Causal effects of endometriosis on cancer risk: A Mendelian randomization study.

Endometriosis has been reported in epidemiological studies to be associated with certain types of cancer. However, the presence of reverse causality and residual confounding due to common risk factors introduces uncertainty regarding the extent to which endometriosis itself contributes to the development of cancer. We performed the Mendelian randomization (MR) to investigate the causal associations between endometriosis and 34 different types of cancers. The results of the inverse-variance-weighted (IVW) model suggested that genetic predisposition to endometriosis was causally associated with an increased risk for ovarian cancer (OR = 3.2913; p-value = .0320). The genetic liabilities to endometriosis had causal associations with the decreased risk for skin cancer (OR = 0.9973; p-value = .0219), hematological cancer (OR = 0.9953; p-value = .0175) and ER- breast cancer (OR = 0.6960; p-value = .0381). The causal association of the above combinations were robust by test of heterogeneity and pleiotropy. Together, our study suggests that endometriosis had causal effect on cancer risk.

Is there an association between endometriosis and subsequent breast cancer? A retrospective cohort study from Germany.

PURPOSE: Given the relatively high incidence of both endometriosis and breast cancer, investigating the potential connection between these gynecological diseases is of substantial clinical significance. However, there is no clear consensus in the literature on the extent to which the risk of breast cancer is increased in patients with endometriosis. Therefore, we conducted a large-scale observational study investigating the association between endometriosis and breast cancer risk. METHODS: This study included women aged ≥ 18 years with an initial endometriosis diagnosis from one of 315 office-based gynecologists in Germany between January 2005 and December 2021. Non-endometriosis patients were matched 1:1 to patients with endometriosis based on age, index year, average yearly consultation frequency, and predefined co-diagnoses within 12 months before or on the index date, including obesity and benign breast disorders. The association between endometriosis and the 10-year incidence of breast cancer was studied using Kaplan-Meier curves and log-rank tests. Finally, a univariable Cox regression analysis was conducted to assess the association between endometriosis and breast cancer. RESULTS: Over a follow-up period of up to 10 years, no significant difference was observed between the endometriosis (2.4%) and the matched non-endometriosis group (2.5%) with regard to breast cancer diagnoses. Furthermore, the regression analysis revealed no significant association between endometriosis and subsequent breast cancer. CONCLUSION: In summary, our comprehensive 10-year study involving a substantial sample of women indicates that endometriosis is not significantly associated with an increased risk of subsequent breast cancer.

Correlation between endometriosis and migraine features: Results from a prospective case-control study.

BACKGROUND: Endometriosis and migraine frequently coexist, but only a limited number of studies have focused on their mutual association. The aim of our study was to investigate, in untreated women with comorbid endometriosis/adenomyosis and migraine, the correlation between headache features and endometriotic subtypes and their possible relationship with pain severity and disease disability. METHODS: Fifty women affected by endometriosis/adenomyosis and migraine matched (1:2) with 100 patients with endometriosis alone and 100 patients with only migraine were recruited and underwent pelvic ultrasound imaging and neurological examination. RESULTS: Severe adenomyosis, posterior and anterior deep infiltrating endometriosis (p = 0.027, p = 0.0031 and p = 0.029, respectively) occurred more frequently in women with migraine. Dysmenorrhea was the most commonly reported symptom in women with endometriosis and migraine and the mean VAS scores of all typical endometriotic symptoms were significantly higher in the presence of comorbidity. Women with both migraine and endometriosis reported significant higher pain intensity (p = 0.004), higher monthly migraine days (p = 0.042) and increased HIT 6-scores (p = 0.01), compared with those without endometriosis. CONCLUSIONS: Our results demonstrated that the co-occurrence of migraine in untreated women with endometriosis is associated with more severe gynecological infiltrations and correlated with increased pain intensity and disease disability.Trial Registration: Protocol number 119/21.

How do women get endometriosis?

How do women get endometriosis? This question has baffled investigators for nearly a century, and the pathogenesis of endometriosis remains an enigma to this day. While Sampson's retrograde menstruation theory is widely accepted, the gaping divide between the near-ubiquity of retrograde menstruation and the moderate prevalence of endometriosis has been difficult to explain. Now, Mumusoglu and Hsueh have provided some much-needed clues by proposing that endometriosis is likely a result of maladaptation of the evolutionary baggage to dramatically changed societies and cultures. These changes are profound, sweeping and across the board, resulting in myriad mismatches between the evolutionary legacy and the changed societies, which, in turn, have generated many potential risk factors for endometriosis that were completely absent in hunter-gatherer societies. These risk factors could conceivably account for the glaring gap between the ubiquity of retrograde menstruation and the moderate prevalence of endometriosis. This perspective may force the viewing of endometriosis from a fresh angle, providing a roadmap for future epidemiological studies, and potentially providing the prospect of development of novel ways for disease prevention and treatment.

Endometriosis and mental health: a population-based cohort study.

BACKGROUND: Endometriosis is a chronic gynecologic disorder that leads to considerable pain and a reduced quality of life. Although its physiological manifestations have been explored, its impact on mental health is less well defined. Existing studies of endometriosis and mental health were conducted within diverse healthcare landscapes with varying access to care and with a primary focus on surgically diagnosed endometriosis. A single-payer healthcare system offers a unique environment to investigate this association with fewer barriers to access care while considering the mode of endometriosis diagnosis. OBJECTIVE: Our objective was to assess the association between endometriosis and the risk for mental health conditions and to evaluate differences between patients diagnosed medically and those diagnosed surgically. STUDY DESIGN: A matched, population-based retrospective cohort study was conducted in Ontario and included patients aged 18 to 50 years with a first-time endometriosis diagnosis between January 1, 2010, and July 1, 2020. Endometriosis exposure was determined through either medical or surgical diagnostic criteria. A medical diagnosis was defined by the use of the corresponding International Classification of Disease diagnostic codes from outpatient and in-hospital visits, whereas a surgical diagnosis was identified through inpatient or same-day surgeries. Individuals with endometriosis were matched 1:2 on age, sex, and geography to unexposed individuals without a history of endometriosis. The primary outcome was the first occurrence of any mental health condition after an endometriosis diagnosis. Individuals with a mental health diagnosis in the 2 years before study entry were excluded. Cox regression models were used to generate hazard ratios with adjustment for hysterectomy, salpingo-oophorectomy, infertility, pregnancy history, qualifying surgery for study inclusion, immigration status, history of asthma, abnormal uterine bleeding, diabetes, fibroids, hypertension, irritable bowel disorder, migraines, and nulliparity. RESULTS: A total of 107,832 individuals were included, 35,944 with a diagnosis of endometriosis (29.5% medically diagnosed, 60.5% surgically diagnosed, and 10.0% medically diagnosed with surgical confirmation) and 71,888 unexposed individuals. Over the study period, the incidence rate was 105.3 mental health events per 1000 person-years in the endometriosis group and 66.5 mental health events per 1000 person-year among unexposed individuals. Relative to the unexposed individuals, the adjusted hazard ratio for a mental health diagnosis was 1.28 (95% confidence interval, 1.24-1.33) among patients with medically diagnosed endometriosis, 1.33 (95% confidence interval, 1.16-1.52) among surgically diagnosed patients, and 1.36 (95% confidence interval, 1.2-1.6) among those diagnosed medically with subsequent surgical confirmation. The risk for receiving a mental health diagnosis was highest in the first year after an endometriosis diagnosis and declined in subsequent years. The cumulative incidence of a severe mental health condition requiring hospital visits was 7.0% among patients with endometriosis and 4.6% among unexposed individuals (hazard ratio, 1.56; 95% confidence interval, 1.53-1.59). CONCLUSION: Endometriosis, regardless of mode of diagnosis, is associated with a marginally increased risk for mental health conditions. The elevated risk, particularly evident in the years immediately following the diagnosis, underscores the need for proactive mental health screening among those newly diagnosed with endometriosis. Future research should investigate the potential benefits of mental health interventions for people with endometriosis with the aim of enhancing their overall quality of life.

Psychiatric disorders and mortality due to external causes following diagnosis of endometriosis at a young age: a longitudinal register-based cohort study in Finland.

BACKGROUND: Endometriosis diagnosed in adults is associated with increased risk of various psychiatric disorders. However, little is known concerning psychiatric comorbidity and mortality due to external causes associated with endometriosis diagnosed at a young age. OBJECTIVE: This longitudinal cohort study aimed to investigate the link between surgical diagnosis of endometriosis at a young age and subsequent psychiatric disorders and mortality due to external causes. In addition, we compared the occurrence of the most common psychiatric disorders between different sites of surgically confirmed endometriosis (ovarian vs other) because of possible differences in pain manifestations. STUDY DESIGN: We conducted a retrospective register-based cohort study. Altogether 4532 women with surgically confirmed diagnosis of endometriosis before the age of 25 years from 1987 to 2012 were identified from the Finnish Hospital Discharge Register. They were matched with women without surgically diagnosed endometriosis for age and municipality on the index day (n=9014). Women were followed up from the index day until the end of 2019 for the outcomes of interest, which included 9 groups of psychiatric disorders (inpatient episodes since 1987, outpatient episodes since 1998) and death due to external causes, including deaths due to accidents, suicides, and violence (Finnish Register of Causes of Death). Cox proportional hazard models were applied to assess the crude and parity-adjusted hazard ratios and 95% confidence intervals. RESULTS: The cohort's median age was 22.9 years (interquartile range, 21.3-24.1) at the beginning and 42.5 years (36.7-48.3) after a median follow-up time of 20.0 years (14.5-25.7). We observed a higher hazard of depressive, anxiety, and bipolar disorders in women with endometriosis compared with the reference cohort, with depressive and anxiety disorders being the two most common psychiatric disorders. These differences appeared early and remained the same during the entire follow-up, irrespective of whether assessed from the data on inpatient episodes only or the data on both in- and outpatient episodes. The corresponding adjusted hazard ratios were 2.57 (95% confidence interval, 2.11-3.14) and 1.87 (1.65-2.12) for depressive disorders, 2.40 (1.81-3.17) and 2.09 (1.84-2.37) for anxiety disorders, and 1.71 (1.30-2.26) and 1.66 (1.28-2.15) for bipolar disorders, respectively. A higher hazard was observed for nonorganic sleeping disorders for the first 10 years only (3.83; 2.01-7.30) when assessed using the data on both in- and outpatient episodes. When based on inpatient records, a higher hazard for alcohol/drug dependence after 15 years of follow-up (2.07; 1.21-3.54) was observed. The difference in hazard for personality disorders tended to increase during follow-up (<10 years, 2.12 [1.28-3.52]; ≥10 years, 3.08 [1.44-6.57]). Depressive and anxiety disorders occurred more frequently in women with types of endometriosis other than ovarian endometriosis. No difference in deaths due to external causes was observed between the endometriosis and reference cohorts. CONCLUSION: Surgical diagnosis of endometriosis at a young age was associated with increased incidence of several psychiatric disorders. Moreover, within the endometriosis population, psychiatric comorbidity was more common in women with types of endometriosis other than ovarian endometriosis. We speculate that chronic pain is essential in the development of these psychiatric disorders, and that early and effective pain management is important in reducing the risk of psychiatric morbidity in young women. More research concerning the associations and management of endometriosis and associated psychiatric disorders is warranted.

Endometriosis risk and hormonal contraceptive usage: A nationwide cohort study.

OBJECTIVE: To investigate whether an early need of hormonal contraceptive (HC), or a failure to find a suitable method, are warning signs for endometriosis. DESIGN: A retrospective cohort study. SETTING: Sweden. POPULATION: The cohort consisted of 720 805 women aged 12-27 years during the period 2005-2017. All women, regardless of whether they received a diagnosis of endometriosis or not (reference group), were included. METHODS: We used data from Swedish national registers. Risks are expressed as crude and adjusted hazard ratios (HRs and aHRs, respectively) with 95% confidence intervals (95% CIs), adjusted for age, education level, civil status, parity, country of birth, and diagnoses of infertility, dysmenorrhea or depression. MAIN OUTCOME MEASURES: A diagnosis of endometriosis between 12 and 27 years of age. RESULTS: During this period, 3268 women were diagnosed with endometriosis (0.45%). Women who started HC at the ages of 12-14 years had a higher risk of receiving the diagnosis (aHR 2.53, 95% CI 2.21-2.90) than those who began at age 17 years or older. Having tried more types of HCs was associated with a twofold increased risk of endometriosis (more that three types of HC, aHR 2.31, 95% CI 1.71-3.12). Using HC for more than 1 year was associated with a decreased risk of endometriosis (>1 year, aHR 0.53, 95% CI 0.48-0.59). Women with endometriosis more commonly had dysmenorrhea, depression or infertility. CONCLUSIONS: The use of HCs at an early age and a failure to find a suitable HC were identified as warning signs of later receiving an endometriosis diagnosis. A longer duration of HC usage reduced the risk of receiving the diagnosis.

Plastic-related endocrine disrupting chemicals significantly related to the increased risk of estrogen-dependent diseases in women.

OBJECTIVE: To evaluate the association between exposure to plastic-related endocrine-disrupting chemicals (EDCs), specifically Bisphenol A (BPA), Phthalates, Cadmium, and Lead, and the risk of estrogen-dependent diseases (EDDs) such as polycystic ovary syndrome (PCOS), endometriosis, or endometrial cancer by conducting a meta-analysis of relevant studies. METHODS: PubMed, Web of Science, and Cochrane Library databases were used for literature retrieval of articles published until the 21st of April 2023. Literature that evaluated the association between BPA, phthalates, cadmium, and/or lead exposure and the risk of PCOS, endometriosis, or endometrial cancer development or exacerbation were included in our analysis. STATA/MP 17.0 was used for all statistical analyses. RESULTS: Overall, 22 articles were included in our meta-analysis with a total of 83,641 subjects all of whom were females aged between 18 and 83 years old. The overall effect size of each study was as follows: endometriosis risk in relation to BPA exposure ES 1.82 (95% CI; 1.50, 2.20). BPA and PCOS risk ES 1.61 (95% CI; 1.39, 1.85). Phthalate metabolites and endometriosis risk; MBP ES 1.07 (95% CI; 0.86, 1.33), MEP ES 1.05 (95% CI; 0.87, 1.28), MEHP ES 1.15 (95% CI; 0.67, 1.98), MBzP ES 0.97 (95% CI; 0.63, 1.49), MEOHP ES 1.87 (95% CI; 1.21, 2.87), and MEHHP ES 1.98 (95% CI; 1.32, 2.98). Cadmium exposure and endometrial cancer risk ES 1.14 (95% CI; 0.92, 1.41). Cadmium exposure and the risk of endometriosis ES 2.54 (95% CI; 1.71, 3.77). Lead exposure and the risk of endometriosis ES 1.74 (95% CI; 1.13, 2.69). CONCLUSION: Increased serum, urinary, or dietary concentration of MBzP and MEHP in women is significantly associated with endometriosis risk. Increased cadmium concentration is associated with endometrial cancer risk.

Causal effects of endometriosis on SLE, RA and SS risk: evidence from meta-analysis and Mendelian randomization.

BACKGROUND: Endometriosis is an underdiagnosed disorder that affects an estimated 6-10% of women of reproductive age. Endometriosis has been reported in epidemiological studies to be associated with autoimmune diseases. However, the relationship remains controversial. METHODS: A meta-analysis of observational studies was undertaken to evaluate the risk of autoimmune diseases in patients with endometriosis. The relevant studies were retrieved via the databases Medline, Embase and Web of Science until July 20, 2023. Mendelian randomization (MR) was subsequently utilized to scrutinize the causal influence of genetic predisposition toward endometriosis on three autoimmune diseases. RESULTS: The meta-analysis findings revealed a relationship between endometriosis and the onset of SLE (cohort studies: RR = 1.77, 95% confidence interval (CI): 1.47-2.13, I2 = 0%; Case-control and cross-sectional studies: OR = 5.23, 95% CI: 0.74-36.98, I2 = 98%), RA (cohort studies: RR = 2.18, 95% CI: 1.85-2.55, I2 = 92%; Case-control and cross-sectional studies: OR = 1.40, 95% CI: 1.19-1.64, I2 = 0%) and SS (cohort studies: RR = 1.49, 95% CI: 1.34-1.66, I2 = 0%). Similarly, in our MR study, the results of the inverse-variance-weighted (IVW) model suggested that genetic predisposition to endometriosis was causally associated with an increased risk for SLE (OR = 1.915, 95% CI: 1.204-3.045, p = 0.006) and RA (OR = 1.005, 95% CI: 1.001-1.009, p = 0.014). CONCLUSIONS: Both our meta-analysis and MR study indicate that endometriosis increases the risk of autoimmune diseases. These findings not only broaden our understanding of the genetic mechanisms underlying the comorbidity of endometriosis and autoimmune diseases, but also offer a new strategy for autoimmune disease prevention.

Association between endometriosis and perinatal complications: a case-control study.

BACKGROUND: Recently, a history of endometriosis has been reported to be associated with several perinatal complications. However, it is unknown whether pre-pregnancy treatment for endometriosis reduces perinatal complications. In this study, we aimed to clarify the association between endometriosis and perinatal complications and investigate whether there is a significant difference in the incidence of placenta previa depending on the degree of surgical completion of endometriosis before pregnancy. METHODS: This case-control study included 2781 deliveries at the Hirosaki University Hospital between January 2008 and December 2019. The deliveries were divided into a case group with a history of endometriosis (n = 133) and a control group without endometriosis (n = 2648). Perinatal outcomes and complications were compared between the case and control groups using a t-test and Fisher's exact test. Multiple logistic regression models were used to identify the risk factors for placenta previa. Additionally, we examined whether the degree of surgical completion of endometriosis before pregnancy was associated with the risk of placenta previa. RESULTS: Patients with a history of endometriosis had a significantly higher risk of placenta previa (crude odds ratio, 2.66; 95% confidence interval, 1.37‒4.83). Multiple logistic regression analysis showed that a history of endometriosis was a significant risk factor for placenta previa (adjusted odds ratio, 2.30; 95% confidence interval, 1.22‒4.32). In addition, among patients with revised American Society for Reproductive Medicine stage III-IV endometriosis, the incidence of placenta previa was significantly lower in patients who underwent complete surgery (3/51 patients, 5.9%) than in those who did not (3/9 patients, 33.3%) (p = 0.038). CONCLUSIONS: A history of endometriosis is an independent risk factor for placenta previa. Given the limitations of this study, further research is needed to determine the impact of endometriosis surgery on perinatal complications.

Relationship between triglyceride-glucose index and endometriosis: a cross-sectional analysis.

BACKGROUND: The link between insulin resistance and endometriosis is not well established. The triglyceride-glucose (TyG) index serves as a straightforward and economical indicator of insulin resistance. This study examines the link between the TyG index and the prevalence of endometriosis in a U.S. METHODS: This cross-sectional study analyzed data from the NHANES conducted between 1999 and 2006. Reproductive health was assessed through questionnaires, and the TyG index was derived from fasting triglyceride and glucose measurements. Weighted logistic regression models were used to analyze the relationship between the TyG index and endometriosis. Restricted cubic spline (RCS) curves explored the linear relationship, while stratified and sensitivity analyses assessed potential interactions and the robustness of the findings. RESULTS: The study included 2,346 women, with 176 diagnosed with endometriosis and 2,170 without. Women with endometriosis exhibited an elevated TyG index compared to those without the condition. The weighted logistic regression analysis revealed that the TyG index is an independent risk factor for endometriosis (OR = 1.58, 95% CI 1.17-2.14, p = 0.004). RCS analysis indicated a significant positive linear association between the TyG index and endometriosis, with a turning point at 8.51. Subgroup analysis indicated a stronger association in certain populations. The post-propensity score matching analysis confirmed the robustness of these findings. CONCLUSION: In the U.S. population, a higher TyG index is positively and linearly associated with endometriosis prevalence. Effective management of blood glucose and lipid levels may reduce the prevalence of endometriosis.

Sleep disorders in patients with endometriosis; a cross-sectional study.

BACKGROUND: Endometriosis affects 10-15% of women of reproductive age and is considered a critical gynecological problem. Endometriosis causes pain and infertility, both of which can impair the patient's quality of life. Sleep disorders account for the most bothersome presentation of impaired quality of life. This study investigated the frequency and severity of sleep disorders in women with endometriosis. METHODS: In this analytical cross-sectional study, 665 women referred to three hospitals in Tehran, Rasool-e-Akram, Pars, and Nikan, were included (463 patients with endometriosis and 202 women without endometriosis). All of them were informed about the study design and the aim of the research, and then they were asked to sign the consent form and complete the Pittsburgh Sleep Quality Index (PSQI). After data gathering and entering, they were analyzed by SPSS version 22 and were considered significant with P < 0.05. RESULTS: The study population's mean age was 35.4 ± 7.9 years. The mean global PSQI score in the case group (endometriosis patients) was higher than in the control group (non-endometriosis patients) (10.6 vs. 7.1; P < 0.001). Patients with dyspareunia, dysuria, pelvic pain, and dyschezia had a significantly higher PSQI score (P < 0.05). CONCLUSION: According to the findings of the present study, the sleep quality in endometriosis patients is low, and there is a need to pay greater attention to these patients. This may result in some changes in the therapeutic strategies for this disease.

Dysmenorrhea pattern in adolescences informing adult endometriosis.

BACKGROUND: Endometriosis (EMs) is a chronic and progressive disease that, if diagnosed late, can lead to infertility and deep infiltrating endometriosis (DIE). Dysmenorrhea is the most prominent symptom of EMs. However, limited research exists on the specific correlation between dysmenorrhea patterns and EMs. Early prevention of EMs is essential to effectively manage the progression of the disease, and is best detected during adolescence. Our objective was to associate the development of EMs with dysmenorrhea patterns during adolescence and quantify the risk of adult EMs for adolescent girls, with the aim of supporting primary intervention strategy planning. METHODS: This case-control study examined predictors for adult EMs based on dysmenorrhea patterns in adolescents. We collected 1,287 cases of 641 EMs and 646 healthy females regarding their basic demographic information, adolescent menstrual characteristics, adolescent dysmenorrheal patterns, and adolescent lifestyles. Age-matching (1-to-1) was employed to control for the confounding effect of age between the groups. Least Absolute Shrinkage and Selection Operator (LASSO) and logistic regression models were utilized to identify predictors for adult EMs. The predictive value of the model was evaluated using the area under the receiver operating characteristic curve (AUC) and the C-index, while Hosmer-Lemeshow Test assessed the goodness of fit of the model. Data from one additional cohort in Shenzhen hospitalized with EMs were used to external validation were analyzed. RESULTS: Individuals who always experienced dysmenorrhea had a risk of adult endometriosis 18.874 (OR = 18.874; 95%CI = 10.309-34.555) times higher than those occasional dysmenorrhea, The risk of developing EMs was 5.257 times higher in those who experienced dysmenorrhea more than 12 months after menarche than in those who experienced dysmenorrhea less than 6 months after menarche (OR = 5.257, 95% CI = 3.343-8.266), AUC in the external validation cohort was 0.794(95%CI: 0.741-0.847). We further found that high-intensity physical activity and sun-sensitive skin of burning were influential factors in high-frequency dysmenorrhea. The AUC value for the internal evaluation of the model was 0.812 and the AUC value for the external validation was 0.794. CONCLUSION: Our findings revealed that the frequency of dysmenorrhea during adolescence contributed to the development of adult endometriosis. The frequency and onset of dysmenorrhea in adolescence were promising predictors for adult EMs. Both internal and external validation proved the model's good predictive ability. TRIAL REGISTRATION: http://www.chictr.org.cn/ , TRN: ChicTR2200060429, date of registration: 2022/06/01, retrospectively registered.

Demographic Correlates of Endometriosis Diagnosis Among United States Women Aged 15-50.

OBJECTIVE: To compare demographic characteristics of women with and without a diagnosis of endometriosis. DESIGN: Data were collected from the National Survey of Family Growth-a publicly available survey designed and administered by the Centers for Disease Control, which uses a nationally-representative sample of the United States population. Univariate data were reported as survey-weighted percentages and means and were analyzed using chi-square, t tests, and logistic regression. Analyses accounted for complex survey design. SETTING: United States. PARTICIPANTS: Interviews were conducted with 6141 female respondents, aged 15 to 50, between 2017 and 2019. INTERVENTIONS: Data were collected through in-person interviews. RESULTS: Nationally, 5.7% reported a diagnosis of endometriosis (95% CI 4.6-6.9%). Those with endometriosis were older, with a mean age of 39 (95% CI 38.1-39.9), compared to 31.7 (95% CI 31.2-32.2) among those without (p <.0005). Endometriosis diagnosis was significantly associated with race. Compared to non-Hispanic White women, Hispanic women had an adjusted odds ratio (aOR) of 0.37 (95% CI 0.21-0.65) for diagnosis of endometriosis, and non-Hispanic Black women had an aOR of 0.54 (95% CI 0.35-0.84). We also observed a difference in diagnosis by health insurance: compared to those with private insurance or Medi-Gap coverage, those with Medicare or military insurance had an aOR for endometriosis diagnosis of 2.49 (95% CI 1.36-4.55). Finally, compared to those with less than a high school education, those who had completed high school or greater had an aOR for endometriosis diagnosis of 2.84 (95% CI 1.15-6.99). CONCLUSION: These disparities in endometriosis diagnosis suggest that intersecting barriers may preclude certain groups from accessing timely endometriosis diagnosis and management. Further studies are warranted to explore these hypothesis-generating data and to identify and address specific barriers to equitable endometriosis diagnosis and management.

The relationship between hypertensive disorders in pregnancy and endometriosis: a systematic review and meta-analysis.

BACKGROUND: Endometriosis is a chronic and debilitating disease that can affect the entire reproductive life course of women, with potential adverse effects on pregnancy. The aim of the present study is to investigate the association between hypertensive disorders in pregnancy and endometriosis. METHOD: Relevant articles were searched from the Cochrane Library, PubMed, Scopus and Web of Science from inception up to December 2023. The full-text observational studies published in English that had a confirmed diagnosis of endometriosis were included. The case group included pregnant women diagnosed with endometriosis at any stage, while the control group consisted of pregnant women who had not been previously diagnosed with endometriosis. Two authors extracted and analyzed the data independently. Disagreements were reconciled by reviewing the full text by a third author. Endnote X9 was used for screening and data extraction. We used fixed and random effects models in Review Manager 5.3 to analyze the pooled data. The quality of the included studies was assessed using the Downs and Black checklist. RESULTS: Out of the 9863 articles reviewed, 23 were selected for meta-analysis. According to the results of this study, there was an association between endometriosis and gestational hypertension (OR = 1.11, 95% CI: 1.06, 1.16; I2 = 45%, P < 0.00001; N = 8), pre-eclampsia (OR = 1.26, 95% CI: 1.18, 1.36; I2 = 37%, P < 0.00001; N = 12), and hypertensive disorders in pregnancy (OR = 1.13, 95% CI: 1.06, 1.21; I2 = 8%, P = 0.0001; N = 8). CONCLUSIONS: This study confirmed that endometriosis may elevate the risk of developing gestational hypertensive disorders. Raising awareness of this issue will help to identify effective strategies for screening and early diagnosis of hypertensive disorders in pregnancy.

Elevated levels of Zn, Cu and Co are associated with an increased risk of endometriosis: Results from a casecontrol study.

BACKGROUND: Endometriosis is a common gynecological disease that affects approximately 5 %∼10 % of reproductive-aged women. Zinc (Zn), selenium (Se), copper (Cu), cobalt (Co) and molybdenum (Mo) are essential trace elements and are very important for human health. However, studies on the relationship between mixtures of essential trace elements and the risk of endometriosis are limited and inconsistent. In particular, studies confirming the association via different sample types are limited. OBJECTIVE: This study aimed to investigate the associations between Zn, Se, Cu, Co and Mo concentrations in blood and follicular fluid (FF) and endometriosis risk in a Chinese population. METHODS: A total of 609 subjects undergoing in vitro fertilization (IVF) were recruited; 836 samples were analyzed, including 451 blood samples (234 controls and 217 cases) and 385 FF samples (203 controls and 182 cases). In addition, 227 subjects provided both blood and FF samples. Zn, Se, Cu, Co and Mo concentrations in blood and FF were quantified via inductively coupled plasma-mass spectrometry (ICP-MS). The associations between the levels of Zn, Se, Cu, Co and Mo and the risk of endometriosis were assessed using single-element models (logistic regression models), and the combined effect of the trace elements on endometriosis risk was assessed using multielement models (Bayesian kernel machine regression (BKMR) and weighted quantile sum (WQS) regression). RESULTS: Based on the single-element models, significant associations of Zn concentrations in blood (high-level vs. low-level group: aOR = 14.17, 95 % CI: 7.31, 27.50) and FF (first tertile vs. second tertile group: aOR = 0.34, 95 % CI: 0.16, 0.71; third tertile vs. second tertile group: aOR = 2.32, 95 % CI: 1.38, 3.91, respectively) and Co concentrations in blood (first tertile vs. second tertile group, aOR = 0.24, 95 % CI: 0.12, 0.48) and FF (third tertile vs. second tertile group: aOR = 3.87, 95 % CI: 2.19, 6.84) with endometriosis risk were found after adjustment for all confounders. In FF, Cu and Mo levels were significantly greater among the cases than among the controls, with a positive association with endometriosis risk (Cu (first tertile vs. second tertile group: aOR = 0.39, 95 % CI: 0.19, 0.81; third tertile vs. second tertile group: aOR = 2.73, 95 % CI: 1.61, 4.66, respectively) and Mo (high-level vs. low-level group: aOR = 14.93, 95 % CI: 7.16, 31.12)). However, similar associations between blood Cu and Mo levels and endometriosis risk were not found. In addition, the levels of these five essential trace element mixtures in blood and in FF were significantly and positively associated with endometriosis risk according to the BKMR analyses; the levels of Zn and Cu in blood and the levels of Mo in FF were significantly related to the risk of endometriosis, and the posterior inclusion probabilities (PIPs) were 1.00, 0.99 and 1.00 for Zn and Cu levels in blood and Mo levels in FF, respectively. Furthermore, Zn and Mo were the highest weighted elements in blood and FF, respectively, according to WQS analyses. CONCLUSION: The risk of endometriosis was associated with elevated levels of several essential trace elements (Zn, Cu and Co). Elevated levels of these elements may be involved in the pathomechanism of endometriosis. However, further studies with larger sample sizes will be necessary to confirm these associations.

Pregnancy, delivery, and neonatal outcomes among women with PCOS and endometriosis: a population database cohort.

PURPOSE: PCOS and endometriosis are independent risk factors for perinatal outcomes. Little research has evaluated the concomitant effects of these conditions, nor have studies been conducted on a population database. We sought to identify the pregnancy, delivery, and neonatal outcomes in women with polycystic ovary syndrome (PCOS) and endometriosis vs. PCOS without endometriosis. METHODS: A retrospective population-based cohort study was performed extracting data using ICD-9 codes from the HCUP-NIS Database from 2004 to 2014. Endometriosis in women with PCOS represented the study group (n = 163), and the remaining PCOS, non-endometriosis patients constituted the reference group (n = 14,719). Subjects were included once per delivery. Demographics were compared using chi-squared tests. Confounding effects in pregnancy outcomes were controlled using binary logistic regression analysis. RESULTS: Concomitant endometriosis and PCOS patients were more likely to be white (88.5% vs.71.0%, p < 0.001), with BMI < 30 kg/m2 (87.1% vs.77.8%, p < 0.004) and from lower income quartiles (27.1% vs.17.1%, p < 0.017) when compared to PCOS without endometriosis. Comparing pregnancy complication rates, placental abruption (p < 0.018, aOR 3.01, 95% CI 1.21-7.50), Cesarean section (p < 0.003, aOR 1.75, 95% CI 1.21-2.53), deep venous thromboses (p < 0.002, aOR 74.31, 95% CI 4.57-1209.21), and venous thromboembolic events (p < 0.031, aOR 10.40, 95% CI 1.24-87.37), were increased in the study group compared to the reference group. CONCLUSION: Women with PCOS and endometriosis were more likely to be white, of lower socioeconomic status, lean, and experience abruptio-placenta, cesarean deliveries, and venous thromboembolisms. Since little was previously known about the combined outcomes of PCOS and endometriosis, it is difficult to counsel patients on risks. Our findings can help clinicians manage pregnant PCOS patients with endometriosis to minimize complications such as abruptio placenta and VTE.

Correlation between pain and depressive symptoms in patients with confirmed endometriosis during COVID-19 pandemic.

BACKGROUND: Endometriosis is a chronic, estrogen-dependent, inflammatory condition which affects women of reproductive age physically and psychologically in their everyday life. The most common symptom is chronic lower abdominal pain. Apart from physical pain, endometriosis often also leads to an unfulfilled desire to give birth. In general, these two main aspects alone lead to emotional stress for patients and often initiate depressive symptoms. To what extent endometriosis patients are additionally affected by the COVID pandemic and its effects is to be determined in this study. METHODS: Patients who presented at our endometriosis center and met the study criteria were offered participation in the study. A link to an online questionnaire (SoSci-Survey) was sent by email. The online questionnaire evaluated depressive symptoms before and during the pandemic as well as the pain perception and perceived support during the pandemic. The data of 167 fully completed questionnaires were evaluated and analyzed using SPSS. RESULTS: The analysis of the questionnaires revealed a significant association between pain levels and depressive symptomatology in endometriosis patients during the pandemic. Patients with more severe pain showed significantly higher depressive symptoms than patients with little or no pain. During the pandemic, patients showed higher depressive symptoms than before. In addition, it was found that those endometriosis patients who felt left alone with their pain due to the consequences of the COVID pandemic, or who felt they had to endure the pain alone, also had higher depressive symptoms. CONCLUSION: In summary, it can be observed that endometriosis patients with a high pain burden had significantly higher depressive symptoms during the COVID pandemic. The consequences of the pandemic often led to the feeling of having to cope with the symptoms alone or having to endure pain alone, which in turn increased the depressive symptoms. As treating physicians, we should be aware of these connections and try to counteract them with targeted offers and support.

Endometriosis Typology and Ovarian Cancer Risk.

Importance: Endometriosis has been associated with an increased risk of ovarian cancer; however, the associations between endometriosis subtypes and ovarian cancer histotypes have not been well-described. Objective: To evaluate the associations of endometriosis subtypes with incidence of ovarian cancer, both overall and by histotype. Design, Setting, and Participants: Population-based cohort study using data from the Utah Population Database. The cohort was assembled by matching 78 893 women with endometriosis in a 1:5 ratio to women without endometriosis. Exposures: Endometriosis cases were identified via electronic health records and categorized as superficial endometriosis, ovarian endometriomas, deep infiltrating endometriosis, or other. Main Outcomes and Measures: Estimated adjusted hazard ratios (aHRs), adjusted risk differences (aRDs) per 10 000 women, and 95% CIs for overall ovarian cancer, type I ovarian cancer, and type II ovarian cancer comparing women with each type of endometriosis with women without endometriosis. Models accounted for sociodemographic factors, reproductive history, and past gynecologic operations. Results: In this Utah-based cohort, the mean (SD) age at first endometriosis diagnosis was 36 (10) years. There were 597 women with ovarian cancer. Ovarian cancer risk was higher among women with endometriosis compared with women without endometriosis (aHR, 4.20 [95% CI, 3.59-4.91]; aRD, 9.90 [95% CI, 7.22-12.57]), and risk of type I ovarian cancer was especially high (aHR, 7.48 [95% CI, 5.80-9.65]; aRD, 7.53 [95% CI, 5.46-9.61]). Ovarian cancer risk was highest in women with deep infiltrating endometriosis and/or ovarian endometriomas for all ovarian cancers (aHR, 9.66 [95% CI, 7.77-12.00]; aRD, 26.71 [95% CI, 20.01-33.41]), type I ovarian cancer (aHR, 18.96 [95% CI, 13.78-26.08]; aRD, 19.57 [95% CI, 13.80-25.35]), and type II ovarian cancer (aHR, 3.72 [95% CI, 2.31-5.98]; aRD, 2.42 [95% CI, -0.01 to 4.85]). Conclusions and Relevance: Ovarian cancer risk was markedly increased among women with ovarian endometriomas and/or deep infiltrating endometriosis. This population may benefit from counseling regarding ovarian cancer risk and prevention and could be an important population for targeted screening and prevention studies.

[Endometriosis, a participatory study in the Serchio Valley (Tuscany Region, Central Italy): state of the art and perspectives]. / Endometriosi, uno studio partecipato nella Valle del Serchio: stato dell'arte e prospettive.

BACKGROUND: endometriosis is a chronic condition with a significant impact on women's health, featured by endometrial tissue outside the uterine cavity. A limited number of studies have been conducted in the general population, and the true prevalence of endometriosis is unknown for many areas of the country. OBJECTIVES: to better estimate the prevalence of endometriosis in three Italian regions (Friuli Venezia Giulia, Tuscany, Apulia) and to assess the relationship between endometriosis and environmental factors in three participating areas (Trieste, Barga, and Taranto), with a focus on Tuscany Region. DESIGN: implementing a specific epidemiological registry for endometriosis, aimed at estimating the incidence and prevalence data. The registry collected information from hospital discharge records and anatomopathological reports of women residing in the three considered regions, aged 15 years or older. Additionally, the analysis includes the assessment of the spatial distribution of endometriosis at both regional and municipal levels in the three study areas. Further research investigations in these areas involve a multilevel screening of a sample of women of childbearing age. Women who test positive in the initial screening (through a self-administered questionnaire) will have the opportunity to undergo a second level of screening, consisting of a gynecological examination, transvaginal ultrasound, a swab for vaginal microbiome analysis, and the collection of blood and urine samples to assess the presence of polychlorinated biphenyls (PCBs) or heavy metals. The adopted scientific approach is based on post-normal science (PNS) concerning the extended peer community. SETTING AND PARTICIPANTS: women aged 15 years or older residing in the three regions. MAIN OUTCOMES MEASURES: estimating the incidence and prevalence of endometriosis based on data collected from the epidemiological registry. The analysis extends to assessing the spatial distribution of endometriosis at municipal levels in the three areas of interest. RESULTS: the preliminary results of the study allowed for the estimation of the spatial distribution of endometriosis incidence in Tuscany. In particular, it was found that there is variability within the region, with some coastal and North-Western areas showing values 20% higher than the regional average. Cities such as Pisa, Lucca, Livorno, Grosseto, Orbetello, and the Serchio Valley with Barga had a probability of excess risk of more than 90% compared to the regional average. CONCLUSIONS: the study is ongoing and requires the active participation of women living in the region to ensure the completeness and accuracy of the collected data. This research effort represents an important contribution to understanding endometriosis in Tuscany and its possible environmental causes.