Marina Kvaskoff

Background: Endometriosis is associated with an increased risk of various chronic diseases, including autoimmune, cardiovascular, atopic, psychiatric, and pain-related conditions. Although many studies have examined the links between endometriosis and individual diseases, very few have focused on multiple comorbidities. Our study aimed to identify comorbidity phenotypes and their characteristics among endometriosis patients.Methods: We performed a cross-sectional analysis within ComPaRe-Endometriosis, a nationwide French e-cohort of 10,761 adult women (median age=36 years old, range=18-82) with endometriosis and/or adenomyosis initiated in 2018. Participants self-reported their chronic conditions using a list of 224 diseases from the International Classification of Primary Care (ICPC-2). We used hierarchical clustering to identify baseline comorbidity clusters, and we described their associated socioeconomic, lifestyle, disease, and patient characteristics.Findings: At baseline, 64.2% reported only endometriosis/adenomyosis, while 35.8% reported at least one comorbidity (one: 52.7%, two: 22.9%, three: 10.2%, four: 5.4%, five+: 8.8%). We identified seven comorbidity clusters: Cluster 1 (n=8,656) included patients with few comorbidities; Cluster 2 (n=693) included mostly those with low-prevalence chronic pain conditions (44.3%), irritable bowel syndrome (40.4%), and fibromyalgia (33.3%); Cluster 3 (n=193) those with depression (99.5%); Cluster 4 (n=532) those with asthma (57.9%), allergies (36.5%), and chronic skin diseases (30.6%); Cluster 5 (n=185) those with ovarian cysts/polyendocrine metabolic ovarian syndrome (100%); Cluster 6 (n=299) those with thyroid diseases (100%); and Cluster 7 (n=203) those with migraine (100%). Each cluster was associated with distinct sets of participant characteristics.Interpretation: This study identified distinct comorbidity clusters in women with endometriosis, underscoring the diversity of health profiles associated with this condition and the need for multidisciplinary care addressing the complex interactions between endometriosis and multiple physiological systems. If confirmed, these findings could lay the foundation for a paradigm shift in endometriosis management, moving towards stratified care to tailor interventions based on patient comorbidity burden.

Endometriosis, particularly ovarian endometrioma, is associated with a 2-fold increased risk of ovarian cancer (OC), especially the clear cell and endometrioid subtypes. However, the absolute lifetime risk of OC in women with endometriosis remains relatively low, estimated at 1.9%. This review provides a focused overview of the relationship between these two conditions, addressing epidemiologic data, molecular links, advances in diagnosis, and clinical management. Somatic mutations in ARID1A, PIK3CA, and KRAS are shared between endometriosis and certain OC subtypes, and the nature of the environment typical of ovarian endometriomas suggests a context-specific oncogenic journey. Although advances in imaging, like transvaginal ultrasound and MRI, have improved endometriosis diagnosis, these modalities remain unreliable for identifying malignant transformation. Biomarkers, including CA-125 and HE4, provide additional diagnostic information, although their low specificity limits their role in clinical practice. Hormonal therapies, particularly the long-term use of combined oral contraceptives (COCs), have proven to be highly effective in reducing OC risk in women with endometriosis. This protective effect persists for more than a decade after discontinuation and has been associated with a risk lower than that of the general population. In addition, COC use has been linked to further protective effects against endometrial and colorectal cancers, highlighting its potential value as a cancer prevention strategy, especially for high-risk groups. Surgical management, particularly the excision of ovarian endometriomas, may also confer protection against OC, although this must be balanced against the risks of recurrence and ovarian reserve loss, especially in younger women. Prophylactic salpingo-oophorectomy is recommended for women with known genetic predispositions, but is not routinely indicated for those with endometriosis alone. Emerging evidence highlights the need for personalized risk prediction models that incorporate genetic, clinical, and environmental factors to guide care. Long-term studies are required to assess the impact of conservative versus surgical management on OC risk and overall survival. This review emphasizes the importance of a multidisciplinary approach to the management of endometriosis in relation to OC risk. While the link between endometriosis and OC is well-established, treatment strategies must be tailored to balance cancer prevention, fertility preservation, and quality of life.

Endometriosis is a chronic inflammatory disease presenting with debilitating symptoms strongly impacting patients’ quality of life (QoL). Assessing QoL is crucial for understanding the full patient experience beyond clinical symptoms. This narrative systematic review specifically aimed to identify and describe non-pharmacological and non-surgical factors associated with QoL in women with endometriosis as reported in the literature. Following PRISMA guidelines, we systematically searched PubMed, MEDLINE, Web of Science, and Embase up to January 15, 2025, for case–control, cohort, randomized controlled trials, and cross-sectional studies. This study was registered in PROSPERO (registration number: CRD42023438457) Eligible studies assessed socio-demographic characteristics, lifestyle factors, symptoms, comorbidities, or coping strategies in relation to QoL among women with endometriosis. Twenty-one studies with a low risk of bias were included. A better QoL was related to favorable socioeconomic profiles (n = 3), high care satisfaction (n = 2), partner involvement (n = 1), healthier lifestyle habits (n = 1), and the use of coping therapeutic strategies. Poor QoL was associated with poor health (n = 5), more severe symptoms (n = 5), unhealthy lifestyle habits (n = 2), and ineffective use of coping strategies (n = 2). This review highlights a broad range of non-medical determinants of QoL, underscoring that clinical measures alone fail to capture the full patient experience. By consolidating evidence across diverse study designs, it offers a comprehensive overview of modifiable factors that could inform holistic, patient-centered approaches to endometriosis care. Further prospective and interventional studies are needed to clarify causal pathways and evaluate the effectiveness of targeted strategies to improve QoL. Lay summary Endometriosis is a chronic disease affecting around 10% of women of reproductive age, associated with pain, infertility, and significant impacts on daily life. Because clinical measures alone fail to capture the full patient experience, assessing QoL is essential to understand the real burden of the disease. This review examined non-pharmacological and non-surgical factors that may be associated with QoL, such as lifestyle habits, socioeconomic conditions, health status, and coping strategies. Across 21 studies, we found that a better QoL was linked to good healthcare access, healthy habits, and effective coping mechanisms. Conversely, severe symptoms, poor health, and unhealthy lifestyles (smoking and alcohol use) were associated with worse QoL. The findings highlight the need for a more holistic approach to endometriosis care, combining psychological support, lifestyle guidance, and improved access to quality healthcare. Future research should use standardized QoL tools and robust study designs to develop evidence-based strategies that can meaningfully enhance patient well-being. Abstract Abstract Endometriosis is a chronic inflammatory disease presenting with debilitating symptoms strongly impacting patients’ quality of life (QoL). Assessing QoL is crucial for understanding the full patient experience beyond clinical symptoms. This narrative systematic review specifically aimed to identify and describe non-pharmacological and non-surgical factors associated with QoL in women with endometriosis as reported in the literature. Following PRISMA guidelines, we systematically searched PubMed, MEDLINE, Web of Science, and Embase up to January 15, 2025, for case–control, cohort, randomized controlled trials, and cross-sectional studies. This study was registered in PROSPERO (registration number: CRD42023438457) Eligible studies assessed socio-demographic characteristics, lifestyle factors, symptoms, comorbidities, or coping strategies in relation to QoL among women with endometriosis. Twenty-one studies with a low risk of bias were included. A better QoL was related to favorable socioeconomic profiles (n = 3), high care satisfaction (n = 2), partner involvement (n = 1), healthier lifestyle habits (n = 1), and the use of coping therapeutic strategies. Poor QoL was associated with poor health (n = 5), more severe symptoms (n = 5), unhealthy lifestyle habits (n = 2), and ineffective use of coping strategies (n = 2). This review highlights a broad range of non-medical determinants of QoL, underscoring that clinical measures alone fail to capture the full patient experience. By consolidating evidence across diverse study designs, it offers a comprehensive overview of modifiable factors that could inform holistic, patient-centered approaches to endometriosis care. Further prospective and interventional studies are needed to clarify causal pathways and evaluate the effectiveness of targeted strategies to improve QoL. Lay summary Endometriosis is a chronic disease affecting around 10% of women of reproductive age, associated with pain, infertility, and significant impacts on daily life. Because clinical measures alone fail to capture the full patient experience, assessing QoL is essential to understand the real burden of the disease. This review examined non-pharmacological and non-surgical factors that may be associated with QoL, such as lifestyle habits, socioeconomic conditions, health status, and coping strategies. Across 21 studies, we found that a better QoL was linked to good healthcare access, healthy habits, and effective coping mechanisms. Conversely, severe symptoms, poor health, and unhealthy lifestyles (smoking and alcohol use) were associated with worse QoL. The findings highlight the need for a more holistic approach to endometriosis care, combining psychological support, lifestyle guidance, and improved access to quality healthcare. Future research should use standardized QoL tools and robust study designs to develop evidence-based strategies that can meaningfully enhance patient well-being.

Supplementary Table from Cigarette Smoking and Endometrial Cancer Risk: Observational and Mendelian Randomization Analyses

Supplementary Table from Cigarette Smoking and Endometrial Cancer Risk: Observational and Mendelian Randomization Analyses

Supplementary Table from Cigarette Smoking and Endometrial Cancer Risk: Observational and Mendelian Randomization Analyses

Supplementary Table from Cigarette Smoking and Endometrial Cancer Risk: Observational and Mendelian Randomization Analyses

Background: An average time to diagnosis of 7 years is commonly described for endometriosis; diagnostic delay for adenomyosis is unknown. This cross-sectional study aimed to describe diagnostic delay for endometriosis and adenomyosis and to investigate the factors associated with this delay. Methods: Community of Patients for Research (ComPaRe)-Endometriosis is a prospective e-cohort of women with endometriosis and/or adenomyosis in France. About 6,949 participants were included. We used linear regression modeling to assess factors associated with diagnostic delay, after adjustment for age, education level, body mass index, number of comorbidities, and family history of the disease or of chronic pelvic pain (CPP). Results: The average diagnostic delay was 10 years for endometriosis and 11 years for adenomyosis. Factors associated with a significantly longer diagnostic delay were year of diagnosis (+0.34 years, p < 0.0001), unemployment (+0.7 years, p = 0.01), number of comorbidities (+0.3 years, p < 0.0001), family history of the disease or of CPP (+1.1 years, p < 0.0001), severe dysmenorrhea before diagnosis (numeric-rating scale: +0.8 years, p < 0.0001), number of health professionals consulted before diagnosis (+0.3 years, p < 0.0001), and presence of multiple symptoms leading to first consultation (+1.6 years, p < 0.0001). In contrast, factors associated with a shorter delay were a financial position perceived as comfortable (-1.4 years, p < 0.0001), age at menarche (-0.6 years, p < 0.0001), and age at first symptoms (-0.8 years, p < 0.0001). Conclusions: This study highlights several factors associated with diagnostic delay among women with self-reported endometriosis and/or adenomyosis and provides new insights to improve care by informing both clinicians and patients. Attention to these profiles may improve disease management.

STUDY QUESTION: How reliable are self-reported endometriosis or adenomyosis data compared with medical reports in online patient surveys? SUMMARY ANSWER: In our sample, reliability was strong to excellent for diagnosis, age at diagnosis, and stage at diagnosis, while reliability for macro-phenotype of endometriosis ranged from fair to substantial. WHAT IS KNOWN ALREADY: Many online surveys rely on self-reported endometriosis data. Previous research has shown validation rates ranging from 72% to 95% for self-reported endometriosis diagnosis in population cohorts, but this rate is unknown in the context of online surveys among patient populations or patient e-cohorts. STUDY DESIGN, SIZE, DURATION: We conducted a specific study within ComPaRe-Endometriosis, a French e-cohort launched in 2018 and following up several thousands of women with endometriosis and/or adenomyosis. Within this study, a total of 215 participants sent their medical reports. We compared participants’ self-reported diagnosis and disease characteristics, as collected in self-reported questionnaires at baseline in the ComPaRe-Endometriosis cohort, with data from contemporaneous medical reports. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were asked to send their medical reports mentioning diagnosis and its date, and type(s) and stage of endometriosis. We assessed the reliability between baseline self-reported data and medical report data using descriptive statistics, intraclass correlation coefficient (ICC), Cohen’s Kappa, and weighted Kappa. MAIN RESULTS AND THE ROLE OF CHANCE: The study included 215 participants with a mean age of 33.8 years (SD = 7.0). Over half (52.1%) reported endometriosis alone, 8.4% adenomyosis alone, and 39.5% reported both diseases. Endometriosis and adenomyosis diagnoses were correctly reported among 95.9% and 90.3% of participants, respectively. Self-reported age at diagnosis showed excellent reliability with ICC = 0.96 for endometriosis and ICC = 0.91 for adenomyosis. Regarding self-reported disease stage, substantial-to-almost perfect agreement (κw = 0.86–0.78) and excellent reliability (ICC = 0.91–0.94) were observed. For self-reported macro-phenotype of endometriosis, agreement varied: substantial for endometrioma (K = 0.62–0.74), moderate-to-substantial for deep endometriosis (K = 0.40–0.61), and fair-to-moderate for superficial peritoneal endometriosis (K = 0.35–0.43). LIMITATIONS, REASONS FOR CAUTION: The most motivated participants may have a particular profile in terms of involvement in their care, which constitutes a limitation to the generalizability of the findings. WIDER IMPLICATIONS OF THE FINDINGS: Several studies assessed the reliability of self-reported endometriosis data in population cohorts and found validation rates ranging from 72% to 95% with medical reports. This figure could vary greatly depending on several criteria (study population, clarity of the question about diagnosis, tool used to confirm diagnosis…). In this work, we found a striking heterogeneity in the way macro-phenotype of disease was described in medical reports. Since many studies rely on self-reported data, this work underscores the importance of harmonizing the report of diagnosis and endometriosis/adenomyosis characteristics in medical reports in order to ease continuity of care and ensure high-quality research on these conditions. STUDY FUNDING/COMPETING INTEREST(S): The ComPaRe cohort was supported by the Assistance Publique-Hôpitaux de Paris (APHP) and the Université Paris Cité. ComPaRe-Endometriosis was funded through grants from the Fondation de France (#00132975/WB-2022-44780) and the Agence Nationale de la Recherche (#ANR-22-CE36-0016-01) and received donations from patient societies and initiatives (EndoMind, EndoFrance, EndoAction, Les Joyeux Boulomanes Farlédois, La Belle et L’endo, Les Chroniques Endométriques). S.G. was supported by a PhD scholarship from the French Ministry of Research and a grant from the Crédit Agricole Ile-de-France Mécénat. Z.B. was supported by the French National Association for Research and Technology (ANRT) and Lyv Healthcare during their PhD. The funders had no role in the design, interpretation, or decision to publish the study. The other authors report no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.