General Gynecology · Gynecologic Oncology
Abstract
Endometriosis is a fascinating disease that we strive to better understand. Molecular techniques are shedding new light on many important aspects of this disease: from pathogenesis to the recognition of distinct disease variants like deep infiltrating endometriosis. The observation that endometriosis is a cancer precursor has now been strengthened with the knowledge that mutations that are present in endometriosis-associated cancers can be found in adjacent endometriosis lesions. Recent genomic studies, placed in context, suggest that deep infiltrating endometriosis may represent a benign neoplasm that invades locally but rarely metastasises. Further research will help elucidate distinct aberrations which result in this phenotype. With respect to identifying those patients who may be at risk of developing endometriosis-associated cancers, a combination of molecular, pathological, and inheritance markers may define a high-risk group that might benefit from risk-reducing strategies.
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By this author
Pelvic Pain · Chronic Pelvic Pain
Endometriosis, symptoms, and risk for depression and/or anxiety: a population-based retrospective study
Goodwin E et al., 2025 · BMC women's health · Free full text on PubMed Central
Endometriosis is a chronic and inflammatory condition that often presents with chronic pelvic pain, dysmenorrhea, and dyspareunia, thus having important effects on quality of life. There are two proposed hypotheses to describe the known association between endometriosis and depression and anxiety: (1) the disease hypothesis, where the inflammatory nature of endometriosis is driving increased risk for depression and anxiety; and (2) the pain hypothesis, where it is the painful symptoms underlying the increased risk. We aimed to shed further light on these two hypotheses by assessing the risk for depression and/or anxiety in three groups of patients pathologically assessed for endometriosis: symptomatic endometriosis patients (Symp Endo), symptomatic patients with no pathological endometriosis diagnosis (Symp No Endo), and asymptomatic endometriosis patients (Asymp Endo). This study included pathologically-confirmed endometriosis patients identified from the pathology records of Vancouver Coastal Health Authority between 2000 and 2008. These data were linked with population-based administrative health data for follow-up to 2017. Depression and anxiety were identified through diagnostics codes from health services use data and prescriptions for antidepressants. Bivariate analyses were performed to assess differences between groups. Cox proportional hazards models were run to generate hazard ratios for incident depression and/or anxiety between the groups. There were 2729 people in Symp Endo, 585 in Symp No Endo, and 326 in Asymp Endo. Symp No Endo was more likely than Symp Endo to be visiting a physician for pelvic pain and to be taking prescription-level pain medications (p < 0.001). After adjusting for several covariates, Symp No Endo had a significantly higher risk of incident depression and/or anxiety (adjusted HR: 1.23, 95% CI: 1.06-1.41) compared to Symp Endo. There was no statistically significant difference in risk of depression and/or anxiety between Symp Endo and Asymp Endo (adjusted HR: 0.94, 95% CI: 0.76-1.17). These results point toward the pain focused hypotheses as Symp No Endo patients were at higher risk for depression/anxiety than the Symp Endo group. However, the results also suggest the disease hypothesis is at play, because the Symp Endo and Asymp Endo groups were at the same level of risk for depression/anxiety.
Sexual Pain · Dyspareunia
Female Dyspareunia and the Relationship to Neurophysiologic Mechanisms: A Scoping Review
Cook E et al., 2026 · Journal of minimally invasive gynecology
This scoping review aims to evaluate recent studies that examine the relationship between dyspareunia and neurophysiologic factors, and to synthesize their results as it pertains to the development and treatment of introital/vulvar dyspareunia and deep dyspareunia A comprehensive search was conducted in PubMed (NLM), Embase (Elsevier), CINAHL (EBSCOhost), Web of Science (Clarivate), Psycinfo (ProQuest), and Cochrane Library (Wiley) to find peer reviewed studies written in English published in 2000 or later that discussed how neurophysiology is related to dyspareunia. Search terms: dyspareunia; painful intercourse; genito-pelvic pain; penetration disorder; neuropsychology; central nervous system sensitization; neur; central sensitization. A total of 1101 studies were screened and 108 were included in the review. Abstract and full text screening were performed by 4 authors. Articles were also excluded if they did not include an objective diagnostic tool or objective treatment outcome of dyspareunia. We included original peer-reviewed published research in the form of randomized control trials, cohort studies, case control studies, case series of greater than 20 participants, and systematic reviews. Multiple study types were noted: 22 randomized control trials, 9 prospective cohort studies, 3 retrospective cohort studies, 30 case control, 16 case series, 17 cross-sectional, and 11 systematic reviews. Of these articles, 72 focused on introital/superficial dyspareunia, 23 focused on deep dyspareunia, and 13 on both. Data was synthesized in text and table format, separated by type of dyspareunia (introital vs deep) and either etiology/diagnosis or treatment. There are complex neurophysiologic mechanisms that influence both introital and deep dyspareunia, highlighting the roles of peripheral and central sensitization, nerve fiber density, and neuroplasticity in this condition. There are several promising treatments, including TENS, botulinum toxin A, physical therapy, and various multimodal approaches; but further research is needed to establish standardized therapeutic guidelines.
Pelvic Pain · Chronic Pelvic Pain
Pain sensitivity questionnaire in endometriosis
Gentles AJ et al., 2025 · The journal of pain · Free to read
There is increasing recognition that nociplastic pain and central sensitization may play a role in endometriosis-associated pain. The Pain Sensitivity Questionnaire Minor (PSQ-M) evaluates subjective widespread pain sensitivity, and is linked to pain outcomes in chronic pain populations. However, evidence connecting the PSQ-M to central sensitization in endometriosis is limited. Using the Central Sensitization Inventory (CSI) as a comparison, this study compared the PSQ-M as a clinical proxy for central sensitization in endometriosis individuals. Data collected from 983 endometriosis participants (mean age of 34 years), between January 2020 and December 2022, were analyzed from a prospective registry. A significant but weak positive correlation was observed between PSQ-M and CSI scores (r=0.099, p<0.001). A significant but weak correlation was found between the number of central sensitivity syndromes and pelvic pain-related comorbidities with the PSQ-M (r=0.093, p<0.001), compared to a stronger correlation with the CSI (r=0.687, p<0.05). PSQ-M scores were not significantly associated with baseline (r=0.013, p=0.797) or post-operative (r=-0.046, p=0.801) quality-of-life. There was no change in the PSQ-M and a small change in CSI after endometriosis surgery, suggesting that surgical treatment of endometriosis does not directly address central sensitization. In conclusion, the PSQ-M may not be the optimal clinical proxy for central sensitization in endometriosis. This study evaluates the Pain Sensitivity Questionnaire - Minor (PSQ-M) as a proxy for central sensitization in endometriosis. The PSQ-M showed weak correlations with central sensitivity syndromes and pain scores and was not associated with post-surgical quality-of-life, suggesting it may not be the optimal tool for assessing central sensitization in endometriosis.
Psychosocial Support · Counseling and Therapy
Mental Health Outcomes of Endometriosis Patients during the COVID-19 Pandemic: Impact of Pre-pandemic Central Nervous System Sensitization
Liu YD et al., 2024 · The journal of pain · Free to read
To correlate pain-related phenotyping for central nervous system sensitization in endometriosis-associated pain with mental health outcomes during the COVID-19 pandemic, the prospective Endometriosis and Pelvic Pain Interdisciplinary Cohort (ClinicalTrials.gov #NCT02911090) was linked to the COVID-19 Rapid Evidence Study of a Provincial Population-Based Cohort for Gender and Sex (RESPPONSE) dataset. The primary outcomes were depression (PHQ-9) and anxiety (GAD-7) scores during the pandemic. The explanatory variables of interest were the Central Sensitization Inventory (CSI) score (0-100) and endometriosis-associated chronic pain comorbidities/psychological variables before the pandemic. The explanatory and response variables were assessed for correlation, followed by multivariable regression analyses adjusting for PHQ-9 and GAD-7 scores pre-pandemic as well as age, body mass index, and parity. A higher CSI score and a greater number of chronic pain comorbidities before the pandemic were both positively correlated with PHQ-9 and GAD-7 scores during the pandemic. These associations remained significant in adjusted analyses. Increasing the CSI score by 10 was associated with an increase in pandemic PHQ-9 by .74 points (P < .0001) and GAD-7 by .73 points (P < .0001) on average. Each additional chronic pain comorbidity/psychological variable was associated with an increase in pandemic PHQ-9 by an average of .63 points (P = .0004) and GAD-7 by .53 points (P = .0002). Endometriosis patients with a history of central sensitization before the pandemic had worse mental health outcomes during the COVID-19 pandemic. As a risk factor for mental health symptoms in the face of major stressors, clinical proxies for central sensitization can be used to identify endometriosis patients who may need additional support. This article adds to the growing literature of the clinical importance of central sensitization in endometriosis patients, who had more symptoms of depression and anxiety during the COVID-19 pandemic. Clinical features of central sensitization may help clinicians identify endometriosis patients needing additional support when facing major stressors.
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Gynecologic Oncology · Ovarian Cancer
Endometriosis-associated ovarian carcinomas: insights into pathogenesis, diagnostics, and therapeutic targets-a narrative review
Samartzis EP et al., 2020 · Annals of translational medicine · Free full text on PubMed Central
Endometriosis is a benign gynecologic condition affecting up to one woman out of ten of reproductive age. It is defined by the presence of endometrial-like tissue in localizations outside of the uterine cavity. It often causes symptoms such as chronic pain, most frequently associated with the menstrual cycle, and infertility, but may also be oligo- or asymptomatic. There is evidence that some ovarian carcinoma (OC) histotypes, mainly the ovarian clear cell (OCCC) and endometrioid (EnOC) carcinoma, may arise from endometriosis. The most frequent genomic alterations in these carcinomas are mutations in the AT-rich interacting domain containing protein 1A (ARID1A) gene, a subunit of the SWI/SNF chromatin remodeling complex, and alterations in the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR pathway, which frequently co-occur. In ARID1A deficient cancers preclinical experimental data suggest different targetable mechanisms including epigenetic regulation, cell cycle, genomic instability, the PI3K/AKT/mTOR pathway, inflammatory pathways, immune modulation, or metabolic alterations as potential precision oncology approaches. Most of these strategies are relying on the concept of synthetic lethality in which tumors deficient in ARID1A are more sensitive to the different compounds. Some of these approaches are currently being or have recently been investigated in early clinical trials. The remarkably frequent occurrence of these mutations in endometriosis-associated ovarian cancer, the occurrence in a relatively young population, and the high proportion of platinum-resistant disease certainly warrants further investigation of precision oncology opportunities in this population. Furthermore, advanced knowledge about oncogenic mutations involved in endometriosis-associated ovarian carcinomas may be potentially useful for early cancer detection. However, this approach may be complicated by the frequent occurrence of somatic mutations in benign endometriotic tissue as recent studies suggest. In this narrative review of the current literature, we will discuss the data available on endometriosis-associated ovarian carcinoma, with special emphasis on epidemiology, diagnosis and molecular changes that could have therapeutic implications and clinical applicability in the future.
Gynecologic Oncology · Ovarian Cancer
Cancer-Associated Mutations in Endometriosis without Cancer
Anglesio MS et al., 2017 · N Engl J Med · Free full text on PubMed Central
Endometriosis, defined as the presence of ectopic endometrial stroma and epithelium, affects approximately 10% of reproductive-age women and can cause pelvic pain and infertility. Endometriotic lesions are considered to be benign inflammatory lesions but have cancerlike features such as local invasion and resistance to apoptosis. We analyzed deeply infiltrating endometriotic lesions from 27 patients by means of exomewide sequencing (24 patients) or cancer-driver targeted sequencing (3 patients). Mutations were validated with the use of digital genomic methods in microdissected epithelium and stroma. Epithelial and stromal components of lesions from an additional 12 patients were analyzed by means of a droplet digital polymerase-chain-reaction (PCR) assay for recurrent activating KRAS mutations. Exome sequencing revealed somatic mutations in 19 of 24 patients (79%). Five patients harbored known cancer driver mutations in ARID1A, PIK3CA, KRAS, or PPP2R1A, which were validated by Safe-Sequencing System or immunohistochemical analysis. The likelihood of driver genes being affected at this rate in the absence of selection was estimated at P=0.001 (binomial test). Targeted sequencing and a droplet digital PCR assay identified KRAS mutations in 2 of 3 patients and 3 of 12 patients, respectively, with mutations in the epithelium but not the stroma. One patient harbored two different KRAS mutations, c.35G→T and c.35G→C, and another carried identical KRAS c.35G→A mutations in three distinct lesions. We found that lesions in deep infiltrating endometriosis, which are associated with virtually no risk of malignant transformation, harbor somatic cancer driver mutations. Ten of 39 deep infiltrating lesions (26%) carried driver mutations; all the tested somatic mutations appeared to be confined to the epithelial compartment of endometriotic lesions.
Gynecologic Oncology · Ovarian Cancer
Allelotyping of endometriosis with adjacent ovarian carcinoma reveals evidence of a common lineage
Jiang X et al., 1998 · Cancer Res
Endometriosis is a common gynecological disease in which tissue similar to the endometrium proliferates at sites outside the uterine cavity. Malignant transformation of endometriosis to endometrioid and clear cell ovarian carcinomas has been documented in histological studies, but no molecular genetic evidence exists to support that endometriosis is the clonal precursor of such malignancies. We examined 14 cases of endometriosis synchronous with ovarian cancer for loss of heterozygosity on 12 chromosome arms, X chromosome inactivation, and TP53 mutation to determine whether they shared genetic alterations. In all four of the cases where the carcinoma had arisen within endometriosis and in five of the seven cases where the carcinoma was adjacent to the endometriosis, common genetic lesions were detected, consistent with a common lineage. A TP53 mutation was also detected in one case of endometriosis adjacent to carcinoma. These findings support the numerous histological observations that endometrioid and clear cell ovarian carcinomas may arise through malignant transformation of endometriotic lesions.
Gynecologic Oncology · Ovarian Cancer
Relationship between endometriosis and ovarian cancer
Erzen M et al., 1999 · Eur J Gynaecol Oncol
To investigate the occurrence of ovarian cancer (OC) arising in ovarian endometriosis (OE) diagnosed in our laboratory, and the relation of the disease to patient age. Histopathological reports were reviewed in cases of endometriosis and ovarian cancer diagnosed between 1982 and 1989 and in 1997. The occurrence of OE and OC was studied in relation to patient age. Of the 796 OE cases, 36 (4.5%) ovarian cancers were found in the eight-year period, and of the 216 OC cases 36 (16.7%) were associated with OE; 12 patients (1.7%) were under 50 years old and 24 (22.9%) were over 50. In 1997 there were 168 cases of OE, and 4 cases were associated with OC. Of the 60 OC cases 4 cases arose in endometriosis. Two patients were over 50 and two under 50. In our report the occurrence of OC arising in OE was most influenced by patient age, the extent of sampling and the consistency of histologic reports about the presence of endometriosis in ovarian adenocarcinoma.
General Gynecology › Gynecologic Oncology › Ovarian Cancer · Endometriosis › Associated Conditions › Malignant Transformation
Amy Dawson, Marta Llauradó Fernandez, Michael Anglesio, Mark S Carey
A Dawson, M Fernandez, Mike Anglesio, M Anglesio, M Carey
PMID 29456620 29456620 DOI 10.3332/ecancer.2018.803 10.3332/ecancer.2018.803 Dawson et al. 2018, Dawson 2018