Published papers

Background: Heated tobacco products (HTPs) have gained global popularity, but their health risks remain unclear. Therefore, the current study aimed to identify plasma metabolites associated with smoking and HTP use in a large Japanese population to improve health risk assessment. Methods: Metabolomics data from 9,922 baseline participants of the Tsuruoka Metabolomics Cohort Study (TMCS) were analyzed to determine the association between smoking habits and plasma metabolites. Moreover, alterations in smoking-related metabolites among HTP users were examined based on data obtained from 3,334 participants involved from April 2018 to June 2019 in a follow-up survey. Results: Our study revealed that cigarette smokers had metabolomics profiles distinct from never smokers, with 22 polar metabolites identified as candidate biomarkers for smoking. These biomarker profiles of HTP users were closer to those of cigarette smokers than those of never smokers. The concentration of glutamate was higher in cigarette smokers, and biomarkers involved in glutamate metabolism were also associated with cigarette smoking and HTP use. Network pathway analysis showed that smoking was associated with the glutamate pathway, which could lead to endothelial dysfunction and atherosclerosis of the vessels. Conclusion: Our study showed that the glutamate pathway is affected by habitual smoking. These changes in the glutamate pathway may partly explain the mechanism by which cigarette smoking causes cardiovascular disease. HTP use was also associated with glutamate metabolism, indicating that HTP use may contribute to the development of cardiovascular disease through mechanisms similar to those in cigarette use.

OBJECTIVE Body weight variability is linked to cardiometabolic outcomes, but its renal impact in type 2 diabetes remains uncertain. We tested whether the magnitude of seasonal BMI fluctuation is independently associated with kidney function decline. RESEARCH DESIGN AND METHODS We analyzed a nationwide, multicenter Japanese cohort (2014-2020). Monthly BMI was modeled using seasonal-trend locally estimated scatterplot smoothing to quantify each participant’s within-year peak-to-trough difference. The primary outcome was ≥40% decline in estimated glomerular filtration rate (eGFR). Secondary outcomes were ≥30% eGFR decline, creatinine doubling, incident chronic kidney disease (CKD) stage ≥3, and kidney failure. Associations were estimated using multivariable Cox models with clinic as a random effect. RESULTS Among 6,700 outpatients (median follow-up: 6.8 years), 779 reached the primary end point. Each 1-SD increase in BMI fluctuation was associated with higher risk of ≥40% eGFR decline (hazard ratio [HR] 1.23, 95% CI 1.16-1.31). The highest versus lowest tertile showed a 1.7-fold increased risk (HR 1.72, 95% CI 1.42-2.09). Patterns were consistent for ≥30% eGFR decline (HR 1.18, 95% CI 1.13-1.23), creatinine doubling (HR 1.30, 95% CI 1.17-1.45), and incident CKD stage ≥3 (HR 1.11, 95% CI 1.07-1.16). Longitudinal analyses showed steeper eGFR decline in the highest-fluctuation group. Results were robust across sensitivity analyses, including models for time-varying medication exposure. CONCLUSIONS In type 2 diabetes, larger intra-annual BMI fluctuations were independently and dose-dependently associated with kidney function decline. Seasonal BMI amplitude may identify higher-risk individuals; whether reducing seasonal BMI fluctuations improves kidney outcomes warrants prospective evaluation.

BACKGROUND The role of the apoptosis inhibitor of macrophages (AIM) in human lipid metabolism remains unclear. OBJECTIVE This study aimed to investigate the cross-sectional associations between serum AIM and plasma metabolites and to determine if baseline AIM concentrations predict incident dyslipidemia. METHODS This study used a community-based cohort of 3139 participants for cross-sectional metabolomic analysis. Among them, 1292 participants without dyslipidemia at baseline were followed prospectively for up to 8.5 years. Cox proportional hazards models were used to estimate hazard ratios for incident high low-density lipoprotein cholesterol (LDL-C) and metabolic dyslipidemia (high triglycerides and/or low high-density lipoprotein cholesterol [HDL-C]) across AIM tertiles. RESULTS Cross-sectionally, higher AIM concentrations were associated with elevated acylcarnitines and tricarboxylic acid cycle intermediates. Longitudinally, higher baseline AIM was associated with an increased risk of developing metabolic dyslipidemia in women (highest vs lowest tertile hazard ratio, 1.84) and showed a similar but smaller nonsignificant trend in men. The risk for high LDL-C was significantly increased in women but not in men. These associations remained robust after multivariable adjustment. CONCLUSION Elevated baseline AIM concentrations were prospectively associated with the development of metabolic dyslipidemia in women, with a similar but nonsignificant trend in men, and with high LDL-C in women. The related metabolomic profile suggests enhanced lipolysis and altered lipid metabolism. Therefore, AIM may serve as a biomarker for future dyslipidemia, particularly for triglyceride and HDL-C dysregulation.

Introduction: Little is known about the association between hypospadias and small fetuses, as well as the pathological implications of fetal growth restriction (FGR). Thus, we aimed to investigate the association between hypospadias and small fetuses using a database of fetal ultrasound and obstetric events. Methods: A cohort of male singleton infants delivered after 22 weeks of gestation at Keio University Hospital between 2013 and 2019 was retrospectively reviewed. FGR was defined according to the Delphi criteria. Logistic regression analysis was performed to identify the significant predictors of hypospadias. Placental pathology was reviewed in cases with hypospadias. Results: Of the 2,040 male infants included in the present study, 23 had hypospadias. The prevalences of a single umbilical artery (SUA), small for gestational age, maternal hypertensive disorders of pregnancy, and a small placenta, were significantly higher in infants with hypospadias. Multiple logistic regression analysis revealed that FGR (odds ratio [OR] = 9.39; 95% confidence interval [CI], 2.50–35.3) and the presence of a SUA (OR = 33.4; 95% CI, 8.00–139.5) were independently and significantly associated with hypospadias. When FGR was stratified by the time of onset, its association with hypospadias was significant regardless of the time of onset. Moreover, placental histological findings suggested that fetal vascular malperfusion might play a role in hypospadias. Discussion: FGR and SUAs are independent prenatal predictors of the development of hypospadias, and fetal vascular malperfusion of the placenta may be involved in the etiology of hypospadias.

Various vaginoplasty procedures have been developed for patients with Mayer–Rokitansky– Küster–Hauser (MRKH) syndrome. Here, we describe a novel laparoscopic vaginoplasty procedure, known as the Kisu modification, using a pull-down technique of the peritoneal flaps with additional structural support to the neovaginal apex using the incised uterine strand in patients with MRKH syndrome. Ten patients with MRKH syndrome (mean age at surgery: 23.9 ± 6.5 years, mean postoperative follow-up period: 17.3 ± 3.7 months) underwent construction of a neovagina via laparoscopic vaginoplasty. All surgeries were performed successfully without complications. The mean neovaginal length at discharge was 10.3 ± 0.5 cm. Anatomical success was achieved in all patients, as two fingers were easily introduced, the neovagina was epithelialized, and the mean neovaginal length was 10.1 ± 1.0 cm 1 year postoperatively. No obliteration, granulation tissue formation at the neovaginal apex, or neovaginal prolapse was recorded. Five of the 10 patients attempted sexual intercourse and all five patients were satisfied with the sexual activity, indicating functional success. Although the number of cases in this case series is few, our favorable experience suggests that the Kisu modification of laparoscopic vaginoplasty procedure is an effective, feasible, and safe approach for neovaginal creation in patients with MRKH syndrome.

Background: Emerging evidence has shown that charged metabolites, such as amino acids, may play an important role in the pathogenesis of various metabolic disorders, many of which women in the postmenopausal period are at high risk of developing. This study examined the metabolic profile of middle-aged Japanese women to investigate alterations in charged metabolites induced by menopausal transition. Methods: The participants were 1193 female residents aged 40–60 at the baseline survey of the Tsuruoka Metabolomics Cohort Study. We investigated the cross-sectional association of menopausal status with 94 metabolomic biomarkers assayed in fasting plasma samples via capillary electrophoresis time-of-flight mass spectrometry using linear regression analysis. Results: Among the participants, 529 were premenopausal, 132 were in menopausal transition (MT), and 532 were postmenopausal. Significant differences were found in age, blood pressure, glucose and lipid levels, and smoking and drinking habits among the three groups. The concentrations of 5 metabolites in the MT group and 15 metabolites in the postmenopausal group were significantly higher than those in the premenopausal group after adjusting for confounding factors. When classified into pathways, these metabolites were related to the tricarboxylic cycle, urea cycle, and homocysteine metabolism, some of which are linked to arteriosclerosis. Conclusion: Multiple charged metabolites were associated with women's menopausal status, showing a gradual increase as women shifted from pre-, to peri-, to postmenopause. These findings might reflect the early changes behind the increased risk of dyslipidemia, diabetes, cardiovascular disease, and osteoporosis in later life.

Radical hysterectomy is often performed to treat early-stage cervical cancer in women of reproductive age, and sexual dysfunction due to postoperative vaginal shortening is a major concern [1,2]. Vaginoplasty using various techniques is commonly performed in patients with congenital vaginal agenesis [3]. However, there are few reports of vaginoplasty being performed for vaginal shortening after radical hysterectomy in a patient with cervical cancer [4,5]. We demonstrate a novel vaginoplasty technique in which peritoneal flaps are used during laparoscopic radical hysterectomy to prevent postoperative vaginal shortening and consequent sexual dysfunction in patients with early-stage cervical cancer. A 37-year-old woman with early-stage cervical cancer who wished to perform sexual activity postoperatively underwent laparoscopic radical hysterectomy and vaginoplasty. After radical hysterectomy, the residual vaginal length was 4 cm. The dissected peritoneum of pouch of Douglas (posterior peritoneal flap) was sutured to the posterior vaginal stump. The supravesical peritoneum was dissected from the ventral to the dorsal side to create an anterior peritoneal flap, which was inverted, pulled down, and sutured to the anterior vaginal stump. The anterior peritoneal flap and suprarectal peritoneum were sutured to create a 10-cm neovaginal vault. Subsequently, a methacrylic resin mold was inserted into the neovagina to prevent postoperative neovaginal stenosis. The patient had sexual intercourse 3 months postoperatively. She was satisfied with the sexual activity and experienced no vaginal shortening or stenosis. Our novel vaginoplasty technique is feasible and effective for preventing sexual dysfunction by lengthening the vagina during laparoscopic radical hysterectomy for early-stage cervical cancer. Trial Registration: Japan Registry of Clinical Trials Identifier: JRCT1030210227.

Aim: This study investigated the relationship between birth physique and cardiovascular risk factors in Japanese urban residents aged 40 years and more. Methods: A self-administered questionnaire on birth physique was performed among 624 individuals (165 men and 459 women) who participated in the KOBE study. We examined whether self-reported birth physique and available recorded birth weights matched for 72 participants. Then the association between birth physique and risk factors for all participants was examined by gender. Body size at birth in the questionnaire (large, medium, small) was set as an exposure and laboratory values from the baseline survey (2010-2011) were used as outcomes. Results: Mean (standard deviation) recorded birth weight of 72 participants was 3665 (318), 3051 (300), and 2653 (199) g, in the large, medium, and small group, respectively. In the analysis for all participants, odds ratio for having both hypertension and impaired glucose tolerance were significantly higher in the small versus large birth weight group, which was 7.42 (95% CI 1.75–31.50) for men and 4.44 (95% CI 1.14–17.30) for women after adjusting for age, body mass index, smoking/alcohol/exercise habits, and menstrual status in women. Similar results were observed in participants with recorded birth weight. Conclusions: The present study indicates that individuals with small physique at birth might be at higher risk for hypertension and impaired glucose tolerance in middle age compared to those with large birth weight.

Objective The pelvic lymphatic drainage system comprises the upper and lower paracervical pathways (LPPs). Lymph node dissection of the LPP, including the cardinal ligament, internal iliac, internal common iliac, and presacral lymph nodes, requires higher surgical skills because of the anatomical limitations of the pelvic cavity and the dissection of vessels while preserving the nerves in the pelvic floor. In this video, we demonstrate rectal mobilization for laparoscopic complete pelvic lymph node dissection of the LPP in patients with uterine cancer. Methods Rectal mobilization was performed before complete pelvic lymph node dissection of the LPP. The pararectal space was opened widely and the connective tissue between the presacral fascia and prehypogastric nerve fascia was dissected bilaterally, allowing the rectum to be pulled. Results This procedure created a wide-open space in the pelvic floor, allowing clear visualization of the nerves and lymph nodes of the LPP. Laparoscopic complete lymph node dissection of the LPP was performed in the open space while preserving the hypogastric and pelvic splanchnic nerves and isolating the extensive network of blood vessels in the pelvic cavity. Conclusion Rectal mobilization enabled the safe execution of laparoscopic complete pelvic lymph node dissection of the LPP in patients with uterine cancer.

Studies examining long-term longitudinal metabolomic data and their reliability in large-scale populations are limited. Therefore, we aimed to evaluate the reliability of repeated measurements of plasma metabolites in a prospective cohort setting and to explore intra-individual concentration changes at three time points over a 6-year period. The study participants included 2999 individuals (1317 men and 1682 women) from the Tsuruoka Metabolomics Cohort Study, who participated in all three surveys—at baseline, 3 years, and 6 years. In each survey, 94 plasma metabolites were quantified for each individual and quality control (QC) sample. The coefficients of variation of QC, intraclass correlation coefficients, and change rates of QC were calculated for each metabolite, and their reliability was classified into three categories: excellent, fair to good, and poor. Seventy-six percent (71/94) of metabolites were classified as fair to good or better. Of the 39 metabolites grouped as excellent, 29 (74%) in men and 26 (67%) in women showed significant intra-individual changes over 6 years. Overall, our study demonstrated a high degree of reliability for repeated metabolome measurements. Many highly reliable metabolites showed significant changes over the 6-year period, suggesting that repeated longitudinal metabolome measurements are useful for epidemiological studies.

Currently, large-scale cohort studies for metabolome analysis have been launched globally. However, only a few studies have evaluated the reliability of urinary metabolome analysis. This study aimed to establish the reliability of urinary metabolomic profiling in cohort studies. In the Tsuruoka Metabolomics Cohort Study, 123 charged metabolites were identified and routinely quantified using capillary electrophoresis-mass spectrometry (CE-MS). We evaluated approximately 750 quality control (QC) samples and 6,720 participants’ spot urine samples. We calculated inter- and intra-batch coefficients of variation in the QC and participant samples and technical intraclass correlation coefficients (ICC). A correlation of metabolite concentrations between spot and 24-h urine samples obtained from 32 sub-cohort participants was also evaluated. The coefficient of variation (CV) was less than 20% for 87 metabolites (70.7%) and 20–30% for 19 metabolites (15.4%) in the QC samples. There was less than 20% inter-batch CV for 106 metabolites (86.2%). Most urinary metabolites would have reliability for measurement. The 96 metabolites (78.0%) was above 0.75 for the estimated ICC, and those might be useful for epidemiological analysis. Among individuals, the Pearson correlation coefficient of 24-h and spot urine was more than 70% for 59 of the 99 metabolites. These results show that the profiling of charged metabolites using CE-MS in morning spot human urine is suitable for epidemiological metabolomics studies.

Objective To consider effective measures against severe acute respiratory syndrome coronavirus 2 (SARSCoV- 2) infection in medical institutions, this study estimated the SARS-CoV-2 infection rate among healthcare workers (HCWs) in Tokyo, Japan, and determined the specific findings for mild coronavirus disease 2019 (COVID-19) cases. Methods This study analyzed the results of serologic tests to detect immunoglobulin G antibodies against SARS-CoV-2 and evaluated the demographic and clinical characteristics of the faculty and HCWs at a Tokyo medical institution in August 2020. The demographic and clinical characteristics of participants with antibody-positive results were compared to those of participants with antibody-negative results. Materials This study recruited 2,341 faculty and HCWs at a Tokyo medical institution, 21 of whom had a COVID-19 history. Results Of the 2,320 participants without a COVID-19 history, 20 (0.862%) had positive serologic test results. A fever and dysgeusia or dysosmia occurred with greater frequency among the participants with positive test results than in those with negative results [odds ratio (OR), 5.475; 95% confidence interval (CI), 1.960-15.293 and OR, 24.158; 95% CI, 2.693-216.720, respectively]. No significant difference was observed in the positivity rate between HCWs providing medical care for COVID-19 patients using adequate protection and other HCWs (OR, 2.514; 95% CI, 0.959-6.588). Conclusion To reduce the risk of COVID-19 spread in medical institutions, faculty and HCWs should follow standard and necessary transmission-based precautions, and those with a fever and dysgeusia or dysosmia should excuse themselves from work as soon as possible.

Background: Menopausal disorders include obscure symptomatology that greatly reduce work productivity among female workers. Quantifying the impact of menopause-related symptoms on work productivity is very difficult because no such guidelines exist to date. We aimed to develop a scale of overall health status for working women in the perimenopausal period. Methods: In September, 2021, we conducted an Internet web survey which included 3,645 female workers aged 45–56 years in perimenopausal period. We asked the participants to answer 76 items relevant to menopausal symptomatology, that were created for this study and performed exploratory and confirmatory factor analyses for the scale development. Cronbach’s alpha, receiver operating characteristic analysis, and logistic regression analysis were used to verify the developed scale. Results: Approximately 85% participants did not have menstruation or disrupted cycles. Explanatory factor analysis using the maximum likelihood method and Promax rotation identified 21 items with a four-factor structure: psychological symptoms (8 items, α = 0.96); physiological symptoms (6 items, alpha = 0.87); sleep difficulty (4 items, alpha = 0.92); human relationship (3 items, alpha = 0.92). Confirmatory factor analyses found excellent model fit for the four-factor model (RMSR = 0.079; TLI = 0.929; CFI = 0.938). Criterion and concurrent validity were confirmed with high correlation coefficients between each of the four factors, previously validated menopausal symptom questionnaire, and Copenhagen Burnout Inventory scales, respectively (all ps < 0.0001). The developed scale was able to predict absenteeism with 78% sensitivity, 58% specificity, and an AUC of 0.727 (95%CI: 0.696–0.757). Higher scores of each factor as well as total score of the scale were more likely to be associated with work absence experience due to menopause-related symptoms even after adjusting for Copenhagen Burnout Inventory subscales (all ps < 0.0001). Conclusion: We found that the developed scale has high validity and reliability and could be a significant indicator of absenteeism for working women in perimenopausal period.

Ovarian cancer has a poor prognosis and is difficult to detect in early stages. Therefore, developing new diagnostic markers for early-stage ovarian cancer is critical.Here, we developeda diagnosticmarker for early-stage ovarian cancer on the basis of fatty acid metabolism characteristics of cancer cells. The expression of various fatty acid metabolizing enzymes such as stearoyl-CoA desaturase 1 (SCD1) was altered in early-stage ovarian cancer tissue compared with that in normal ovarian tissue. Changes in the expression of fatty acid metabolizing enzymes, particularly SCD1, in cancer tissues were found to alter concentrations of multiple free fatty acids (FFA) in serum. We were the first to show that fatty acid metabolic characteristics in tissues are related to the FFA composition of serum. Surprisingly, patients with stage I/II ovarian cancer also showed significant changes in serum levels of eight FFAs, which can be early diagnostic markers. Finally, using statistical analysis, an optimal early diagnosticmodel combining oleic and arachidic acid levels, fatty acids associated with SCD1, was established and confirmed to have higher diagnostic power than CA125, regardless of histology. Thus, our newly developed diagnostic model using serum FFAs may be a powerful tool for the noninvasive early detection of ovarian cancer. Significance: Measurement of serum FFA levels by changes in the expression of fatty acid metabolizing enzymes in tumor tissue would allow early detection of ovarian cancer. In particular, the SCD1-associated FFAs, oleic and arachidic acid, would be powerful new screening tools for early-stage ovarian cancer.

Background: Progress in reducing the global low birthweight (LBW) has been insufficient. Although the focus has been on preventing preterm birth, evidence regarding LBW in term births is limited. Despite its low preterm birth prevalence, Japan has a higher LBW proportion than other developed countries. This study aimed to examine the prevalence of LBW in term singleton births and its associated factors using a national database. Methods: We retrospectively analyzed the data of neonates registered in the Japan Society of Obstetrics and Gynecology Successive Pregnancy Birth Registry System who were born 2013–2017. Exclusion criteria included stillbirths, delivery after 42 gestational weeks, and missing data. Logistic regression analyses were performed to investigate the maternal and perinatal factors associated with LBW in term singletons using the data of 715,414 singleton neonates. Results: The overall prevalence of LBW was 18.3%, and 35.7% of LBWs originated from singleton term pregnancies. Multiple logistic regression analyses indicated that both modifiable and non-modifiable factors were independently associated with LBW in term neonates. The modifiable maternal factors included pre-pregnancy underweight, inadequate gestational weight gain, and smoking during pregnancy, while the non-modifiable factors included younger maternal age, nulliparity, hypertensive disorders of pregnancy, cesarean section delivery, female offspring, and congenital anomalies. Conclusion: Using the Japanese pregnancy birth registry data, more than one-third of LBWs were found to originate from singleton term pregnancies. Both modifiable and non-modifiable factors were independently associated with LBW in term neonates. Prevention strategies on modifiable risk factor control will be effective in reducing LBW worldwide.

Purpose: This study aimed to examine the association between sleep duration and quality and sarcopenia, assessed by factors such as low muscle mass (LMM), low muscle strength (LMS), and low physical performance (LPP) among older community-dwellers in Japan. Methods: In this cross-sectional study, a total of 2,069 (men, 902; women, 1,167) participants aged 65 to 80 years were included. Sarcopenia and each low physical function were defined using the definitions of the Asian Working Groups of Sarcopenia 2019. Sleep duration was stratified into three categories: short sleep (<6 h), normal sleep (6-8 h), and long sleep (>8 h). Sleep quality was classified into two groups based on 8-item Athens Insomnia Scale score: insomnia (≥6), and non-insomnia (<6). We analyzed the association between sleep parameters and sarcopenia, including low physical functions, by logistic regression analysis. Results: Compared to normal sleepers, long sleepers had a positive association with sarcopenia (odds ratio [OR] 2.11, 95% confidence interval [CI] 1.25-3.58). In particular, long sleep was strongly associated with LMS (OR 1.77, 95%CI 1.07-2.94) and LPP (OR 1.90, 95%CI 1.25-2.88). On the other hand, poor sleep quality was not associated with sarcopenia in long sleepers, but in normal sleepers. Conclusions: Long sleep was associated with sarcopenia, including LMS and LPP. However, in long sleepers, insomnia was not associated with sarcopenia or any of its components.

Objective: We aim to investigate the quantity and quality of scientific evidence dealing with comprehensive health issues of working women in occupational health. Methods: This scoping review of original articles that investigated comprehensive health issues of working women aged 19–64 years in Japan was published in PubMed (1967–2022) and Igaku Chuo Zasshi (or Ichu-shi, 1982–2022). Using identical broad search terms, we first identified 17 122 English and 6154 Japanese articles. We excluded those with clinically relevant topics, or ethnicity other than Japanese and included 853 English and 855 Japanese articles for review and classified them into nine research areas considered to be critical factors for women in the workforce and five study design groups to investigate the quality of the evidence accumulated. Results: Among 853 English-language articles in PubMed, “Mental health” was the most frequent area studied, followed by “Work-related disease” and “Lifestyle-related disease.” Among 855 Japanese-language articles from Ichu-shi, “Mental health” was the most frequently studied area followed by “Work and balance,” and “Work-related disease.” “Infertility, pregnancy, and childbirth” and “Menstruation, menopause, and genital disease” were well studied in Ichu-shi but scarcely published in PubMed. “Harassment and discrimination” were sparsely reported in both databases. As for research designs, many articles in both PubMed and Ichu-shi employed descriptive or cross-sectional study designs. However, a few studies employed cohort/longitudinal or interventional studies. Conclusion: The results underscored the need for higher-quality study designs with more scientific evidence on working women's health in the field of occupational health.

This study explored the factors associated with healthcare avoidance behavior for menstrual disorders and menopausal symptoms among women in Japan. Using data from a nationally representative cross-sectional online survey conducted in September 2022, responses from 4,950 women aged 25–59 were analyzed. This study applied binomial logistic regression models specifically to participants who reported having ever felt the need to seek healthcare assistance due to health issues related to menstruation and menopause. We computed adjusted odds ratios for key sociodemographic traits, work environment factors, health literacy, menstrual and menopausal symptoms, and attitudes and understanding regarding women's health, associated with healthcare avoidance behavior in the past 12 months. As a sensitivity analysis, a regression was performed limited to those who are working. The results showed that 50.6% of respondents recognized the need for healthcare support for menstrual or menopausal health issues, but 22.8% exhibited healthcare avoidance in the past year. Younger and high-income individuals showed higher avoidance rates. Those with diagnosed gynecological conditions and those perceiving menstrual pain as something to endure also displayed increased avoidance tendencies. Women experiencing significant health effects beyond work and those lacking understanding of the purpose of health check-ups were more prone to healthcare avoidance. Our results underscore the importance of implementing strategically tailored health education initiatives, and re-examining societal attitudes concerning women's health, in order to cultivate enhanced healthcare-seeking behaviors among women.

Background: Although self-reported questionnaires are widely employed in epidemiologic studies, their validity has not been sufficiently assessed. The aim of this study was to evaluate the validity of a self-reported questionnaire on medication use by comparison with health insurance claims and to identify individual determinants of discordance in the Tsuruoka Metabolomics Cohort Study. Methods: Participants were 2,472 community-dwellers aged 37 to 78 years from the Tsuruoka Metabolomics Cohort Study. Information on lifestyle and medications was collected through a questionnaire. Sensitivity and specificity were determined using health insurance claims from November 2014 to March 2016, which were used as a standard. Potential determinants of discordance were assessed using multivariable logistic regression. Results: The self-reported questionnaire on medication use showed high validity. Sensitivity and specificity were 0.95 (95% CI, 0.93–0.96) and 0.97 (95% CI, 0.96–0.98) for antihypertensive medications, 0.94 (95% CI, 0.91–0.97) and 0.98 (95% CI, 0.98–0.99) for diabetes medications, and 0.84 (95% CI, 0.82–0.87) and 0.98 (95% CI, 0.97–0.99) for dyslipidemia medications, respectively. Males without high education and those who currently smoke cigarettes were found to be associated with discordant reporting which affected sensitivity, especially those with medication use for dyslipidemia. Conclusions: In this population-based cohort study, we found that the self-reported questionnaire on medication use was a valid measure to capture regular medication users. Sensitivity for dyslipidemia medications was lower than those for the other medications. Type of medication, sex, education years, and smoking status influenced discordance, which affected sensitivity in self-reporting.