Adverse childhood experiences, obesity, and endometrial cancer: A case series and scoping review.

Haley D. Frerichs: . Jenna B. Wowdzia: Writing – review & editing, Investigation, Conceptualization. Allison Sivak: Writing – review & editing, Methodology, Data curation. Sarah Chapelsky: Writing – review & editing, Funding acquisition, Conceptualization. Christa Aubrey: Writing – review & editing, Supervision, Funding acquisition, Conceptualization. Sophia Pin: Writing – review & editing, Supervision, Funding acquisition, Conceptualization.

This was a retrospective single institution chart review drawn from a population of 92 gynecologic oncology patients enrolled in a preoperative weight loss study from 2020 through 2022 at the Royal Alexandra Hospital in Edmonton, Alberta, Canada. ( Aubrey et al., 2021 ) This study was prospectively registered and approved through the Health Research Ethics Board of Alberta Cancer Committee ( HREBA.CC -19–0357). Operational approval was obtained through the Northern Alberta Clinical Trials and Research Centre and Alberta Health Services. The preoperative weight loss study aimed to assess the feasibility of an acute preoperative weight loss protocol in adults with BMI ≥ 40 kg/m 2 who were referred to gynecologic oncology for lower-risk conditions requiring surgery (low-risk adnexal masses, endometrial hyperplasia, or low-grade endometrioid carcinoma without evidence of metastasis). This cohort consisted of 92 patients. After assessment by a gynecologic oncologist, patients were referred to an internal medicine specialist who determined candidacy for an acute preoperative weight loss protocol. This consisted of a low-calorie liquid diet for a planned duration of 12 weeks, where surgery would be planned at the conclusion of this period. While no formal assessment of ACEs was done in these appointments, patients were screened for disordered eating patterns, and history of ACEs often arose during these discussions. In this case series, we included patients enrolled in the preoperative weight loss program who had confirmed endometrioid carcinoma or atypical endometrial hyperplasia and disclosed a history of at least one ACE, as documented in their consultation. Our definition of ACEs was exposure to maltreatment, household dysfunction, peer dysfunction, or community dysfunction prior to the age of 18 years. ( Karatekin and Hill, 2019 ) We also included patients who reported a history of childhood trauma with no further details on the specific ACE type. We used electronic medical records to extract data, which included demographics, characteristics of ACE exposure, medications, and comorbidities at the time of the preoperative weight loss consultation. Endometrial pathology was recorded from post-hysterectomy surgical pathology. We used descriptive statistics for analysis and summarized continuous variables using means and standard deviation and described categorical variables using frequencies and proportions. We developed a scoping review protocol according to the PRISMA extension for scoping reviews (PRISMA-ScR) ( Tricco et al., 2018 ) (Supplementary Figure). This protocol was registered in Open Science Framework on August 17, 2023 ( https://doi.org/10.17605/OSF.IO/HJ7PV) . Our population included adults 18 years or older with a uterus. Although the terms “women” and “females” do not capture all individuals susceptible to endometrial cancer, they are widely used to describe this population and we therefore included them as search terms. We reported findings using the gender and sex terminology from the original papers, despite limitations in these language choices. Included studies documented exposure to one or more ACEs, as previously defined. ( Karatekin and Hill, 2019 ) Comparator groups, where applicable, included adults with a uterus without a history of ACEs. Outcomes included endometrial cancer and/or adulthood obesity, defined as BMI ≥ 30 kg/m 2 . Despite its limitations, we used this definition of obesity because it is the most universally used in research settings and is associated with elevated endometrial cancer risk. ( Kokts-Porietis et al., 2021 ). We excluded literature reviews, book chapters, conference abstracts, and dissertations. There were no other exclusions in the types of study design. With the expertise of a health sciences librarian, we designed a systematic search strategy which we performed on July 9, 2023 across the following databases: MEDLINE (via Ovid), Global Health (via Ovid), HealthSTAR (via Ovid), Embase (via Ovid), Scopus, CINAHL Plus with Full Text (via EBSCO), Web of Science (All Databases), and APA PsycINFO (via Ovid). We repeated the search on July 9, 2024, using MEDLINE (via Ovid) to identify recently published studies. There were no restrictions on the date of publication, country of origin, or original language of articles, as long as articles were available in English. Databases were searched from inception through the date of the search. We hand-searched reference lists of identified articles and Google and Proquest Theses and Dissertations Global (via EBSCO) in August 2023. One author was successfully contacted to clarify information. Detailed search strategies for selected databases are available in Supplementary Table 1. We uploaded all identified papers into Covidence systematic review software ( Veritas Health Innovation, 2023 ) for automatic deduplication and screening. Two independent reviewers screened titles and abstracts against inclusion and exclusion criteria. The two reviewers resolved conflicts through discussion and consensus with a third reviewer available when necessary. Studies deemed relevant moved to full-text screening by the same three reviewers. The reviewers recorded and counted reasons for exclusion at the full-text stage. Studies that met all criteria after the full-text review moved to the data extraction stage. We developed a data charting form in Covidence to extract qualitative information from included studies including the authors, year of publication, source of evidence type, country, population and sample size, methodology, aims, types of experiences measured, relevant outcomes measured, and key findings. The first reviewer independently extracted data from full-text papers. The second reviewer verified the data and any discrepancies were resolved by discussion and consensus. Access to the full extraction table is available upon request. We organized results in a tabular format with descriptive summaries to address the research questions. Findings regarding ACEs and endometrial cancer or class 2–3 obesity were summarized narratively.

Seventeen out of 92 patients met the inclusion criteria for the case series. Demographic information is summarized in Table 1 . At the time of the initial preoperative weight loss consultation, patients' ages ranged from 25 to 68 years with a mean age of 52 ± 11.8 years. The majority had a BMI of 40.0–49.9 kg/m 2 (10/17, 58.8%), with four having a BMI of 50.0–59.9 kg/m 2 (23.5%), and three with a BMI ≥ 60 kg/m 2 (17.6%). Twelve of 17 (70.6%) patients had grade 1 or 2 endometrioid endometrial carcinoma, 9/12 (75.0%) were pathologic stage 1, and five had atypical endometrial hyperplasia. Table 1 Demographic information of the study population. SD, standard deviation; BMI, body mass index; FIGO, International Federation of Gynecology and Obstetrics; EOSS, Edmonton Obesity Staging System. Demographic Total (n = 17) Age (years) 52 ± 11.84 BMI (kg/m 2 ) 50.6 ± 9.47 Post-surgical endometrial pathology Grade 1 endometrioid carcinoma 8 (47.1%) Grade 2 endometrioid carcinoma 4 (23.5%) Atypical endometrial hyperplasia 5 (29.4%) FIGO stage Stage 1 9 (52.9%) Stage 2 2 (11.8%) Stage 3 1 (5.9%) N/A (endometrial hyperplasia) 5 (29.4%) EOSS stage a 1 0 2 2 (11.76%) 3 7 (41.18%) 4 1 (5.88%) Undetermined 7 (41.18%) Data are mean ± SD or n (%). a EOSS was adjusted to incorporate endometrial hyperplasia as an obesity-related comorbidity at stage 2, and endometrioid carcinoma at stage 3 for local disease and stage 4 for metastatic disease. Demographic information of the study population. SD, standard deviation; BMI, body mass index; FIGO, International Federation of Gynecology and Obstetrics; EOSS, Edmonton Obesity Staging System. Data are mean ± SD or n (%). EOSS was adjusted to incorporate endometrial hyperplasia as an obesity-related comorbidity at stage 2, and endometrioid carcinoma at stage 3 for local disease and stage 4 for metastatic disease. Comorbidities and medications of included patients are summarized in Table 2 . The mean number of comorbidities per patient, aside from obesity and endometrial carcinoma or hyperplasia, was 6.4 ± 2.5. The most commonly reported comorbidities were dyslipidemia, hypertension, and depression. Thirteen of 17 patients (76.5%) were diagnosed with at least one mental health disorder, with 8/17 (47.1%) reporting two or more concurrent mental health disorders. Depression was the most frequent mental health disorder, followed by anxiety and attention-deficit hyperactivity disorder. Seven patients (41.2%) reported current or previous tobacco smoking. Excluding vitamins and supplements, patients reported taking an average of 4.7 ± 3.1 different medications, with the most common medication types being antihypertensives and depression/anxiety medications. Table 2 Baseline comorbidities and medications of the study population. Characteristic Total (n = 17) Cardiovascular and metabolic disorders Dyslipidemia 9 (52.9%) Hypertension 9 (52.9%) Type 2 diabetes mellitus 8 (47.1%) Hepatic steatosis 4 (23.5%) Obstructive sleep apnea 3 (17.6%) Chronic kidney disease 3 (17.6%) Pre-diabetes 2 (11.8%) Coronary artery disease 1 (5.9%) Mental health and neurocognitive disorders Depression 9 (52.9%) Anxiety 5 (29.4%) Attention deficit hyperactivity disorder 4 (23.5%) Borderline personality disorder 2 (11.8%) Bipolar disorder 1 (5.9%) Agoraphobia 1 (5.9%) Schizoaffective disorder 1 (5.9%) Bulimia nervosa 1 (5.9%) Dyslexia 1 (5.9%) History of smoking 5 (29.4%) Currently smoking 2 (11.8%) Osteoarthritis 7 (41.2%) Asthma 6 (35.3%) Gastroesophageal reflux disease 6 (35.3%) Other chronic pain a 6 (35.3%) Hypothyroidism 5 (29.4%) Inflammatory disorder b 4 (23.5%) Previous cancer (bladder) 1 (5.9%) Glaucoma 1 (5.9%) Asherman’s syndrome 1 (5.9%) Prescribed medications Antihypertensives 9 (52.9%) Anxiety or depression medications 9 (52.9%) Pain medications 8 (47.1%) Lipid-lowering medications 8 (47.1%) Thyroid medications 6 (35.3%) Anti-reflux medications 5 (29.4%) Diabetes medications 4 (23.5%) Inhaler for asthma 3 (17.6%) Weight-loss medications 2 (11.8%) Data are mean ± SD or n (%). a Including migraine, peripheral neuropathy, sciatica, and trigeminal neuralgia. b Including gout, rheumatoid arthritis, pulmonary sarcoidosis, and rosacea. Baseline comorbidities and medications of the study population. Data are mean ± SD or n (%). Including migraine, peripheral neuropathy, sciatica, and trigeminal neuralgia. Including gout, rheumatoid arthritis, pulmonary sarcoidosis, and rosacea. Fifteen of 17 patients described experiencing specific ACE types, which are summarized in Table 3 . Equal proportions of patients described one, two, and three different ACE types. The most frequently reported ACE type was psychological abuse, followed by sexual abuse, then physical abuse. Other reported childhood adversities included anorexia, exposure to substance abuse or mental illness, parental separation, food insecurity, and peer dysfunction or bullying. Table 3 Adverse childhood experience types reported by the study population. ACE, adverse childhood experience. ACE characteristic Total (n = 15) Number of ACE types 1 5 (33.33%) 2 5 (33.33%) 3 5 (33.33%) ACE type Psychological abuse 7 (46.7%) Sexual abuse 6 (40%) Physical abuse 4 (26.7%) Anorexia in childhood 3 (20%) Exposure to substance abuse 2 (13.3%) Exposure to mental illness 2 (13.3%) Parental separation 2 (13.3%) Food insecurity 2 (13.3%) Peer dysfunction or bullying 2 (13.3%) Data are mean ± SD or n (%). Adverse childhood experience types reported by the study population. ACE, adverse childhood experience. Data are mean ± SD or n (%). The results of the search and inclusion decisions are outlined in the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) flow diagram ( Fig. 1 ). The database searches identified 7127 studies and grey literature and citation searching yielded 17 studies. 3994 duplicates were removed, leaving 3150 studies subject to review in the title and abstract screen. 193 papers underwent full-text review and 151 were excluded at this stage. A total of 42 studies were included in the final review, with three studies examining endometrial cancer and 38 studies examining obesity in women and transgender men. Seven papers specifically assessed class 2 and 3 obesity. A summary of all included studies is reported in Supplementary Table 2. Fig. 1 PRISMA flow diagram for study inclusion. Class 2 and 3 obesity were defined as BMI ≥ 35 and 40 kg/m 2 , respectively. Abbreviations: PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-analysis; BMI, body mass index; CINAHL, Cumulated Index in Nursing and Allied Health Literature; ACEs, adverse childhood experiences. PRISMA flow diagram for study inclusion. Class 2 and 3 obesity were defined as BMI ≥ 35 and 40 kg/m 2 , respectively. Abbreviations: PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-analysis; BMI, body mass index; CINAHL, Cumulated Index in Nursing and Allied Health Literature; ACEs, adverse childhood experiences. Three studies explored ACEs in patients with endometrial cancer. One cross-sectional study ( Modesitt et al., 2006 ) examined the incidence of adulthood and childhood violence exposure in 101 patients with ovarian, cervical, breast, and endometrial cancer. Eleven out of 25 (44%) patients with endometrial cancer reported a history of childhood or adulthood violence, which was similar to the reported incidence in the other included cancer types. Cancer patients with a history of violence in childhood or adulthood had increased odds of cancer diagnosis at later stages, although this analysis combined all four cancer types. In a retrospective analysis of 66 patients with endometrial cancer receiving vaginal brachytherapy, ( Saripalli et al., 2024 ) 88% screened positive for lifetime trauma exposure and 12% had specifically experienced childhood physical abuse. While the researchers assessed patients for various types of trauma exposure, they did not include any other specific childhood trauma categories. BMI > 25 kg/m 2 was associated with trauma exposure and vaginal brachytherapy triggered an increase in thoughts or flashbacks to traumatic events in 11% of patients. Among patients with a history of sexual trauma, 38% reported experiencing trauma symptoms related to brachytherapy. However, experiencing trauma symptoms was not significantly associated with having a history of sexual trauma. A qualitative component collected patient feedback about treatment. The two main suggestions for improvement from patients were to provide better education about the treatment ahead of time and to increase patient privacy during treatment. A longitudinal study of 230 gynecologic oncology patients receiving chemotherapy found that patients who experienced very high levels of anxiety during treatment were more likely to have experienced physical neglect and foster care or adoption. ( Pozzar et al., 2023 ) In this population, 29% of patients had uterine cancer. This study assessed a range of ACEs including family violence in childhood, physical and sexual abuse under the age of 16, and parental separation, but did not perform a separate analysis for endometrial cancer. Thirty-nine studies examined the relationship between ACEs and adult obesity in women, with seven specifically examining class 2 and 3 obesity. A full summary of all studies investigating obesity is included in Supplementary Table 3. All studies that assessed class 2 and 3 obesity in women identified an association with ACEs. Class 2 and 3 obesity were associated with cumulative ACE exposure, ( Grigsby et al., 2020 , Loxton et al., 2021 ) sexual abuse, ( Aaron and Hughes, 2007 ) household dysfunction, ( Sandsæter et al., 2023 ) bullying, ( Salmela et al., 2019 ) and combined ACE categories. ( Richardson et al., 2014 , Wall et al., 2019 ) Further, cumulative ACE exposure increased the risk of class 2 and 3 obesity in women but not men. ( Grigsby et al., 2020 , Wall et al., 2019 ).

Patients with endometrial cancer or hyperplasia and class 3 obesity in our study reported various ACE types, especially childhood abuse. These patients were medically complex with a high frequency of cardiovascular, metabolic, and psychiatric conditions. The scoping review indicated that ACEs can impact endometrial cancer care, leading to advanced stage at diagnosis and discomfort during treatment. Additionally, ACEs are widely associated with obesity in women and gender-diverse individuals, with a stronger impact on women compared to men. The medical complexity we observed may be related to both obesity and ACEs. Both are associated with cardiometabolic comorbidities such as diabetes and hypertension, ( Jakubowski et al., 2018 ) of which were prevalent in our cohort. Further, obesity is associated with psychiatric disorders with a more pronounced relationship in women. ( Leutner et al., 2023 ) In a large cohort of patients undergoing bariatric surgery, 30.5% of individuals with a BMI of 40–49.9 kg/m 2 reported preoperative depression, ( Coughlin et al., 2023 ) which was lower than our prevalence of 52.9%. Further, a meta -analysis identified an estimated ACEs prevalence of 51% in patients undergoing bariatric surgery, and that ACEs were associated with symptoms of depression postoperatively. ( Konrad et al., 2023 ) The association between psychiatric disorders and ACEs may contribute to our elevated prevalence. ( McKay et al., 2022 ) Although our sample size limits the ability to make comparisons, the burden of comorbidities in this population has implications for morbidity, mortality, and quality of life. Although sexual abuse was one of the most frequent ACE types in our cohort, patients may have perceived this ACE as pertinent to their gynecologic care and been more willing to disclose it. Survivors of childhood sexual abuse are more likely to find gynecologic exams anxiety-provoking, with over half reporting that their abuse history influences their gynecologic care. ( Leeners et al., 2007 ) Further, women with higher BMI are more likely to have negative healthcare experiences, ( Kapera et al., 2024 ) compounding this experience for patients with obesity. Our patients self-disclosed their abuse, but others may not share their trauma histories with healthcare providers. These findings highlight the importance of universal trauma-informed examinations and screening for trauma in gynecology patients. Despite the growing emphasis on the importance of trauma-informed care in gynecology, ( Caring for Patients Who Have Experienced Trauma, 2021 ) this scoping review revealed a paucity of literature surrounding ACEs in endometrial cancer patients. The included studies either combined endometrial cancer with other cancer types or assessed a limited range of ACEs, limiting the ability to assess their prevalence and impacts. This is especially important given the unique characteristics of patients with endometrial cancer, such as an elevated obesity prevalence. Our review findings are consistent with literature suggesting that ACE exposure increases the risk of adult obesity, ( Wiss and Brewerton, 2020 ) but indicate that ACEs may be a more important risk factor for obesity in women than in men. Consequently, ACEs might be viewed both as a risk factor for endometrial cancer mediated by obesity and as a complicating factor in patient care. The major strength of our case series is that we represented a high BMI homogeneous population with endometrial cancer and hyperplasia, a unique but clinically relevant population with the rising prevalence of obesity. We examined a wide range of self-reported ACEs in this population, for which there is a paucity of literature. Although this scoping review was limited by a lack of existing literature, utilizing a comprehensive search with broad inclusion criteria for ACEs allowed us to evaluate the extent of current evidence. A key limitation in the case series was that patients were not specifically surveyed about ACEs, given the retrospective methodology. This reliance on self-disclosure prevented accurate assessment of ACE prevalence, which is likely under-reported, and resulted in a small sample size in this case series. Due to this methodology, we were also unable to accurately compare this cohort to a control group that had not been exposed to ACEs. Consequently, our study focused on characterizing patients who disclosed ACEs rather than examining specific outcomes related to ACE exposure, although the sample size limits the generalizability of our findings. Additionally, race and ethnicity were not analyzed in the case series, as these data were not routinely documented in the electronic medical record. The scoping review’s main weaknesses are related to the lack of available evidence and inconsistencies in terminology in the literature. Given the nature of a scoping review, a quality assessment of studies was not included, and varying definitions and measurements of ACEs limited interpretation. Given the paucity of literature, future studies should assess ACEs in endometrial cancer patients using validated questionnaires covering a wide range of ACE types. While several questionnaires exist, the Childhood Trauma Questionnaire (CTQ) ( Bernstein et al., 2003 ) is a reliable and thorough screening tool for ACEs that has been successfully utilized in populations of patients with cancer. ( Hinnen et al., 2024 ). Key areas of interest include the prevalence of ACEs in patients with endometrial cancer and whether cancer treatment outcomes are affected by ACE exposure. As obesity is a well-established risk factor for endometrial cancer and closely associated with ACEs, formally comparing incidence in patients with obesity and ACEs versus BMI-matched controls without ACE exposure would be valuable. This would allow a more thorough understanding of this integration between ACEs, obesity, and endometrial cancer, and potentially improve risk stratification in primary care and general gynecology settings. Finally, qualitative studies regarding the experiences of patients with endometrial cancer and trauma histories would help reveal areas of improvement for gynecologic care providers.

Endometrial cancer is the sixth most common cancer among women and the most common gynecologic malignancy in high-income countries. ( Sung et al., 2021 ) Although early-stage disease can be managed effectively, its incidence is increasing globally, with patterns mirroring the rising prevalence of obesity. ( Liu et al., 2023 ) Obesity is defined as body mass index (BMI) exceeding 30 kg/m 2 and is categorized into three classes: class 1 (BMI 30–34.9), class 2 (BMI 35–39.9), and class 3 (BMI ≥ 40). ( Wharton et al., 2020 ) It is one of the most well-established risk factors for endometrial cancer, with risk increasing proportionally to BMI. ( Aune et al., 2015 ) A comprehensive understanding of obesity and its associated factors is important for providing optimal care to the growing population of patients with endometrial cancer and obesity. A risk factor for both adulthood obesity and cancer is exposure to adverse childhood experiences (ACEs), which include childhood abuse, neglect, and household dysfunction. ( Hughes et al., 2017 ) ACEs have been discussed in the context of prenatal care ( Johnson et al., 2023 ) and chronic pelvic pain, ( Moussaoui et al., 2023 ) and even appear to be associated with endometriosis and uterine fibroids. ( Berndt et al., 2025 ) However, little is known about the prevalence or impacts of ACEs in individuals with endometrial cancer. This study aimed to characterize patients with endometrial cancer, class 3 obesity, and self-disclosed ACEs, specifically in a population undergoing a preoperative weight loss protocol, and to review literature investigating ACEs in patients with endometrial cancer. Secondarily, we aimed to examine the relationship between ACEs and obesity specifically in women, with a focus on class 2–3 obesity. This work intends to guide future research for informing clinical practice and trauma-informed patient care approaches.

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.