Uncovering moderators of pain perception by women with endometriosis from Latin America and Spain: the roles of sociodemographics, racial self-identity, and pain catastrophizing

The EPhect questionnaire was completed by 1,378 participants from 27 countries ( Table 1 ). Details of the study population have been described elsewhere [ 12 ]. Table 2 summarizes the demographic characteristics of the study cohort. When analyzing the self-identified racial category proportions by country we found that, overall, their distribution was as previously reported per country [ 13 ]. For example, Spain, Uruguay and Argentina had the highest proportions of women self-identified as White, while women who self-identified as Black had the highest relative proportion in Dominican Republic, Panamá and Puerto Rico, three countries with strong African heritage. Countries with high Amerindian heritage such as Ecuador, Perú and Mexico had the lowest proportions of both White and Black self-identified race. The “Other Race” group is composed of only 52 patients who did not identify with being White, Black or Mixed Race that are the standard denominations used in cross-sectional surveys. Most individuals in this group identified with a variation of the “Mixed Race” including “Trigueña”, “Mestiza”, “Morena”, “Criolla” (n=17), or with an ethnic group (rather than race): “Latina”, “Hispana” (n=12). Thus, the data show that our study population was, in general, representative of the race distribution in each of the countries included as shown in Table 1 . Notably, the study had appropriate representation of non-White women (either equal to or higher than expected) in some countries, which are not often well represented in research cohorts. Utilizing multiple regression models, we evaluated the likelihood of reporting severe vs mild-moderate pain in seven pain categories ( Table 3 ). Regression model 1 included: age, education level, medical insurance (a proxy for socioeconomic status), PCS score, and self-identified race. Regression model 2 included the same variables and demographic cluster . In regression model 1 there was a statistically significant association between severity (severe vs. moderate/mild) of dysmenorrhea at worst and PCS score (p<0.0001). No significant differences were identified in other variables, including self-identified race. In regression model 2, there was a statistically significant association between severity of dysmenorrhea at worst and PCS score (p<0.0001). Pain severity was significantly correlated with demographic cluster (p=0.004). Participants in clusters A and B were more likely to report severe dysmenorrhea at worst than cluster C (p=0.008, p=0.0003, respectively). In regression model 1, there was a statistically significant association between severity of dysmenorrhea during the last 12 months and PCS score (p<0.001). No significant differences were identified on other variables, including self-identified race. In regression model 2, there was a statistically significant association between severity of dysmenorrhea during the last 12 months and total PCS score (p<0.001). No significant differences were identified in other variables, including demographic cluster. In regression model 1, there was a statistically significant association between severity of dysmenorrhea during last menses and PCS score (p<0.0001). No significant differences were identified on other variables, including self-identified race. In regression model 2, there was a statistically significant association between severity of dysmenorrhea during last menses and PCS score (p<0.0001). No significant differences were identified in other variables including demographic cluster. In regression model 1, there was a statistically significant association between severity dyspareunia during the last coitus and PCS score (p<0.0001). No significant differences were identified on other variables, including self-identified race. In regression model 2, there was a statistically significant association between severity of dyspareunia during last coitus and PCS score (p<0.0001). No significant differences were identified in other variables, including demographic cluster. In regression model 1, severity of dyspareunia 24 hrs after last coitus and PCS score were not significantly associated (p=0.59). Trends towards significance were observed for self-identified race (p=0.059) and age (p=0.08). No significant differences were identified for other variables. In regression model 2, severity of dyspareunia 24 hrs after last coitus and PCS score were not significantly associated (p=0.69). A trend towards significance was observed for age (p=0.08). No significant differences were identified for other variables, including demographic cluster. In regression model 1, there was a statistically significant association between severity of dyspareunia at its worst and PCS score (p<0.0001). Trends towards significance were observed for age (p=0.07) and medical insurance (p=0.08). No significant differences were identified for other variables, including self-identified race. In regression model 2, there was a statistically significant association between severity of dyspareunia at its worst and PCS score (p<0.0001). Older age was associated with a higher likelihood of reporting severe vs mild-moderate pain (p=0.047). Severity of dyspareunia at its worst was significantly different in those categorized on the ‘Other’ demographic cluster compared to the three main clusters (p=0.007), which were not significantly different among them. No significant differences were identified for other variables. In regression model 1, there was a statistically significant association between severity of pelvic pain in the last 3 months and PCS score (p<0.0001). Older age was associated with a higher likelihood of reporting severe vs. mild-moderate pelvic pain (p=0.03). A trend towards significance was observed for education (p=0.09). No significant differences were identified for other variables, including self-identified race. In regression model 2, there was a statistically significant association between severity of pelvic pain in the last 3 months and PCS score (p<0.0001) Increased age was associated with a higher likelihood of reporting severe vs mild-moderate pelvic pain (p=0.009). Participants with a Master’s degree were less likely to report severe vs. mild-moderate pelvic pain compared to College or High School degree (p=0.036, p=0.005, respectively). No significant differences were identified for other variables, including demographic cluster.

The study was approved by the Institutional Review Board (IRB) of the Ponce Health Sciences University (PHSU) (#1811001620). The validated Spanish version of the EPhect’s ECQ survey was used to collect cross-sectional, self-reported data from women with endometriosis 15 to 66 years old living in Latin America (South and Central America, the Caribbean, Mexico) and Spain. Data collected included pelvic pain intensity (0–10 numerical rating scale-NRS in which 0 is no pain and 10 is the worst imaginable pain), sociodemographics, obstetric and gynecological history, medical history, QoL, and the Pain Catastrophizing Scale (PCS) [ 12 ; 21 ; 41]. Seven types of pain were evaluated: Dysmenorrhea (at last menstrual period, last year, when at worst), Dyspareunia (last coitus, 24 hrs after last coitus, at its worst), and Pelvic Pain in the past three months. The electronic survey was distributed from April 2019 to February 2020 via social media platforms of endometriosis patient associations in the region. The process of validating the survey and additional details on the demographics and clinical history of the study population has been described in detail here [ 15 ]. The PCS evaluates three dimensions of catastrophizing: helplessness, rumination, and magnification [ 31 ]. The scale has a total score of 52 with items scored from 0 (‘not at all’) to 4 (‘all the time’) [ 39 ]. A PCS score higher than 30 is considered clinically significant and identifies those with a higher risk of chronicity and disability due to pain [ 16 ]. Race is a social construct defined herein as “a group of people connected by common descent or origin” or “having distinct physical features or shared ethnicity” was self-identified with a drop-down list of four options: Black, Mixed, White, or Other [ 11 ]. There were no follow-up questions addressing the complexities inherent to the “race” variable, or whether there were differences among racial categories and health care access, discrimination, doctor’s perceptions based on the patient’s race, resilience or other considerations. Although people from Latin America and Spain are often regarded as a single ethnic group, they are a heterogeneous population with diverse sociocultural backgrounds, including different ancestral genetic compositions reflecting the history of each country. In order to get insights into the sociocultural context of pain reporting, which may be influenced by country-specific cultural heritage, perceptions of disease/pain, stigma, social environments, and societal norms [ 21 ; 30 ], we conducted a non-biased, hierarchical geographic cluster analysis with a divisive approach with the Ward method using JMP Pro version 16. This analysis generated a dendrogram clustering countries into three demographic groups based on the relative proportions of self-reported race of the study subjects by country ( Table 1 , Figure 1 ). The resulting clusters were based on raw data without influence from investigators. The three groups were: Cluster A Countries with relatively higher proportion of Black self-identity (Puerto Rico, Venezuela, Colombia Panamá, Dominican Republic), Cluster B. Countries with a predominance of White self-identity (Argentina, Spain, Chile, Costa Rica, Uruguay). Cluster C: Consisted of Mexico, Peru, Ecuador that have relatively higher proportion of Mixed race and lower proportions of both Black and White self-identities. The “Other sub-ethnicity” group was composed of patients from countries with a small sample size precluding their unbiased categorization in the main demographic clusters. We conducted a multiple regression analysis to account for sociodemographic variables (e.g., age, education, health insurance), psychological traits (e.g., PCS scores) with either racial category or demographic cluster as potential moderators of pain severity and to determine effect size (Odds Ratios). Endometriosis-related pain severity was recoded as a dichotomous variable (mild-moderate vs. severe) to differentiate the more severe symptomatology that will most likely result in incapacitation, disruptions on wellbeing and mental health, and seeking urgent and long-term medical care, thus requiring more aggressive interventions. Mild and moderate pain (which we defined as 0–7 in the NRS) had less than half responses than severe pain (8–10 in the NRS) in this cohort; for mild pain (1–4 in the NRS) there were very few responses. Patients reporting no pain (1 in the NRS scale) were excluded from the analysis, which ranged from 0.14% to 1%, except dyspareunia after 24 hrs at 9.38% (n=56 out of 597 who responded this question). In the question about intensity of dysmenorrhea at worst no patients selected no pain.

We have recently reported the clinical-demographic profile of women with endometriosis from Latin America and Spain, documenting substantial severity and impact of symptoms in this understudied patient population [ 12 ]. Secondary analysis of this dataset allows a better understanding of the universality of endometriosis symptoms, signs, and biopsychosocial impact. This study was conducted to evaluate if the severity of pelvic pain could be moderated by socioeconomic variables, psychological traits (e.g., pain catastrophizing) and self-perceptions of race encompassing this population. Our goal was to better understand the influence of these psychosocial factors on disease presentation as this knowledge could inform clinical management. We show a high likelihood of the PCS score predicting the severity of six of the seven types of pelvic pain studied. Results also show that self-identified race was not a predictive factor for pain severity reported by women with endometriosis from Latin American and Spain. This is a novel finding that contributes to filling a gap in the literature regarding potential moderators of pain thresholds in admixed patient populations. It must be noted that the question about self-identified race in the EPHect questionnaire does not encompass all the complexities inherent to this variable [ 11 ]. Because of the cross-sectional study design, we cannot differentiate if subjects answered this question based on biological parameters (skin color, physical features, heritage, ancestry) or on a broader definition that takes in consideration cultural and sociopolitical contexts. We are also aware that there are sub-identities across a self-reported race, very apparent in genetically admixed populations with unique sociopolitical environments and cultural connotations. Moreover, beyond possible differences based on race in the pain experiences of women from Latin America/Spain, there are also commonalities manifested as nationalities (“I am Puerto Rican first, then I am a Black woman from Puerto Rico”) that our study design cannot identify. Thus, in this context, the race variable is regarded as a social construct rather than a biological category, i.e., it does not represent genetic ancestry, in accord with current scholarship [ 11 ; 23 ; 36 ]. Our study did not explore all the biopsychosocial factors and individual differences that could influence the experience of pain [ 3 ; 17 ; 29 ]. For example, the cross-sectional survey does not gather data about social determinants of health, including sociopolitical contexts, social inequalities, or health care accessibility or misconceptions, therefore we are unable to assess whether the various self-identified races represented in each country constitute a “racialized group”[ 29 ]. Such analysis would require additional in-depth investigations of the sociopolitical situation of each country, which is beyond the scope of our study. Additional studies would be necessary to determine whether self-identified race in each of the countries studied could impact health care access, discrimination, resilience, and other social and environmental conditions (i.e., social determinants of health) that could possibly impact on disease presentation and endometriosis pain outcomes. Our results indicate that in the context of Latin America and Spain race as a self-conception of a patient’s identity should not influence medical practice, nor used to perpetuate racial stereotypes related to pain reporting [ 4 ]. In general, the different racial demographic clusters identified through unbiased analysis of the population stratification of self-reported race did not account for differences in reporting of severe pain symptoms. There was one exception: patients from countries that have relatively higher Mixed race representation (Cluster C) reported less severe dysmenorrhea when experienced at its worst compared to Clusters A and B. This may be due to reported differences in health/illness perceptions, pain beliefs that affect help-seeking behaviors (“a natural part of life” that must be endured vs. “a sign of illness” that requires medical intervention), coping strategies, and self-efficacy among the diverse sociocultural sub-groups represented in our study [ 28 ]. There are reported differences associated with coping strategies towards pain among Hispanic/Latino Americans, including a tendency to catastrophize, stoicism and praying/religiousness [ 20 ; 21 ]. Overall, despite the racial and sociocultural heterogeneity intrinsic to people from Latin American and Spain, we did not document significant differences in pain severity reporting based on self-identified race. Therefore, our data show that physician assessments and clinical decisions should not be based on the patient’s racial identity nor the doctor’s perceptions of the patient’s race. Having a private vs. public health insurance plan was not significantly associated with pain reporting, and education level played a limited role. Although this needs to be investigated further, this observation indicates a limited role in access to care and having higher education on whether a patient perceives their pain to be of high severity. Older age was strongly associated with reporting severe dyspareunia at its worse when controlling for demographic cluster, and with recent (during the last three months) pelvic pain regardless of both self-reported race and demographic cluster. This may indicate an impact of years with the disease on symptom presentation and supports the importance for early diagnosis and treatment to prevent worsening of pain. Hypoestrogenism is known to cause dyspareunia, irrelevant of endometriosis. However, the age range of our cohort was 15–66 (median=34), and most respondents (96.0 %) referred to being pre-menopausal, therefore it is unlikely that this result was due to a high proportion of participants being post-menopausal. The association between chronic pain, including dysmenorrhea and endometriosis-associated pain, and pain catastrophizing is well established [ 8 ; 42 ]. Pain catastrophizing was associated with health-related QoL (HRQoL) and with the persistence of pain after one year in patients with endometriosis [ 19 ]. More recently, endometriosis patients were not only shown to have significantly higher menstrual pain severity and pain catastrophizing than women with primary dysmenorrhea, but pain catastrophizing (in particular, the helplessness score) was identified as a predictor of menstrual pain severity[ 18 ]. Our study showed that high PCS scores were associated with reporting severe pain in most pain types studied, except for dyspareunia after last coitus [ 12 ]. PCS total score was a much better predictor of pain severity, and this association was not dependent on self-reported race or demographic cluster, despite previous research documenting moderation of catastrophizing by these variables [ 9 ; 20 ; 22 ]. Importantly, it must be noted that the catastrophizing-pain relationship is bi-directional: it is possible that patients with the most severe pain feel less hopeful and thus catastrophize more when facing such intense, disruptive symptomatology. Thus, our results are in accord with other studies documenting a relationship between pain and catastrophizing, while adding valuable insights negating a potential moderating effect of self-reported race on pain reporting. Regardless of the direction of the pain:catastrophizing interaction, our results suggest that it would be of high value to incorporate pain catastrophizing assessments into the multidisciplinary management of endometriosis [ 2 ]. Left untreated, pain catastrophizing may limit the efficacy of pharmacological interventions, contributing to frustration, stress, and feelings of helplessness [ 25 ]. Given that an elevated PCS score has been linked with pain persistence, disability, and poorer QoL, there is great potential for improving therapeutic outcomes and wellbeing in endometriosis patients by including psychological interventions in their treatment plan [ 21 ; 31 ; 35 ]. Both Cognitive Behavioral Therapy (CBT) and Acceptance and Commitment Therapy (ACT) could be used to control pain interference in patients who catastrophize thus improving clinical outcomes and HRQoL [ 7 ; 37 ; 40 ]. A word of caution: patients may find the word ‘catastrophizing’ as stigmatizing and referrals to mental health providers as invalidating their pain. Providers must educate patients on the benefits of psychological therapy as an essential component of multidisciplinary pain management programs. In sum, our data indicate that catastrophizing is a robust predictor of endometriosis pain severity that is not influenced by self-reported race in a patient cohort from Latin America and Spain. We are aware of other sociocultural factors that may influence pain reporting including mental health, stress perception, and resilience/coping mechanisms, which were not studied herein [ 14 ; 21 ]. Additional public health and sociological research is required to investigate further whether there may be differences in access to care or health seeking behaviors among the different patient groups in these countries. Future research is also needed to better understand the underlying biopsychosocial mechanisms of the observed association of catastrophizing and pain severity, with the goal of tailoring clinical and psychological interventions for endometriosis-associated pain.

The severe painful symptoms of endometriosis negatively impact patients’ physical and emotional well-being, and quality of life (QoL) [ 25 ; 43 ]. Despite affecting millions of women, adolescents, and menstruating persons globally [ 1 ], there is still limited knowledge of differences in prevalence and clinical presentation of endometriosis across racial, ethnic and socioeconomic groups [ 32 ]. A recent systematic review [ 6 ] showed that the endometriosis risk in Hispanic/Latina was half, but not statistically significant, compared to non-Hispanic Whites (NHWs). Compared to 16 studies of NHWs vs. Black women, and 10 studies of NHWs vs. Asian women, there are only 5 published studies that included Hispanic/Latina patients with endometriosis at a proportion of 1:4.4 compared to NHWs (n=14,951 vs. n=65,332, respectively). The underrepresentation of Hispanic/Latina patients in research creates a gap in understanding biopsychosocial factors influencing female pelvic pain [ 5 ; 26 ]. To fill this gap, we recently conducted an international collaborative study to evaluate the clinic-demographic profile of women with endometriosis from Latin America and Spain using a validated Spanish version of the Endometriosis Phenome Project’s (EPhect) Clinical Questionnaire (ECQ) [ 24 ; 41 ]. The study involving ~1,400 women with endometriosis from 23 countries in Latin America (South and Central America, the Caribbean, Mexico) and Spain found a high prevalence of pelvic pain symptomatology, including dysmenorrhea (pelvic pain experienced during menses), dyspareunia (pelvic pain experienced during or after sexual intercourse), and chronic pelvic pain (CPP; defined as pain felt for six months or more, not necessarily associated with menses). This study also identified risk factors and diagnostic features that could impact the clinical management of this patient population [ 12 ]. The experience of pain is multidimensional and is influenced by many biopsychosocial factors [ 3 ; 21 ; 27 ]. Sex, age, culture, race and ethnicity are widely reported to be correlated with experimental and clinical pain experiences [ 9 ; 10 ; 30 ]. Pain catastrophizing, a robust predictor of pain intensity, chronicity, disability, and psychological distress, is moderated by race/ethnicity [ 20 – 22 ; 31 ; 34 ; 38 ]. Given that people from Latin America and Spain encompass diverse sociocultural populations, and that countries vary in their proportions of Indigenous, European, and African ancestries and cultural heritage [ 33 ], we hypothesized that the experience of pelvic pain could be perceived differently across these sub-groups. We sought to assess the moderating role of self-identified race, pain catastrophizing and socioeconomic variables in endometriosis pain severity among this patient population[ 14 ]. Herein, ‘race’ is viewed as a social construct and subjective measure that is influenced by personal, familial, cultural and societal factors, and does not correlate with the individual’s genetic makeup [ 23 ; 36 ]. Our results demonstrate that racial categories –White, Black or Mixed race– do not influence endometriosis pain reporting, while pain catastrophizing and certain socioeconomic correlates do. Together, these data will impact clinical decisions and care pathways leading to optimal care for all patients with endometriosis.