Subgroups of pelvic pain are differentially associated with endometriosis and inflammatory comorbidities: a latent class analysis.

ABSTRACT: Chronic pelvic pain is heterogeneous with potentially clinically informative subgroups. We aimed to identify subgroups of pelvic pain based on symptom patterns and investigate their associations with inflammatory and chronic pain-related comorbidities. Latent class analysis (LCA) identified subgroups of participants (n = 1255) from the Adolescence to Adulthood (A2A) cohort. Six participant characteristics were included in the LCA: severity, frequency, and impact on daily activities of both menstruation-associated (cyclic) and non-menstruation-associated (acyclic) pelvic pain. Three-step LCA quantified associations between LC subgroups, demographic and clinical variables, and 18 comorbidities (10 with prevalence ≥10%). Five subgroups were identified: none or minimal (23%), moderate cyclic only (28%), severe cyclic only (20%), moderate or severe acyclic plus moderate cyclic (9%), and severe acyclic plus severe cyclic (21%). Endometriosis prevalence within these 5 LCA-pelvic pain-defined subgroups ranged in size from 4% in "none or minimal pelvic pain" to 24%, 72%, 70%, and 94%, respectively, in the 4 pain subgroups, with statistically significant odds of membership only for the latter 3 subgroups. Migraines were associated with significant odds of membership in all 4 pelvic pain subgroups relative to those with no pelvic pain (adjusted odds ratios = 2.92-7.78), whereas back, joint, or leg pain each had significantly greater odds of membership in the latter 3 subgroups. Asthma or allergies had three times the odds of membership in the most severe pain group. Subgroups with elevated levels of cyclic or acyclic pain are associated with greater frequency of chronic overlapping pain conditions, suggesting an important role for central inflammatory and immunological mechanisms.

The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions.

Endometriosis is a common condition associated with debilitating pelvic pain and infertility. A genome-wide association study meta-analysis, including 60,674 cases and 701,926 controls of European and East Asian descent, identified 42 genome-wide significant loci comprising 49 distinct association signals. Effect sizes were largest for stage 3/4 disease, driven by ovarian endometriosis. Identified signals explained up to 5.01% of disease variance and regulated expression or methylation of genes in endometrium and blood, many of which were associated with pain perception/maintenance (SRP14/BMF, GDAP1, MLLT10, BSN and NGF). We observed significant genetic correlations between endometriosis and 11 pain conditions, including migraine, back and multisite chronic pain (MCP), as well as inflammatory conditions, including asthma and osteoarthritis. Multitrait genetic analyses identified substantial sharing of variants associated with endometriosis and MCP/migraine. Targeted investigations of genetically regulated mechanisms shared between endometriosis and other pain conditions are needed to aid the development of new treatments and facilitate early symptomatic intervention.

Trends in pelvic pain symptoms over 2 years of follow-up among adolescents and young adults with and without endometriosis.

ABSTRACT: We described trends in pelvic pain characteristics over 2 years of follow-up among adolescents and adults with and without endometriosis participating in the longitudinal observational cohort of the Women's Health Study: From Adolescence to Adulthood, using data reported at baseline and at years 1 and 2 of follow-up. Participants completed a questionnaire at baseline (between November 2012 and May 2019) and annually thereafter that included validated measures of severity, frequency, and life interference of dysmenorrhea, acyclic pelvic pain, and dyspareunia. Our study population included 620 participants with surgically confirmed endometriosis (rASRM stage I/II = 95%) and 671 community-based and hospital-based controls, with median age = 19 and 24 years, respectively. The proportion reporting hormone use varied across the 3 years ranging from 88% to 92% for cases and 56% to 58% for controls. At baseline, endometriosis cases were more likely to report severe, frequent, and life-interfering dysmenorrhea, acyclic pelvic pain, and dyspareunia compared with controls. Among cases, frequency and severity of dysmenorrhea and dyspareunia were relatively static across 2 years. However, acyclic pelvic pain improved. Severe acyclic pain decreased from 69% at baseline to 46% at year 2. Daily pain decreased from 28% to 14%, and life interference from 68% to 38%. Trends among controls remained fairly stable across 2 years. Among endometriosis cases who completed the questionnaire at all 3 time points, 18% reported persistent, severe acyclic pelvic pain at all 3 time points. Over time, different trends were observed by pelvic pain type among endometriosis cases and controls, supporting the importance of assessing multidimensional features of pelvic pain.

Is Endometriosis More Common and More Severe Than It Was 30 Years Ago?

OBJECTIVE: Current estimates of endometriosis prevalence and incidence are highly variable, leading to uncertainty regarding true endometriosis frequency or validity of quantified changes over time. We present a comprehensive review of the prevalence, incidence, and stage of endometriosis worldwide as reported over the past 30 years. DATA SOURCES: We conducted a systematic search of observational studies using the PubMed, Web of Science, EMBASE, and CINAHL databases to identify research papers published in English between January 1989 and June 2019. Search terminologies were limited to titles containing endometriosis and prevalence or incidence, or epidemiology, or frequency, or occurrence, or statistics. METHODS OF STUDY SELECTION: Two independent reviewers screened abstracts for study eligibility, and data from included studies were abstracted. TABULATION, INTEGRATION, AND RESULTS: Overall, 69 studies describing the prevalence and/or incidence of endometriosis met the inclusion criteria. Among these, 26 studies involved general population samples, 17 of which were from regional/national hospitals or insurance claims systems. The other 43 studies were conducted in single clinic or hospital settings. Prevalence estimates for endometriosis widely varied from 0.2% to 71.4% depending on the population sampled. The prevalence reported in general population studies ranged from 0.7% to 8.6%, whereas that reported in single clinic- or hospital-based studies ranged from 0.2% to 71.4%. When defined by indications for diagnosis, endometriosis prevalence ranged from 15.4% to 71.4% among women with chronic pelvic pain, 9.0% to 68.0% among women presenting with infertility, and 3.7% to 43.3% among women undergoing tubal sterilization. A meta-regression was conducted with year as the predictor of prevalence. No trend across time was observed among "general population in country/region" studies (ß = 0.04, p = .12) or among "single hospital or clinic" studies (ß = -0.02, p = .34); however, a decrease over time was observed among general population studies abstracted from health systems or insurance systems (ß = -0.10, p = .005). CONCLUSION: As with all human studies, population sampling and study design matter. Heterogeneity of inclusion and diagnostic criteria and selection bias overwhelmingly account for variability in endometriosis prevalence estimated across the literature. Thus, it is difficult to conclude if the lack of observed change in frequency and distribution of endometriosis over the past 30 years is valid.

Proximate determinants of tuberculosis in Indigenous peoples worldwide: a systematic review.

BACKGROUND: Indigenous peoples worldwide carry a disproportionate tuberculosis burden. There is an increasing awareness of the effect of social determinants and proximate determinants such as alcohol use, overcrowding, type 1 and type 2 diabetes, substance misuse, HIV, food insecurity and malnutrition, and smoking on the burden of tuberculosis. We aimed to understand the potential contribution of such determinants to tuberculosis in Indigenous peoples and to document steps taken to address them. METHODS: We did a systematic review using seven databases (MEDLINE, Embase, CINAHL, Global Health, BIOSIS Previews, Web of Science, and the Cochrane Library). We identified English language articles published from Jan 1, 1980, to Dec 20, 2017, reporting the prevalence of proximate determinants of tuberculosis and preventive programmes targeting these determinants in Indigenous communities worldwide. We included any randomised controlled trials, controlled studies, cohort studies, cross-sectional studies, case reports, and qualitative research. Exclusion criteria were articles in languages other than English, full text not available, population was not Indigenous, focused exclusively on children or older people, and studies that focused on pharmacological interventions. FINDINGS: Of 34 255 articles identified, 475 were eligible for inclusion. Most studies confirmed a higher prevalence of proximate determinants in Indigenous communities than in the general population. Diabetes was more frequent in Indigenous communities within high-income countries versus in low-income countries. The prevalence of alcohol use was generally similar to that among non-Indigenous groups, although patterns of drinking often differed. Smoking prevalence and smokeless tobacco consumption were commonly higher in Indigenous groups than in non-Indigenous groups. Food insecurity was highly prevalent in most Indigenous communities evaluated. Substance use was more frequent in Indigenous inhabitants of high-income countries than of low-income countries, with wide variation across Indigenous communities. The literature pertaining to HIV, crowding, and housing conditions among Indigenous peoples was too scant to draw firm conclusions. Preventive programmes that are culturally appropriate targeting these determinants appear feasible, although their effectiveness is largely unproven. INTERPRETATION: Indigenous peoples were generally reported to have a higher prevalence of several proximate determinants of tuberculosis than non-Indigenous peoples, with wide variation across Indigenous communities. These findings emphasise the need for community-led, culturally appropriate strategies to address smoking, food insecurity, and diabetes in Indigenous populations as important public health goals in their own right, and also to reduce the burden of tuberculosis. FUNDING: Canadian Institutes of Health Research.