1130566 research-article2022 WHE0010.1177/17455057221130566Women’s HealthMedina-Perucha et al. Original Research Article Women’s Health Endometriosis prevalence and incidence Volume 18: 1­–11 © The Author(s) 2022 Article reuse guidelines: trends in a large population-based study in sagepub.com/journals-permissions DOI: 10.1177/17455057221130566 https://doi.org/10.1177/17455057221130566 Catalonia (Spain) from 2009 to 2018 journals.sagepub.com/home/whe Laura Medina-Perucha1,2*, Andrea Pistillo1*, Berta Raventós1,2, Constanza Jacques-Aviñó1,2 , Jordina Munrós-Feliu3,4 , Cristina Martínez-Bueno4,5,6, Carme Valls-Llobet7, Francisco Carmona8, Tomàs López-Jiménez1,2, Georgina Pujolar-Díaz1,2, Eva Flo Arcas9, Anna Berenguera1,2,10† and Talita Duarte-Salles1,2† Abstract Objective: Endometriosis greatly impacts women’s health and quality of life. However, research on the prevalence and incidence of endometriosis remains inconclusive. This study assesses time trends in the prevalence and incidence of endometriosis diagnoses in Catalonia (Spain) from 2009 to 2018, considering differences by age and socioeconomic status. Methods: Population-based cohort study using data from the Information System for Research in Primary Care (SIDIAP) database. Data were included from over 2.4 million women aged 15–55 years between 1 January 2006 and 31 December 2018. Results: A total of 2,337,717 women were selected as the incident population; 0.7% had an endometriosis diagnosis. Median (interquartile range) age at diagnosis was 37 (32–43) years. Most women were European (92.3%) and lived in urban areas (73.6%). Overall prevalence of endometriosis consistently increased during the 2009–2018 period, and it was 1.24% in 2018. Trends were the highest for women with less socioeconomic deprivation and for the 35–44 years age group. Median incidence rates were 94.9 (92.6–102.9) per 100,000 women-years, being the highest in women aged 35–44 years throughout the whole study period. Overall, incidence increased between 2015 and 2017, and plateaued or decreased in 2018. Incidence rates in women from the most deprived and rural areas were lower, although incidence time trends by socioeconomic status were unclear. Conclusion: Healthcare services and public health strategies need to be strengthened to ensure timely endometriosis diagnosis and treatment. Special attention should be given to the most affected populations and the social inequities of health. Keywords endometriosis, epidemiology, incidence, prevalence, social inequities of health, time trends, women Date received: 29 April 2022; revised: 15 September 2022; accepted: 16 September 2022 1 F undació Institut Universitari per a la Recerca a l’Atenció Primària de August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain Spain 2 Universitat Autònoma de Barcelona, Barcelona, Spain 9 Associació d’Afectades d’Endometriosi de Catalunya (EndoCat), 3 Atenció a la Salut Sexual i Reproductiva (ASSIR) Muntanya/La Mina, Barcelona, Spain Institut Català de la Salut, Barcelona, Spain 10 Departament d’Infermeria, Universitat de Girona, Girona, Spain 4 Sexual and Reproductive Health Care Research Group (GRASSIR), University Institute in Primary Care Research Jordi Gol (IDIAP Jordi *Joint senior authors. Gol), Barcelona, Spain †Joint first authorship. 5 Servei d’Atenció a la Salut Sexual i Reproductiva (ASSIR), Direcció Corresponding author: Assistencial d’Atenció Primària, Institut Català de la Salut, Barcelona, Spain Talita Duarte-Salles, Fundació Institut Universitari per a la recerca a 6 Universitat de Barcelona, Barcelona, Spain l’Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Gran Via 7 Centro de Análisis y Programas Sanitarios (CAPS), Barcelona, Spain Corts Catalanes, 587 àtic, 08007 Barcelona, Spain. 8 Institute Clinic of Gynecology, Obstetrics and Neonatology, Email: tduarte@idiapjgol.org Hospital Clinic de Barcelona, Institut d’Investigacions Biomèdiques Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). 2 Women’s Health Introduction decisions.10 The main aim of this study was to assess time trends in the prevalence and IRs of endometriosis diagno- Endometriosis has direct and indirect impacts on women’s sis in Catalonia (Spain) from 2009 to 2018, considering lives which compromise quality of life, emotional health, differences by age and socioeconomic status. social relationships, and sexuality.1,2 It is thus imperative to consider the social, occupational, and economic impact of endometriosis.3,4 Despite the known burden of endome- Methods triosis, accurate estimates of prevalence and incidence rates (IRs) are lacking in many countries, including Spain.5 We conducted a population-based cohort study using data A systematic review and meta-analysis which considered from the Information System for Research in Primary Care endometriosis diagnoses based on self-reported data, sur- (SIDIAP; https://www.sidiap.org/),11,12 a database contain- gery, and imaging showed that the prevalence and IRs of ing pseudo-anonymized data collected by primary health- endometriosis vary depending on the study design.6 Pooled care professionals starting in 2006. It includes 5.8 million prevalence estimates were 5% based on self-reported data, individuals (>75% of the total population of Catalonia) 1% in population-based integrated information systems, and is representative of the geographic, sex, and age distri- and 4% based on other methodological designs. Pooled butions of the overall population of Catalonia.11 IRs also varied from 1.36 per 1000 women-years in hospi- In this study, we included all women aged 15–55 years tal discharge–based studies, to 3.53 per 1000 women-years between January 2006 and December 2018 who were fol- in cohort studies, and 1.89 per 1000 women-years in stud- lowed for at least 1 year of study (prevalent population). ies using population-based integrated information sys- We excluded prevalent diagnoses of endometriosis prior to tems.6 In another systematic review which included 1 January 2009 to estimate incidence in order to have a self-reported, clinically, surgically, and imagery-based 10-year window (incident population). We used the endometriosis diagnoses, the estimated overall prevalence International Classification of Diseases–Tenth Revision was 4.4% (range of 0.8%–28.6%).7 In the United States, a (ICD-10) codes to identify our outcome and its related study including 332,056 women followed for 10 years conditions. Endometriosis was identified with the ICD-10 showed an average IR of 2.43 cases per 1000 women- codes N80. Endometriosis-related symptoms were also years.8 The authors also observed that, in most years, IRs included dysmenorrhea (ICD-10 codes N94.4, N94.5, and were the highest among women aged 36–45 years. The N94.6), dyspareunia (ICD-10 code N94.1), intermenstrual prevalence of endometriosis was 1.9%, based on diag- pain (ICD-10 code N94.0), and pelvic pain (remaining nosed cases of women who were being followed by the in ICD-10 codes of N94, including vulvodynia), utilizing the study 2015.8 This study used data from 2863 incident first registered symptom in the database. Endometriosis cases, with a distribution of diagnosis modality of 48.8% and endometriosis-related symptoms were recorded by clinical, 45.5% surgical, and 5.7% imaging. Moreover, and primary healthcare professionals. Information on the tools finally, a recent retrospective population-based study eval- and procedures for endometriosis diagnoses, however, is uated the IRs of endometriosis in Spain, using hospital dis- not available (e.g. to identify clinically vs surgically diag- charge data from 2014 to 2017. Overall IRs were 1.61 nosed endometriosis). cases per 1000 women-years (range = 0.68–2.4). Annual We also extracted data on age (15–24; 25–34; 35–44; IRs decreased from 0.44 to 0.39 per 1000 women-years 45–55 years); nationality (categorized in four geographical from 2014 to 2017.9 In this study, all participants had a regions (Africa, North and Latin America, Asia, Europe) clinically confirmed diagnosis of endometriosis. based on the data available (e.g. no participants from Most previous population-based studies have used hos- Oceania)); endometriosis-related sick leaves from a wom- pital or health insurance data to estimate endometriosis an’s first record in the database onward (to calculate: the prevalence and IRs.9 However, in Spain, primary health- percentage of women who had taken at least one, the mean care centers are the customary first point of contact for number per person, and the total amount of days); primary women seeking medical care. Therefore, assessing the healthcare visits (total number of visits since 2006; catego- prevalence and IRs of endometriosis through longitudinal rized in: gynecology, nursing, midwifery, and general electronic primary healthcare records may provide accu- medicine); socioeconomic status; and urban/rural resi- rate estimates and greatly contribute to existing evidence. dence. Socioeconomic status was assessed using the Furthermore, previous research has often disregarded “Mortalidad en áreas pequeñas españolas y desigualdades social axes of health inequities, such as sociodemographic socio-económicas y ambientales” (MEDEA) deprivation and socioeconomic characteristics, which are crucial to index.13 The index is based on three work-related indica- understanding prevalence and IRs. Thus, assessing preva- tors (rates of unemployment, manual, and eventual work- lence and IRs based on sociodemographic and socioeco- ers), two education-related indicators (rates of illiteracy nomic factors is significantly relevant. Likewise, and uncompleted studies, and rates among young people), time-trend studies can provide an accurate view of preva- and the Spanish 2001 national census. The MEDEA depri- lence and IRs over time and, in turn, inform public health vation index is only available for urban areas (>10,000 Medina-Perucha et al. 3 habitants and population density of >150 habitants/km2). participated in the interpretation of the findings and the Other areas were considered rural. The index is calculated preparation of the final reports. at the census tract level and was categorized into quintiles by the SIDIAP for anonymization purposes. The first (Q1) Results and fifth (Q5) quintiles represented the least and most deprived areas, respectively. The index used the census The study population included 2,452,282 women, 16,258 of tract of the women at the end of the study (patient’s death, whom had an endometriosis diagnosis recorded between transfer, or end of 2018). Smoking status (current smoker, 2009 and 2018. Demographic characteristics were similar previous smoker, and never smoker); alcohol risk (high among cases in the prevalent and incident populations risk, low risk, and no alcohol consumption); Charlson’s (Table 1). For the incident population, the median (IQR) age index (0, 1, 2, and 3+)—a method to estimate mortality at diagnosis was estimated to be 37.0 (32.0–43.0). Diagnosed risk based on comorbid conditions and long-term progno- women were predominantly European (92.3%) and lived in sis and survival14—and body mass index (BMI) at were urban areas (73.6%). More women diagnosed with endome- also extracted, considering the closest measurement to the triosis were current of previous smokers (29.3% vs 21.6% date of entry into the database. and 7.2% vs 4.4%, respectively). Alcohol risk did not differ significantly between women with or without endometrio- sis, although more women who did not consume alcohol Statistical analysis consumers had an endometriosis diagnosis (60.0% vs We described the prevalent and incident populations in 50.4%). More women with endometriosis had a concurrent terms of sociodemographic characteristics, symptoms, health disorder compared to women without endometriosis sick leaves, and healthcare visits with percentages for cat- (Charlson’s index score of 0; 74.2% vs 80.1%), but had a egorical variables and median and interquartile range similar BMI compared to women without endometriosis (IQR) for continuous variables, categorized by endome- (median (IQR) = 23.6 (21.1–27.0) vs 24.2 (21.5–28.1)). triosis status (with/without endometriosis diagnosis). We found a notable difference in the total number of Annual prevalence of endometriosis was calculated as the healthcare visits between women diagnosed with endome- number of women aged 15–55 years with a diagnosis of triosis and those not, particularly in healthcare visits endometriosis (on/prior to 1 January of each year) divided involving general practitioners (median (IQR) = 40.0 by the number of women aged 15–55 years on 1 January. (22.0–67.0) vs 25.0 (10.0–49.0)) and gynecologists (8.0 We assessed the p-value for prevalence trends by fitting a (3.0–14.0) vs 5.0 (2.0–10.0)). All the symptoms studied logistic regression of endometriosis diagnosis (binary had a higher occurrence in women with endometriosis, dependent variable), with study year as the continuous especially dysmenorrhea and pelvic pain (14.4% vs 4.3% independent variable. We assigned an SIDIAP entry date and 2.5% vs 0.8%, respectively). Almost a third of women for women without an endometriosis diagnosis, stratifying with endometriosis (29.8%) had been on sick leave for by age group and MEDEA. For incidence, women with no endometriosis-related reasons, with a median (IQR) of prior (to 1 January 2009) history of endometriosis contrib- 18.0 (7.0–37.0) days in total (Table 1). uted to person-time from the date when they became eligi- The prevalence of endometriosis in 2018 was 1.24%. ble for the study (aged 15 years at any time during Prevalence trends showed a constant increase during the follow-up) to the earliest date of endometriosis diagnosis, 2009–2018 period (p < 0.001 for each strata; Figure 1 and their 55th birthday, death, transferring out of SIDIAP, or Supplemental Table S1). Throughout the entire period of the end of the study on 31 December 2018. study, the highest prevalence was identified in the 35– Annual IRs of endometriosis diagnosis were calculated 44 years age group followed by women aged 45–55 years. from 2009 to 2018 by dividing the number of new cases of The difference between these two groups reduced/lessened endometriosis by 100,000 women-years at risk. Only first in the more recent years of study. Women from the least ever diagnoses were considered. We stratified IRs by socioeconomically deprived quintiles (U1, U2, U3) 10-years age groups (calculated annually) and MEDEA. showed higher prevalence compared to the more deprived We used Poisson’s 95% confidence intervals (95% CIs). (U4, U5) and women in rural areas (R). We calculated incidence rate ratios (IRRs) to compare dif- The median incidence (IQR) was 94.9 per 100,000 ferences in incidence in different time periods (2013–2015; women-years (92.6–106.9). IRs [95% CI] fluctuated 2016–2018; 2009–2012). All analyses were performed throughout the study period, ranging from 85.8 per 100,000 using R version 4.0.3. women-years [81.5–90.2] in 2011 to 110.2 per 100,000 women-years in 2017 [105.1–115.5]. We observed an increasing trend in the IR from 2014 to 2017 before slightly Public and patient involvement decreasing in 2018 (Supplemental Table S2.1). Annual IRs The study was conducted in collaboration with the stratified by age groups and MEDEA deprivation index Association of Women living with Endometriosis in can be found in Supplemental Table S2.2 and S2.3. Higher Catalonia (EndoCat). Co-researchers from EndoCat IRs among women aged 25–34 and 35–44 years were 4 Women’s Health Table 1. Population characteristics of women between 15 and 55 years old. Prevalent population (N = 2,452,282) Incident population (N = 2,337,717) Without endometriosis With endometriosis Without endometriosis With endometriosis N (%) 2,426,357 (98.9) 25,925 (1.1) 2,321,459 (99.3) 16,258 (0.7) Age at diagnostic, median (IQR) – 36.0 (31.0–42.0) – 37.0 (32.0–43.0) Continent of nationality (%) Africa 93,279 (3.8) 290 (1.1) 92,229 (4.0) 236 (1.5) North/Latin America 210,101 (8.7) 1274 (4.9) 206,674 (8.9) 951 (5.8) Asia 18,508 (0.8) 81 (0.3) 18,406 (0.8) 70 (0.4) Europe 2,104,469 (86.7) 24,280 (93.7) 2,004,150 (86.3) 15,001 (92.3) Smoking status (%) Current smoker 517,238 (21.3) 7551 (29.1) 502,592 (21.6) 7528 (29.3) Never smoker 1,224,388 (50.5) 13,795 (53.2) 1,151,231 (49.6) 13,604 (53.0) Previous smoker 107,816 (4.4) 1865 (7.2) 102,061 (4.4) 1841 (7.2) Missing 576,915 (23.8) 2714 (10.5) 565,575 (24.4) 2707 (10.5) Alcohol risk (%) Alcohol high risk 21,466 (0.9) 270 (1.0) 20,240 (0.9) 267 (1.0) Alcohol low risk 405,078 (16.7) 5337 (20.6) 382,158 (16.5) 5296 (20.6) No alcohol 1,236,867 (51.0) 15,602 (60.2) 1,170,676 (50.4) 15,416 (60.0) Missing 762,946 (31.4) 4716 (18.2) 748,385 (32.2) 4701 (18.3) Charlson’s index (%) 0 1,913,982 (78.9) 19,169 (73.9) 1,859,354 (80.1) 19,051 (74.2) 1 414,460 (17.1) 5464 (21.1) 379,003 (16.3) 5377 (20.9) 2 87,685 (3.6) 1185 (4.6) 75,118 (3.2) 1155 (4.5) 3+ 10,230 (0.4) 107 (0.4) 7984 (0.3) 97 (0.4) BMI at entry BMI, median (IQR) 24.4 (21.6–28.4) 23.6 (21.2–27.1) 24.2 (21.5–28.1) 23.6 (21.1–27.0) Missing 905,606 (37.3) 5571 (21.5) 887,383 (38.2) 5542 (21.6) MEDEA deprivation index (%), quintile Q1 (least deprived) 380,817 (15.7) 4263 (16.4) 362,254 (15.6) 2673 (16.4) Q2 349,373 (14.4) 4044 (15.6) 333,385 (14.4) 2523 (15.5) Q3 340,141 (14.0) 3808 (14.7) 324,658 (14.0) 2434 (15.0) Q4 339,534 (14.0) 3599 (13.9) 324,910 (14.0) 2322 (14.3) Q5 (most deprived) 332,132 (13.7) 3103 (12.0) 319,583 (13.8) 2013 (12.4) Living in rural areas 397,025 (16.4) 4220 (16.3) 379,052 (16.3) 2478 (15.2) Missing 287,335 (11.8) 2888 (11.1) 277,617 (12.0) 1815 (11.2) Symptoms Dysmenorrhea (%) 99,485 (4.1) 3014 (11.6) 99,329 (4.3) 2340 (14.4) Dyspareunia (%) 18,052 (0.7) 375 (1.4) 17,505 (0.8) 295 (1.8) Pelvic pain (%) 19,886 (0.8) 583 (2.2) 19,162 (0.8) 402 (2.5) Intermenstrual pain (%) 1126 (0.0) 40 (0.2) 1122 (0.0) 32 (0.2) All (%) 138,549 (5.7) 4012 (15.5) 137,118 (5.9) 3069 (18.9) Sick leaves related to endometriosis  Women with a sick leave – 7932 (30.6) – 4848 (29.8) related to endometriosis, n (%) Per person, median (IQR) – 1.0 (1.0–1.0) – 1.0 (1.0–1.0)  Days on sick leave, median – 18.0 (7.0–37.0) – 18.0 (7.0–37.0) (IQR) Healthcare visits number, median (IQR) Gynecology 5.0 (2.0–10.0) 7.0 (3.0–14.0) 5.0 (2.0–10.0) 8.0 (3.0–14.0) Nursing 8.0 (4.0–17.0) 10.0 (5.0–20.0) 8.0 (3.0–17.0) 9.0 (4.0–18.0) Midwifery 4.0 (2.0–10.0) 4.0 (2.0–9.0) 4.0 (2.0–10.0) 4.0 (2.0–10.0) General medicine 26.0 (10.0–50.0) 42.0 (23.0–70.0) 25.0 (10.0–49.0) 40.0 (22.0–67.0) IQR: interquartile range; BMI: body mass index; MEDEA: Mortalidad en áreas pequeñas españolas y desigualdades socio-económicas y ambientales. Medina-Perucha et al. 5 Figure 1. Time trends in prevalence of endometriosis 2009–2018 stratified by: (a) age group and (b) MEDEA deprivation index. U1: least deprived quintile; U5: most deprived quintile; R: living in rural areas. 290,222 (11.8%) individuals had no information on the deprivation index. *For all the strata. 6 Women’s Health Figure 2. Time trends in incidence rates between 2009 and 2018 stratified by: (a) age group and (b) MEDEA deprivation index. IR: incidence rates; Q1: least deprived quintile; Q5: most deprived quintile; R: living in rural areas. Medina-Perucha et al. 7 Table 2. Incidence rate ratios (95% CI) of diagnoses of endometriosis stratified by age group and MEDEA deprivation index. Year periods 2009–2012 2013–2015 2016–2018 Overall (16,176,493 women-year) Reference 1.03 [0.99–1.07] 1.17 [1.13–1.21] MEDEA deprivation index, quintile Q1 (least deprived) Reference 1.02 [0.93–1.12] 1.11 [1.02–1.22] Q2 Reference 1.10 [1.00–1.21] 1.22 [1.11–1.34] Q3 Reference 1.03 [0.94–1.14] 1.09 [0.99–1.20] Q4 Reference 1.00 [0.91–1.11] 1.17 [1.06–1.29] Q5 (most deprived) Reference 1.03 [0.93–1.15] 1.24 [1.12–1.38] Rural Reference 1.02 [0.92–1.12] 1.13 [1.03–1.24] Age groups (years) 15–24 Reference 1.04 [0.89–1.22] 1.38 [1.19–1.60] 25–34 Reference 1.02 [0.95–1.08] 1.15 [1.08–1.23] 35–44 Reference 1.03 [0.97–1.09] 1.21 [1.14–1.28] 45–55 Reference 1.08 [0.99–1.19] 1.20 [1.10–1.31] MEDEA: Mortalidad en áreas pequeñas españolas y desigualdades socio-económicas y ambientales. 279,432 (11.9%) individuals had no information on the deprivation index. observed throughout the entire study period (Figure 2(a)). and adenomyosis) in Italy,15 1.9% in the United States,8 We observed an increase in IRs between 2015 and 2017 in 1.5% in the United Kingdom,16 1.5% in hospitalized all age groups except for the 15–24 years age group, whose women of childbearing age in France,17 1.08% in Israel,18 diagnoses peaked slightly in 2016. Incident diagnoses sta- 0.1% in Germany,19 and 2.12–3.56 per 1000 women in bilized or slightly decreased in 2018 for all age groups, South Korea.20 Increasing trends in prevalence rates in this except the 25–34 years age group. study could be attributed to improvements in the detection There was no clear pattern in IRs across MEDEA dep- and treatment of endometriosis in the national21,22 and rivation index quintiles (Figure 2(b)), although more endo- Catalan23 healthcare systems or to the population’s and metriosis diagnoses occurred as socioeconomic status healthcare professionals’ increased awareness of endome- increased (Table 1). In addition, we observed lower IRs triosis as a result of recent public campaigning.24 among women living in the most deprived and rural areas However, median IRs in this study are significantly from 2009 to 2017. A pronounced increase in incident lower than those reported in previous research. A recent diagnoses from 2014 to 2018 among the two most deprived study using hospital discharge data has indicated that quintiles and among women in rural areas can also be Catalonia is the Spanish region with the third highest IRs noted (i.e. IR [95% CI] among the most deprived quintile of endometriosis, with an overall IR of 20 per 10,000 increased from 79.1 [67.9–91.5] in 2014 to 105.0 [92.0– women-years in Catalonia between 2014 and 2017.9 119.3] per 100,000 women-year in 2018). IRs by age and Evidence in other countries is also inconsistent, with inci- MEDEA can be found in Supplemental Figure S1. dence reports of 10.8 per 1000 women-years in Israel,18 IRRs during 2013–2015 and 2016–2018 compared to 0.14% in Italy,15 0.4%–1.6% in France,17 12.8 per 1000 2009–2012 are reported in Table 2. We found no significant women-years in Germany,19 and 2.43 cases per 1000 differences in IRs in 2013–2015 compared to 2009–2012 women-years in the United States.8 However, comparisons for all strata except for the second deprivation quintile (IRR between countries are challenging, mainly given substan- [95% CI] = 1.10 [1.00–1.21]) and all age groups. Conversely, tial structural differences in their respective healthcare sys- we observed a statistically significant increase in the IRs of tems. Variance in IRs could be explained by differences in endometriosis (i.e. IRR > 1) in 2016–2018 for all strata the health records used,25 time-periods studied, the poten- except for the third deprivation quintile (1.09 [0.99–1.20]) tial under- and mis-reporting of endometriosis diagnoses and all age groups, with the greater increase among the and related symptoms, or double healthcare coverage.26 youngest group (1.38 [1.19–1.60]) (see Supplemental Table Barriers for diagnosing endometriosis merit consideration S3 for IRR by age and MEDEA). as well. First, the generalized normalization of menstrual pain, both by women and healthcare professionals, serves as a barrier for health exploration and diagnosis.27–29 Second, Discussion the extensive use of hormonal contraception suppresses Prevalence rates found in our research are consistent with and masks endometriosis-related symptoms.28,30 Third, previous cohort studies. Other studies have found preva- power dynamics in healthcare consultations,31,32 with women lence rates of 2% (including diagnoses of endometriosis reporting systematic refusals of health explorations for 8 Women’s Health endometriosis-related symptoms by clinicians28,31–33, a poverty,39 characterized by employment precariousness lack of knowledge from healthcare professionals,5,34 and and decreased socioeconomic resources, has a lasting their disregard of the impact of late diagnosis on women’s impact on vulnerable women and is an obstacle to access health and wellbeing.30,34 healthcare services. However, IRs in this study increased While this study showed a clearly increasing trend in in among women of a lower socioeconomic status between endometriosis IRs between 2014 and 2017, Ávalos Marfil 2014 and 2018. This suggests that strategies to timely et al.9 showed a decrease in IRs during the same time diagnose endometriosis may have had a positive impact on period in Spain. These differences are again likely to be reducing social inequity gaps. Yet, women living in rural explained by the nature of the data used in both studies and areas have the lowest IRs, pointing to rurality as a factor by the increasing involvement of primary healthcare in that may hinder endometriosis diagnosis. Ensuring equita- endometriosis-related diagnoses and consultations, espe- ble healthcare access and the timely diagnosis and treat- cially since the implementation of national clinical guide- ment of endometriosis are imperative to address social lines for endometriosis in 201321 and in Catalonia in inequities associated with the disease.38 Public health 2018.23 Another explanation for the increasing incidence interventions should also consider the potential direct and trends in this study could be related to a positive shift in indirect economic costs associated with living with endo- healthcare resources in the last few years, slowly overcom- metriosis,39 and how this may differentially impact socio- ing the 2008 economic crisis and its profound impact on economically vulnerable, rural, and migrant populations. primary healthcare resources and quality of care, espe- These strategies should also account for and address the cially between 2009 and 2010.35 As for increased preva- increased barriers that vulnerable populations face when lence, endometriosis awareness campaigns may have had a accessing healthcare services.37,38 These strategies should positive impact on shifting healthcare professionals’ atti- also account for and address the logistical difficulties asso- tudes and knowledge on endometriosis and the need for ciated with educating healthcare professionals and the early detection. The efforts of women’s associations and increased barriers that vulnerable populations face when professionals to increase the visibility of women’s health accessing healthcare services. promote gender-based research may have also influenced these trends. Furthermore, we observed a higher preva- Strengths and limitations lence of endometriosis-related symptoms and in the number of healthcare visits in women diagnosed with One of the main strengths of this study was the large sam- endometriosis. This may hint at a higher burden of disease ple size. Also, participants included in the SIDIAP are rep- and more undiagnosed cases, highlighting the need to resentative of the general population living in Catalonia in strengthen endometriosis detection efforts. terms of age, sex, and geographic distribution, meaning Women between 25 and 44 years had the highest endo- that these findings can possibly be extended to other com- metriosis IRs in this study. Meanwhile, the plateau in the parable regions. Another strength is the quality of the data, increasing incidence trends in 2018 did not affect women as they are longitudinally collected by healthcare profes- aged 25–34 years. This is consistent with previous stud- sionals based on diagnostic criteria and guidelines. The ies,8,18,19 and it can be attributed to endometriosis being limitations identified were the potential underestimation of commonly detected in the context of infertility problems, the prevalence and incidence of endometriosis, due to sev- the decision to stop using hormonal contraception, and/or eral reasons. First, 30.2% of women in Catalonia are esti- once women have sought endometriosis-related consulta- mated to have double healthcare coverage by attending tions for 6–10 years.28,29,34 It may also be that younger both public and private healthcare services, which may women make less use of healthcare services, in part translate into missing or out of date public healthcare because sexual and reproductive health routinely screen- records. Second, identifying (and therefore recording) ing services are not recommended before the age of endometriosis-related symptoms might be challenging due 25 years in Catalonia (e.g. for uterine cancer prevention). to a lack of knowledge or disregard for symptoms (e.g. Awareness and education campaigns directed to younger menstrual pain) and menstrual health patterns among populations could help the early detection of endometrio- women and healthcare professionals, meaning we may sis, given that we observe the lowest prevalence and inci- have missed mild and asymptomatic cases in a higher pro- dence in the youngest women throughout the study period. portion as a result. In line with this, it is important to con- Although we did not find a clear pattern in incidence sider the barriers to reporting endometriosis-related time trends associated with deprivation levels, we observed symptoms as women often fear being dismissed and stig- diagnoses to be more common in women with a higher matized when seeking care. Moreover, we are unaware of socioeconomic status.18,36 There is already sound evidence how healthcare professionals may have recorded and/or on the decreased utilization of healthcare services by soci- diagnosed endometriosis, while at the same time the lack oeconomically deprived and vulnerable populations,37,38 of surgically confirmed endometriosis cases may have led which may explain our findings. Particularly, time to diagnosis misclassification. Third, the assessment of Medina-Perucha et al. 9 healthcare visits must be performed with caution, given Constanza Jacques-Aviñó: Conceptualization; Investigation; that we could not exclude non-endometriosis-related vis- Methodology; Writing – review & editing. its, such as prenatal appointments. Finally, comparisons Jordina Munrós-Feliu: Conceptualization; Investigation; across tobacco and alcohol use are limited by data large Writing – review & editing. Cristina Martínez-Bueno: Conceptualization; Investigation; amount of missing data among women without a diagnosis Writing – review & editing. of endometriosis, potentially due to their lower utilization Carme Valls-Llobet: Conceptualization; Investigation; Writing of the healthcare system. – review & editing. Francisco Carmona: Conceptualization; Investigation; Writing Conclusion – review & editing. Tomàs López-Jiménez: Conceptualization; Investigation; Endometriosis prevalence and IRs increased between 2009 Writing – review & editing. and 2018 and 2015 and 2017, respectively, suggesting a Georgina Pujolar-Díaz: Conceptualization; Investigation; potential positive impact of the implementation of diagnos- Writing – review & editing. tic guidelines. While prevalence and incidence were the Eva Flo Arcas: Conceptualization; Investigation; Writing – highest in women aged 35–44 years, there was a tendency review & editing. Anna Berenguera: Conceptualization; Formal analysis; for them to be lower among women of a lower socioeco- Investigation; Resources; Writing – review & editing. nomic status and those living in rural areas. Strengthening Talita Duarte-Salles: Conceptualization; Formal analysis; diagnostic pathways could lessen the profound negative Funding acquisition; Investigation; Methodology; Resources; impact of delayed endometriosis diagnoses on women’s Writing – review & editing. health and wellbeing. It is crucial for primary healthcare and specialty care services to be well coordinated to ensure Acknowledgements comprehensive, interdisciplinary, and high-quality care for The authors thank all women whose health records have been women living with endometriosis. Further analyses essential to this study. The authors thank Matthew Bennett for his accounting for social determinants of health are necessary contributions to language revisions and editing. to determine how social inequities impact the endometrio- sis diagnostic processes and women’s health. Funding The author(s) disclosed receipt of the following financial support Declarations for the research, authorship and/or publication of this article: Funding for the Information System for Research in Primary Care Ethics approval and consent to participate (SIDIAP) data extraction for this study was obtained from Wereld Ethical approvals were obtained by the Ethics Committee at Kanker Onderzoek Fonds (WKOF, grant no.: 2017/1630), as part IDIAPJGol (21/236-P). Data protection legislation was con- of the international grants from the World Cancer Research Fund. sidered and risk assessment evaluations were performed to The funders had no role in study design, data collection, analysis, ensure participants’ anonymity and confidentiality. SIDIAP decision to publish, or preparation of the manuscript. includes pseudo-anonymized data; thus, identifying individ- ual women is not possible and consent was waived as per the Competing interests International Ethical Guidelines for Epidemiological Studies The author(s) declared no potential conflicts of interest with respect (Council for International Organizations of Medical Sciences, to the research, authorship, and/or publication of this article. 2012) and the IDIAPJGol Ethics Committee. The Reporting of Studies Conducted Using Observational Routinely Collected Health Data (RECORD) checklist was used to ensure research Availability of data and materials quality. Data may be obtained from a third party and are not publicly available. In accordance with the current European and national Consent for publication law, the data used in this study are only available for the researchers participating in this study. Thus, we are not allowed Not applicable as identifying individual women is not possible to distribute or make publicly available the data to other parties. and consent for publication was waived as per the International However, researchers from public institutions can request data Ethical Guidelines for Epidemiological Studies (Council for from SIDIAP if they comply with certain requirements. Further International Organizations of Medical Sciences, 2012) and the information is available online (https://www.sidiap.org/index. IDIAPJGol Ethics Committee. php/menu-solicitudesen/application-proccedure) or by contact- ing SIDIAP (sidiap@idiapjgol.org). Author contribution(s) Laura Medina-Perucha: Conceptualization; Formal analysis; ORCID iDs Investigation; Methodology; Writing – original draft. Constanza Jacques-Aviñó https://orcid.org/0000-0001-8506- Andrea Pistillo: Formal analysis; Investigation; Methodology; 780X Writing – original draft. Berta Raventós: Formal analysis; Investigation; Writing – origi- Jordina Munrós-Feliu https://orcid.org/0000-0001-6663-0943 nal draft. Talita Duarte-Salles https://orcid.org/0000-0002-8274-0357 10 Women’s Health Supplemental material development and validation. J Chronic Dis 1987; 40(5): 373–383. Supplemental material for this article is available online. 15. Morassutto C, Monasta L, Ricci G, et al. Incidence and estimated prevalence of endometriosis and adenomyosis References in northeast Italy: a data linkage study. PLoS ONE 2016; 1. Alcalde AM, Martínez-Zamora MÁ, Gracia M, et al. 11(4): e0154227. Assessment of quality of life, sexual quality of life, and pain 16. Ballard KD, Seaman HE, de Vries CS, et al. Can symptom- symptoms in deep infiltrating endometriosis patients with or atology help in the diagnosis of endometriosis? Findings without associated adenomyosis and the influence of a flex- from a national case-control study-part 1. BJOG 2008; ible extended combined oral contraceptive regimen: results 115(11): 1382–1391. of a prospective, observational study. J Sex Med 2022; 17. von Theobald P, Cottenet J, Iacobelli S, et al. Epidemiology 19(2): 311–318. of endometriosis in France: a large, nation-wide study based 2. Culley L, Law C, Hudson N, et al. The social and psycho- on hospital discharge data. Biomed Res Int 2016; 2016: logical impact of endometriosis on women’s lives: a critical 3260952–3260956. narrative review. Hum Reprod Update 2013; 19(6): 625– 18. Eisenberg VH, Weil C, Chodick G, et al. Epidemiology 639. of endometriosis: a large population-based database study 3. Mundo-López A, Ocón-Hernández O, Lozano-Lozano M, from a healthcare provider with 2 million members. BJOG et al. Impact of symptom burden on work performance sta- 2018; 125(1): 55–62. tus in Spanish women diagnosed with endometriosis. Eur J 19. Abbas S, Ihle P, Köster I, et al. Prevalence and incidence Obstet Gynecol Reprod Biol 2021; 261: 92–97. of diagnosed endometriosis and risk of endometriosis in 4. Gao X, Outley J, Botteman M, et al. Economic burden of patients with endometriosis-related symptoms: findings endometriosis. Fertil Steril 2006; 86(6): 1561–1572. from a statutory health insurance-based cohort in Germany. 5. As-Sanie S, Black R, Giudice LC, et al. Assessing research Eur J Obstet Gynecol Reprod Biol 2012; 160(1): 79–83. gaps and unmet needs in endometriosis. Am J Obstet 20. Kim H, Lee M, Hwang H, et al. The estimated prevalence Gynecol 2019; 221(2): 86–94. and incidence of endometriosis with the Korean National 6. Sarria-Santamera A, Orazumbekova B, Terzic M, et al. Health Insurance Service-National Sample Cohort (NHIS- Systematic review and meta-analysis of incidence and prev- NSC): a national population-based study. J Epidemiol alence of endometriosis. Healthcare 2020; 309(1): 29. 2021; 31(12): 593–600, https://pubmed.ncbi.nlm.nih.gov 7. Parazzini F, Roncella E, Cipriani S, et al. The frequency /32863371 of endometriosis in the general and selected populations: a 21. Ministerio de Sanidad Servicios Sociales e Igualdad. Guía systematic review. J Endometr Pelvic Pain Disord 2020; de atención a las mujeres con endometriosis en el Sistema 212(3–4): 176–189. Nacional de Salud (SNS), 2013, https://www.sanidad. 8. Christ JP, Yu O, Schulze-Rath R, et al. Incidence, preva- gob.es/organizacion/sns/planCalidadSNS/pdf/equidad/ lence, and trends in endometriosis diagnosis: a United States ENDOMETRIOSIS.pdf population-based study from 2006 to 2015. Am J Obstet 22. Blasco-Amaro JA, Sabalete-Moya T, Carlos-Gil A, et al. Gynecol 2021; 225(5): 500.e1–500.e9. Modelo de atención a las mujeres con endometriosis. 9. Ávalos Marfil A, Barranco Castillo E, Martos García R, Revisión sistemática de guías de práctica clínica, 2020, et al. Epidemiology of endometriosis in Spain and its https://portal.guiasalud.es/wp-content/uploads/2020/11/ autonomous communities: a large, nationwide study. Int J opbe_endometriosis_aetsa.pdf Environ Res Public Health 2021; 18(15): 7861. 23. Departament de Salut de la Generalitat de Catalunya. Model 10. Ely JW, Dawson JD, Lemke JH, et al. An introduction to d’atenció a l’endometriosi a Catalunya, 2018, https:// time-trend analysis. Infec Control Hosp Epidemiol 1997; canalsalut.gencat.cat/web/.content/_A-Z/E/endometriosi/ (4): 267–274. Model-datencio-a-lendometriosi.pdf 11. Bolíbar B, Fina Avilés F, Morros R, et al. Base de datos 24. Guidone HC. The womb wanders not: enhancing endome- SIDIAP: la historia clínica informatizada de atención pri- triosis education in a culture of menstrual misinformation. maria como fuente de información para la investigación In: Bobel C, Winkler I, Fahs B, et al. (eds) The Palgrave epidemiológica. Med Clín 2012; 138(14): 617–621, https:// handbook of critical menstruation studies. Singapore: www.elsevier.es/es-revista-medicina-clinica-2-articulo- Springer, 2020, pp. 269–86. base-datos-sidiap-historia-clinica-S0025775312001339 25. Ghiasi M, Kulkarni MT and Missmer SA. Is endometriosis 12. García-Gil M, Hermosilla E, Prieto-Alhambra D, et al. more common and more severe than it was 30 years ago? J Construction and validation of a scoring system for the Minim Invasive Gynecol 2020; 27(2): 452–461. selection of high-quality data in a Spanish population pri- 26. Direccio General de Planificacio en Salut. L’estat de salut, mary care database (SIDIAP). J Innov Health Inform 2011; els comportaments relacionats amb la salut i l’ús de serveis 19(3): 135–45. sanitaris a Catalunya 2020, 2022, https://salutweb.gencat. 13. Domínguez-Berjón MF. Borrell C, Cano-Serral G, et al. cat/web/.content/_departament/estadistiques-sanitaries/ Construcción de un índice de privación a partir de datos cen- enquestes/Enquesta-de-salut-de-Catalunya/Resultats-de- sales en grandes ciudades españolas (Proyecto MEDEA). lenquesta-de-salut-de-Catalunya/documents/2020/resum- Gaceta Sanitaria 2008; 22: 179–187. executiu-ESCA-2020.pdf 14. Charlson ME, Pompei P, Ales KL, et al. A new method of 27. Valls-Llobet C. Mujeres invisibles para la medicina. classifying prognostic comorbidity in longitudinal studies: Madrid: Capitán Swing, 2021. Medina-Perucha et al. 11 28. Young K, Fisher J and Kirkman M. Women’s experiences 34. van der Zanden M, Teunissen DA, van der Woord IW, et al. of endometriosis: a systematic review and synthesis of qual- Barriers and facilitators to the timely diagnosis of endome- itative research. J Fam Plann Reprod Health Care 2015; triosis in primary care in the Netherlands. Fam Pract 2019; 41(3): 225–234. 37: 131–136. 29. Ballard K, Lowton K and Wright J. What’s the delay? A 35. Lostao L, Ronda E, Pascual C, et al. Erosion of universal qualitative study of women’s experiences of reaching a health coverage and trend in the frequency of physician con- diagnosis of endometriosis. Fertil Steril 2006; 86(5): 1296– sultations in Spain. Int J Equity Health 2020; 19(1): 121. 1301. 36. Eisenberg VH, Decter DH, Chodick G, et al. Burden of 30. Weintraub A, Soriano D, Seidman D, et al. Think endome- endometriosis: infertility, comorbidities, and healthcare triosis: delay in diagnosis or delay in referral to adequate resource utilization. J Clin Med 2022; 11(4): 1133. treatment? JFIV Reprod Med Genet 2014; 2(3): 1000127. 37. Dalmau-Bueno A, García-Altés A, Vela E, et al. Frequency 31. Bullo S. Exploring disempowerment in women’s accounts of health-care service use and severity of illness in undocu- of endometriosis experiences. Discourse Commun 2018; mented migrants in Catalonia, Spain: a population-based, 12(6): 569–586. cross-sectional study. Lancet Planet Health 2021; 5(5): 32. Young K, Fisher J and Kirkman M. Partners instead of e286–e296. patients: women negotiating power and knowledge within 38. Pons-Vigués M, Puigpinós-Riera R, Rodríguez-Sanz M, et al. medical encounters for endometriosis. Fem Psychol 2019; Preventive control of breast and cervical cancer in immigrant 30: 22–41. and native women in Spain: the role of country of origin and 33. Young K, Fisher J and Kirkman M. “Do mad people get social class. Int J Health Serv 2011; 41(3): 483–499. endo or does endo make you mad?”: clinicians’ discursive 39. Hyde E, Greene ME and Darmstadt GL. Time poverty: constructions of medicine and women with endometriosis. obstacle to women’s human rights, health and sustainable Fem Psychol 2019; 29: 337–356. development. J Glob Health 2020; 10(2): 020313.