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This study aimed to assess the diagnosis of diabetes after detecting high blood glucose levels through screening among insured individuals in Gunma, Japan. Data for men and women 35 to 74 years of age were provided by Japan Health Insurance Association, and 4133 individuals with high blood glucose levels while not currently being treated for diabetes were included in the study. About 13% received a diagnosis of diabetes at a subsequent physician visit, and individuals who were under treatment for hypertension were less likely to receive the added diagnosis of diabetes compared with those not being treated for hypertension (odds ratio = 0.42 from a logistic regression model). Fasting blood glucose levels were significantly improved in the next year only among individuals with a confirmed diagnosis of diabetes.

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BACKGROUND: In aged society, health policies aimed at extending healthy life expectancy are critical. Maintaining physical activity is essential to prevent the deterioration of body functions. Therefore, it is important to understand the physical activity levels of the target age group and to know the content and intensity of the required physical activity quantitatively. Especially we focused the role of non-exercise activity thermogenesis and sedentary time, which are emphasized more than the introduction of exercise in cases of obesity or diabetes. METHODS: A total of 193 patients from 25 institutions were included. Participants underwent a locomotive syndrome risk test (stand-up test, 2-step test, and Geriatric Locomotive Function Scale-25 questionnaire) and were classified into three stages. Physical activity was quantitatively monitored for one week with 3-axial accelerometer. Physical activity was classified into three categories; (1) Sedentary behavior (0 ∼ ≤ 1.5 metabolic equivalents (METs)), (2) Light physical activity (LPA:1.6 ∼ 2.9 METs), and (3) Moderate to vigorous physical activity (MVPA: ≥3 METs). We investigated the relationship between physical activity, including the number of steps, and the stages after gender- and age- adjustment. We also investigated the relationship between social isolation using Lubben's Social Network Scale (LSNS), as social isolation would lead to fewer opportunities to go out and less outdoor walking. RESULTS: Comparison among the three stages showed significant difference for age (p = 0.007) and Body Mass Index (p < 0.001). After gender-and age-adjustment, there was a significant relation with a decrease in the number of steps (p = 0.002) and with MVPA. However, no relation was observed in sedentary time and LPA. LSNS did not show any statistically significant difference. Moderate to high-intensity physical activity and the number of steps is required for musculoskeletal disorders. The walking, not sedentary time, was associated to the locomotive stages, and this finding indicated the importance of lower extremity exercise. CONCLUSIONS: Adjusting for age and gender, the number of steps and moderate to vigorous activity levels were necessary to prevent worsening, and there was no effect of sedentary behavior. Merely reducing sedentary time may be inadequate for locomotive disorders. It is necessary to engage in work or exercise that moves lower extremities more actively.

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We investigated the relationship between shift work and excessive daytime sleepiness (EDS) among participants in the Japan Nurses' Health Study (JNHS). Responses of 9,728 female nurses to the 6th follow-up questionnaire were cross-sectionally analyzed. EDS was defined as an Epworth Sleepiness Scale score ≥11. EDS-associated factors were evaluated using Poisson regression analysis after adjustment for multiple confounders. Of the participants (mean age, 52.2 ± 8.0 yr), 28.7% were engaged in shift work, and the overall prevalence of EDS was 24.6%. EDS-associated factors were investigated separately in women aged <40 yr (n=250), 40-59 yr (n=7,467), and ≥60 yr (n=2,011). Current engagement in shift work (prevalence ratio: 1.92 [95% confidence interval: 1.20-3.06], compared with no experience of shift work) and obesity (2.08 [1.11-3.88] for BMI ≥30 and 1.39 [1.02-1.90] for BMI of 25.0-30.0, compared with BMI of 18.5-25.0) showed an independent association with EDS in women aged ≥60 yr. The effect of shift work on EDS in female nurses differed by age, as shift work and obesity contributed to EDS only in older participants. Shift work should be assigned after full consideration of age, sleep, and health status to minimize medical errors.

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BACKGROUND: Today we experience "Super-aged society", and a drastic increase in the number of older people needing assistance is an urgent matter for everyone from medical and socio-economical standpoints. Locomotive organ dysfunction due to musculoskeletal disorders is one of the main problems in these patients. Although the concepts of frailty and sarcopenia have been proposed for functional decline, pain remains the main and non-negligible complaint in these of such disorders. This prospective cohort study aimed to observe the changes of reduced mobility in patients with locomotive disorders and to determine the risk factors for functional deterioration of those patients using statistical modeling. METHODS: A cohort of older adults with locomotive disorders who were followed up every 6 months for up to 18 months was organized. Pain, physical findings related to the lower extremities, locomotive function in performing daily tasks, and Geriatric Locomotive Function Scale-25 (GLFS-25) score were collected to predict the progress of deterioration. Group-based trajectory analysis was used to identify subgroups of changes of GLFS-25 scores, and multinomial logistic regression analysis was performed to investigate potential predictors of the GLFS-25 trajectories. RESULTS: Overall, 314 participants aged between 65 and 93 years were included. The participants were treated with various combinations of orthopedic conservative treatments on an outpatient basis. The in-group trajectory model analysis revealed a clear differentiation between the four groups. The mild and severe groups generally maintained their GLFD-25 scores, while the moderate group included a fluctuating group and a no change group.　This study showed that comorbidity of osteoporosis was related to GLFS-25 score over 18 months. Age was a weak factor to be moderate or severe group, but gender was not. In addition, the number of pain locations, number of weak muscles, one-leg standing time, grip strength and BMI significantly contributed to the change in GLFS-25 score. CONCLUSIONS: This study proposes an effective statistical model to monitor locomotive functions and related findings. Pain and comorbid osteoporosis are significant factors that related to functional deterioration of activities. In addition, the study shows a patient group recovers from the progression and their possible contributing factors.

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OBJECTIVE: To investigate associations between age at natural menopause, particularly premature ovarian insufficiency (POI) (natural menopause before age 40 years), and incident type 2 diabetes (T2D) and identify any variations by ethnicity. RESEARCH DESIGN AND METHODS: We pooled individual-level data of 338,059 women from 13 cohort studies without T2D before menopause from six ethnic groups: White (n = 177,674), Chinese (n = 146,008), Japanese (n = 9,061), South/Southeast Asian (n = 2,228), Black (n = 1,838), and mixed/other (n = 1,250). Hazard ratios (HRs) of T2D associated with age at menopause were estimated in the overall sample and by ethnicity, with study as a random effect. For each ethnic group, we further stratified the association by birth year, education level, and BMI. RESULTS: Over 9 years of follow-up, 20,064 (5.9%) women developed T2D. Overall, POI (vs. menopause at age 50-51 years) was associated with an increased risk of T2D (HR 1.31; 95% CI 1.20-1.44), and there was an interaction between age at menopause and ethnicity (P < 0.0001). T2D risk associated with POI was higher in White (1.53; 1.36-1.73), Japanese (4.04; 1.97-8.27), and Chinese women born in 1950 or later (2.79; 2.11-3.70); although less precise, the risk estimates were consistent in women of South/Southeast Asian (1.46; 0.89-2.40), Black (1.72; 0.95-3.12), and mixed/other (2.16; 0.83-5.57) ethnic groups. A similar pattern, but with a smaller increased risk of T2D, was observed with early menopause overall (1.16; 1.10-1.23) and for White, Japanese, and Chinese women born in 1950 or later. CONCLUSIONS: POI and early menopause are risk factors for T2D in postmenopausal women, with considerable variation across ethnic groups, and may need to be considered in risk assessments of T2D among women.

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OBJECTIVES: Little is known about what type of women use hormone replacement therapy (HRT) in Japan. Based on the Japan Nurses' Health Study (JNHS), a large population cohort study, we determined the characteristics of HRT users by comparing the characteristics of new HRT users and the characteristics of women who did not use HRT during a 10-year follow-up period. STUDY DESIGN: Of the 15,019 JNHS participants, 4886 women reported an experience of menopausal transition during the 10-year follow-up period. MAIN OUTCOME MEASUREMENT: Characteristics of new HRT users. RESULTS: The proportion of HRT users during the 10-year period was 8.5 %. Advanced age at menopause was significantly associated with a low rate of use of HRT. Past use of oral contraceptives, dysmenorrhea with disturbance in daily life and vasomotor symptoms were significantly associated with a high rate of use of HRT. The occupations of public health nurse and midwife and a history of bilateral oophorectomy were also significantly associated with a high rate of use of HRT. CONCLUSIONS: We determined the characteristics of new HRT users among middle-aged women during a 10-year follow-up period. Women who had sufficient knowledge about endocrinological hormones and women who had less reluctance to visit doctors for gynecological problems were likely to use HRT.

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BACKGROUND: Some reproductive factors (such as age at menarche and parity) have been shown to be associated with age at natural menopause, but there has been little quantitative analysis of the association between infertility, miscarriage, stillbirth, and premature (<40 years) or early menopause (40-44 years). In addition, it has been unknown whether the association differs between Asian and non-Asian women, although the age at natural menopause is younger among Asian women. OBJECTIVE: This study aimed to investigate the association of infertility, miscarriage, and stillbirth with age at natural menopause, and whether the association differed by race (Asian and non-Asian). STUDY DESIGN: This was a pooled individual participant data analysis from 9 observational studies contributing to the InterLACE consortium. Naturally postmenopausal women with data on at least 1 of the reproductive factors (ie, infertility, miscarriage, and stillbirth), age at menopause, and confounders (ie, race, education level, age at menarche, body mass index, and smoking status) were included. A multinomial logistic regression model was used to estimate relative risk ratios and 95% confidence intervals for the association of infertility, miscarriage, and stillbirth with premature or early menopause, adjusting for confounders. Between-study difference and within-study correlation were taken into account by including study as a fixed effect and indicating study as a cluster variable. We also examined the association with number of miscarriages (0, 1, 2, ≥3) and stillbirths (0, 1, ≥2), and tested whether the strength of association differed between Asian and non-Asian women. RESULTS: A total of 303,594 postmenopausal women were included. Their median age at natural menopause was 50.0 years (interquartile range, 47.0-52.0). The percentages of women with premature and early menopause were 2.1% and 8.4%, respectively. The relative risk ratios (95% confidence intervals) of premature and early menopause were 2.72 (1.77-4.17) and 1.42 (1.15-1.74) for women with infertility; 1.31 (1.08-1.59) and 1.37 (1.14-1.65) for women with recurrent miscarriages; and 1.54 (1.52-1.56) and 1.39 (1.35-1.43) for women with recurrent stillbirths. Asian women with infertility, recurrent miscarriages (≥3), or recurrent stillbirths (≥2) had higher risk of premature and early menopause compared with non-Asian women with the same reproductive history. CONCLUSION: Histories of infertility and recurrent miscarriages and stillbirths were associated with higher risk of premature and early menopause, and the associations differed by race, with stronger associations for Asian women with such reproductive history.

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Using the "periodic confirmation sheet" employed in the safety management procedure of thalidomide drugs, we looked at whether patients' knowledge of compliance with the procedure varies depending on the length of the gap between confirmations. In 31 centers, 215 participants were male patients and female patients who might be pregnant participants. Subjects have treated a group of patients who used periodic confirmation slips at the standard confirmation interval and a group of patients who increase the confirmation interval to 4 or 6 months, the % of respondents that correctly answered each of all six questions in questions 1-6 on the second comprehension questionnaire, excluding question 7 to confirm behavior change, was 87.0%. Comparing the percentage of correct answers to all questions the first time and the second time, no pregnancy cases were observed and there was no decline in the percentage of accurate responses after the second attempt for either group. One cannot judge changes in behavior. The mixed-effect model also additionally demonstrated non-inferiority in the patient group with the extended confirmation interval (a difference of -6.7% in the proportion of correct answers on the comprehension test (95%CI: -20.3-7.0%)), thus it appears that going forward, both male patients and female patients of potential pregnancy should complete the periodic confirmation form once every 4 or 6 months.

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BACKGROUND: There are no effective pharmacologic interventions for preventing postoperative cognitive dysfunction in daily practice. Since the antibiotic minocycline is known to suppress postoperative neuroinflammation, this study hypothesized and investigated whether minocycline might have a preventive effect on postoperative cognitive dysfunction after noncardiac surgery. METHODS: This study included patients aged more than 60 yr undergoing total knee arthroplasty under general anesthesia. They were randomly assigned to minocycline and placebo groups, to orally receive 100 mg of minocycline or placebo twice daily from the day before surgery until the seventh day after surgery. Cognitive function was evaluated before surgery, and 1 week and 3 months after surgery, using a battery of four cognitive function tests, including Visual Verbal Learning Test, Trail Making Test, Stroop Color and Word Test, and Letter-Digit Coding Task. Additionally, 30 healthy volunteers were subjected to the same tests as the patients to examine the learning effect of repeated tests. The occurrence of postoperative cognitive dysfunction was judged from the results of the neurocognitive test battery, with consideration of the learning effect. The secondary endpoints were the effects of minocycline on postoperative delirium and postoperative pain. RESULTS: A total of 100 patients were randomized to the minocycline group, and 102 were randomized to the placebo group. The average age of patients was 75 yr. Evaluation showed no significant difference in the incidence of postoperative cognitive dysfunction between the minocycline and placebo groups at both 1 week (8 of 90 [8.9%] vs. 4 of 95 [4.2%]; odds ratio, 2.22 [95% CI, 0.64 to 7.65]; P = 0.240) and 3 months (15.3 of 90 [17.0%] vs. 15.3 of 95 [16.1%]; odds ratio, 1.07 [95% CI, 0.49 to 2.32]; P = 0.889) postoperatively. Missing data 3 months after surgery were corrected by the multiple imputation method. There were no differences between the two groups in postoperative delirium and postoperative pain. CONCLUSIONS: Minocycline is likely to have no preventive effect on postoperative cognitive dysfunction.

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The development of vaccines against infectious diseases requires a different approach from that of therapeutics, because vaccines are inoculated into healthy individuals and have a preventive effect by activating the immunity of the inoculated human. In Japan, "The Guideline for Clinical Trials of Vaccines for the Prevention of Infectious Diseases" was published in 2010 before changes occurred in the vaccine development environment in Japan, such as the introductions of foreign vaccines and simultaneous global development. This study aimed to identify current challenges in vaccine development through a questionnaire-based survey of pharmaceutical companies in Japan and by comparing the domestic and international guidelines and surveying review reports of 35 vaccines approved in Japan between April 2010 and December 2020. Identified challenges included the requirement for protective efficacy trials, efficacy evaluation of combination vaccines, development of multiregional and foreign clinical trials, and immunization of older adults and immunocompromised patients. We propose that new vaccines against infectious diseases should be evaluated for the protective efficacy, preferably through multiregional clinical trials. Additionally, differences in the incidence of infectious diseases or in epidemic virus strains between regions may affect the trials, when multiregional clinical trials are conducted, but immunogenicity-based studies can be conducted if a correlation between protective efficacy and immunogenicity has been established. We suggest that licensed combination vaccines can be used as comparators when an antigen is added to a licensed combination vaccine. We also proposed that the efficacy of a vaccine in non-major subjects, such as older adults or immunocompromised patients could be evaluated by comparing immunogenicity in major subjects with the confirmed protective effects of the vaccine. It is expected that these revisions will lead to the rapid advancement of vaccine development, which should contribute to the improvement of public health.

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BACKGROUND: Many women experience various symptoms during the period of menopausal transition, including complaints of reduced cognitive functioning. However, these complaints are not necessarily recognized as core menopausal symptoms. In this study, we sought to characterize subjective complaints of reduced cognitive functioning by analyzing cross-sectional data from the Japan Nurses' Health Study (JNHS). METHODS: The JNHS 4-year follow-up questionnaire containing a 21-item climacteric symptom checklist, which included a question about "poor memory or forgetfulness", was mailed between 2005 and 2011 to all JNHS participants, regardless of their age at the time of the survey. We estimated the prevalence of slight and severe complaints in 5-year age-groups. We used principal component analysis to explore the underlying factors among the 21 symptoms during the menopausal transition period in women aged 45-54 years at the time of the survey. We also examined risk factors for complaints using multivariable modified Poisson regression analysis. RESULTS: In total, 12,507 women responded to the 4-year survey. The mean age at the time of the 4-year survey was 46.5 years (range 27-82). "Poor memory or forgetfulness" showed a peak prevalence of 81.7% (severe 27.9%; slight 53.8%) at 50-54 years, and gradually decreased after 55 years. Principal component analysis indicated that "poor memory or forgetfulness" belonged to somatic symptoms and was close to psychological symptoms in women aged 45-54 years. In women aged 45-54 years, the complaint was also significantly associated with hot flashes and sweats. Multivariable modified Poisson regression analysis showed that menopausal status (uncertain and postmenopausal), less sleep (sleep of < 5 h and sleep of 5- < 6 h), night-shift work, and severe vasomotor symptoms (VMS) were significantly associated with the prevalence of severe complaints of reduced cognitive functioning in women aged 45-54 years. CONCLUSIONS: We found that prevalence of "poor memory or forgetfulness" was highest during the menopausal transition period and among perimenopausal women. This subjective complaint was associated with somatic, psychological complaints and VMS. It may be useful for women with cognitive problems in the transition period to consider management of comorbid menopausal symptoms.

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The use of dietary supplements has become a common way to maintain good health. This study evaluated the status of supplement use and supplement user characteristics among participants from the Japan Nurses' Health Study, which comprised a cohort of Japanese female nursing professionals. A questionnaire survey covering the use of vitamins and supplements was conducted. Supplements were classified according to their constituents and formulations. Logistic regression analyses were performed to determine the characteristics of supplement users. Results were as follows. There were 4,017 supplement users (34.4% of 11,665 valid answers). The supplement types used were: vitamins (n=2,655), minerals (n=1,121), amino acids and proteins (n=139), botanical products (n=714), animal by-products (n=849), herbal medicines (n=152), nutritional drinks (n=19), others (n=117), and unclassified supplements (n=320). Logistic regression analyses showed that supplement use was significantly associated with age and body mass index, and there were significantly higher proportions of supplement users among pregnant women, black tea drinkers, soy milk consumers, and lactobacillus beverage drinkers. In conclusion, the overall percentage of supplement users was 34.4%. A high prevalence of supplement use was observed among older, non-obese, and pregnant participants, and those who paid more attention to their health. The prevalence of supplement users was significantly higher among those who habitually drank black tea, soy milk, and lactobacillus beverages, suggesting participants used supplements to maintain their health or prevent diseases based on high health consciousness.

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OBJECTIVE: To examine the associations of infertility, recurrent miscarriage, and stillbirth with the risk of first non-fatal and fatal stroke, further stratified by stroke subtypes. DESIGN: Individual participant pooled analysis of eight prospective cohort studies. SETTING: Cohort studies across seven countries (Australia, China, Japan, Netherlands, Sweden, the United Kingdom, and the United States) participating in the InterLACE (International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events) consortium, which was established in June 2012. PARTICIPANTS: 618 851 women aged 32.0-73.0 years at baseline with data on infertility, miscarriage, or stillbirth, at least one outcome event (non-fatal or fatal stroke), and information on covariates were included; 93 119 women were excluded. Of the participants, 275 863 had data on non-fatal and fatal stroke, 54 716 only had data on non-fatal stroke, and 288 272 only had data on fatal stroke. MAIN OUTCOME AND MEASURES: Non-fatal strokes were identified through self-reported questionnaires, linked hospital data, or national patient registers. Fatal strokes were identified through death registry data. RESULTS: The median follow-up for non-fatal stroke and fatal stroke was 13.0 years (interquartile range 12.0-14.0) and 9.4 years (7.6-13.0), respectively. A first non-fatal stroke was experienced by 9265 (2.8%) women and 4003 (0.7%) experienced a fatal stroke. Hazard ratios for non-fatal or fatal stroke were stratified by hypertension and adjusted for race or ethnicity, body mass index, smoking status, education level, and study. Infertility was associated with an increased risk of non-fatal stroke (hazard ratio 1.14, 95% confidence interval 1.08 to 1.20). Recurrent miscarriage (at least three) was associated with higher risk of non-fatal and fatal stroke (1.35, 1.27 to 1.44, and 1.82, 1.58 to 2.10, respectively). Women with stillbirth were at 31% higher risk of non-fatal stroke (1.31, 1.10 to 1.57) and women with recurrent stillbirth were at 26% higher risk of fatal stroke (1.26, 1.15 to 1.39). The increased risk of stroke (non-fatal or fatal) associated with infertility or recurrent stillbirths was mainly driven by a single stroke subtype (non-fatal ischaemic stroke and fatal haemorrhagic stroke), while the increased risk of stroke (non-fatal or fatal) associated with recurrent miscarriages was driven by both subtypes. CONCLUSION: A history of recurrent miscarriages and death or loss of a baby before or during birth could be considered a female specific risk factor for stroke, with differences in risk according to stroke subtypes. These findings could contribute to improved monitoring and stroke prevention for women with such a history.

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OBJECTIVE: Cesarean deliveries must be optimally timed to minimize their effects on mothers and neonates. This study aimed to determine the optimal timing of elective repeat cesarean deliveries to reduce the incidence of neonatal respiratory disorders and of emergent cesarean deliveries. MATERIALS AND METHODS: This multi-center, cross-sectional, retrospective analysis evaluated data on the maternal and neonatal outcomes of 856 singleton pregnancies scheduled for elective repeat cesarean deliveries at 37-39 weeks' gestation. The emergent cesarean delivery and neonatal respiratory disorder risks were analyzed according to the scheduled cesarean delivery times. RESULTS: The elective cesarean delivery rates were 91.0% during the first and 92.6% during the second half of the 37th week of gestation, 88.7% during the first and 82.9% during the second half of the 38th week of gestation, and 62.5% during the first and 33.3% during the second half of the 39th week of gestation. The neonatal respiratory disorder rates were 21.8% for elective cesarean deliveries during the first half of the 37th week of gestation and approximately 8% for elective cesarean deliveries during the second half of the 37th week until the first half of the 38th week of gestation. No neonatal respiratory disorders occurred among the babies delivered by elective cesarean deliveries during the 39th week of gestation. CONCLUSION: For improved maternal and neonatal outcomes in the Asian population, it may be better to perform scheduled elective repeat cesarean deliveries from the second half of the 37th week of gestation until the 38th week of gestation following confirmation of gestational age by early first trimester ultrasonography.

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The efficacy and safety of vaccines for the prevention of infectious diseases are mostly evaluated based on the induction of an immune response against antigens, and do not necessarily depend on the dose administered. Therefore, there are some specific aspects that need to be considered in the development of vaccines and have been described in "The Guidelines for the non-clinical studies of vaccines for the prevention of infectious disease" in Japan. Recent changes in the vaccine development field, such as the introduction of vaccines developed overseas in Japan and vaccine development on a global scale have increased the need for revision of these guidelines. In this study, we identified the current challenges in the development of vaccines through comparison of Japanese and international guidelines. We conducted a questionnaire-based survey of pharmaceutical industries in Japan, and found issues related to non-clinical studies, such as the necessity of safety pharmacology studies and repeated-dose toxicity studies for each route of administration. We examined international guidelines on these issues as well as review reports by regulatory authorities, and determined that the results of repeated-dose toxicity studies can be used to decide whether safety pharmacology studies are required, and that studies to evaluate toxicity due to systemic effects may not be necessary for both intramuscular and subcutaneous administration. We propose revision of the guidelines for the non-clinical studies of vaccines in Japan taking international harmonizaion into account. We expected that the revised guidelines will promote smooth and rational vaccine development.

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BACKGROUND: The Japan Nurses' Health Study (JNHS) is a large-scale, nationwide prospective cohort study of female nurses. This study aimed to examine the validity of self-reported diagnosis of cancer among the JNHS cohort members (N=15,019). METHODS: For women who reported any diagnosis of five cancers (stomach, colorectal, liver, lung and thyroid) in the biennial follow-up surveys, an additional outcome survey, medical facility survey, and confirmation of death certificate (DC) were conducted. The JNHS Validation Study Committee (referred to as "the committee") made a final decision on the reported outcomes. To examine the validity of self-reported diagnosis of cancer, the positive predictive value (PPV) was calculated using the committee's decision as the gold standard. To examine the validity of the committee's decision based on self-reports and DCs, PPV was calculated using physician-reported information as the gold standard. RESULTS: The PPV of self-reported diagnosis in the biennial follow-up surveys was 77.8% for stomach, 66.2% for colorectal, 41.7% for liver, 60.2% for lung, and 64.6% for thyroid cancer. The corresponding PPVs in the additional outcome survey were 96.2%, 80.7%, 62.5%, 82.5%, and 96.9%, respectively. The PPV of the committee's decision was 100% for stomach, 87.5% for colorectal, 94.7% for lung, and 100% for thyroid cancer (data not available for liver cancer). The proportion of DC-only cases among committee-defined cases was below 10% for all cancers except liver cancer (28.6%). CONCLUSIONS: The validity of identifying cancer diagnosis based on self-reported information in the JNHS was favorable for stomach, colorectal, lung and thyroid cancer.

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BACKGROUND: There have been few community-based epidemiological studies in which the prevalence of exogenous hormone use, including the use of oral contraceptives (OCs) and hormone replacement therapy (HRT), has been accurately assessed in Japan. METHODS: We have been conducting repeated surveys of participants in the Japan Nurses' Health Study (JNHS), as a nationwide prospective cohort study, since 2001. We determined the prevalence of exogenous hormone use at baseline and during a 10-year follow-up period. A total of 15,019 female nurses participated in the JNHS follow-up cohort. We determined the prevalence of OC use in 14,839 women <60 years of age at baseline and the prevalence of HRT use in 7,915 women, excluding premenopausal women, at the last time they answered a questionnaire. The duration of HRT use was estimated using the Kaplan-Meier method. RESULTS: Six percent of the participants used OCs. The proportion of HRT users who stopped HRT before the baseline survey, the proportion of women using HRT during the follow-up period, and the proportion of all of the participants who had used HRT were 3.2%, 10.6%, and 13.8%, respectively. The median duration of HRT use was 2 years. CONCLUSIONS: The lifetime prevalences of exogenous hormone use during this prospective study conducted in Japanese nurses were 6.0% for OCs and 13.8% for HRT. The information obtained in this study will be useful for clarification of the association between exogenous estrogen exposure and estrogen-related diseases as future research.

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OBJECTIVE: In this study, we aimed to investigate the prevalence and factors associated with urinary symptoms using cross-sectional data from the Japan Nurses' Health Study, a prospective cohort study among female nurses. METHODS: A total of 12,198 women were included. We calculated the prevalence of urinary symptoms. Odds ratios with 95% confidence intervals were estimated to determine the odds for overactive bladder (OAB), stress urinary incontinence, and mixed urinary incontinence. RESULTS: The mean age and body mass index (standard deviation, range) were 46.5 (±8.1, 27-82) years and 22.1 (±3.1, 12.9-44.6) kg/m2, respectively. The prevalence of OAB was 9.5% (OAB with urinary incontinence [-wet]: 5.4%, OAB without urinary incontinence: 4.1%), that of stress urinary incontinence (without OAB-wet) was 13.9%, and that of mixed urinary incontinence was 2.1%. Multivariable-adjusted logistic regression analysis showed a significant association between OAB and age 45 to 54 years, and postmenopausal status was moderately associated with OAB in that analysis. In the multivariable-adjusted model, age groups 45 to 49 and 50 to 54 years, body mass index 23-27.4 and ≥ 27.5 kg/m2, and parous status were significantly associated with stress urinary incontinence (without OAB-wet). CONCLUSIONS: This study showed a significant association of OAB with ages 45 to 54 years and postmenopausal status. Further studies should consider the association between time since menopause and OAB symptoms in the perimenopausal period. A high body mass index and parous status are strongly associated with stress urinary incontinence, and stress urinary incontinence symptoms may become less frequent after menopause.

Video Summary:http://links.lww.com/MENO/A853 .

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OBJECTIVE: We aimed to investigate whether hypertensive disorders of pregnancy (HDP) are associated with problematic hot flashes in Japanese women. METHODS: In this study, we included participants in the Japan Nurses' Health Study who were women aged 41 to 55 years at baseline, parous, and completed a 4-year follow-up questionnaire. The main outcome was self-reported problematic hot flashes. At the 4-year follow-up survey, we investigated hot flashes using the Climacteric Symptom Checklist for Japanese Women, which was developed by a subcommittee of the Japan Society of Obstetrics and Gynecology. RESULTS: At the baseline survey, of the 4,627 women included in the analysis, 610 (13.2%) reported a history of HDP. At the 4-year follow-up survey, 394 women (8.5%) reported problematic hot flashes, 529 (11.4%) were diagnosed with premenopausal hypertension, and 2,389 (51.5%) were postmenopausal. Multivariable logistic regression analysis revealed a multivariable-adjusted odds ratio (95% confidence interval) of problematic hot flashes for women with a history of HDP of 1.42 (1.04-1.94), compared with women without this history. Among women without premenopausal hypertension, the odds ratio increased to 1.55 (1.10-2.19) among women with HDP as compared with those without these disorders. CONCLUSIONS: In this prospective study, we found that women with a history of HDP have a significantly increased risk of problematic hot flashes, compared with their counterparts without a history of HDP.

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OBJECTIVES: To validate the self-reported diagnoses of gynaecological and breast cancers in a nationwide prospective cohort study of nursing professionals: the Japan Nurses' Health Study (JNHS). DESIGN AND SETTING: Retrospective analysis of the JNHS. PARTICIPANTS AND MEASURES: Data were reviewed for 15 717 subjects. The mean age at baseline was 41.6±8.3 years (median: 41), and the mean follow-up period was 10.5±3.8 years (median: 12). Participants are regularly mailed a follow-up questionnaire once every 2 years. Respondents who self-reported a positive cancer diagnosis were sent an additional confirmation questionnaire and contacted the diagnosing facility to confirm the diagnosis based on medical records. A review panel of experts verified the disease status. Regular follow-up, confirmation questionnaires and expert review were validated for their positive predictive value (PPV) and negative predictive value (NPV). RESULTS: New incidences were verified in 37, 47, 26 and 300 cervical, endometrial, ovarian and breast cancer cases, respectively. The estimated incidence rates were 22.0, 25.4, 13.8 and 160.4 per 100 000 person-years. These were comparable with those of national data from regional cancer registries in Japan. For regular follow-up, the corresponding PPVs for cervical, endometrial, ovarian and breast cancer were 16.9%, 54.2%, 45.1% and 81.4%, and the NPVs were 100%, 99.9%, 99.9% and 99.9%, respectively. Adding the confirmation questionnaire improved the PPVs to 31.5%, 88.9%, 76.7% and 99.9%; the NPVs were uniformly 99.9%. Expert review yielded PPVs and NPVs that were all ~100%. CONCLUSIONS: Gynaecological cancer cannot be accurately assessed by self-reporting alone. Additionally, the external validity of cancer incidence in this cohort was confirmed.

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