{"paper_id":"6f42b5e5-21c6-41b0-9277-5c8f434f8fd6","body_text":"RESEARCH Open Access\n© The Author(s) 2025. Open Access  This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 \nInternational License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you \ngive appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the \nlicensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or \nother third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the \nmaterial. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or \nexceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit  h t t p  : / /  c r e a  t i  \nv e c  o m m  o n s .  o r  g / l  i c e  n s e s  / b  y - n c - n d / 4 . 0 /.\nLi et al. BMC Women's Health          (2025) 25:268 \nhttps://doi.org/10.1186/s12905-025-03759-3\nBMC Women's Health\n*Correspondence:\nZhaolian Wei\nweizhaolian_1@126.com\nFull list of author information is available at the end of the article\nAbstract\nBackground Despite proposed mechanisms hypotheses, the etiology of adenomyosis remains unclear. The \nlimited efficacy of current therapeutic approaches may stem from insufficient understanding of its pathobiological \nunderpinnings and the pronounced heterogeneity in clinical presentation and treatment responsiveness among \nsubtypes. This study seeks to compare clinical and sonographic profiles of adenomyosis subtypes to elucidate distinct \ndisease mechanisms and inform subtype-specific management strategies.\nMethods In this retrospective cohort of 1,350 surgically treated and pathologically confirmed adenomyosis cases \n(2017–2022), patients were categorized into diffuse versus focal and anterior versus posterior lesion groups according \nto sonographic features. Comparative analyses of demographics, symptomatology, concurrent gynecological \nconditions, and laboratory profiles were conducted to delineate subtype-specific patterns.\nResults 1074 (79.56%) had a definitive adenomyotic sonographic signs, with 329 (30.63%) focal adenomyosis \nand 745 (69.37%) diffuse adenomyosis. Multivariate logistic regression analysis revealed that, compared with focal \nadenomyosis, diffuse adenomyosis were older (OR, 1.09; 95%CI: 1.06–1.12), had more pregnancies (OR, 1.22; 95%CI: \n1.11–1.33), 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 \nof moderate to severe dysmenorrhea (OR, 1.88; 95%CI: 1.36–2.60). Divided to the location of adenomyosis lesion \nindicated by sonographic, patients in the posterior wall group (n = 418) have higher risk of moderate to severe \ndysmenorrhea (OR, 1.88; 95% CI: 1.36–2.60), more endometriosis combination (OR, 3.24; 95%CI: 1.85–5.68) and \nintraoperative blood loss (OR, 1.001; 95%CI: 1.001–1.003).\nConclusion By stratifying adenomyosis into diffuse/focal and anterior/posterior subtypes, we identified distinct \nclinical-pathological profiles: (1) Diffuse adenomyosis was independently associated with older age, higher gravidity, \nand severe dysmenorrhea, suggesting a progressive phenotype driven by tissue injury mechanisms; (2) Posterior \nlesions exhibited a 3.24-fold risk of concurrent endometriosis and increased surgical complexity, implicating shared \nThe etiology differs regards to the locations \nof the lesion: a clinical experience of 1350 \npatients with adenomyosis confirmed \nby postoperative pathology\nWanqing Li1,2, Yuting Hang1,2, Yunyu Xu1,2, Wen Zhang1, Ye He1, Wei Ye1, Xinyue Hu2 and Zhaolian Wei1*\n\nPage 2 of 9\nLi et al. BMC Women's Health          (2025) 25:268 \nIntroduction\nAdenomyosis is a common gynecological condition in \nwomen of reproductive age that is characterized by the \npresence of ectopic endometrial tissue within the myo -\nmetrium, causing myometrial hypertrophy, hyperplasia, \nand fibrosis [ 1]. Adenomyosis is clinically characterized \nby progressive dysmenorrhea, menorrhagia, secondary \nanemia, infertility, and obstetric complications [2]. While \nnone of the above symptoms are specific to adenomyo -\nsis, the presence and/or worsening of painful symptoms \nhelp identify patients at higher risk of disease progression \nand is increasingly recognized as a hallmark feature of \nadvanced disease [3]. Similarly, a large percentage of uteri \nremoved at hysterectomies performed because of abnor -\nmal uterine bleeding (AUB) are reported to have adeno -\nmyosis either as the sole or the main pathology [4]. These \nsymptoms not only compromise patients’ health and \nquality of life but also serve as critical indicators for early \ndiagnostic suspicion, particularly in women unresponsive \nto conventional hormonal therapies [ 5]. Although histo -\npathological diagnosis following hysterectomy remains \nthe gold standard for adenomyosis confirmation, recent \nadvances in imaging modalities have enabled non-inva -\nsive diagnostic approaches. Notably, transvaginal pelvic \nultrasonography (TVUS) and magnetic resonance imag -\ning (MRI) demonstrate promising diagnostic perfor -\nmance, both achieving sensitivity and specificity rates of \n78% [6].\nA broader patient populations, including asymptom -\natic patients, women undergoing fertility evaluations, \nand even adolescents, were identified earlier with imag -\ning features of adenomyosis. Clinically, the manifesta -\ntions of adenomyosis exhibit marked heterogeneity, with \ndistinct profiles associated with lesion topography. Kishi \net al. classified the lesions according to their location in \nthe myometrium and found that the patients with diffuse \ninternal adenomyosis were older and more often had a \nhistory of uterine curettage, while those exhibiting focal -\nized adenomyosis of the external myometrium had more \noften never been pregnant and more often exhibited \nendometriosis [ 7– 9]. When comparing diffuse and nod -\nular adenomyosis, it was found that endometrial lesions \nwere more common in diffuse adenomyosis and nodular \nadenomyosis was more often associated with AUB [ 10]. \nThese findings collectively suggest that phenotypic vari -\nability may reflect distinct adenomyosis entities governed \nby divergent pathophysiological mechanisms and risk \nprofiles, underscoring the critical role of imaging in both \ndiagnostic stratification and mechanistic investigation of \ndisease progression.\nHowever, prior studies remain limited by insuffi -\ncient histopathological validation, small sample sizes, \nor incomplete characterization of lesion subtypes. The \nlimitations obstruct a mechanistic understanding of dis -\nease initiation and hinder the creation of etiology-based \ntaxonomies. This ambiguity complicates clinical deci -\nsion-making, as diffuse and focal subtypes may require \ndivergent management strategies (e.g., hormonal sup -\npression vs. surgical excision). To address these chal -\nlenges, we conducted a large-scale retrospective analysis \nof 1,350 histologically confirmed adenomyosis cases, sys -\ntematically integrating demographic, clinical, and comor-\nbidity data to establish a comprehensive phenotypic \nframework. By stratifying lesions into diffuse/focal and \nanterior/posterior subtypes via ultrasound, we dissected \netiological divergences, offering mechanistic insights into \nhow anatomical distribution and lesion extent dictate \ndisease behavior. These insights underpin the proposal \nof subtype-specific management strategies tailored to \naddress divergent pathological pathways.\nMaterials and methods\nPopulation\nThe patients who underwent partial or total hysterec -\ntomy for various gynecological diseases and diagnosed \nadenomyosis pathologically between January 2017 \nand December 2022 at the Department of Obstetrics \nand Gynecology, the First Affiliated Hospital of Anhui \nMedical University were included retrospectively. In \naccordance with the Declaration of Helsinki, the study \nprotocol was approved by the Ethics Committee of the \nFirst Affiliated Hospital of Anhui Medical University (Lot \nNo.: FAH.AMU.EC-Fast-PJ 2023-09-15).\nData extraction\nThe following data of all eligible patients were detailly \ncollected and compiled from their medical records: (1) \ndemographic characteristics, (2) symptoms presented, \n(3) the details of preoperative examination and surgical \nprocedures, and (4) pathological reports. The pathologic \ndiagnostic criteria of adenomyosis were the presence of \nendometrial glands at a distance of 3 mm from the endo -\nmetrial-myometrial junction.\nDysmenorrhea severity was classified using a 4-grade \nVerbal Descriptor Scale (None, Mild, Moderate, Severe) \n[11, 12]. Full criteria are provided in Supplementary File \nS1. “ Abnormally heavy or prolonged menstruation (> 7 \npathways with deep infiltrating endometriosis. These findings redefine adenomyosis as a heterogeneous disorder \nwith subtype-specific pathophysiology, advocating for tailored therapeutic strategies.\nKeywords Adenomyosis, Sonographic classification, Pathophysiology, Clinical heterogeneity\n\nPage 3 of 9\nLi et al. BMC Women's Health          (2025) 25:268 \ndays) was considered to be menorrhagia, and irregular \nuterine bleeding interval time (< 21 days or > 35 days) was \nsupposed to be irregular menstrual cycle. The course of \ndisease namely the duration interval from the occurrence \nof adenomyosis-related symptoms to the uterine opera -\ntion, also was recorded.\nRoutine preoperative pelvic ultrasonography was \nrecorded. The presence or absence of the following sono-\ngraphic signs for adenomyosis was evaluated: The uter -\nine shape (globular or normal); Symmetry of anterior \nand posterior wall; Presence of myometrial alterations. \nAdenomyosis is categorized as focal and diffused. Focal \nadenomyosis refers to a well-defined area in the myome -\ntrium that presents one or more of the above-mentioned \ntypical adenomyosis ultrasound signs, while diffuse ade -\nnomyosis refers to adenomyosis signs that extend to the \nentire myometrium or less than 25% of the lesions are \nsurrounded by the normal myometrium [13].\nPatients were stratified into anterior or posterior \nwall cohorts according to ultrasound-localized pri -\nmary adenomyotic lesions. Exclusion criteria comprised \npostmenopausal status, malignancy, acute abdomi -\nnal pathology, and multifocal leiomyomatosis (≥ 1 \nlesion ≥ 5 cm in maximum diameter). Unclassifiable cases \n(e.g., circumferential lesions spanning both uterine walls) \nwere systematically excluded to maintain phenotypic \nhomogeneity.\nThe uterus size was measured and calcu -\nlated by the prolate ellipse equation: Uterine Vol -\nume = D1×D2×D3 × π/6(D1, D2, and D3 represent the \nvertical, transverse, and anteroposterior diameter of the \nuterus, respectively) [14].\nBlood markers were recorded, such as systemic immu -\nnoinflammatory index (SII = platelet count × neutrophil \ncount / lymphocyte count), D-dime and carbohydrate \nantigen 125(CA125).\nThe surgery records and pathology reports from hys -\nterectomies were also reviewed. Postoperative findings, \nsuch as leiomyomas, the presence of endometriosis, and \nother gynecological conditions, were recorded.\nStatistical analysis\nData were coded and entered into a statistical analysis \nsoftware, Statistical Package for the Social Sciences(SPSS \n25.0). Continuous variables were presented as \nmeans ± standard deviations, and intragroup differences \nwere investigated using independent sample t-tests. Cat -\negorical variables were expressed as the number of cases \nand percentages. Differences between categorical data \nwere evaluated using the Chi-squared test or Fisher exact \ntest when necessary. Multivariate logistic regression anal-\nysis was performed to identify independent predictors of \nadenomyosis subtypes, adjusting for covariates as previ -\nously described with diffuse and posterior adenomyosis \npresented as odds ratios (ORs) and 95% confidence \nintervals (CIs). A two-tailed p-value less than 0.05 was \naccepted as statistically significant.\nResults\nIn the present study we included 1350 patients with \na diagnosis of adenomyosis based on histopathologi -\ncal results from uterine-sparing or non-uterine-sparing \nspecimens. The mean age of patients was 46.67 ± 5.74(23, \n81)years old (at the time of operation), 91 (6.7%)of them \nwere post-menopausal, while the remaining 1259 (93.3%)\npatients were premenopausal.\nThe main indications for operation were treatment-\nresistant menorrhagia, moderate to severe dysmenor -\nrhea, abnormal endometrial or cervical pathology, and \novarian neoplasm. A group of 213(15.8%)patients had no \ntypical symptoms and pathologically confirmed adeno -\nmyosis after surgery for other benign or malignant gyne -\ncological conditions. The characteristics of all patients \nare listed in Table 1.\nOf the patients ( n = 1350) who underwent ultrasound \nscan before surgeries, 1074 (79.56%) with a defini -\ntive adenomyotic sonographic signs. Among them, 329 \ncases (30.63%) were focal adenomyosis, while 745 cases \n(69.37%) had diffuse adenomyosis. There is no statisti -\ncally significant difference between the diffuse and focal \nadenomyosis groups regarding the age of first birth, uter -\nine operation history, and other gynecological condi -\ntion. Patients with diffuse adenomyosis tend to be older \n(46.80 ± 4.30 vs. 44.76 ± 6.56), heavier (24.41 ± 3.29 vs. \n23.86 ± 3.18) and have more pregnancies (3.58 ± 1.75 vs. \n2.86 ± 1.68) and births (1.58 ± 0.78 vs. 1.40 ± 0.72).\nOn the comparison of clinical symptoms, the propor -\ntion of patients with moderate to severe dysmenorrhea \n(66.7% vs. 45.3%) and menorrhagia (65.2% vs. 52%) in \nthe diffuse adenomyosis was higher than that in the focal \ngroup. About one-third of the patients in both groups \nhad irregular menstruation. In the diffuse adenomyosis \ngroup, 8.3% of the patients had anemia manifestations \nsuch as dizziness, weakness, and palpitations, which \nwere significantly higher than the 4.6% in the focal group. \nThere is a higher proportion of patients in the focal ade -\nnomyosis group combined with lumbosacral pain rather \nthan the diffused group (4.3% vs. 2.0%). Both groups had \nsimilar symptoms of bladder compression (4.7% vs. 4.0%) \nand rectal irritation (1.7% vs. 0.9%). The characteristics of \nthe patients are listed in Table 2.\nThe variables with statistically significant difference \nbetween the groups were included in multinomial logis -\ntic regression analysis for determining independent risk \nfactors of diffuse adenomyosis, using the focal adeno -\nmyosis group as the reference category. After adjusting \nfor confounding factors, the variables age, gravidity, BMI, \ncourse of disease, moderate to severe dysmenorrhea, and \n\nPage 4 of 9\nLi et al. BMC Women's Health          (2025) 25:268 \nasymptomatic were included in the regression model. \nThe results showed that patients in the diffuse adenomy -\nosis group were older ( OR, 1.09; 95% CI: 1.06–1.12), had \nmore pregnancies ( OR, 1.22; 95% CI: 1.11–1.33), higher \nBMI (OR, 1.05; 95% CI: 1.00-1.09), long course of disease \n(OR, 1.06; 95% CI: 1.02–1.11) and higher risk of moder -\nate to severe dysmenorrhea ( OR, 1.88; 95%CI: 1.36–2.60) \n(Table 3).\nMultinomial logistic regression with focal adenomyosis \nas the reference group, adjusted for natural labor, parity, \nabortion, the presence of menorrhagia, and symptoms of \nanemia.\nTable 1 Characteristics of the 1350 patients with pathologically \ndiagnosed adenomyosis\nVariables Results (n = 1350)\nAge(years) 46.67 ± 5.74(23, 81)\n <30 7(0.52)\n 30–40 127(9.41)\n 40–50 821(60.81)\n 50–60 378(28)\n ≥ 60 17(1.26)\nGravidity(times) 3.29 ± 1.72(0, 12)\nParity(times) 1.55 ± 0.80(0, 6)\nBMI(kg/m2) 24.21 ± 3.27(15.82, 42.06)\nMenopause(n,%)\n Yes 91(6.7)\n No 1259(93.3)\nSonographic Signs(n,%)\n Yes 1074(79.6)\n No 276(20.4)\nAsymptomatic(n,%) 213(15.8)\nHistory of Hormone Therapy(n,%) 259(19.2)\nSurgical Modality(n,%)\n non-uterine-sparing 1127(83.5)\n uterine-sparing 223(16.5)\nCombined Gynecological Conditions(n,%)\n Uterine Leiomyomas 666(49.3)\n Endometriosis 224(16.6)\n Endometrial polyps 177(13.1)\n Benign ovarian tumor 81(6.0)\n Ovarian cancer 18(1.3)\n CIN 52(3.9)\n Cervical cancer 47(3.5)\n Endometrial hyperplasia 60(4.4)\n Endometrial cancer 37(2.7)\n Other Malignant Gynecological conditions 6(0.4)\nEducation status(n,%)\n Primary 546(40.4)\n Secondary 432(32.0)\n High school 160(11.9)\n University 212(15.7)\nFor continuous variables, data are presented as means ± the standard deviation \nand (minimum, maximum) values; and for qualitative variables, the data are \nreported as number (percentage)\nBMI, body mass index; CIN, cervical intraepithelial neoplasia\nTable 2 Comparison between diffuse and focal adenomyosis \nfeatures\nVariables Diffuse(n = 745) Focal(n = 329) P\nAge(year) 46.80 ± 4.30 44.74 ± 6.46 0.000\nAge of First Birth(year) 24.16 ± 3.06 24.23 ± 3.17 0.723\nGravidity(times) 3.58 ± 1.75 2.86 ± 1.68 0.000\nParity(times) 1.58 ± 0.78 1.40 ± 0.73 0.000\n Natural Labor 1.32 ± 0.91 1.12 ± 0.85 0.001\n Cesarean Section 0.26 ± 0.52 0.28 ± 0.56 0.579\nAbortion(times) 2.00 ± 1.62 1.46 ± 1.49 0.000\nBMI(kg/m²) 24.41 ± 3.29 23.86 ± 3.18 0.012\nCourse of Disease(year) 4.94 ± 4.25 3.56 ± 3.56 0.000\nHistory of Uterine \nOperation(n,%)\n200(26.8) 92(28.0) 0.704\nClinical Symptom(n,%)\n Moderate to Severe \nDysmenorrhea\n497(66.7) 149(45.3) 0.000\n Menorrhagia 486(65.2) 171(52.0) 0.000\n Irregular Menstrual Cycle 236(33.3) 94(32.8) 0.268\n Symptoms of Anemia 62(8.3) 15(4.6) 0.028\n Bladder Compression 35(4.7) 13(4.0) 0.597\n Rectum Irritation 13(1.7) 3(0.9) 0.227\n Lumbosacral Pain 15(2.0) 14(4.3) 0.037\n Asymptomatic 40(5.4) 65(19.8) 0.000\nSurgical Modality(n,%) 0.000\n non-uterine-sparing 722(96.9) 192(58.4)\n uterine-sparing 23(3.1) 137(41.6)\nCombined Gynecological \nConditions(n,%)\n Uterine Leiomyomas 269(36.1) 131(39.8) 0.246\n Endometrial Polyps 96(12.9) 44(13.4) 0.827\n Endometriosis 130(17.4) 74(22.5) 0.052\n Benign Ovarian Tumor 37(5.0) 21(6.4) 0.344\n Ovarian Cancer 6(0.8) 3(0.9) 1.000\n CIN 17(2.3) 11(3.3) 0.314\n Cervical Cancer 15(2.0) 6(1.8) 0.836\n Endometrial Hyperplasia 38(5.1) 12(3.6) 0.297\n Endometrial Cancer 16(2.1) 2(0.6) 0.070\n Uterine Malformation 8(1.1) 4(1.2) 0.764\nData are presented as means ± the standard deviation values or n (%) as \nappropriate\nBMI, body mass index; CIN, cervical intraepithelial neoplasia\nTable 3 Risk factors of diffuse and focal adenomyosis\nVariables Diffuse adenomyosis (versus \nFocal adenomyosis)\nOR 95%CI P\nAge(years) 1.09 1.06–1.12 0.000\nGravidity(times) 1.22 1.11–1.33 0.000\nBMI(kg/m2) 1.05 1.00-1.09 0.036\nCourse of Disease(year) 1.06 1.02–1.11 0.003\nModerate to Severe Dysmenorrhea 1.88 1.36–2.60 0.000\nAsymptomatic 0.34 0.21–0.54 0.000\n\nPage 5 of 9\nLi et al. BMC Women's Health          (2025) 25:268 \nBMI: body mass index; CI: confidence interval; OR: \nodds ratio.\nFollowing the predefined exclusion criteria, 645 \npatients were eligible for subgroup analysis, including \n227 cases in the anterior wall group and 418 cases in the \nposterior wall group. There was no difference in the com-\nparison of age, BMI, uterine operation history, and course \nof disease between the two groups. The terms of gravidity \n(3.53 ± 1.82 vs. 3.12 ± 1.65) and abortion (2.00 ± 1.68 vs. \n1.67 ± 1.47) were higher in the anterior group than in the \nposterior group. Still, there was no difference in delivery, \neither natural labor (1.25 ± 0.90 vs. 1.17 ± 0.84) or cesar -\nean Sect. (0.26 ± 0.50 vs. 0.28 ± 0.56).\nMenorrhagia was significantly more common in the \nanterior group than the posterior group (67.0% vs. 54.8%, \nP = 0.003). The rate of moderate to severe dysmenor -\nrhea in the posterior group was higher than that in the \nanterior group (70.6% vs. 58%, P = 0.002). The posterior \ngroup had a higher proportion of patients with endome -\ntriosis (9.3% vs. 27.8%, P = 0.000) also more intraopera -\ntive blood loss (68.88 ± 75.53 vs. 95.08 ± 131.97, P = 0.001). \nNo significant difference was observed between the two \ngroups regarding other combined gynecological condi -\ntions. SII、D-dimer, and uterine volume were not differ -\nent between the two groups, and CA125 in the posterior \ngroup was significantly higher than in anterior group \n(Table 4).\nSII = platelet count × neutrophil count / lymphocyte \ncount; Uterine Volume = vertical diameter × transverse \ndiameter × anteroposterior diameter × π/6.\nThe variables with statistically significant difference \nbetween the groups were included in further multinomial \nlogistic regression analysis. Adjusting for gravidity, abor -\ntion, the presence of menorrhagia, symptoms of anemia, \nand CA125, the results showed that patients in the poste-\nrior adenomyosis group have higher risk of moderate to \nsevere dysmenorrhea (OR, 1.88; 95% CI: 1.36–2.60), more \nendometriosis combination (OR, 3.24; 95%CI: 1.85–5.68) \nand intraoperative blood loss ( OR, 1.001; 95% CI: 1.001–\n1.003) (Table 5).\nDiscussion\nTo our knowledge, this is most significant number of \ncases to date to investigate clinical differences between \ndiffuse and focal adenomyosis, and it is also a rare study \nto analyze lesions of the anterior and posterior walls of \nthe uterus. Adenomyosis, characterized by the ectopic \npresence of endometrial tissue within the myometrium, \nmanifests heterogeneously in terms of lesion distribu -\ntion (diffuse vs. focal) and anatomical location (anterior \nvs. posterior uterine walls). While previous studies have \nhighlighted differences in clinical and imaging features \nbetween subtypes, our study, encompassing 1,350 histo -\nlogically confirmed cases, provides novel insights into the \ndistinct pathophysiological and clinical profiles of these \nsubtypes, bridging critical gaps in understanding their \netiological and therapeutic implications.\nBased on histologically confirmed cases, we compre -\nhensively evaluated patients’ medical histories, trans -\nvaginal ultrasound (TVUS) features, and intraoperative \nfindings. Our results revealed that the “adenomyosis” was \nincidentally detected in approximately one in six cases \nduring postoperative histopathological examination. \nCompared to endometriosis, which typically requires \n6.7 to 11.7 years for diagnosis [ 15], adenomyosis exhib -\nited a shorter symptom-to-diagnosis interval, averaging \n4.3 years. Notably, 821 patients (60.81%) were aged 40 to \n50 years at the time of surgery, and fewer than 10% were \npostmenopausal. Consistent with previous studies [ 16, \n17], adenomyosis was frequently diagnosed alongside \nother gynecological comorbidities. In our cohort, 49.3% \nof cases coexisted with uterine leiomyomas, followed by \nendometriosis (16.6%) and endometrial polyps (13.1%). \nThe majority of patients presented with prominent symp-\ntoms, including moderate-to-severe dysmenorrhea, \nmenorrhagia, and irregular menstrual cycles. However, \napproximately 20% of patients had not received hormone \ntherapy, likely due to a prevalent belief among Chinese \nwomen that long-term hormonal management is “harm -\nful. ” This reluctance may contribute to accelerated disease \nprogression, highlighting the urgent need for enhanced \npublic education and primary care initiatives to improve \nearly symptom recognition and timely medical interven -\ntion. While some studies suggest that adenomyosis may \nelevate the risk of gynecological malignancies, such as \nendometrial or ovarian cancer [18], our data did not sup-\nport this association. Cervical cancer was observed in \n3.5% of adenomyosis patients, followed by endometrial \ncancer (2.7%) and ovarian cancer (1.3%). These findings \nalign with a prior study of 647 adenomyosis cases [ 19], \nwhich also found no significant increase in malignancy \nrisk among affected women.\nAbout 80% of patients had at least one definitive ade -\nnomyotic sonographic signs, with 329 (30.63%) focal ade-\nnomyosis and 745 (69.37%) diffuse adenomyosis. A study \ncomparing the ultrasound and clinical features of adeno -\nmyosis in early (18–35) and advanced (> 35) reproductive \nage found that the incidence of severe dysmenorrhea and \nfocal adenomyosis was higher in younger patients, while \nolder women present more frequently menorrhagia, dif -\nfuse and severe adenomyosis [ 20]. Our findings reinforce \nthat diffuse adenomyosis is associated with more severe \nsymptomatology, including higher rates of moderate-\nto-severe dysmenorrhea (66.7% vs. 45.3%, P < 0.001) \nand menorrhagia (65.2% vs. 52.0%, P < 0.001), compared \nto focal adenomyosis. Notably, our multivariate analy -\nsis identified older age, higher gravidity, and prolonged \ndisease duration as independent risk factors for diffuse \n\nPage 6 of 9\nLi et al. BMC Women's Health          (2025) 25:268 \nadenomyosis, suggesting a progressive nature of the dis -\nease, possibly evolving from focal lesions over time.\nAs described by Byun et al. [ 21], diffuse adenomyosis \ntypically presents as global junctional zone thickening \non MRI, whereas focal lesions appear as circumscribed \nmasses. Our data corroborate these patterns, with dif -\nfuse cases showing widespread myometrial involvement \non preoperative ultrasound, while focal lesions exhib -\nited localized hyperechoic islets. The absence of criti -\ncal quantitative data—including lesion size, thickness of \nthe affected uterine wall, and the number of direct/indi -\nrect sonographic signs—precluded standardized sever -\nity grading of adenomyosis based on established criteria \nTable 4 Comparison between anterior and posterior adenomyosis features\nVariables Anterior (n = 227) Posterior (n = 418) P\nAge(year) 45.52 ± 4.98 45.38 ± 5.24 0.747\nAge of First Birth(year) 24.11 ± 3.01 24.11 ± 3.12 0.986\nGravidity(times) 3.53 ± 1.82 3.12 ± 1.65 0.005\nParity(times) 1.52 ± 0.80 1.45 ± 0.72 0.304\n Natural Labor 1.25 ± 0.90 1.17 ± 0.84 0.239\n Cesarean Section 0.26 ± 0.50 0.28 ± 0.56 0.647\nAbortion(times) 2.00 ± 1.68 1.67 ± 1.47 0.010\nBMI(kg/m²) 24.20 ± 3.39 23.95 ± 3.07 0.353\nCourse of Disease(year) 5.45 ± 7.04 5.45 ± 6.48 0.994\nHistory of Uterine Operation(n,%) 65(28.6) 117(28.0) 0.862\nClinical Symptom(n,%)\n Moderate to Severe Dysmenorrhea 133(58.6) 295(70.6) 0.002\n Menorrhagia 152(67.0) 229(54.8) 0.003\n Irregular Menstrual Cycle 71(31.3) 149(35.6) 0.264\n Symptoms of Anemia 33(14.5) 36(8.6) 0.020\n Bladder Compression 12(5.3) 18(4.3) 0.572\n Rectum Irritation 3(1.3) 8(1.9) 0.755\n Lumbosacral Pain 2(0.9) 9(2.2) 0.344\n Asymptomatic 12(5.3) 30(7.2) 0.353\nCombined Gynecological Conditions(n,%)\n Uterine Leiomyomas 80(35.2) 131(31.3) 0.313\n Endometriosis 21(9.3) 116(27.8) 0.000\n Endometrial polyps 32(14.1) 42(10.0) 0.123\n Benign ovarian tumor 16(7.0) 23(5.5) 0.431\n Endometrial hyperplasia 11(4.8) 13(3.1) 0.266\n CIN 7(3.1) 11(2.6) 0.739\nType of adenomyosis(n,%) 0.637\n Diffuse 146(64.3) 261(62.4)\n Focal 81(35.7) 157(37.6)\nSurgical Modality(n,%) 0.877\n non-uterine-sparing 182(80.2) 333(79.7)\n uterine-sparing 45(19.8) 85(20.3)\nIntraoperative Blood Loss(ml) 68.88 ± 75.53 95.08 ± 131.97 0.001\nSII 580.34 ± 342.27 580.10 ± 386.91 0.994\nD-dimer(ug/ml) 0.29(0.11, 17.89) 0.27(0.10, 15.25) 0.197\nCA125(U/ml) 87.96 ± 65.94(171) 112.83 ± 111.97(347) 0.002\nUterine Volume(cm3) 266.18 ± 139.12(168) 265.82 ± 159.08(280) 0.981\nData are presented as means ± the standard deviation values or n (%) as appropriate\nBMI, body mass index; CIN, cervical intraepithelial neoplasia; SII, systemic immunoinflammatory index\nTable 5 Risk factors of anterior and posterior adenomyosis\nVariables Posterior adenomyosis (ver-\nsus anterior adenomyosis)\nOR 95%CI P\nModerate to Severe Dysmenorrhea 1.58 1.06–2.36 0.026\nCombined Endometriosis 3.24 1.85–5.68 0.000\nIntraoperative Blood Loss(ml) 1.001 1.001–1.003 0.015\nMultinomial logistic regression with anterior adenomyosis as the reference \ngroup, adjusted for gravidity, abortion, the presence of menorrhagia, symptoms \nof anemia, and CA125\nCI: confidence interval; OR: odds ratio\n\nPage 7 of 9\nLi et al. BMC Women's Health          (2025) 25:268 \n(e.g., lesion volume, myometrial infiltration depth). How-\never, studies have indicating that lesion distribution and \nanatomical location may serve as indirect proxies for dis -\nease severity in clinical practice [ 22– 25]. Early diagnosis \nin young women suffering from focal adenomyosis may \nhelp to interrupt the mechanisms that drive the devel -\nopment of adenomyosis, starting immediately the right \ntreatment. It has been observed that there was no differ -\nence in estrogen receptors (ER) /progesterone receptors \n(PR) expression in gland cells/stromal cells of adenomy -\notic lesions on the ipsilateral side of focal adenomyosis \nand the anterior/posterior walls of diffuse adenomyosis \n[26]. For diffuse adenomyosis, the severity of symptoms \nand responsiveness to hormonal therapies may necessi -\ntate early consideration of uterine-sparing interventions \n(e.g., gonadotropin-releasing hormone agonists) or hys -\nterectomy in refractory cases. Conversely, focal adeno -\nmyosis, with its localized pathology, may benefit from \ntargeted surgical excision, particularly in patients desir -\ning fertility preservation.\nThe pathogenesis of adenomyosis has not yet been \ndefinitively clarified. Two main theories dominate the \nliterature; the widely accepted one involves tissue injury \nand repair (TIAR) at the endo-myometrial interface, trig-\ngered by physiological or iatrogenic tissue injury, which \nfacilitates invasion of the endometrial basalis epithelial \nw/o stromal cells into the myometrium [ 27]. Another \none is metaplasia, which means that displaced embryonic \npluripotent Müllerian remnants or endometrial stem \ncells may behave aberrantly for some unknown reason \nand disintegrate into endometrial tissues [ 28, 29]. When \nstratifying patients into anterior and posterior uterine \nwall lesion groups based on adenomyosis lesion indicated \nvia ultrasonography, we observed that patients with ante-\nrior wall lesions exhibited significantly higher gravidity \nand abortion frequency compared to the posterior group. \nConversely, the posterior wall group demonstrated a \nmarkedly higher incidence of coexisting endometrio -\nsis (27.8% vs. 9.3%, P < 0.001). Furthermore, menorrha -\ngia was more prevalent in the anterior group, whereas \nmoderate-to-severe dysmenorrhea predominated in the \nposterior group. These distinct clinical profiles suggest \npotential etiopathogenetic differences between anterior \nand posterior lesions.\nPrevious studies have demonstrated that adolescent \nadenomyosis without a history of pregnancy, is charac -\nterized by coexisting endometriosis, severe dysmenor -\nrhea, and a predilection for the posterior uterine wall and \nextrinsic myometrial layer [22]. Khan et al. [30] proposed \nanother classification of adenomyosis into intrinsic and \nextrinsic types, in which the extrinsic subtype is char -\nacterized by its strong association with deep infiltrating \nendometriosis (DIE), aligns closely with our observations \nof posterior wall adenomyosis. As a diagnostic parameter \nand follow-up tool for patients with adenomyosis, the \npreoperative CA125 levels is significantly correlated with \npelvic adhesion [ 31, 32]. Our data also found that, in the \nabsence of differences in uterine volume, patients in the \nposterior wall group with higher CA125 values also expe-\nrienced more intraoperative blood loss, possibly related \nto more severe pelvic adhesions. These findings reflect \nKhan et al. ‘s report that extrinsic adenomyosis has the \nsame histopathological and molecular features as DIE, \nincluding stromal invasion and inflammatory cytokine \noverexpression, and also suggest that posterior wall ade -\nnomyosis, which is similar to extrinsic adenomyosis, may \nhave the same metaplasia as endometriosis. In contrast, \nanterior wall lesions could be linked to physiological or \niatrogenic tissue injury—potentially attributed to anterior \nuterine wall vulnerability during procedures like cesarean \nsections or curettage. It has already been experimentally \nconfirmed that mechanical or heat-induced disruption of \nthe endometrium-myometrium interface can cause ade -\nnomyosis in mice, perioperative protective measures can \nreduce the incidence of adenomyosis [ 33]. Such injury \nmay disrupt endometrial integrity, leading to endometrial \ncell migration, while simultaneously triggering aberrant \ntissue repair processes that drive adenomyosis develop -\nment. Our data show that patients with anterior lesions \nwere predominantly associated with menorrhagia, possi -\nbly due to disrupt to endometrial integrity and function. \nIn addition, consistent with observations by Khan et al., it \nrarely coexists with endometriosis, simplifying treatment \noptions such as hormonal suppression or focal resection.\nThis study elucidates distinct clinical and patho -\nphysiological profiles of adenomyosis subtypes. Diffuse \nadenomyosis, characterized by older age, higher gravid -\nity, prolonged disease duration, and severe dysmenor -\nrhea, likely represents a progressive phenotype driven \nby tissue injury and repair mechanisms. In contrast, \nfocal adenomyosis, while associated with milder symp -\ntoms and younger age, exhibited unique features such \nas higher rates of lumbosacral pain and asymptomatic \npresentation, suggesting early-stage or localized pathol -\nogy. Regarding anatomical localization, posterior wall \nlesions demonstrated a 3.24-fold increased risk of coex -\nisting endometriosis and elevated intraoperative blood \nloss, likely reflecting inflammatory complexity akin to \ndeep infiltrating endometriosis. While these findings \nhighlight the technical challenges of managing posterior \nlesions, we recommend enhance preoperative screening \n(CA125, endometriosis) (e.g., preoperative CA125 assess-\nment, endometriosis screening). Conversely, anterior \nwall lesions, linked to menorrhagia and mechanical dis -\nruption, may benefit from uterine-sparing interventions \ntargeting focal pathology.\nThis study has several limitations. First, while our \nfindings suggest potential etiopathogenetic distinctions \n\nPage 8 of 9\nLi et al. BMC Women's Health          (2025) 25:268 \nbetween anterior and posterior adenomyosis subtypes—\nwhether driven by TIAR (tissue injury and repair) \nmechanisms in anterior cases or metaplastic processes \nin posterior cases—remains speculative and require fur -\nther validation through rigorously designed studies, ide -\nally incorporating molecular profiling and longitudinal \ncohorts. Second, the retrospective inclusion of only sur -\ngically confirmed cases of adenomyosis introduced a bias \nin the selection of symptomatic or treatation-resistant \npopulations, while a majority of cases were combined \nwith uterine leiomyoma, which may confuse the cause of \nsymptoms (e.g., menorrhagia and dysmenorrhea). Third, \nwhile we stratified lesions by anterior/posterior location, \ninternal/external myometrial involvement was not sys -\ntematically evaluated. This limits our ability to correlate \nsymptom severity with specific myometrial layers, an \narea warranting prospective investigation.\nConclusion\nIn summary, our data integrated anatomical (anterior/\nposterior), distributional (diffuse/focal), and etiological \n(intrinsic/extrinsic) classifications provides a multidi -\nmensional view of adenomyosis, providing a framework \nfor subtype-driven management. By evaluating imag -\ning, biomarker (e.g., CA125), and symptomatology data, \nclinicians can better stratify patients for personalized \ntherapeutic strategies, ultimately improving outcomes in \nthis complex patient population. Future studies should \nfocus on molecular subtyping and longitudinal designs \nto unravel the mechanistic underpinnings of these \ndifferences.\nSupplementary Information\nThe online version contains supplementary material available at  h t t p  s : /  / d o i  . o  r \ng /  1 0 .  1 1 8 6  / s  1 2 9 0 5 - 0 2 5 - 0 3 7 5 9 - 3.\nSupplementary Material 1\nAcknowledgements\nWe are grateful to our study participants for their detailed medical history. \nWe thank the staff of the Record Room at the First Affiliated Hospital of Anhui \nMedical University for their support.\nAuthors’ information (optional): ZLW is Director of Obstetrics and Gynaecology, \nthe First Affiliated Hospital of Anhui Medical University (China). Her research \ninterests include endometriosis, adenomyosis, and endometrial injury.\nAuthor contributions\nZLW and WQL designed the study. WQL was a major contributor in writing the \nmanuscript. YTH and XYH collected, analyzed the data. WY and YYX collected \nthe data and assisted in literature search. YH gave suggestions, and WZ revised \nthe manuscript. All authors contributed to the article and approved the \nsubmitted version.\nFunding\nThis study was supported by“Research Funds of Center for Data and \nPopulation Health of IHM”(JKS2022009) and the National Natural Science \nFoundation of China (No.82171619).\nData availability\nThe datasets used and/or analysed during the current study are available from \nthe corresponding author on reasonable request.\nDeclarations\nEthics approval and consent to participate\nIn accordance with the Declaration of Helsinki, the study protocol was \napproved by the Ethics Committee of the First Affiliated Hospital of Anhui \nMedical University (Lot No.: FAH.AMU.EC-Fast-PJ 2023-09-15). All participants \ngave informed consent for this study.\nConsent for publication\nNot applicable.\nCompeting interests\nThe authors declare no competing interests.\nAuthor details\n1Department of Obstetrics and Gynecology, the First Affiliated Hospital of \nAnhui Medical University, No 218 Jixi Road, Hefei 230022, Anhui, China\n2Anhui Medical University, No 81 Meishan Road, Hefei 230032, Anhui, \nChina\nReceived: 25 October 2024 / Accepted: 28 April 2025\nReferences\n1. Mosele S, Stratopoulou CA, Camboni A, Donnez J, Dolmans M-M. Investiga-\ntion of the role of platelets in the aetiopathogenesis of adenomyosis. Reprod \nBiomed Online. 2021;42(4):826–34.\n2. Horton J, Sterrenburg M, Lane S, Maheshwari A, Li TC, Cheong Y. Reproduc-\ntive, obstetric, and perinatal outcomes of women with adenomyosis and \nendometriosis: a systematic review and meta-analysis. Hum Reprod Update. \n2019;25(5):592–632.\n3. Borghese G, Doglioli M, Orsini B, Raffone A, Neola D, Travaglino A, Rovero G, \nDel Forno S, de Meis L, Locci M, et al. Progression of adenomyosis: rate and \nassociated factors. Int J Gynaecol Obstet. 2024;167(1):214–22.\n4. Habiba M, Guo S-W, Benagiano G. Adenomyosis and abnormal uterine bleed-\ning: review of the evidence. Biomolecules 2024;14(6).\n5. Alcalde AM, Martínez-Zamora MÁ, Gracia M, Ros C, Rius M, Nicolás I, Carmona \nF. Impact of adenomyosis on women’s psychological health and work pro-\nductivity: A comparative Cross-Sectional study. J Womens Health (Larchmt). \n2021;30(11):1653–9.\n6. Tellum T, Nygaard S, Lieng M. Noninvasive diagnosis of adenomyosis: A struc-\ntured review and Meta-analysis of diagnostic accuracy in imaging. J Minim \nInvasive Gynecol 2020;27(2).\n7. Kishi Y, Suginami H, Kuramori R, Yabuta M, Suginami R, Taniguchi F. Four \nsubtypes of adenomyosis assessed by magnetic resonance imaging and their \nspecification. Am J Obstet Gynecol. 2012;207(2):e114111–7.\n8. Bourdon M, Santulli P , Oliveira J, Marcellin L, Maignien C, Melka L, Bordonne C, \nMillisher A-E, Plu-Bureau G, Cormier J, et al. Focal adenomyosis is associated \nwith primary infertility. Fertil Steril. 2020;114(6):1271–7.\n9. Bourdon M, Oliveira J, Marcellin L, Santulli P , Bordonne C, Maitrot Mantelet L, \nMillischer AE, Plu Bureau G, Chapron C. Adenomyosis of the inner and outer \nmyometrium are associated with different clinical profiles. Hum Reprod. \n2021;36(2):349–57.\n10. Selvi Demirtas G, Uyar I. The value of adenomyosis type in clinical assessment: \nA Single-center experience of 755 nodular and diffuse adenomyosis cases. \nArch Iran Med. 2021;24(5):374–82.\n11. Raymond AP , Chan K, Deans R, Bradbury R, Vancaillie TG, Abbott JA. A com-\nparative, Single-Blind, randomized trial of pain associated with Suction or \nNon-Suction drains after gynecologic laparoscopy. J Minim Invasive Gynecol. \n2010;17(1):16–20.\n12. Li X, Liu X, Guo S-W. Clinical profiles of 710 premenopausal women with \nadenomyosis who underwent hysterectomy. J Obstet Gynaecol Res. \n2014;40(2):485–94.\n\nPage 9 of 9\nLi et al. BMC Women's Health          (2025) 25:268 \n13. Han B, Liang T, Zhang W, Ma C, Qiao J. The effect of adenomyosis types on \nclinical outcomes of IVF embryo transfer after ultra-long GnRH agonist proto-\ncol. Reprod Biomed Online. 2023;46(2):346–51.\n14. Donnez J, Donnez O, Tourniaire J, Brethous M, Bestel E, Garner E, Charpentier \nS, Humberstone A, Loumaye E. Uterine Adenomyosis Treated by Linzagolix, \nan Oral Gonadotropin-Releasing Hormone Receptor Antagonist: A Pilot \nStudy with a New ‘Hit Hard First and then Maintain’ Regimen of Administra-\ntion. J Clin Med 2021;10(24).\n15. Nnoaham KE, Hummelshoj L, Webster P , d’Hooghe T, de Cicco Nardone F, de \nCicco Nardone C, Jenkinson C, Kennedy SH, Zondervan KT. Impact of endo-\nmetriosis on quality of life and work productivity: a multicenter study across \nten countries. Fertil Steril 2011;96(2).\n16. Brucker SY, Huebner M, Wallwiener M, Stewart EA, Ebersoll S, Schoenfisch B, \nTaran FA. Clinical characteristics indicating adenomyosis coexisting with leio-\nmyomas: a retrospective, questionnaire-based study. Fertil Steril 2014;101(1).\n17. Genc M, Genc B, Cengiz H. Adenomyosis and accompanying gynecological \npathologies. Arch Gynecol Obstet. 2015;291(4):877–81.\n18. Shen F, Liu Y, Lin L, Zhao M, Chen Q. Association of benign gynaeco-\nlogical diseases and risk of endometrial and ovarian cancers. J Cancer. \n2020;11(11):3186–91.\n19. Matalliotakis M, Zervou MI, Matalliotaki C, Goulielmos GN, Krithinakis K, \nKapetanios G, Kalogiannidis I. There is no significant correlation of adeno-\nmyosis with benign, premalignant and malignant gynecological pathologies. \nRetrospective study on 647 specimens. Ginekol Pol. 2022;93(6):467–72.\n20. Piccioni MG, Rosato E, Muzii L, Perniola G, Porpora MG. Sonographic and clini-\ncal features of adenomyosis in women in early (18–35) and advanced (> 35) \nreproductive ages. Minerva Obstet Gynecol. 2021;73(3):354–61.\n21. Byun JY, Kim SE, Choi BG, Ko GY, Jung SE, Choi KH. Diffuse and focal adeno-\nmyosis: MR imaging findings. Radiographics 1999; （19 Spec No ）:S161–\nS170.  h t t p s :   /  / d o  i .  o r  g  /  1 0  . 1 1   4 8  / r a  d i o  g r a p  h   i c s   . 1 9  . s  u  p  p  l _ 1 . g 9 9 o c 0 3 s 1 6 1\n22. Exacoustos C, Lazzeri L, Martire FG, Russo C, Martone S, Centini G, Piccione E, \nZupi E. Ultrasound findings of adenomyosis in adolescents: type and grade of \nthe disease. J Minim Invasive Gynecol 2022;29(2).\n23. Bergeron C, Amant F, Ferenczy A. Pathology and physiopathology of adeno-\nmyosis. Best Pract Res Clin Obstet Gynaecol. 2006;20(4):511–21.\n24. Tomassetti C, Meuleman C, Timmerman D, D’Hooghe T. Adenomyosis and \nsubfertility: evidence of association and causation. Semin Reprod Med. \n2013;31(2):101–8.\n25. Vercellini P , Consonni D, Dridi D, Bracco B, Frattaruolo MP , Somigliana E. \nUterine adenomyosis and in vitro fertilization outcome: a systematic review \nand meta-analysis. Hum Reprod. 2014;29(5):964–77.\n26. Khan KN, Fujishita A, Koshiba A, Mori T, Kuroboshi H, Ogi H, Itoh K, Nakashima \nM, Kitawaki J. Biological differences between focal and diffuse adeno-\nmyosis and response to hormonal treatment. Reprod Biomed Online. \n2019;38(4):634–46.\n27. Habiba M, Benagiano G, Guo S-W. An appraisal of the tissue injury and repair \n(TIAR) theory on the pathogenesis of endometriosis and adenomyosis. \nBiomolecules 2023;13(6).\n28. Guo S-W. Cracking the enigma of adenomyosis: an update on its pathogen-\nesis and pathophysiology. Reproduction. 2022;164(5):R101–21.\n29. Vannuccini S, Tosti C, Carmona F, Huang SJ, Chapron C, Guo S-W, Petraglia F. \nPathogenesis of adenomyosis: an update on molecular mechanisms. Reprod \nBiomed Online. 2017;35(5):592–601.\n30. Khan KN, Fujishita A, Koshiba A, Kuroboshi H, Mori T, Ogi H, Itoh K, Nakashima \nM, Kitawaki J. Biological differences between intrinsic and extrinsic adeno-\nmyosis with coexisting deep infiltrating endometriosis. Reprod Biomed \nOnline. 2019;39(2):343–53.\n31. Jiang C, Liu C, Guo J, Chen L, Luo N, Qu X, Yang W, Ren Q, Cheng Z. CA125 \nmodified by PLT and NLR improves the predictive accuracy of adenomyosis-\nderived pelvic dense adhesion. Medicine. 2017;96(19):e6880.\n32. Tang Y, Wen M-B, Xiang R-M, Yang M-T, Shu B, Xu F, Li J, Hu H-Q, Shi Q. Serum \nCA125 as a biomarker for dysmenorrhea in adenomyosis. Int J Gynaecol \nObstet. 2023;163(1):131–9.\n33. Wang X, Liu X, Guo S-W. Perioperative suppression of Schwann cell dedif-\nferentiation reduces the risk of adenomyosis resulting from Endometrial-\nMyometrial interface disruption in mice. Biomedicines 2022;10(6).\nPublisher’s note\nSpringer Nature remains neutral with regard to jurisdictional claims in \npublished maps and institutional affiliations.","source_license":"CC0","license_restricted":false}