The spectrum of non-fatal immune-related adverse events following COVID-19 vaccination: The population-based cohort study in Seoul, South Korea (preprint)

ObjectiveTo examine the incidence rate and risk of non-fatal irAEs, including gynecological, hematological, dermatological, ophthalmological, otologic, and dental problems following the COVID-19 vaccination. MethodsWe conducted a population-based cohort study from the National Health Insurance Service (NHIS) database in Seoul, South Korea. The non-fatal irAEs included gynecological, hematological, dermatological, ophthalmological, ear, and periodontal problems as reported by the Vaccine Adverse Event Reporting Center. The cumulative incidence rate per 10,000 population, Odds ratio, and Hazard ratio (HR) with 95% Confidence Interval (CI) were measured to assess the non-fatal irAEs after COVID-19 vaccination. ResultsThe cIR of non-fatal irAEs for three months was significantly higher in vaccinated subjects than in non-vaccinated subjects, except for endometriosis. The vaccination significantly increased the risks of all the non-fatal irAEs except for visual impairment. The risk of inner ear disease showed the highest HRs (HR [95% CI] = 2.368 [2.153-2.604]) among the non-fatal irAEs following COVID-19 vaccination. Among the vaccinated subjects, heterologous vaccination was associated with the increased risk of most of the non-fatal irAEs. ConclusionsThe three-month risks of incidental non-fatal irAEs are substantially higher in the COVID-19 vaccinated subjects than in non-vaccinated controls. Our findings suggested that vaccinated subjects with predisposition are potentially vulnerable to the occurrence of diverse irAEs although the COVID-19 vaccines may not be fatal.

Evaluation of menstrual symptoms after Coronavirus disease 2019 vaccination in women with endometriosis.

BACKGROUND: Vaccination can have an impact on menstruation, and this impact may be more notable in women with inflammatory gynecological pathologies such as endometriosis. OBJECTIVES: We aimed to investigate the impact of mRNA-based SARS-CoV-2 vaccines on menstrual cycle-related symptoms in women with endometriosis and assess the effect of hormonal therapy on potential SARS-CoV-2 vaccination-induced menstrual changes. DESIGN: A total of 848 women who received at least two doses of mRNA-based COVID-19 vaccines were prospectively recruited: 407 with endometriosis (endometriosis group) and 441 healthy controls (non-endometriosis group). METHODS: Data regarding demographics, clinical characteristics, hormonal treatment, and menstrual-associated symptoms in the first and second cycle after vaccination were collected through an online survey. RESULTS: A similar percentage of patients in both the endometriosis and the non-endometriosis group self-reported menstrual-associated changes the first (52.6% versus 48.8%, respectively) and second cycle after vaccination (29.0% versus 28.1%, respectively). Although the total symptoms recorded were not different between the two groups, several specific symptoms were statistically more frequent in the endometriosis group. These were pain disorders and fatigue in the first cycle after vaccination and pain disorders, menstrual headache and fatigue in the second cycle after vaccination. Bleeding frequency/regularity disorders were found to be more frequent in the non-endometriosis group in the first cycle after vaccination. Patients under hormonal treatment reported fewer changes in menstrual symptoms in the first and second cycle after vaccination compared with those not receiving this treatment. Similarly, patients in the endometriosis group receiving hormonal treatment reported fewer changes in menstrual-associated symptoms compared with those not following any hormonal treatment in the first and second menstrual cycle after the last vaccination. CONCLUSION: Women with endometriosis immunized with mRNA-based SARS-CoV-2 vaccines did not perceive greater worsening or new menstrual-associated symptoms after complete COVID-19 vaccination compared with healthy controls. Hormonal treatment may have a protective effect against worsened or new menstrual symptoms induced by COVID-19 vaccination.

Establishment and application of the "electronic follow-up platform for endometriosis" during the COVID-19 pandemic.

The management of endometriosis has been complicated by the COVID-19 pandemic. We aimed to introduce the establishment and application of a new follow-up method during the COVID-19 pandemic-the electronic follow-up (e-follow-up) platform for endometriosis-and to test the applicability of the platform-based follow-up management model and patient satisfaction. We used the platform for information entry and post-operative follow-up of 152 patients with endometriosis from January 2021 to August 2022, and compared patients' Zung's Self-Rating Depression Scale (SDS), Self-Rating Anxiety Scale (SAS), and Visual Analogue Score (VAS) (range: 0 - 10, indicating: no pain-extreme pain) scores preoperatively and after 6-month of follow-up, together with recording patients' follow-up satisfaction and number of recurrence of lesions. Eventually, the SDS, SAS, and VAS scores were significantly lower than those at pre-surgery (p < .001), and the follow-up satisfaction rate reached 100%, with 91.41% expressing great satisfaction. The cumulative number of recurrences was 2 out of 138. Follow-up using this platform reduce the risk of COVID-19 transmission, enabled more efficient access to healthcare resources for patients with endometriosis, improved the efficiency of follow-up management, met the mental health needs of the patients.

True Prevalence of Diaphragmatic Endometriosis and Its Association with Severe Endometriosis: A Call for Awareness and Investigation.

STUDY OBJECTIVE: To identify characteristics indicating preoperatively the presence of diaphragmatic endometriosis (DE). DESIGN: Comparison of characteristics of patients with diaphragmatic endometriosis (DE) with characteristics of patients with abdominal endometriosis without diaphragmatic involvement, in a prospective cohort study. SETTING: Tertiary referral center; endometriosis center. PATIENTS: A total of 1372 patients with histologically proven endometriosis. INTERVENTIONS: Surgery performed laparoscopically under general anesthesia. All patients with suspected endometriosis underwent a complete bilateral inspection of the diaphragm. MEASUREMENTS AND MAIN RESULTS: Demographic and clinical pathologic characteristics were evaluated using basic descriptive statistics (comparison of the groups using the χ2 test and the Mann-Whitney t test). A logistic regression analysis was performed to evaluate the relationship (hazard ratio) between symptoms and the presence of DE. DE was diagnosed in 4.7% of the patients (65 of 1372). There was no significant difference between the 2 groups (patients with abdominal endometriosis with or without DE) with regard to typical endometriosis pain (dysmenorrhea, dyschezia, dysuria, and/or dyspareunia). However, in the DE group, diaphragmatic pain was present significantly more often preoperatively (27.7% vs 1.8%, p <.001). Four DE patients (6.1 %) were asymptomatic (with infertility the indication for surgery). In the DE group, 78.4 % had advanced stages of endometriosis (revised American Fertility Society III° or IV°); the left lower pelvis was affected in more patients (73.8%). In cases of ovarian endometriosis, patients with DE showed a significantly higher prevalence of left ovaries involvement (left 63% vs right 35.7%, p <.001). Patients with DE had a significantly higher rate of infertility (49.2% vs 28.7%, p <.05). CONCLUSION: Patients with shoulder pain, infertility, and/or endometriosis in the left pelvis have a significant higher risk of DE and therefore need specific preoperative counseling and if indicated surgical treatment.

Patients with endometriosis may experience worse clinical manifestations and therapeutic outcomes during COVID-19 in western China- a case series comparative analysis.

BACKGROUND: Endometriosis is a crippling, ongoing, chronic inflammatory condition. The management of these patients has been impacted by the current COVID-19 pandemic, which is still controversial. This study compared the clinical therapy outcomes and psychological scores between before and during- the epidemic. METHOD: The data of patients who were diagnosed with endometriosis in the Department of Gynecology, Chongqing Traditional Chinese Medicine Hospital from January 2018 to December 2022 were collected. The patients were divided into pre- and intra-COVID groups. The treatment results and psychological status of the two groups were compared. RESULTS: A total of 1022 patients with endometriosis were enrolled, with a mean age of 33.16 ± 9.81 years and a BMI of 23.90 ± 3.04 kg/m2, of which 434 cases (434/1022, 42.5%) were in the pre-COVID group and 588 cases (588/1022, 57.5%) in the intra-COVID group. Both groups were well balanced for age, BMI, history of abdominopelvic surgery, family relationships, education level, and duration between initial diagnosis and admission. Compared to the Pre-COVID group, the intra-COVID group had a higher proportion of patients with chronic pelvic pain (297/434, 68.4% vs. 447/588, 76.0%, p = 0.007) and dysmenorrhea (249/434, 62.8% vs. 402/588, 70.0%, p < 0.001), more patients requiring surgery (93/434, 21.4% vs. 178/588, 30.3%, p = 0.002) and longer hospital stays (5.82 ± 2.24 days vs. 7.71 ± 2.15 days, p < 0.001). A total of 830 questionnaires were completed. In the Intra-COVID group, PHQ-2 (2 (2, 3) vs. 3 (2,4), p < 0.001), GAD-2 (2 (1, 2) vs. 3 (2, 3), p < 0.001), PHQ-4 (4 (3, 5) vs. 5 (4, 7), EHP-5 (20.26 ± 6.05 vs. 28.08 ± 7.95, p < 0.001) scores were higher than that in the pre-COVID group, while BRS (3.0 (2.2, 4.0) vs. 2.4 (1.8, 3.8), p = 0.470) were not significantly different. CONCLUSION: During the COVID-19 epidemic, patients with endometriosis may have reduced visits to the hospital, more severe related symptoms, longer length of hospital stays, and worse quality of life, with the possible cause being a disturbance in hormone levels through increased anxiety and depression. This provides a valid clinical basis for optimizing the management of patients with endometriosis and for early psychological intervention during the epidemic.

Association of laparoscopically-confirmed endometriosis with long COVID-19: a prospective cohort study.

BACKGROUND: Women are at greater risk than men of developing chronic inflammatory conditions and "long COVID." However, few gynecologic health risk factors for long COVID-19 have been identified. Endometriosis is a common gynecologic disorder associated with chronic inflammation, immune dysregulation, and comorbid presentation with autoimmune and clotting disorders, all of which are pathophysiological mechanisms proposed for long COVID-19. Therefore, we hypothesized that women with a history of endometriosis may be at greater risk of developing long COVID-19. OBJECTIVE: This study aimed to investigate the association between history of endometriosis before SARS-CoV-2 infection and risk of long COVID-19. STUDY DESIGN: We followed 46,579 women from 2 ongoing prospective cohort studies-the Nurses' Health Study II and the Nurses' Health Study 3-who participated in a series of COVID-19-related surveys administered from April 2020 to November 2022. Laparoscopic diagnosis of endometriosis was documented prospectively in main cohort questionnaires before the pandemic (1993-2020) with high validity. SARS-CoV-2 infection (confirmed by antigen, polymerase chain reaction, or antibody test) and long-term COVID-19 symptoms (≥4 weeks) defined by the Centers for Disease Control and Prevention were self-reported during follow-up. Among individuals with SARS-CoV-2 infection, we fit Poisson regression models to assess the associations between endometriosis and risk of long COVID-19 symptoms, with adjustment for potential confounding variables (demographics, body mass index, smoking status, history of infertility, and history of chronic diseases). RESULTS: Among 3650 women in our sample with self-reported SARS-CoV-2 infections during follow-up, 386 (10.6%) had a history of endometriosis with laparoscopic confirmation, and 1598 (43.8%) reported experiencing long COVID-19 symptoms. Most women were non-Hispanic White (95.4%), with a median age of 59 years (interquartile range, 44-65). Women with a history of laparoscopically-confirmed endometriosis had a 22% greater risk of developing long COVID-19 (adjusted risk ratio, 1.22; 95% confidence interval, 1.05-1.42) compared with those who had never been diagnosed with endometriosis. The association was stronger when we defined long COVID-19 as having symptoms for ≥8 weeks (risk ratio, 1.28; 95% confidence interval, 1.09-1.50). We observed no statistically significant differences in the relationship between endometriosis and long COVID-19 by age, infertility history, or comorbidity with uterine fibroids, although there was a suggestive trend indicating that the association may be stronger in women aged <50 years (<50 years: risk ratio, 1.37; 95% confidence interval, 1.00-1.88; ≥50 years: risk ratio, 1.19; 95% confidence interval, 1.01-1.41). Among persons who developed long COVID-19, women with endometriosis reported on average 1 additional long-term symptom compared with women without endometriosis. CONCLUSION: Our findings suggest that those with a history of endometriosis may be at modestly increased risk for long COVID-19. Healthcare providers should be aware of endometriosis history when treating patients for signs of persisting symptoms after SARS-CoV-2 infection. Future studies should investigate the potential biological pathways underlying these associations.

Non-oncological gynecological diagnoses in a women's health care service during the pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2.

OBJECTIVE: Analyze clinical factors and non-oncological gynecological diagnoses before and during the initial months of the COVID-19 pandemic. METHOD: Crosssectional study at an Outpatient Gynecology Clinic in Brazil involving medical consultations performed during the pre-pandemic and pandemic periods. The number of visits, prevalence of non-oncological gynecological diagnoses, and clinical-demographic data were analyzed. Parametric continuous variables were evaluated by Student's t-test and ANOVA tests, non-parametric variables were evaluated by the Mann-Whitney and Wilcoxon tests, and categorical or binary variables were evaluated by chi-square and Fisher's exact tests. Univariate logistic regression tests were performed, and variables with p ≤ 0.20 were subjected to multivariate logistic regression. Statistical significance was set at p < 0.05. RESULTS: There were 1,236 records during the pre-pandemic period and 530 during the pandemic, reflecting a significant reduction (57.88%; p = 0.001) in medical consultations. The outpatient prevalence of women older than 50 y (OR 0.85; 95%CI 0.68-1.05) reduced, and the outpatient prevalence of postmenopausal women with hot flashes (OR 1.34; 95%CI 1.09-1.65; p = 0.005) and alcohol consumption habits (OR 2.76; 95%CI 1.15-6.59; p = 0.023) increased. There was a 6% proportional increase in noninflammatory disorders of the female genital tract (p = 0.030) and a 72.4% decrease in general physical examinations, contraception, and procreation (p = 0.001). Multivariate analysis showed that there was an increased prevalence of abnormal uterine bleeding (OR, 1.7; 95% CI 1.34-2.16; p = 0.001) and endometriosis (OR 1.65; 95% CI 1.13-2.42; p = 0.01). CONCLUSION: Medical consultations for benign gynecological diseases during the pandemic prevented non-inflammatory disorders of the female genital tract, with an emphasis on abnormal uterine bleeding and endometriosis. There was an increased prevalence of women under 50 years of age, women with symptoms of hot flashes, and alcohol consumption habits and a reduction in the prevalence of general physical examinations, contraception, and procreation.

COVID-19 susceptibility in endometriosis patients: A case control study.

PROBLEM: Starting from November 2019, the world has had to face a devastating pandemic caused by SARS-CoV-2. Various studies have identified potential risk factors facilitating the infection, however it has not been demonstrated whether endometriosis might represent one of them. The purpose of this study was to evaluate if patients with endometriosis had a higher risk of contracting COVID-19 infection and, in such case, whether they developed a more severe infection than the general population. Furthermore, this study evaluated the possible correlation with the stage of endometriosis, based on the r-ASRM score, and the potential worsening of the disease during the SARS-CoV-2 infection. METHOD OF STUDY: A case-control study was conducted from March 2020 to April 2021 at Macedonio Melloni Hospital, in Milan. A total of 401 women were recruited. The cases were 201 women with clinical or surgical diagnosis of endometriosis. The control group consisted of 200 women, without the disease. All women completed a self-administered questionnaire which evaluated their demographic and clinical characteristics, as well as a potential diagnosis of Covid-19. RESULTS: Comparison between the two groups showed that women with endometriosis had a higher frequency of COVID-19 than the control subjects (23% vs. 13.5%, P = .014), with a greater prevalence of fever (14.4% vs. 6%, P = .008) and myalgias or arthralgias (11.4% vs. 4.5%, P = .01). In multivariable logistic regression analyses, women with endometriosis had a higher risk of contracting SARS-CoV-2 infection (OR = 2.11, 95% IC: 1.20-3.80), regardless the stage of the disease. CONCLUSION: Endometriosis increases the susceptibility to COVID-19, and women who suffer from it should be considered as fragile patients, worthy of prior access to SARS-CoV-2 vaccination campaign.

Does Quality of Care (QoC) Perception Influence the Quality of Life (QoL) in Women with Endometriosis? Results from an Italian Nationwide Survey during Covid Pandemic.

(1) Background: Endometriosis is a chronic and progressive illness that generates a slew of issues, lowering the quality of life of women. The purpose of this study was to look at the quality of life in women with endometriosis and how it relates to the quality of care. (2) Methods: This study is an online survey performed in Italy during the COVID pandemic using the Italian version of the Health Questionnaire SF-36 and a questionnaire for assessing the quality of care received. (3) Results: 1052 women with a self-reported diagnosis of endometriosis participated in the survey. The mean levels of Physical Component Summary (PCS) and Mental Component Summary (MCS) were 38.89 ± 10.55 and 34.59 ± 11.17, respectively. A total of 77% of women judged the services they received positively, and 51% considered the coordination between healthcare professionals to be satisfactory. The satisfaction index mean was 23.11 ± 4.80. PCS was positively related to Occupation, high educational level, physical activity, and health care satisfaction. MCS was positively related to higher age, physical activity, and health care satisfaction. (4) Conclusions: The study indicated that satisfaction with health care was a significant predictor of QoL in women with endometriosis, for both physical and mental health.

Endometriosis and COVID-19: A Systematic Review and Meta-Analysis.

Endometriosis is defined as ectopic endometrial tissues dispersed outside the endometrium. This can cause disruption in hormonal and immunological processes, which may increase susceptibility to SARS-CoV-2 infection. Worsening of endometriosis symptoms may occur as a result of this infection. The aim of our review was to estimate the pooled prevalence of SARS-CoV-2 infection and the health impacts of the COVID-19 pandemic in endometriosis patients. We conducted a systematic review and meta-analysis. MEDLINE, Science Direct, Scopus, and Google Scholar databases were searched, using the keywords: (endometriosis) AND (COVID-19 OR SARS-CoV-2). Forest plots and pooled estimates were created using the Open Meta Analyst software. After screening 474 articles, 19 studies met the eligibility criteria for the systematic review, and 15 studies were included in the meta-analyses. A total of 17,799 patients were analyzed. The pooled prevalence of SARS-CoV-2 infection in endometriosis patients was 7.5%. Pooled estimates for the health impacts were 47.2% for decreased access to medical care, 49.3% increase in dysmenorrhea, 75% increase in anxiety, 59.4% increase in depression, and 68.9% increase in fatigue. Endometriosis patients were undeniably impacted by the COVID-19 pandemic, which caused the worsening of symptoms such as dysmenorrhea, pelvic pain, anxiety, depression, and fatigue.

A rapid evidence map of womens health (preprint)

The rapid evidence map focuses on identifying the nature and extent of published literature on the following topic areas: healthcare professionals communication with women about womens health issues and broader health problems during clinical encounters; access to specialist healthcare; endometriosis; menopause; womens health and mental health issues, and mental health issues associated with specific conditions related to menopause or menstrual health (adenomyosis; endometriosis; fibroids; heavy menstrual bleeding, polycystic ovary syndrome and premenstrual dysphoric disorder). The purpose of this rapid evidence map was to identify research gaps and priorities that will be beneficial to womens health in Wales. The rapid evidence map uses abbreviated systematic mapping or scoping review methods to provide a description of the nature, characteristics and volume of the available evidence. There is a lack of primary and secondary research that explores communication between women and healthcare professionals within primary and secondary care settings. Secondary research evidence exists but there are gaps in the evidence base regarding access to services providing minor gynaecological procedures and pain management, or care for menstrual health and wellbeing, endometriosis, polycystic ovarian syndrome, menopause, heart conditions, autoimmune diseases, hypermobility spectrum disorders, myalgic encephalomyelitis, long COVID, fibromyalgia, skin conditions, or palliative and end of life care, which are priority areas identified by the Womens Health Wales Coalition (2022). There are no active funding calls exploring these topics. Regarding endometriosis, there is a lack of review evidence regarding education and resources for health care professionals and doctors to reduce diagnostic times and improve care. There is an evidence gap for primary research regarding information, support interventions and tools for women with endometriosis to help them manage their symptoms and improve their quality of life. A substantial amount of secondary evidence exists on menopause along with a plethora of research priorities around treatment and symptom management. It was beyond the scope of this work to determine if any research had been conducted in these priority areas since the production of the guidelines and recommendations. There is a lack of research recommendations and review evidence that address mental health issues and specific issues that affect a womens menstrual health such as adenomyosis, fibroids, heavy menstrual bleeding and premenstrual dysphoric disorder. Funding statement The Wales Centre for Evidence Based Care was funded for this work by the Wales COVID-19 Evidence Centre, itself funded by Health and Care Research Wales on behalf of Welsh Government. Wales COVID-19 Evidence Centre (WCEC) Rapid Evidence Map: Women’s health Report number – REM 00045 (October 2022) Rapid Evidence Map Details Review conducted by Wales Centre For Evidence Based Care Review Team ▪ Deborah Edwards ▪ Judit Csontos ▪ Elizabeth Gillen Review submitted to the WCEC October 2022 Stakeholder consultation meeting 24 th October 2022 Rapid Evidence Map report issued by the WCEC November 2022 WCEC Team ▪ Adrian Edwards, Ruth Lewis, Alison Cooper, Micaela Gal involved in drafting the topline summary, reviewing, editing, publication process. This review should be cited as REM00045. Wales COVID-19 Evidence Centre, Rapid Evidence map: Womens health. October 2022 Disclaimer The views expressed in this publication are those of the authors, not necessarily Health and Care Research Wales. The WCEC and authors of this work declare that they have no conflict of interest. Rapid Evidence Map: Women’s health Report number – REM00045 (October 2022) TOPLINE SUMMARY What are Rapid Evidence Maps? Our Rapid Evidence Maps (REMs) use abbreviated systematic mapping or scoping review methods to provide a description of the nature, characteristics and volume of the available evidence for a particular policy domain or research question. They are mainly based on the assessment of abstracts and incorporate an a priori protocol, systematic search, screening, and minimal data extraction. They may sometimes include critical appraisal, but no evidence synthesis is conducted. Priority is given, where feasible, to studies representing robust evidence synthesis. They are designed and used primarily to identify a substantial focus for a rapid review, and key research gaps in the evidence-base . ( N . B. Evidence maps are not suitable to support evidence-informed policy development, as they do not include a synthesis of the results .) Who is this summary for? Health and Care Research Wales Background / Aim of Rapid Evidence Map (REM) The Welsh Government Research and Development Division intends to run a commissioned funding call on understanding and tackling gender inequalities in health and social care in Wales. The purpose of this REM was to identify research gaps and priorities that will be beneficial to women’s health in Wales to inform the proposed funding call. It was decided, based on a preliminary review of the literature, feedback from an NHS public consultation exercise in Wales, and further discussion with the stakeholder group, that the REM would focus on identifying the nature and extent of the literature on the following prioritised topic areas: healthcare professionals’ communication with women about women’s health issues and broader health problems during clinical encounters; access to specialist healthcare ; endometriosis ; menopause ; women’s health and mental health issues, and mental health issues associated with specific conditions related to menopause or menstrual health (adenomyosis; endometriosis; fibroids; heavy menstrual bleeding, polycystic ovary syndrome and premenstrual dysphoric disorder). Research gaps in other areas and health conditions, in which women might also experience inequality, were not explored in this REM. Key Findings Extent of the evidence base ▪ Communication within health care encounters The evidence base included one systematic review (of endometriosis) and nine primary studies. The primary studies focused on breast cancer (n=2), maternal medicine (n=3), perinatal mental health (n=1), gynaecological conditions (n=1), and non-specific conditions (n=2). Three studies focused on specific populations: urban Africans, Iraqi Muslim refugees, and undocumented migrants. Planned and ongoing NIHR funded projects include clinicians’ perspectives of listening to women’s health, menstrual and gynaecological conditions, menopause, and women’s cancers ▪ Access to specialist healthcare The evidence base consisted of 19 reviews and 9 protocols. Conditions covered were maternal medicine (n=8), sexual and reproductive health (n=5), cancer and cancer screening (n=4), perinatal mental health (n=4), mental health (n=2), HIV (n=2), and non-specific conditions (n=3). Specific populations investigated were refugees or displaced people (n=6), those in differing social, economic, and environmental circumstances (n=4), physical disabilities (n=3), homeless (n=2), migrants (n=2), experiencing intimate partner violence (n=1), and minority ethnicity black (n=1). The reviews focused on barriers and facilitators (n=10), barriers (n=5), experiences (n=3), mapping the evidence (n=3), factors (n=2), management (n=1), facilitators (n=1), predictors (n=1), associations (n=1), and prevalence (n=1). ▪ Endometriosis The evidence base included 121 systematic reviews covering different topics including medical management (n=22), surgical management (n=15), biology/molecular (n=12), risk factors (n=11), and comorbid conditions (n=9). Research priorities were identified by the James Lind Alliance (JLA), NICE guideline, a Wales-specific primary study (Boivin et al 2018), and researchers within the field (n=2). Recent UK funding calls were identified covering laboratory research, aetiology of endometriosis and uterine disorders, and medical and surgical management. ▪ Menopause The evidence base included 108 systematic reviews covering different topics including hormonal therapies (n=17), homeopathic therapies (n=13), non-hormonal therapies (n=10), genitourinary symptoms of menopause (n=7), alternative therapies (n=6), and lifestyle interventions (n=6). Research priorities were identified as part of a NICE guideline, by the British Menopause Society, and researchers within the field (n=3). Recent UK funding calls were identified covering reproductive and menopausal health, testosterone for the treatment of symptoms, women’s reproductive health in the workplace, and women’s health hub landscape. ▪ Women’s health and mental health issues The evidence base included 37 reviews covering: perinatal mental health (n=23), general mental health (n=9), polycystic ovary syndrome (n=3), and intimate partner violence (n=2). Some reviews focused on specific populations including women in prison, women in inpatient mental health services, mental health of migrants and refugee women, and mental health of women from different minority groups. Recent UK funding calls were identified covering: young women’s mental health, women and partners who have experienced pregnancy not ending in live births, and perimenopause and the risk of psychiatric disorders. ▪ Mental health issues associated with specific conditions related to menopause or menstrual health The evidence base included 10 systematic reviews covering: polycystic ovary syndrome (n=4), endometriosis (n=4) menopause (n=1), and menstruation (n=1). The reviews focused on prevalence (n=4), associations (n=4), and management (n=2). Recency of the evidence base ▪ The review included evidence available (from 2012, 2018, and 2021) up until September 2022. (Separate searches were conducted for different topics, with variable time limits due to the varying volume of research published in certain areas.) Summary of the evidence gaps ▪ There is a lack of primary and secondary research that explores communication between women and healthcare professionals (HCPs) within primary and secondary care settings. ▪ Secondary research evidence exists but there are gaps in the evidence base regarding access to services providing minor gynaecological procedures and pain management, or care for menstrual health and wellbeing, endometriosis, polycystic ovarian syndrome, menopause , heart conditions, autoimmune diseases, hypermobility spectrum disorders, myalgic encephalomyelitis, long COVID, fibromyalgia, skin conditions, or palliative and end of life care, which are priority areas identified by the Women’s Health Wales Coalition (2022). There are no active funding calls exploring these topics. ▪ Regarding endometriosis, there is a lack of review evidence regarding education and resources for HCPs and doctors to reduce diagnostic times and improve care . There is an evidence gap for primary research regarding information, support interventions and tools for women with endometriosis to help them manage their symptoms and improve their quality of life . ▪ A substantial amount of secondary evidence exists on menopause along with a plethora of research priorities around treatment and symptom management . It was beyond the scope of this REM to determine if any research had been conducted in these priority areas since the production of the guidelines and recommendations. Researchers in the field would like to see primary research conducted in the area of quality of life . ▪ There is a lack of research recommendations and review evidence that address mental health issues and specific issues that affect a women’s menstrual health such as adenomyosis, fibroids, heavy menstrual bleeding and premenstrual dysphoric disorder .

Clinical profiling of subgroups of women with chronic pelvic pain (preprint)

Study question Do subgroups of women with chronic pelvic pain (CPP) report different clinical symptoms and differing impact of pain on their quality of life? Summary answer Clinical profiles of women with CPP show variability of clinical symptoms both within and between subgroups. However, there is an obvious negative impact of pain on the patients’ lives across all subgroups with the comorbid endometriosis and bladder pain symptoms group (EABP) presenting with the higher pain intensities and the lower quality of life. What is known already CPP is a common condition affecting up to 26.6% of women, with many suffering for several years before diagnosis and/or treatment. The clinical presentation of CPP is varied and there are frequently comorbid conditions both within and outside the pelvis. Evidence from the literature show that there is an overlap of symptoms in chronic pain conditions whatever the underlying cause which suggests that chronic pain could be a condition itself. Study design, size, duration The study is part of The Translational Research in Pelvic Pain (TRiPP) project ( https://www.imi-paincare.eu/PROJECT/TRIPP/ ) which is a cross-sectional observational cohort study. The present study includes 769 female participants sampled from two existing endometriosis-focused cohort studies in Oxford, UK and Boston, MA, USA and newly recruited from the Instituto de Biologia Molecular e Celular (IBMC)) in Porto. The participants completed an extensive set of questions derived from standardised WERF EPHect questionnaires. Within this study population we defined a control group (reporting no pelvic pain, no bladder pain syndrome (BPS), and no endometriosis diagnosis, N=230) and four pain groups: endometriosis-associated pain (EAP, N=237), (BPS, N=72), comorbid endometriosis-associated pain and BPS (EABP, N=120), and pelvic pain only (PP, N=127). Participants/materials, setting, methods All participants were women of reproductive age (13-50 years) and were recruited at three different sites: Oxford (University of Oxford), Boston (Boston Center for Endometriosis (BCE)) and Porto (Instituto de Biologia Molecular e Celular (IBMC)). The questionnaire included: demographics; reproductive history; pelvic pain intensity assessed using 10-point numerical rating scales (NRS) for dysmenorrhoea, non-cyclical pain, dyspareunia and bladder pain; medical comorbidities; factors relieving and worsening pain; quality of life assessed using the SF-36 questionnaire; and pain catastrophising. Main results and the role of chance The EAP (Mean:7.37) and EABP (Mean:7.88) groups scored higher on the pain intensity scales for non-cyclical pelvic pain than the PP (Mean:6.82) group (p<0.001) and higher on the dysmenorrhoea scale than both the BPS and PP groups (p<0.001). The EABP (Mean:6.61) and BPS (Mean:6.52) groups had significantly higher bladder pain scores than the EAP (Mean:0.95) and PP (Mean:0.78) (p<0.001). The EABP group also had significantly higher pain scores for dyspareunia (p<0.001), even though more than 50% of participants (who were sexually active) in each of the pain groups reported interrupting and/or avoiding sexual intercourse due to pain in the last 12 months. Exploring the factors reported to worsen or relieve pain found that across the pain groups the three most reported factors for worsening pelvic pain were: stress (23.6%), full bladder/urinating (23.3%) and exercising (20.2%). The most common factors for relieving pelvic pain were: pain medication (31.4%), lying down (31.0%), and use of a heat pad (29.5%). Analysis of the quality-of-life questionnaire (SF-36) subscales revealed significant differences between the study groups across all SF-36 subscales (p<0.001). In line with the pain results the EABP group reported the negative highest impact across all the health measures while the PP group’s profile was closest to the control group’s profile. Significant effects were also observed between the pain groups for pain interference with their work (F(3,209)=9.76, p<0.001) and daily lives (F(3,244)=10.51, p<0.001), with the EABP suffering more compared to the EAP and PP groups (p<0.001). Limitations, reasons for caution Data for this study were derived predominantly from existing cohorts where data have been collected over time and thus different versions of questionnaires have been used. Thus, for some questions only a subgroup may have had an opportunity to complete the measure of interest. Recruitment of participants was impacted due to the COVID-19 pandemic. As a result, sample sizes overall were smaller than originally designed, and our BPS group was predominantly identified from gynaecological rather than urological clinics making it potentially different from other published BPS cohorts. Wider implications of the findings Overall, our results demonstrate the negative impact that chronic pain has on CPP patients’ quality of life and suggests that further exploration of interventions targeting quality of more broadly is important. Furthermore, it demonstrates the importance of dyspareunia in women with CPP, highlighting the need for more research in this area. Importantly, we show significant differences between the sub-groups of CPP suggesting the need for better patient stratification in future clinical studies and trials. However, the marked variability both within and between CPP sub-groups raises the question whether subgrouping on the basis of clinical diagnosis is the most appropriate strategy or whether alternative approaches could be identified allowing prioritisation of treatments better suited to the individual patient. Study funding/competing interest(s) This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 777500. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA Companies. Financial support was provided by the J. Willard and Alice S. Marriott Foundation for establishment of and baseline data collection within the A2A cohort - from which the Boston-based TRiPP population was sampled. Trial registration number NCT04001244

Endometriosis and Cannabis Consumption During the COVID-19 Pandemic: An International Cross-Sectional Survey.

Introduction: Endometriosis affects 1 in 10 women worldwide, with most experiencing difficulties achieving adequate symptom control. These difficulties have been compounded by the onset of the COVID-19 pandemic due to worldwide shifts in health care resource allocation. As cannabis is a relatively common form of self-management in endometriosis, this study aims to explore the impact of the COVID-19 pandemic on cannabis consumption in those with endometriosis. Methods: An anonymous, cross-sectional online international survey was developed and promoted by endometriosis advocacy/support organizations worldwide. Respondents needed to have a diagnosis of endometriosis and be aged between 18 and 55. Results: A total of 1634 responses were received from 46 different countries. The average age of respondents was 30, with a mean diagnosis age of 25. Eight hundred forty-six respondents (51%) reported consuming cannabis in the past 3 months, with 55% of these reporting use for symptom management only. One in five respondents (20%) reported having consumed cannabis previously, the most common reason for discontinuation (65%) was access difficulties during COVID. Those who had legal access were more likely to consume cannabis than those without (p<0.0001) and were more likely to disclose usage to health care professionals (p<0.0001). The most common reasons for consuming cannabis during COVID was increased stress/anxiety (59%) and lack of access to normal medical care (48%). Pre-pandemic, cannabis was mostly consumed at least once a day (61%) and in inhaled forms (51.6%). Consumption increased for most people (57%) during the pandemic. During the pandemic just under a quarter (23%) of respondents changed their mode of consumption, with a reduction in inhaled forms (39.5%) and an increase in consumption of edibles (40%) or oil (25.2%). Conclusions: Cannabis consumption, especially for symptom relief, was relatively common among those with endometriosis, with some people starting their consumption of cannabis due to health care restrictions that occurred due to the COVID-19 pandemic. Difficulties accessing cannabis and unpleasant/unwanted side effects were the most common reasons for lack of current cannabis consumption in those who had previously consumed it. Cannabis consumption may form an important part of endometriosis management especially when access to routine medical care is restricted.

Impact of endometriosis on women's life decisions and goal attainment: a cross-sectional survey of members of an online patient community.

OBJECTIVES: To examine women's perceptions of endometriosis-associated disease burden and its impact on life decisions and goal attainment. DESIGN: An anonymous online survey was distributed in October 2018 through the social media network MyEndometriosisTeam.com. PARTICIPANTS: Women aged 19 years and older living in several English-speaking countries who self-identified as having endometriosis. OUTCOME MEASURES: Patients' perspectives on how endometriosis has affected their work, education, relationships, overall life decisions and attainment of goals. Subanalyses were performed for women who identified as 'less positive about the future' (LPAF) or had 'not reached their full potential' (NRFP) due to endometriosis. RESULTS: 743 women completed the survey. Women reported high levels of pain when pain was at its worst (mean score, 8.9 on severity scale of 0 (no pain) to 10 (worst imaginable pain)) and most (56%, n=415) experienced pain daily. Women reported other negative experiences attributed to endometriosis, including emergency department visits (66%, n=485), multiple surgeries (55%, n=406) and prescription treatments for symptoms of endometriosis (72%, n=529). Women indicated that they believed endometriosis had a negative impact on their educational and professional achievements, social lives/relationships and overall physical health. Most women 'somewhat agreed'/'strongly agreed' that endometriosis caused them to lose time in life (81%, n=601), feel LPAF (80%, n=589) and feel they had NRFP (75%, n=556). Women who identified as LPAF or NRFP generally reported more negative experiences than those who were non-LPAF or non-NRFP. CONCLUSIONS: Women who completed this survey reported pain and negative experiences related to endometriosis that were perceived to negatively impact major life-course decisions and attainment of goals. Greater practitioner awareness of the impact that endometriosis has on a woman's life course and the importance of meaningful dialogue with patients may be important for improving long-term management of the disease and help identify women who are most vulnerable.

Determinants of Pain-Induced Disability in German Women with Endometriosis during the COVID-19 Pandemic.

(1) Background: The main aim of this research was to examine the factors leading to pain-induced disability by assessing the impact of demographic, endometriosis-specific, pandemic-specific, and mental health factors. (2) Methods: Women with endometriosis who attended online support groups were invited to respond to an online survey during the first wave of the COVID-19 pandemic in Germany. The Pain Disability Index (PDI) was employed to assess disability-related daily functioning. Independent predictors of pain-induced disability were determined using univariate and multivariate logistic regression analyses. (3) Results: The mean PDI score of the study population was 31.61 (SD = 15.82), which was significantly higher (p < 0.001) than that reported in a previously published normative study of the German population. In the present study, a high level of pain-induced disability, as defined by scores equal to or higher than the median of the study population, older age (OR 1.063, 95% CI 1.010-1.120, p = 0.020), dysmenorrhea (OR 1.015, 95% CI 1.005-1.026, p = 0.005), dysuria (OR 1.014; 95% CI 1.001-1.027, p = 0.029), lower back pain (OR 1.018, 95% CI 1.007-1.029, p = 0.001), and impaired mental health (OR 1.271, 95% CI 1.134-1.425, p < 0.001) were found to be independent risk factors. Pandemic-specific factors did not significantly influence the pain-induced disability of the participants in this study. (4) Conclusions: The level of pain-induced disability was significantly higher among the women with endometriosis than among women in the normative German validation study. Our findings identified risk factors for experiencing a high level of pain-induced disability, such as demographic and specific pain characteristics. Pandemic-specific factors did not significantly and independently influence the pain-induced disability during the first wave of the COVID-19 pandemic in Germany. Impaired mental health negatively influenced functioning during daily activities. Thus, women with endometriosis should be managed by a multidisciplinary team of healthcare professionals to prevent negative effects of pain-induced disability on their quality of life.

Impact of SARS-COV2 Pandemic on Patients with Endometriosis and Their Health Care.

Background: Endometriosis is a debilitating chronic inflammatory disease. The current SARS-COV2 pandemic has had an impact on the management of these patients. Tele-health care has been a relevant tool. The aim of this study was to analyze the impact of the SARS-COV2 pandemic on the perceived clinical health status and the type of care received in patients with endometriosis. Materials and Methods: We evaluated 945 premenopausal women treated at the Hospital Clinic of Barcelona between October 1 and December 31, 2020. Five hundred forty-nine women had endometriosis, and 396 had other benign gynecological diseases. An online health survey was sent to these patients. Clinicopathological features data were recorded. Results: Compared to patients with other benign gynecological diseases, a higher proportion of patients with endometriosis reported worsening of their symptoms (148/549, 27% vs. 85/396, 21.5%) and concern about their disease (515/549, 93.8% vs. 342/396, 86.4%), and more frequently received tele-health care (73.8% vs. 54.0%) during the pandemic. Patients with endometriosis and "significant" pelvic pain reported more concern and worsening than patients without "significant" pelvic pain, and evaluated the assistance received poorly. Multivariate analysis showed pelvic pain, limitation in usual activity, and sadness as risk factors of perception of disease worsening. Awaiting surgery and the feeling of sadness were risk factors of concern. Conclusions: Patients with endometriosis, and especially patients with "significant" pelvic pain, reported greater concern and the perception of worsening during the SARS-COV2 pandemic. Tele-health is a useful tool in patients with endometriosis, and face-to-face visit should be considered in those reporting "significant" pelvic pain. Clinical Trial Registration Number: HCB 1202011497.

Predictors of Psychological Distress in Women with Endometriosis during the COVID-19 Pandemic.

BACKGROUND: Endometriosis is a multifaceted chronic pain condition that can have a negative impact on mental health. Patients suffering from chronic pain may face an additional psychological burden during adversity, such as the COVID-19 pandemic. The main aim of this research was to evaluate the prevalence of self-reported depression and anxiety, the influence of demographic, endometriosis-specific, pandemic-specific factors, and resilience on mental health outcomes of patients with endometriosis. METHODS: An online survey was conducted through patient support groups of women suffering from endometriosis during the first wave of the COVID-19 pandemic. The PHQ-4 questionnaire, which combines two items of the Patient Health Questionnaire for Depression (PHQ-2) and two items from the Generalized Anxiety Disorder Scale (GAD-2) was used to assess self-reported mental health. The Brief Resilience Score (BRS) was employed to evaluate resilience. Independent risk and protective factors for mental health were investigated by multivariate logistic regression analyses. RESULTS: The PHQ-4 questionnaire was completed by 274 respondents. More than 40% reached depression (PHQ-2) and anxiety (GAD-2) scores of ≥3, and more than 20% achieved PHQ-2 and GAD-2 scores of ≥5. High resilience was found to be a reliable and strong independent protector for the probability of developing adverse psychological outcomes: OR 0.295, p < 0.001 for developing generalized anxiety disorder (GAD-2 ≥ 3), and OR 0.467, p < 0.001 for having major depression (PHQ-2 ≥ 3). CONCLUSIONS: Pain-induced disability is an independent risk factor for developing major depression and anxiety, while resilience was identified as a potential protective parameter in terms of positive psychological outcomes in women with endometriosis. The results of this study may help to identify women at risk for adverse mental health outcomes and should encourage healthcare practitioners to establish strategies for the reduction of negative psychological and psychiatric impacts on patients with endometriosis.

Di-(2-ethylhexyl) Phthalate Triggers Proliferation, Migration, Stemness, and Epithelial-Mesenchymal Transition in Human Endometrial and Endometriotic Epithelial Cells via the Transforming Growth Factor-ß/Smad Signaling Pathway.

Di-(2-ethylhexyl) phthalate (DEHP) is a frequently used plasticizer that may be linked to the development of endometriosis, a common gynecological disorder with a profound impact on quality of life. Despite its prevalence, vital access to treatment has often been hampered by a lack of understanding of its pathogenesis as well as reliable disease models. Recently, epithelial-mesenchymal transition (EMT) has been suggested to have a significant role in endometriosis pathophysiology. In this study, we found that DEHP treatment enhanced proliferation, migration, and inflammatory responses, along with EMT and stemness induction in human endometrial and endometriotic cells. The selective transforming growth factor-ß (TGF-ß) receptor type 1/2 inhibitor LY2109761 reversed the DEHP-induced cell proliferation and migration enhancement as well as the increased expression of crucial molecules involved in inflammation, EMT, and stemness, indicating that DEHP-triggered phenomena occur via the TGF-ß/Smad signaling pathway. Our study clearly defines the role of DEHP in the etiology and pathophysiological mechanisms of endometriosis and establishes an efficient disease model for endometriosis using a biomimetic 3D cell culture technique. Altogether, our data provide novel etiological and mechanistic insights into the role of DEHP in endometriosis pathogenesis, opening avenues for developing novel preventive and therapeutic strategies for endometriosis.

Endometriosis Susceptibility to Dapsone-Hydroxylamine-Induced Alterations Can Be Prevented by Licorice Intake: In Vivo and In Vitro Study.

Endometriosis, an estrogen-dependent chronic gynecological disease, is characterized by a systemic inflammation that affects circulating red blood cells (RBC), by reducing anti-oxidant defenses. The aim of this study was to investigate the potential beneficial effects of licorice intake to protect RBCs from dapsone hydroxylamine (DDS-NHOH), a harmful metabolite of dapsone, commonly used in the treatment of many diseases. A control group (CG, n = 12) and a patient group (PG, n = 18) were treated with licorice extract (25 mg/day), for a week. Blood samples before (T0) and after (T1) treatment were analyzed for: i) band 3 tyrosine phosphorylation and high molecular weight aggregates; and ii) glutathionylation and carbonic anhydrase activity, in the presence or absence of adjunctive oxidative stress induced by DDS-NHOH. Results were correlated with plasma glycyrrhetinic acid (GA) concentrations, measured by HPLC-MS. Results showed that licorice intake decreased the level of DDS-NHOH-related oxidative alterations in RBCs, and the reduction was directly correlated with plasma GA concentration. In conclusion, in PG, the inability to counteract oxidative stress is a serious concern in the evaluation of therapeutic approaches. GA, by protecting RBC from oxidative assault, as in dapsone therapy, might be considered as a new potential tool for preventing further switching into severe endometriosis.