Association of the presence of adenomyosis and clinical characteristics in post-hysterectomy patients

Introduction: It has been estimated that the prevalence of adenomyosis is 5-70% in Mexico. For the correct study of ade - nomyosis, the histopathological study of the hysterectomy specimen remains the only confirmatory diagnosis. For this reason, there are not many current studies that tell us the prevalence of this pathology, which is why it is important to carry out intentional searches. Objective: T o estimate the prevalence of adenomyosis in patients undergoing total and subtotal hyster - ectomy, abdominal, laparoscopic, and vaginal hysterectomy in the period from 2019 to 2021 in Ciudad Juárez and to determine whether there are clinical factors associated with the presence of adenomyosis. Material and methods: Cross-sectional, retrospective, descriptive study. This study was conducted in patients who underwent total and subtotal abdominal, laparo - scopic, and vaginal hysterectomy, whose histopathological reports were collected from January 2019 to December 2021 . Patients with a subtotal hysterectomy were excluded. Results: A  total of 332 patients were studied, in which a prevalence of 29.5% was observed, like that established in the general biblio graphy. Conclusions: Adenomyosis is the second gyneco - logical pathology in order of frequency, only below leiomyomatosis, by histopathological diagnosis. According to the study, the clinical profile of patients to be ruled out for adenomyosis would be a history of previous uterine surgery, multiparity, in the fifth decade of life (specifically between 40 and 50 years of age), overweight, or obese.

Adenomyosis. Hysterectomy. Uterine hemorrhage. Uterine diseases. Mexico. *Correspondence: Luis A. Pantoja-Quezada E-mail: [email protected] Available online: 01-10-2025 Rev Med Hosp Gen Mex. 2025;88(4):196-201 www.hospitalgeneral.mx Date of reception: 14-12-2024 Date of acceptance: 03-04-2025 DOI: 10.24875/HGMX.24000096 0185-1063/© 2025 Sociedad Médica del Hospital General de Mexico. Published by Permanyer. This is an open access article under the CC BY -NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Dysfunctional uterine bleeding is the main cause of bleeding in adult women; its diagnosis is the exclusion of anatomical alterations, so the clinician must initially rule out any organic or endocrinological pathology. It is estimated that around 10 million women in Mexico suffer from uterine bleeding, and annually, only 6 million of them seek medical attention 1. The exact pathogenesis of adenomyosis has not been established, but some theories have been widely accepted and adopted by physicians 2. The most com - mon theory suggests that adenomatosis results from the invagination of endometrial glands and stroma in the thickness of the myometrium, together with hyper - plasia and hypertrophy of smooth muscle fibers of the latter3. Another possible theory is that the adenomyotic lesions are due to the metaplasia of displaced Müllerian remains or to the differentiation of adult stem cells 4. The prevalence of adenomyosis as an anatomo - pathological finding is highly variable, ranging from 5% to 70%, depending on the depth limit considered in the microscopic finding of foci in myometrial thickness1. Arel- lano Pichardo et al. in a study carried out in the Mexican population, they showed that the prevalence of Revista Médica del Hospital General de México C.M. Rivas-Arredondo et al. Adenomyosis in hysterectomized women 197 adenomyosis in hysterectomy specimens was 33.33% (86 out of 258 patients) 3, as well as a study carried out in the United States in which a total of 135,162 women between 16 and 60 years of age were analyzed in 2015, in which 1,068 women had a previous diagnosis of adenomyosis. Thus, the prevalence of adenomyosis in 2015 was observed to be 0.8-1.5%; being higher among women aged 41-45 years 5. The confirmatory diagnosis requires hysterectomy, in order to study the entire piece. The minimum distance required to make the diagnosis has remained under debate, but ranges from half to two low-power fields from the endomyometrial junction or a minimum depth of invasion ranging from 1 to 4 mm. The involvement of at least 25% to one-third of myometrial thickness is another diagnostic criterion that has been used in mag - netic resonance imaging (MRI) 6,7. Hysterectomy is the only definitive treatment for ade - nomyosis, which allows us to perform the histopatho - logical study of the specimen and thus obtain the microscopic result and obtain the definitive diagnosis 8. The objective of this study is to determine if there is an association between clinical variables and the pres - ence of adenomyosis in patients undergoing total abdominal and subtotal hysterectomy at the Ciudad Juárez Women’s Hospital, with the following specific

(1) to know the age groups with the highest frequency of adenomyosis at the Ciudad Juárez Wom - en’s Hospital, (2) to identify the comorbidities present in patients diagnosed with adenomyosis at the Wom - en’s Hospital of Ciudad Juárez, (3) to perform inference between patients with adenomyosis and without ade - nomyosis, and (4) to perform a multivariate model to identify variables associated with the presence of adenomyosis.

An observational, retrospective, cross-sectional, descriptive, and analytical study was conducted in 332 women after total and subtotal non-obstetric hysterec - tomy at the Hospital de la Mujer of Ciudad Juarez, from January 01, 2019, to December 31, 2021. Clinical records were reviewed, and a database was built in Microsoft Excel 2019. As selection criteria, patients undergoing hysterectomy, both of obstetric and gyne - cological origin, with total or subtotal technique, from January 01, 2019 to December 31, 2021, had a histo - pathological report, as well as patients who had in their clinical history the variables studied (age, multigesta - tion, and body mass index [BMI], history of previous gynecology and obstetrics, adenomyosis, diabetes mel - litus, and systemic arterial hypertension), as non-inclu - sion criteria we take patients who are not in the virtual or physical clinical record, patients whose clinical his - tory lacks the previously mentioned variables and finally because they do not have a pathology report. Statistical analysis To perform the analysis and graph s of this work, the statistical program IBM Statistical Packages for the Social Sciences V.23 for Windows 10 was used. Kolm - ogorov-Smirnov normality tests were applied to assess the distribution of variables. The inference analysis for the quantitative variables was performed using Stu - dent’s t-test or Mann-Whitney’s U-test, as appropriate, while Pearson’s Chi-square test was used for the qual - itative variables. Logistic regression was performed considering statistically significant variables as inde - pendent variables for adenomyosis status. The best model was constructed using the backward step tech - nique considering Wald’s statistic. A value of p < 0.05 was considered to be statistically significant for all sta - tistical tests used.

In a sample of 332 women post-operated obstetric hysterectomy at the Hospital de la Mujer of Ciudad Juarez, from January 01, 2019 to December 31, 2021 . A  total of 98  (29.5%) patients with histopathological diagnosis of adenomyosis were detected; in this way, it was determined that the prevalence of adenomyosis in the studied population was 29.5% (98 of 332 patients). The sample found a median age of 45  years with an interquartile range of 39-50 years. In our sample, a total of 234 women (70.4%) had a BMI > 25 kg/m 2. A total of 212 women (63.9%) had a history of cesarean sec- tion, and 242 (72.9%) were categorized as multigesta- tion. 19% (63) of the women in this study had a diagnosis of diabetes and 28.6% (95) had hypertension. Among the causes of hysterectomy, it was found that 63.6% (211) were due to uterine myomatosis, 11 .7% (39) were due to pelvic organ prolapse, 9.9% (33) due to obstetric hemorrhage, and 6.6% (22) due to placental alteration, the rest of the causes are described in table 1 . A total of 98 women (29.5%) had a diagnosis of ade- nomyosis according to the pathological study (Table 1 ). Patients were grouped according to the histopathologi - cal diagnosis of adenomyosis, finding that the median age in women without adenomyosis was 44  (36-49) Revista Médica del Hospital General de México. 2025;88(4) 198 while in women with adenomyosis it was 47  (42-50), p = 0.010 (Fig . 1 ). In the group of women without ade - nomyosis, 68.8% had a BMI > 25  kg/m 2 and in the group of women with adenomyosis, 75.5% had a BMI > 25 kg/m 2 (p = 0.220). Regarding the history of previ - ous obstetric surgeries, the history was present in 57 .1% of the women in the group with a diagnosis of adenomyosis, whereas the history was present in 66.7% of the women without adenomyosis (p = 0.099) (Table 1). Regarding the categorization of multigest, 73.9% and 70.4% of the group without adenomyosis and with a diagnosis of adenomyosis were found to be multigest, respectively (p = 0.510). 18.4% of women without ade - nomyosis had diabetes, and the same diagnosis occurred in 20.4% of women with adenomyosis (p = 0.667). 28.6% of women with and without adenomyosis had hypertension (p = 0.991). 2 logistic models were performed, in the first (Table 2), all binary variables were entered, taking the presence of adenomyosis as a dependent variable, finding statistical significance with age (B = 0.026 [odds ratio (OR) = 1 .026 95% confidence interval (CI) = 1 .002-1 .051], p = 0.035). Due to the result obtained, the elimination of covariates was carried out using Wald’s statistical criterion (Table 3), finding statis- tical significance for age (B = 0.026 [OR = 1 .026 95% CI = 1 .003-1 .049], p = 0.026].

Total hysterectomy is the most common gynecolog - ical surgery in the world. In our study, hysterectomies performed in 1 year (n = 332) were considered, using laparotomy, laparoscopy, and vaginality. The type of surgery to be performed is decided according to the characteristics of the uterus and the concomitant pathologies 3,9. Table 1. General characteristics of the population Variable Total (%) Adenomyosis (%) p No (234) Yes (98) Age (years) 45 (39‑50) 44 (36‑49) 47 (42‑50) 0.010*u BMI > 25 kg/m 2 Yes No 235 (70.8) 97 (29.2) 161 (68.8) 73 (31.2) 74 (75.5) 24 (24.5) 0.220 Xi Previous gynecological and obstetrical surgeries Yes No 212 (63.9) 120 (36.1) 156 (66.7) 78 (33.3) 56 (57.1) 42 (42.9) 0.099 Xi Multigesta Yes No 242 (72.9) 90 (27.1) 173 (73.9) 61 (26.1) 69 (70.4) 29 (29.6) 0.510 Xi Causes of hysterectomy Placental alteration Obstetric bleeding Myomatosis NIC 1 NIC 2 NIC 3 Oncologic process Pelvic organ prolapse Others 22 (6.6) 33 (9.9) 211 (63.6) 3 (0.9) 4 (1.2) 5 (1.5) 8 (2.4) 39 (11.7) 7 (2.1) 19 (8.1) 27 (11.5) 145 (62) 2 (0.9) 4 (1.7) 5 (2.1) 5 (2.1) 22 (9.4) 3 (3.1) 6 (6.1) 66 (67.3) 1 (1) 0 (0) 0 (0) 3 (3.1) 17 (17.3) 0.035* Xi Diabetes Yes No 63 (19) 269 (81) 43 (18.4) 191 (81.6) 20 (20.4) 78 (79.6) 0.781 Xi Hypertension Yes No 95 (28.6) 268 (81) 67 (28.6) 167 (71.4) 28 (28.6) 70 (71.4) > 0.999 pXi This table shows median and IQR 25‑75% and frequency in number and percentage *: statistical significance (p < 0.05). u: Mann Whitney´s U test. Xi: Pearson´s Chi squared. BMI: body mass index; NIC: neoplasia intraepitelial cervical. C.M. Rivas-Arredondo et al. Adenomyosis in hysterectomized women 199 In the literature, abnormal uterine bleeding with or without leiomyomatosis is reported as the main cause of hysterectomy. Leiomyomatosis is the cause of up to 55%10. In our study, uterine leiomyomatosis was the most frequent definitive diagnosis, with 211 cases, rep - resenting 63.5% of the sample, a percentage higher than what was reported worldwide. Either alone or in combination with other conditions, was the second most frequent diagnosis, with a prevalence of 29.5%. This finding is consistent with global reports, where prevalence ranges from 2.6% to 70% in pathology specimens. However, in none of the procedures was adenomyosis the primary indication for hysterectomy, as it was diagnosed histopathologically and justified by other clinical causes 11,12. Endovaginal ultrasound is the most important imag - ing technique in gynecological patients. The radiologist requires experience to identify adenomyosis. This is explained by the great difficulty in making the prior diagnosis. There are studies that mention that ultra - sound and MRI can establish the diagnosis with a sensitivity of 89% 13-15. However, to suspect adenomyo - sis, a detailed description of the myometrium described in the morphological uterus sono graphic assessment criteria is required, which is not done routinely and only has the experience of some physicians assigned to gynecology; for this reason, it is emphasized that each of these criteria is made known to all personnel and thus be able to carry out an adequate approach to this pathology16. Adenomyosis is a condition with variable frequency depending on the population studied. It is most com - monly diagnosed between 40 and 50 years of age, accounting for up to 80% of cases. For the purposes of this study, and to better localize the pathology, patients were grouped by decades. The highest fre - quency of diagnosis was found in the 40-50-year age group, with a rate of 63.2%, which is consistent with findings reported in the global literature 9. Regarding obstetric history, 70.4% of patients with adenomyosis were multigested. Patients with 2 or fewer gestates accounted for 29.6% of reported cases of adenomyo - sis. According to several authors, most cases of ade - nomyosis occur in multigestation patients (90%), consolidating itself as one of the main risk factors 4,7,17. Regarding the history of previous uterine surgery and the presence of adenomyosis, it occurred in 57.1% of the patients, specifically the history of cesarean section and instrumented uterine curettage. Uterine trauma during a cesarean section, curettage, or myomectomy are the classic risk factors 17. BMI also plays an import - ant role18. Overweight patients or with some degree of obesity make up 70.7% of the total number of patients Table 2. Multiple logistic regression for the presence of adenomyosis in women after hysterectomy obstetric Variable B Wald p OR (95% CI) BMI > 25 kg/m2 0.307 1.189 0.275 1.359 (0.783‑2.359) Previous gyneco‑ obstetrical surgeries 0.306 1.436 0.231 1.358 (0.823‑2.240) Multigesta −0.259 0.871 0.521 0.772 (0.448‑1.329) Diabetes 0.111 0.124 0.725 1.117 (0.603‑2.068) Hypertension −0.188 0.430 0.512 0.829 (0.473‑1.452) Age 0.026 4.442 0.035* 1.026 (1.002‑1.051) B: logistic regression coefficient; Wald: Wald statistic; p: value of p; OR: odds ratio; 95% CI: Confidence interval at 95%. ; BMI: body mass index. *: statistical significance (p < 0.05). Table 3. Multiple logistic regression for the presence of adenomyosis in women after obstetric hysterectomy Variable B Wald p OR (95% CI) Age 0.026 4.935 0.026* 1.026 (1.003‑1.049) B: logistic regression coefficient; Wald: Wald statistic; p: value of p; OR: odds ratio; 95% CI: confidence interval at 95%. *: statistical significance (p < 0.05). Figure 1. Age of the patients included in the study according to diagnosis of adenomyosis. The p value corresponds to the Mann’s U‑test. Revista Médica del Hospital General de México. 2025;88(4) 200 studied in our sample, of which 75.5% were diagnosed with adenomyosis. In adenomyosis, the role of hyper - estrogenism plays an important role, as it is a risk factor and is frequently found in overweight or obese women 11. The presence of diabetes mellitus or systemic arterial hypertension are variables that in our study, we did not find with statistical significance, a total of 63  patients presented a diagnosis of diabetes mellitus (18.9%), of which twenty presented a diagnosis of adenomyosis (20.4%), similar figures with systemic arterial hyperten - sion, in which we have 95 reported cases (28.6%) of which 28 patients presented a diagnosis of adenomy - osis (28.6%). However, we found that age is associated with the presence of adenomyosis (OR = 1.026, [95% CI = 1.003-1.049], p = 0.026). Clinical diagnosis is difficult, due to nonspecific signs and symptoms, which often coexist with other pelvic diseases 1. In the present study, most of the patients had abnormal uterine bleeding as their main anteced - ent; in 73.4% of them, so in all patients with a study protocol for abnormal uterine bleeding, adenomyosis should be considered as a diagnostic probability, and the appropriate protocol for its diagnosis should be performed. Currently, there is a limited series of studies, but important to perform for presurgical diagnosis, which are, in addition to clinical suspicion, ultrasound and, in some cases, MRI, this in an attempt by gynecologists to define the various characteristics resulted in the criteria for morphological sonograph ic evaluation of the uterus 19. In these cases, adenomyosis is consid - ered when the uterus has a globular con figuration and multiple areas of shadow, sometimes described as fan-shaped, are visible, with difficulty in differentiating the myometrium from the junction zone and cystic changes in the junction zone and myometrium 20. Addi- tional features that can be observed include an irreg - ular or interrupted area of conjunction with islands 18,20. Unfortunately, there are no classic findings on physical examination or laboratory studies that identify it as a probable diagnosis 20. Future applications of artificial intelligence (AI) in medicine, specifically related to our topic of adenomy - osis classification 16,18, and need to be discussed. Sys - tems based on conjunction zone anomalies have shown promising results in terms of observer agreement and correlation with clinical symptoms. Recently, there has been growing interest in the potential of AI to improve the accuracy and consistency of the diagnosis and classification of adenomyosis. It has been suggested that AI-based ultrasound or MRI image analysis could accurately identify and classify different types of ade - nomyosis based on the abnormalities of the conjunc - tion zone16. This approach has the potential to improve the standardization and reproducibility of presurgical diagnosis of adenomyosis, as AI algorithms can ana - lyze large datasets and identify patterns that may not be immediately apparent to human physicians 15,16,21. However, as in many areas of medicine, more research is needed to evaluate these approaches and explore whether they provide answers to clinically relevant questions.

The prevalence of adenomyosis at the Ciudad Juárez Women’s Hospital is 29.4%. Adenomyosis is the second gynecological pathology in order of frequency, only below leiomyomatosis, by histopathological diagnosis. According to the study, the clinical profile of patients to be ruled out for adenomyosis would be a history of pre - vious uterine surgery, multiparity, in the fifth decade of life (specifically between 40 and 50 years of age), over - weight, or obese. Previous uterine surgery is an import - ant factor, found in 57.2% of patients. The most common surgery is cesarean section. It is essential to include in the study protocol of patients with suspected adenomy - osis, an ultrasound that includes a complete description of the myometrium, subendometrial space, and endome- trium. The outpatient service does not have sonography equipment, so the diagnosis of adenomyosis is impos - sible. In none of the patients who underwent hysterec - tomy was the presence of adenomyosis diagnosed before the surgical event. Training is required for the resident and affiliated physicians of our institute due to the evident lack of knowledge and expertise for the pre - operative diagnosis of adenomyosis. None of the patients was the suspicion of adenomyosis contemplated in the clinical file. Age may be a factor associated with the presence of adenomyosis; however, more observational studies are required to corroborate these findings. Funding The authors declare that they have not received funding. Conflicts of interest The authors declare no conflicts of interest. C.M. Rivas-Arredondo et al. Adenomyosis in hysterectomized women 201 Ethical considerations Protection of humans and animals. The authors declare that no experiments involving humans or ani - mals were conducted for this research. Confidentiality, informed consent, and ethical approval. The authors have obtained approval from the Ethics Committee for the analysis of routinely obtained and anonymized clinical data, so informed consent was not necessary. Relevant guidelines were followed. Declaration on the use of artificial intelligence. The authors declare that no generative artificial intelli - gence was used in the writing of this manuscript.

1. Ibarra Chavarría V, Plasencia Lira J. Diagnóstico y Tratamiento de la Hemorragia Uterina Disfuncional. Ciudad de México: Secretaría de Salud; 2013. Available from: https://www.gob.mx/cms/uploads/attach - ment/file/28954/HemorragiaUterinaDisfuncional.pdf [Last accessed on 2024 Oct 18]. 2. Shubham D, Kawthalkar AS. Critical evaluation of the PALM-COEIN classification system among women with abnormal uterine bleeding in low-resource settings. Int J Gynaecol Obstet. 2018;141:217-21. 3. Arellano Pichardo EI, Labastida Torres J. Prevalencia de Adenomiosis en Piezas Quirúrgicas de Histerectomía y Factores de Riesgo Clínicos Relacionados. Ciudad de México; 2018. Available from: https://www. medigraphic.com/cgi-bin/new/resumen.cgi?IDARTICULO=80497 [Last accessed on 2024 Oct 18]. 4. Bulun SE, Yildiz S, Adli M, Wei JJ. Adenomyosis pathogenesis: insights from next-generation sequencing. Hum Reprod Update. 2021;27:1086-97. 5. Yu O, Schulze-Rath R, Grafton J, Hansen K, Scholes D, Reed SD, et al. Adenomyosis incidence, prevalence and treatment: United States popu - lation-based study 2006-2015. Am J Obstet Gynecol. 2020;222:94.e1-10. 6. Zhai J, Vannuccini S, Petraglia F, Giudice LC. Adenomyosis: mecha - nisms and pathogenesis. Semin Reprod Med. 2020;38:129-43. 7. Moawad G, Kheil MH, Ayoubi JM, Klebanoff JS, Rahman S, Sharara FI. Adenomyosis and infertility. J Assist Reprod Genet. 2022;39:1027-31. 8. Pirtea P, De Ziegler D, Ayoubi JM. Endometrial receptivity in adenomyo - sis and/or endometriosis. Fertil Steril . 2023;119:741-5. 9. Falcone T, Flyckt RL. Clinical management of endometriosis. Obstet Gynecol. 2018;131:557-71. 10. Güzel AI, Akselim B, Erkilinç S, Kokanali K, Tokmak A, Dolmuş B, et al. Risk factors for adenomyosis, leiomyoma and concurrent adenomyosis and leiomyoma. J  Obstet Gynaecol Res. 2015;41:932-7. 11. Vannuccini S, Petraglia F. Recent advances in understanding and mana - ging adenomyosis. F1000Res. 2019;8:F1000 Faculty Rev-283; pages. 2-10. 12. Di Donato N, Montanari G, Benfenati A, Leonardi D, Bertoldo V, Monti G, et al. Prevalence of adenomyosis in women undergoing surgery for endometriosis. Eur J Obstet Gynecol Reprod Biol. 2014;181:289-93. 13. Cunningham RK, Horrow MM, Smith RJ, Springer J. Adenomyosis: a sonographic diagnosis. Radiographics. 2018;38:1576-89. 14. Moawad G, Fruscalzo A, Youssef Y, Kheil M, Tawil T, Nehme J, et al. Adenomyosis: an updated review on diagnosis and classification. J Clin Med. 2023;12:4828. 15. Struble J, Reid S, Bedaiwy MA. Adenomyosis: a clinical review of a cha - llenging gynecologic condition. J Minim Invasive Gynecol. 2016;23:164-85. 16. Canis M, Gremeau AS, Bourdel N. Elusive adenomyosis: a plea for an international classification system to allow artificial intelligence approa - ches to reset our clinical management. Fertil Steril. 2018;110:1039-40. 17. Rocha TP, Andres MP, Borrelli GM, Abrão MS. Fertility-sparing treatment of adenomyosis in patients with infertility: a systematic review of current options. Reprod Sci. 2018;25:480-6. 18. Raimondo D, Raffone A, Aru AC, Giorgi M, Giaquinto I, Spagnolo E, et al. Application of deep learning model in the sonograph ic diagnosis of ute - rine adenomyosis. Int J Environ Res Public Health. 2023;20:1724. 19. Lazzeri L, Morosetti G, Centini G, Monti G, Zupi E, Piccione E, et al. A sono graphic classification of adenomyosis: interobserver reproducibility in the evaluation of type and degree of the myometrial involvement. Fertil Steril. 2018;110:1154-61.e3. 20. Abbott JA. Adenomyosis and abnormal uterine bleeding (AUB-A)-pathogenesis, diagnosis, and management. Best Pract Res Clin Obstet Gynaecol. 2017;40:68-81. 21. Harmsen MJ, Van den Bosch T, De Leeuw RA, Dueholm M, Exacoustos C, Valentin L, et al. Consensus on revised definitions of morphological uterus sonographic assessment (MUSA) features of adenomyosis: results of modified Delphi procedure. Ultrasound Obstet Gynecol. 2022;60:118-31.