Epidemiology of endometriosis in women of Arab ancestry

Introduction: Investigating the epidemiology of endometriosis in women of Arab ancestry, in the context of regionally important environmental and genetic effects, will provide us with a better understanding on the endometriosis phenome across different populations. Under the following initiative, the Middle Eastern Women Research Association: the MAR'A project, the study aimed to investigate for the first time in women of Arab ancestry: (1) Associations of symptomatology, risk factors, phenotypic profile, and comorbidities with endometriosis (2) Assess the impact of endometriosis on health-related quality of life (HRQoL), work productivity, activity impairment, physical activity, and diagnostic delay (3) Conduct a candidate gene association study (CGAS) on variants in wingless-type MMTV integration site family member 4 (WNT4) and the Vezatin (VEZT) in women with endometriosis. Method: The MAR'A Project is a case-control study with multiple hospital and population-based sites across the United Arab Emirates, between August 2018 and August 2019. In total, 2,610 (518 endometriosis cases; 2092 controls) premenopausal women, aged 18-50 years, without a previous surgical diagnosis of endometriosis and self-reported ethnically Arab, were recruited. The study design of a case-control study compared incident endometriosis cases (n=518) with the following two comparison groups to evaluate potential risk factors: (1) ascertainment criteria (hospital controls (n=1251) vs. population controls (n=841)); and (2) symptomatic criteria (symptomatic controls (n=1331) vs. asymptomatic controls (n=761)). A subset of the samples (100 endometriosis cases and 100 hospital controls) was selected for the CGAS. Standardized, validated questionnaires, basic anthropometric measurements and saliva samples were collected from consenting participants. Results: (1) Women with endometriosis had a lower BMI and WHRadjBMI, reported a higher frequency of pain phenotypes (dysmenorrhea, chronic pelvic pain, dysuria, and dyschezia) with greater severity, earlier age of symptom onset, and higher pain catastrophizing score, in comparison to controls. Similar to the Western population studies, women with endometriosis had earlier age at menarche, shorter menstrual cycle, heavier menstrual flow, and longer duration of menstrual phase. Women with endometriosis had a higher frequency of miscarriages, ectopic pregnancy, preterm birth, and emergency caesarean section. (2) The average diagnostic delay was 11.61 years, with single women experiencing 15.81 years of diagnosis delay. HRQoL scores were significantly impaired in women with endometriosis, for both the Physical and Mental Composite Scores, affecting work productivity and activity impairment. (3) A significant association was observed for SNP rs12320196 (OR=1.60 (95% CI: 1.05, 2.45), p=0.027) intronic to the VEZT gene, and SNPs rs12037376 (OR=1.89 (95% CI: 1.06, 3.37), p=0.029) and rs3820282 (OR=1.90 (95% CI: 1.05, 3.46), p=0.033) intronic to the WNT4 gene. Conclusion: This study provided novel findings of the clinical presentation and risk factors of endometriosis among Arab women from a combined hospital and population-based sites. Along with the presence, duration and severity of the pain phenotypes, adverse reproductive outcomes, and comorbidities, Arab women experience among the highest diagnostic delay of endometriosis. Social exacerbation and cultural factors may influence management of endometriosis-associated pain, leading to psychological distress and significant impacts on HRQoL. Further research must be conducted among Arab women to improve early diagnosis and provide culturally sensitive clinical care.