Occupational characteristics and risk factors associated with endometriosis among Korean female workers

Endometriosis is a common, benign, estrogen-dependent, chronic inflammatory condition characterized by endometrial tissue growth outside the uterus. The symptoms associated with endometriosis vary, including chronic pelvic pain, menstrual irregularities, dysmenorrhea, dyspareunia, dysuria, dyschezia, and infertility [ 1 ]. Consequently, endometriosis can lead to a marked deterioration in the lives of individuals by interfering with daily and social activities, sexual and reproductive health, and physical and emotional well-being [ 2 ]. Approximately 10% of reproductive-aged women have endometriosis worldwide. The prevalence of endometriosis varies by race and ethnicity, and Asian women are generally more likely to be affected than Caucasians. According to the most recent data, the estimated prevalence of endometriosis in South Korea is 3.5 per 1,000 women [ 3 ]. Despite the effect of endometriosis on health and quality of life, the etiology and pathogenesis of endometriosis are not fully understood. Race, ethnicity, body mass index (BMI), lifestyle behaviors (i.e., diet, exercise, alcohol consumption, cigarette smoking, and sleep habits), and menstrual and reproductive characteristics (i.e., early menarche, short menstrual cycles, long menstruation duration, and low parity) have been proposed to be possible risk factors for endometriosis [ 4 ]. Occupational and environmental risk factors of endometriosis have been investigated with some studies suggesting that night shift work and exposure to certain chemical agents are linked to endometriosis. Indeed, a large prospective cohort study reported that night-shift work increased the risk of endometriosis in an exposure duration-dependent manner [ 5 ]. As endometriosis is a highly estrogen-dependent disorder, increased estrogen levels caused by decreased melatonin production in circadian disrupted night shift workers may promote endometriosis growth [ 6 ]. However, most epidemiological and clinical studies have estimated the risk of endometriosis from work-related factors as a single independent variable [ 7 ]. Thus, our primary objective was to characterize the various factors associated with endometriosis and estimate their risks in the Korean working population based on the 2007–2015 National Health Insurance Service–Female Employees (NHIS-FEM) database.

Of the 185,144 participants in the NHIS-FEM in 2007, 151,386 participants were selected after excluding 29,382 participants without information about health examinations and 4,376 participants with missing or refusal to share data ( Fig 1 ). The baseline characteristics of the study participants, with and without endometriosis, are presented in Table 1 . Of the 151,386 participants, 4,457 (2.9%) were diagnosed with endometriosis. Endometriosis was most common in the age group of 21–40 years (3.3%), followed by the age group of 41–60 years (2.4%). Participants with endometriosis were found to have a higher income, were more likely to be underweight and anemic, and less likely to have a medical history of hypertension or diabetes. There were no significant differences in smoking or drinking behaviors between the participants with and without endometriosis. In terms of occupational characteristics, endometriosis was more common in office workers and longer-duration workers than in manual workers and shorter-duration workers. The multivariate cox regression results of endometriosis during follow-up period are represented in Table 2 . When categorized by socioeconomic status, workers aged 41–60 years had a significantly higher HR, (1.47 (95% CI 1.06–2.04)), than workers aged 15–20 years. Regarding the health status, underweight workers had a higher HR than those with normal BMI (HR = 1.16 (95% CI 1.05, 1.27)). Note: Statistically significant results are highlighted in bold. There was no significant association between the risk of endometriosis and the type of work. However, the cumulative prevalence rate of endometriosis from 2007 to 2015 continued to rise in office workers, manual workers, and in both types of workers combined, as shown in Fig 2 . Fig 3 illustrates the age-standardized prevalence ratio according to the ISIC. The occupational groups with financial and insurance activities (K), public administration and defence, compulsory social security (O), and manufacturing (C) had significantly higher prevalence ratios.

In conclusion, this study found a significant association between endometriosis risk and the occupational characteristics of Korean female workers, providing an overview of general characteristics based on the presence or absence of endometriosis. Furthermore, it offers valuable insights into the age-standardized prevalence rate of endometriosis based on the ISIC through data analysis of the nationwide representative NHIS-FEM database. Our findings will serve as a crucial foundation for future studies, underscoring the need for further research to strengthen the evidence supporting these discoveries.

The Korea National Health Insurance Service (NHIS) maintains a database for the entire population of the Republic of Korea with several sub-cohort databases. The NHIS-FEM (2007–2015) was established to understand and evaluate the health status and women-specific disease risk of Korean working women. The NHIS-FEM was started with data on 185,144 working women extracted from approximately 3 million economically active women aged 15–64 years in 2007 [ 8 ]. The NHIS-FEM maintains patients’ insurance qualification information and claims for disease diagnosis codes of the Korean Standard Classification of Diseases 7th (KCD-7), correlated with the International Statistical Classification of Diseases and Related Health Problems 10th (ICD-10) by the World Health Organization from 2007 to 2015 [ 9 ]. The database had five sections, including general specifications (year, age, gender, region, grade of disability, contribution amount, etc.), health examinations (year, working type, disease history, physical activity, current medications, smoking, drinking, height, weight, blood pressure, laboratory tests, etc.), medical institution (year, location, number of doctors, number of nurses, number of pharmacists, number of beds, etc.), death information (death year and month), and medical examination of cancer (medical examination experience, medical history, year, family history, etc.). Data were anonymized and collected with written informed consent from all the NHIS-FEM participants by the NHIS of Korea. In NHIS-FEM data base, none health examinations during follow-up periods and any missing or refusal data was excluded. The schematic diagram of study participants are shown in Fig 1 . This study was conducted in accordance with the ethical standards of the Declaration of Helsinki (1964) and its subsequent amendments. The data from the NHIS of Korea were collected with written informed consent from all participants. Furthermore, all the data were anonymized to ensure that no individual participants could be identified. This study was approved by the relevant Institutional Review Board (IRB no. GCIRB2020-070). Medical facility visit history from the NHIS-FEM was used to define endometriosis. The endometriosis was defined as patients who had visited a hospital as an inpatient and whose records included KCD-7 diagnosis code ‘N80 Endometriosis’ using diseases claim information based on medical history. This study included participants with the following codes: ‘N80.0 Endometriosis of uterus’; ‘N80.1 Endometriosis of ovary’; ‘N80.2 Endometriosis of fallopian tube’; ‘N80.3 Endometriosis of pelvic peritoneum’; ‘N80.4 Endometriosis of rectovaginal septum and vagina’; ‘N80.5 Endometriosis of intestine’; ‘N80.6 Endometriosis in cutaneous scar’; ‘N80.8 Other endometriosis’; ‘N80.9 Endometriosis, unspecified’. We selected three occupational characteristics from the working status and workplace information in the NHIS-FEM. Work type was categorized into two groups: office and manual. In Korea, national health examinations for the working population differ according to the type of work. Office workers are examined biannually, while, manual workers, annually. This can be used to distinguish office workers from manual workers. Work duration was estimated using monthly insurance payment information from the NHIS. We divided working duration into three categories: 12 months. The size of the enterprise based on the number of workers and the International Standard Industrial Classification (ISIC) was collected as the basic information of enterprises in the NHIS-FEM. Age and household income level were used to demonstrate socioeconomic status based on insurance qualification information. Health status and lifestyle behaviors were included in health examination information. We focused on hypertension, diabetes, anemia, and BMI as health status indicators associated with endometriosis, based on previous studies [ 10 , 11 ]. Lifestyle behaviors included smoking and drinking habits. Previous studies have indicated a close association between endometriosis and lifestyle behaviors [ 12 , 13 ]. Data on smoking and drinking statuses were collected from participants enrolling in national health examination. Chi-squared test was used to compare the characteristics of participants with and without endometriosis. Hazard ratios (HR) and 95% confidence intervals (CI) for endometriosis were estimated using multivariate Cox regression analyses. For the proportional hazard assumption, a regression model of scaled Schoenfeld residuals against time was assessed for zero slope, and a p -value was calculated to be > 0.1, indicating that the proportional hazards assumptions for endometriosis were satisfactory. We estimated the cumulative prevalence of endometriosis according to the type of work during the follow-up year. The age-standardized prevalence ratio (SPR) and 95% CI of endometriosis according to the ISIC were calculated with all current study participants as the reference group using the indirect standardization method. SPR is the ratio of the observed to expected number of cases. In this study, to estimate the SPR, we stratified age into 5-year groups and calculated the weighted average of age-specific prevalence density rates. Age-specific endometriosis prevalence rates and the number of person-years were estimated for each age group of the entire study population. The expected number of endometriosis cases was calculated after adjusting for age. In the analysis, if SPR and lower limit of 95% CI were > 1, the risk of endometriosis in each ISIC group was considered to be significantly increased. While, for SPR and upper limit of 95% CI < 1, the risk of endometriosis in each ISIC group was considered to be significantly decreased. All analyses were performed using SAS version 9.4 (SAS Institute, Cary, NC, USA).

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