test when necessary. Multivariate logistic regression analysis was performed to identify independent predictors of adenomyosis subtypes, adjusting for covariates as previously described with diffuse and posterior adenomyosis presented as odds ratios (ORs) and 95% confidence intervals (CIs). A two-tailed p -value less than 0.05 was accepted as statistically significant.

Adenomyosis is a common gynecological condition in women of reproductive age that is characterized by the presence of ectopic endometrial tissue within the myometrium, causing myometrial hypertrophy, hyperplasia, and fibrosis [ 1 ]. Adenomyosis is clinically characterized by progressive dysmenorrhea, menorrhagia, secondary anemia, infertility, and obstetric complications [ 2 ]. While none of the above symptoms are specific to adenomyosis, the presence and/or worsening of painful symptoms help identify patients at higher risk of disease progression and is increasingly recognized as a hallmark feature of advanced disease [ 3 ]. Similarly, a large percentage of uteri removed at hysterectomies performed because of abnormal uterine bleeding (AUB) are reported to have adenomyosis either as the sole or the main pathology [ 4 ]. These symptoms not only compromise patients’ health and quality of life but also serve as critical indicators for early diagnostic suspicion, particularly in women unresponsive to conventional hormonal therapies [ 5 ]. Although histopathological diagnosis following hysterectomy remains the gold standard for adenomyosis confirmation, recent advances in imaging modalities have enabled non-invasive diagnostic approaches. Notably, transvaginal pelvic ultrasonography (TVUS) and magnetic resonance imaging (MRI) demonstrate promising diagnostic performance, both achieving sensitivity and specificity rates of 78% [ 6 ]. A broader patient populations, including asymptomatic patients, women undergoing fertility evaluations, and even adolescents, were identified earlier with imaging features of adenomyosis. Clinically, the manifestations of adenomyosis exhibit marked heterogeneity, with distinct profiles associated with lesion topography. Kishi et al. classified the lesions according to their location in the myometrium and found that the patients with diffuse internal adenomyosis were older and more often had a history of uterine curettage, while those exhibiting focalized adenomyosis of the external myometrium had more often never been pregnant and more often exhibited endometriosis [ 7 – 9 ]. When comparing diffuse and nodular adenomyosis, it was found that endometrial lesions were more common in diffuse adenomyosis and nodular adenomyosis was more often associated with AUB [ 10 ]. These findings collectively suggest that phenotypic variability may reflect distinct adenomyosis entities governed by divergent pathophysiological mechanisms and risk profiles, underscoring the critical role of imaging in both diagnostic stratification and mechanistic investigation of disease progression. However, prior studies remain limited by insufficient histopathological validation, small sample sizes, or incomplete characterization of lesion subtypes. The limitations obstruct a mechanistic understanding of disease initiation and hinder the creation of etiology-based taxonomies. This ambiguity complicates clinical decision-making, as diffuse and focal subtypes may require divergent management strategies (e.g., hormonal suppression vs. surgical excision). To address these challenges, we conducted a large-scale retrospective analysis of 1,350 histologically confirmed adenomyosis cases, systematically integrating demographic, clinical, and comorbidity data to establish a comprehensive phenotypic framework. By stratifying lesions into diffuse/focal and anterior/posterior subtypes via ultrasound, we dissected etiological divergences, offering mechanistic insights into how anatomical distribution and lesion extent dictate disease behavior. These insights underpin the proposal of subtype-specific management strategies tailored to address divergent pathological pathways.

Below is the link to the electronic supplementary material. Supplementary Material 1 Supplementary Material 1