Serum Soluble IL-2 Receptors Are Elevated in Febrile Illnesses and Useful for Differentiating Clinically Similar Malignant Lymphomas from Kikuchi Disease: A Cross-Sectional Study.

Background: The use of serum soluble interleukin 2 receptor (sIL-2R) for the diagnosis of febrile illnesses has not been examined. In this study, febrile patients were classified according to etiology and disease, and serum sIL-2R levels were evaluated. We determined whether serum sIL-2R is a useful marker for differentiating between malignant lymphoma (ML) and non-ML patients and between patients with ML and Kikuchi disease, which present similar clinical manifestations. Methods: This study was a cross-sectional study and included 344 patients with uncomplicated hemophagocytic syndrome, who had a fever of 38 °C or higher within 1 week of admission to our institution. Patient serum sIL-2R was measured, and the serum sIL-2R values are shown as median and IQR. Results: Serum sIL-2R increased above the upper reference limit in all disease groups with fever. The serum sIL-2R level in ML patients (n = 13) was 4760 (2120-6730) U/mL and significantly higher (p < 0.001) than the level of 998 (640-1625) U/mL in non-ML patients (n = 331). The serum sIL-2R level in ML patients (n = 13) was also significantly higher (p < 0.001) compared with that in patients with Kikuchi disease (n = 20; 705 (538-1091) U/mL). Conclusions: Serum sIL-2R tends to exceed the upper reference limit in patients with febrile illnesses. We conclude that the measurement of serum sIL-2R is useful for differentiating ML from non-ML and ML from Kikuchi disease.

Associations between Work-Related Factors and Happiness among Working Older Adults: A Cross-Sectional Study.

BACKGROUND: As the global population ages, the number of older adults working after retirement is increasing. However, knowledge regarding working conditions for health and happiness among this population is insufficient. Therefore, we examined the association between work-related factors (e.g., employment status, daily working time, work-related stress) and happiness among working older adults. METHODS: This cross-sectional study recruited Japanese older adults, aged 65 years and older, who were engaged in paid work, during their annual health checkups. Self-administered questionnaires were used to assess happiness, employment status, daily working time, and work-related stress (i.e., job strain, job control, job suitability, and relationships at work). RESULTS: The data of 520 men and 168 women were analyzed (mean ages, 68.5 years and 68.0 years, respectively). The results of the multivariable ordinal logistic regression analysis indicated that low job suitability was negatively associated with happiness in men (odds ratio [OR]=0.46; 95% confidence interval [CI], 0.28-0.78; p=0.004). In women, long working hours and low job control were negatively associated with happiness-working >8 hours daily (OR=0.29; 95% CI, 0.12-0.71; p=0.008) and low job control (OR=0.29; 95% CI, 0.12-0.72; p=0.009). CONCLUSION: The results showed that low job suitability for men and long daily working time and low job control for women were negatively associated with happiness. These findings suggest the need to improve working conditions to enhance the well-being of working older adults.

The Association between Family Caregiver Burden and Subjective Well-Being and the Moderating Effect of Social Participation among Japanese Adults: A Cross-Sectional Study.

We examined the association between family caregiver burden and subjective well-being with social participation's moderating effect among Japanese adults. Data were obtained from a cross-sectional survey by the Japan Multi-Institutional Collaborative Cohort Study in the Okazaki area between 2013 and 2017. Study participants included 5321 adults who visited the Public Health Center for annual health check-ups and answered a questionnaire regarding health status and lifestyle. Subjective well-being was assessed by a single item, out of 10 points, and analyzed with multivariable linear regression analysis models by subjective family caregiver burden ("none", "mild", "severe"), stratified by gender. Ultimately, 2857 men and 2223 women were included. Mean participant age (standard deviation) in years was 64.7 (10.4) for men and 61.3 (10.0) for women. Multivariable analysis revealed that, among women, higher caregiver burden was inversely associated with subjective well-being (p for trend < 0.001), and the interaction of severe caregiver burden and social participation on subjective well-being was positive and significant (p for interaction < 0.05). High family caregiver burden was inversely associated with subjective well-being among Japanese women, but moderated by the caregiver's social participation, suggesting the importance of community development that enables family caregivers' social participation to protect their subjective well-being.

Association Between Second-hand Smoke Exposure and Depressive Symptoms Among Japanese Adults: A Cross-sectional Study.

BACKGROUND: Second-hand smoke exposure has been associated with poor mental health. However, among Japanese adults, little is known about the association between second-hand smoking and depressive symptoms. We examined this association in a cross-sectional study among a Japanese general adult population sample. METHODS: Japanese adults were recruited from the Japan Multi-Institutional Collaborative Cohort Study in the Okazaki area between 2012 and 2017. Second-hand smoke exposure and smoking status were assessed using a self-administered questionnaire. Based on their frequency of exposure to second-hand smoke, non-smokers and smokers were categorized as "almost never," "sometimes," and "almost every day". Depressive symptoms were defined by a Kessler 6 score ≥5 points. We performed a multivariable Poisson regression analysis to obtain adjusted prevalence ratios (PRs) and 95% confidence intervals (CIs) for depressive symptoms. RESULTS: Overall, 5,121 participants (4,547 non-smokers and 574 smokers) were included whose mean age was 63.6 (standard deviation [SD], 10.3) years for non-smokers and 59.33 (SD, 10.2) years for smokers. The association between second-hand smoking and depressive symptoms was significant among non-smokers, but not among smokers. Among non-smokers, PRs compared with "almost never" were 1.25 (95% CI, 1.09-1.42) for "sometimes" and 1.41 (95% CI, 1.09-1.84) for "almost every day" (P for trend <0.001); among smokers, PRs compared with "almost never" were 1.30 (95% CI, 0.82-2.06) for "sometimes" and 1.44 (95% CI, 0.90-2.33) for "almost every day" (P for trend = 0.144). CONCLUSIONS: Second-hand smoking and depressive symptoms were associated among non-smokers. Our findings indicate the importance of tobacco smoke control for mental health.

Genome-wide association meta-analysis and Mendelian randomization analysis confirm the influence of ALDH2 on sleep durationin the Japanese population.

Usual sleep duration has substantial heritability and is associated with various physical and psychiatric conditions as well as mortality. However, for its genetic locus, only PAX8 and VRK2 have been replicated in previous genome-wide association studies (GWAS). We conducted a GWAS meta-analysis of self-reported usual sleep duration using three population-based cohorts totaling 31 230 Japanese individuals. A genome-wide significant locus was identified at 12q24 (p-value < 5.0 × 10-8). Subsequently, a functional variant in the ALDH2 locus, rs671, was replicated in an independent sample of 5140 Japanese individuals (p-value = 0.004). The association signal, however, disappeared after adjusting for alcohol consumption, indicating the possibility that the rs671 genotype modifies sleep duration via alcohol consumption. This hypothesis explained a modest genetic correlation observed between sleep duration and alcohol consumption (rG = 0.23). A Mendelian randomization analysis using rs671 and other variants as instrumental variables confirmed this by showing a causal effect of alcohol consumption, but not of coffee consumption on sleep duration. Another genome-wide significant locus was identified at 5q33 after adjusting for drinking frequency. However, this locus was not replicated, nor was the PAX8 and VRK2. Our study has confirmed that a functional ALDH2 variant, rs671, most strongly influences on usual sleep duration possibly via alcohol consumption in the Japanese population, and presumably in East Asian populations. This highlights the importance of considering the involvement of alcohol consumption in future GWAS of usual sleep duration, even in non-East Asian populations, where rs671 is monomorphic.

Handling missing data in an FFQ: multiple imputation and nutrient intake estimates.

OBJECTIVE: We aimed to examine missing data in FFQ and to assess the effects on estimating dietary intake by comparing between multiple imputation and zero imputation. DESIGN: We used data from the Okazaki Japan Multi-Institutional Collaborative Cohort (J-MICC) study. A self-administered questionnaire including an FFQ was implemented at baseline (FFQ1) and 5-year follow-up (FFQ2). Missing values in FFQ2 were replaced by corresponding FFQ1 values, multiple imputation and zero imputation. SETTING: A methodological sub-study of the Okazaki J-MICC study.ParticipantsOf a total of 7585 men and women aged 35-79 years at baseline, we analysed data for 5120 participants who answered all items in FFQ1 and at least 50% of items in FFQ2. RESULTS: Among 5120 participants, the proportion of missing data was 3·7%. The increasing number of missing food items in FFQ2 varied with personal characteristics. Missing food items not eaten often in FFQ2 were likely to represent zero intake in FFQ1. Most food items showed that the observed proportion of zero intake was likely to be similar to the probability that the missing value is zero intake. Compared with FFQ1 values, multiple imputation had smaller differences of total energy and nutrient estimates, except for alcohol, than zero imputation. CONCLUSIONS: Our results indicate that missing values due to zero intake, namely missing not at random, in FFQ can be predicted reasonably well from observed data. Multiple imputation performed better than zero imputation for most nutrients and may be applied to FFQ data when missing is low.

Established Stem Cell Model of Spinal Muscular Atrophy Is Applicable in the Evaluation of the Efficacy of Thyrotropin-Releasing Hormone Analog.

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by the degeneration of spinal motor neurons. This disease is mainly caused by mutation or deletion of the survival motor neuron 1 (SMN1) gene. Currently, no effective treatment is available, and only symptomatic treatment can be provided. Our purpose in the present study was to establish a human SMA-derived induced pluripotent stem cell (SMA-iPSC) disease model and assay a therapeutic drug in preparation for the development of a novel treatment of SMA. We generated iPSCs from the skin fibroblasts of a patient with SMA and confirmed that they were pluripotent and undifferentiated. The neural differentiation of SMA-iPSCs shortened the dendrite and axon length and increased the apoptosis of the spinal motor neurons. In addition, we found activated astrocytes in differentiated SMA-iPSCs. Using this model, we confirmed that treatment with the thyrotropin-releasing hormone (TRH) analog, 5-oxo-l-prolyl-l-histidyl-l-prolinamide, which had marginal effects in clinical trials, increases the SMN protein level. This increase was mediated through the transcriptional activation of the SMN2 gene and inhibition of glycogen synthase kinase-3ß activity. Finally, the TRH analog treatment resulted in dendrite and axon development of spinal motor neurons in differentiated SMA-iPSCs. These results suggest that this human in vitro disease model stimulates SMA pathology and reveal the potential efficacy of TRH analog treatment for SMA. Therefore, we can screen novel therapeutic drugs such as TRH for SMA easily and effectively using the human SMA-iPSC model. Significance: Platelet-derived growth factor (PDGF) has recently been reported to produce the greatest increase in survival motor neuron protein levels by inhibiting glycogen synthase kinase (GSK)-3ß; however, motor neurons lack PDGF receptors. A human in vitro spinal muscular atrophy-derived induced pluripotent stem cell model was established, which showed that the thyrotropin releasing hormone (TRH) analog promoted transcriptional activation of the SMN2 gene and inhibition of GSK-3ß activity, resulting in the increase and stabilization of the SMN protein and axon elongation of spinal motor neurons. These results reveal the potential efficacy of TRH analog treatment for SMA.

Association of cigarette smoking with skin colour in Japanese women.

OBJECTIVES: Having a lighter skin tone is highly valued among many Asian women. If skin colour is affected by smoking, women may be motivated to avoid tobacco or quit smoking. The present study examined the association of tobacco smoking with skin colour in Japanese women. METHOD: Information on smoking habits was obtained through a self-administered questionnaire completed by 939 Japanese women aged 20-74 in Gifu, Japan, during 2003-2006. Skin colour was examined on the inner side of the upper and lower arm and on the forehead using a Mexameter device (a narrow-band reflective spectrophotometer), which expressed results as a melanin index and erythema index. RESULTS: Current smokers had higher melanin indices than never-smokers and former smokers for all measured sites. The number of cigarettes smoked per day, the years of smoking and pack-years were significantly positively associated with melanin indices for all measured sites after adjustments for age, body mass index, lifetime sun exposure, and room temperature and humidity. Smoking was also significantly associated with erythema indices on the inner upper and lower arms. CONCLUSIONS: These data suggest that smoking is associated with a darker skin colour. If our findings are confirmed by further studies, they could be used in antismoking campaigns or by smoking cessation services.

Association between tinnitus and sleep disorders in the general Japanese population.

OBJECTIVES: There are few studies about the association between tinnitus and sleep disorders in the general population worldwide. This study assessed this association in a Japanese community. METHODS: A total of 14,027 participants 45 to 79 years of age who were in the Takayama Study responded to a self-administered questionnaire about tinnitus and sleep disorders. RESULTS: Of this population, 13.3% of men and 10.6% of women had current tinnitus. The percentages of insomnia, respectively, among individuals with and without tinnitus were 28.1% in men and 36.1% in women and 18.8% in men and 21.5% in women. There were 1.7-fold (95% confidence interval [CI], 1.4 to 2.1) and 1.8-fold (95% CI, 1.5 to 2.2) increases in the odds ratios (ORs) of insomnia for those with tinnitus compared with those without tinnitus in men and women, respectively. Loud or very loud tinnitus was associated with 2.8-fold (95% CI, 1.8 to 4.3) and 3.3-fold (95% CI, 1.9 to 5.6) increases in the OR of insomnia in men and women, respectively. Even low (ie, quiet) or moderate tinnitus was significantly associated with insomnia. Difficulty initiating sleep, difficulty maintaining sleep, and a poor perceived quality of sleep were also significantly associated with tinnitus. CONCLUSIONS: Insomnia and other sleep disorders were significantly associated with tinnitus in Japanese adults.

Branched-chain amino acid intake and the risk of diabetes in a Japanese community: the Takayama study.

Dietary supplementation with branched-chain amino acids (BCAAs), including leucine, isoleucine, and valine, has shown potential benefits for the metabolic profile. However, higher blood BCAA levels have been associated with insulin resistance. To our knowledge, there has been no study on dietary BCAAs and the risk of diabetes. We examined the association between BCAA intake and risk of diabetes in a population-based cohort study in Japan. A total of 13,525 residents of Takayama City, Japan, who enrolled in a cohort study in 1992 responded to a follow-up questionnaire seeking information about diabetes in 2002. Diet at baseline was assessed by means of a validated food frequency questionnaire. A high intake of BCAAs in terms of percentage of total protein was significantly associated with a decreased risk of diabetes in women after controlling for covariates; the hazard ratio for the highest tertile versus the lowest was 0.57 (95% confidence interval: 0.36, 0.90; P-trend = 0.02). In men, leucine intake was significantly marginally associated with the risk of diabetes; the hazard ratio for the highest tertile versus the lowest was 0.70 (95% confidence interval: 0.48, 1.02; P-trend = 0.06). Data suggest that a high intake of BCAAs may be associated with a decrease in the risk of diabetes.

Associations of endogenous melatonin and sleep-related factors with behavioral problems in preschool Japanese children.

PURPOSE: We aimed to investigate the associations of sleep disturbance and sleep time with behavioral problems and to assess whether endogenous melatonin was associated with sleep-related factors and behavioral problems. METHODS: Subjects were 234 boys and 203 girls, aged 3-6 years, in a cross-sectional study in Japan in 2006. Information related to children's sleep disturbance, sleep time, and behavioral problems was obtained from parent-administered questionnaires. Children's behavioral problems were assessed by the Strengths and Difficulties Questionnaire. The 6-sulfatoxymelatonin levels in first-void morning urine were measured by radioimmunoassay. RESULTS: After multiple adjustments for covariates, children who often snore at night (P = .011), awake at night (P = .019), and looked tired in the daytime (P = .041) had a higher total difficulties score. Earlier time of waking (trend P = .021) and earlier time for bed (trend P = .014) were associated with a lower total difficulties score. Children with higher creatinine-corrected 6-sulfatoxymelatonin had lower total difficulties scores (trend P = .011). There were no associations between creatinine-corrected 6-sulfatoxymelatonin and sleep-related factors. CONCLUSIONS: Sleep disturbance, later times of sleeping and waking up, and lower melatonin levels might be involved in the development of pediatric behavioral disorders.

Diabetes mellitus and risk of cancer in Takayama: a population-based prospective cohort study in Japan.

Diabetes mellitus (DM) has been reported to be associated with an increased risk of site-specific cancers; however, few studies have assessed associations of DM with both total and site-specific cancers in Japan. We examined the association of a history of DM with cancer incidence in a population-based prospective cohort study in Japan. A total of 14 173 men and 16 547 women over 35 years old, who completed a self-administered baseline questionnaire in 1992, were followed up for cancer incidence from September 1992 to March 2008. At baseline, 6.3% men and 2.9% women had a history of diabetes. A total of 1974 men and 1514 women were identified as newly diagnosed with cancer. Hazard ratios (HR) and 95% confidence intervals (CI) were determined using Cox proportional hazards models. After controlling for potential confounders, men with DM had a modest risk increase of total cancer occurrence compared with those without DM (HR, 1.09; 95% CI, 0.93-1.29). Increased risk of cancer of the liver (HR, 2.18; 95% CI, 1.27-3.74), bile duct (HR, 2.17; 95% CI, 1.01-4.66), and larynx (HR, 3.61; 95% CI, 1.16-11.2) in diabetic men were observed. In women, significant increased risk of total cancer (HR, 1.35; 95% CI, 1.06-1.73) and stomach cancer (HR, 2.15; 95% CI, 1.30-3.54) were observed among diabetic subjects. These data suggest that people with DM may be at increased risk of both total and some site-specific cancers.

Soy isoflavone intake and breast cancer risk in Japan: from the Takayama study.

The effects of soy or isoflavone intake on breast cancer need to be examined further in epidemiologic studies. We assessed the associations of soy and isoflavone intake with breast cancer incidence in a population-based prospective cohort study in Japan. Participants were members from the Takayama study, aged 35 years or older in 1992. The follow-up was conducted from the time of the baseline study (September 1, 1992) to the end of March 2008. Cancer incidence was mainly confirmed through regional population-based cancer registries. Breast cancer was defined as code C50 according to ICD-10. Soy and isoflavone intakes were assessed with a validated food frequency questionnaire. Using the Cox proportional hazard models, the association of soy and isoflavone intake with breast cancer was assessed after adjustments for age, body mass index, physical activity, smoking, alcohol consumption, education, age at menarche, age at first delivery, menopausal status, number of children and history of hormone replacement therapy. Among the 15,607 women analyzed, 172 had developed breast cancer. The relative risks of postmenopausal breast cancer were lower among women with higher intakes of soy (trend p = 0.023) and isoflavone (trend p = 0.046), although the relative risks of premenopausal breast cancer were not associated with intakes of soy and isoflavone. Decreased risks of breast cancer were found even among women with a moderate intake of soy and isoflavone. These results suggested that soy and isoflavone intakes have a protective effect on postmenopausal breast cancer.

Cadmium exposure and the risk of breast cancer in Japanese women.

Non-occupational exposure to cadmium has been suspected to be a risk factor for breast cancer. The present study examined the association between urinary cadmium level and the risk of breast cancer in a case-control study among Japanese women. Cases were 153 women newly diagnosed and histologically confirmed with breast cancer at a general hospital in Gifu, Japan. A total of 431 controls individually matched to cases by age, menopausal status, and the period of urine sampling were selected from those who attended a breast cancer mass screening at this hospital. Urinary cadmium levels were measured using spot urine samples. Spot urine samples were collected from cases after surgery but before any cancer therapy. For controls, spot urine samples were obtained at the date of the screening visit. Information on known or suggested breast cancer risk factors was obtained by a self-administered questionnaire. The odds ratios (ORs) and 95 % confidence intervals (CIs) of breast cancer according to the tertile of the creatinine-adjusted cadmium level were calculated using conditional logistic regression models. Women in the highest tertile of the creatinine-adjusted cadmium level (>2.620 µg/g) had significantly elevated OR of breast cancer relative to those in the lowest tertile (<1.674 µg/g) after controlling for covariates [OR = 6.05, (95 % CI 2.90, 12.62)]. The trend of increase in risk with increasing cadmium level was also statistically significant [OR = 1.67, (95 % CI 1.39, 2.01) for every 1.0 µg/g increase in urinary cadmium level, P-trend <0.01]. These data suggested that exposure to cadmium was associated with a risk of breast cancer in Japanese women.

Associations of intake of antioxidant vitamins and fatty acids with asthma in pre-school children.

OBJECTIVE: Increasing childhood asthma rates may be due to changing dietary lifestyle. We investigated the association of dietary intake of antioxidant vitamins and fatty acids with asthma in Japanese pre-school children. DESIGN: Cross-sectional study. SETTING: School-based survey on lifestyle/diet and health status in children in Japan. SUBJECTS: Parents of 452 children aged 3-6 years completed a questionnaire on the children's and parents' lifestyle and demographics. Children were classified into asthma cases and non-asthma cases in accordance with the ATS-DLD(American Thoracic Society and Division of Lung Diseases of the National Heart, Lung, and Blood Institute) questionnaire. Children's diet was assessed using a 3 d dietary record completed by parents. Children's age, sex, BMI, history of food allergy, maternal age, parental history of allergy, maternal education,family size and second-hand smoking were included as covariates. Logistic regression models were used to examine the association between children's diet and asthma. RESULTS: Compared with children with the lowest intake tertile for vitamin C and vitamin E, those in the highest were significantly inversely associated with asthma; adjusted OR (95% CI) were 0?35 (0?14, 0?88) and 0?32 (0?12, 0?85),respectively. A statistically significant trend was also observed. Fruit intake showed an inverse but insignificant association with asthma. There were no associations of any type of fatty acids with asthma. CONCLUSIONS: These data suggest that children with high intakes of vitamins C and E may be associated with a reduced prevalence of asthma.

Associations of urinary 6-sulfatoxymelatonin with demographics, body mass, sex steroids, and lifestyle factors in preschool Japanese children.

PURPOSE: We aimed to assess the associations of sex, age, body mass, sex steroid hormones, and lifestyle factors with the levels of melatonin in young children. METHODS: This study followed a cross-sectional design and was conducted two preschools in Japan. Subjects were 235 boys and 203 girls, aged 3-6 years. Information related to demographics, body mass, and lifestyle factors was obtained from parent-administered questionnaires. The levels of 6-sulfatoxymelatonin and dehydroepiandrosterone in first-void morning urine were measured by radioimmunoassay. Urinary estrone, estradiol, testosterone, and 5-androstene-3ß, 17α diol levels were measured by liquid chromatography-electrospray ionization tandem mass spectrometry. RESULTS: The creatinine-corrected 6-sulfatoxymelatonin levels and the estimated value of 6-sulfatoxymelatonin excretion were higher in girls than in boys. After adjustments for age, the creatinine-corrected 6-sulfatoxymelatonin was negatively associated with weight and body mass index among boys and with weight and height among girls. However, the estimated value of 6-sulfatoxymelatonin excretion was not associated with any indices of body mass. No significant relationships of urinary sex steroids, light exposure at night, sleep time, sedentary lifestyles, or passive smoking with urinary 6-sulfatoxymelatonin were observed. CONCLUSIONS: Our findings suggest that melatonin levels depend on sex and body size among young healthy children. Our results should be confirmed in future researches.

Total fat intake is associated with decreased mortality in Japanese men but not in women.

Dietary guidelines generally recommend avoiding a high-fat diet. However, the relationship between fat subtypes and mortality remains unclear especially in a population with a relatively low intake of fat. We aimed to prospectively examine the relationship between dietary fat intake and all-cause and cause-specific mortality in a Japanese community. In 1992, a total of 28,356 residents of Takayama, Japan, without cancer, stroke, or coronary heart disease, responded to a validated 169-item FFQ. We identified 4616 deaths during a 16-y follow-up. The HR of mortality according to the percentage of energy from the total and subtypes of fat when substituted for an isoenergic quantity of carbohydrate was calculated after controlling for potential confounders. A high intake of total fat and PUFA was associated with a decrease in all-cause mortality in men; the HR for the highest compared with the lowest quintile were 0.83 (95% CI: 0.70, 0.99; P-trend = 0.048) for total fat and 0.77 (95% CI: 0.62, 0.95; P-trend = 0.05) for PUFA. Both fats were associated with a decrease in mortality from cancer and diseases other than cardiovascular disease. In women, a higher SFA intake was associated with higher all-cause mortality [HR = 1.22 (95% CI: 0.99, 1.49; P-trend = 0.03)]. A favorable effect was suggested for total fat and PUFA intakes on mortality in men except for that from cardiovascular disease, whereas increased SFA intake may be associated with adverse health consequences in women.

Associations of intakes of fat, dietary fiber, soy isoflavones, and alcohol with levels of sex hormones and prolactin in premenopausal Japanese women.

OBJECTIVE: Endogenous sex hormones have been implicated in the etiology of breast cancer. Dietary factors such as fat, dietary fiber, soy isoflavones, and alcohol have been suggested to influence endogenous estrogen and other steroid hormone levels. We examined the relationship among these dietary factors and plasma sex hormone levels in premenopausal Japanese women. METHODS: We measured the plasma concentrations of estradiol, estrone, testosterone, dehydroepiandrosterone sulfate, sex hormone-binding globulin, a follicle-stimulating hormone, a luteinizing hormone, and prolactin among 393 premenopausal women who had regular menstrual cycles fewer than 40 days apart. The dietary intakes were estimated with a validated food frequency questionnaire. RESULTS: After controlling for age, BMI, phase of the menstrual cycle, number of births, age at first birth, history of breastfeeding, and smoking status, the saturated fat intake was significantly positively associated with total estradiol and free estradiol levels. Intakes of the other types of fat, dietary fiber, soy isoflavones, and alcohol were not significantly associated with levels of any hormone measured. CONCLUSIONS: These data suggest that a high intake of saturated fat is associated with increased estradiol levels in premenopausal Japanese women. Saturated fat intake may have implications in the etiology of breast cancer.

Associations of physical activity and diet with the onset of menopause in Japanese women.

OBJECTIVE: Prospective studies on physical activity and diet and the onset of natural menopause are scarce. The aim of this study was to examine the association of physical activity and dietary factors potentially related to endogenous estrogen levels such as fats, dietary fiber, soy isoflavones, and alcohol with the onset of menopause in a cohort of premenopausal women. METHODS: Study participants were 3,115 premenopausal Japanese women aged 35 to 56 years derived from the participants in the Takayama Study. Physical activity was assessed by a validated questionnaire at baseline, and the metabolic equivalent score was calculated. The dietary intakes were estimated by a validated food frequency questionnaire at baseline and adjusted for total energy. Menopause status was defined as the absence of menstruation for 12 months or more. The Cox proportional hazard model was used to estimate the hazard ratio of the occurrence of menopause after controlling for age, parity, body mass index, smoking status, years of education, and lifelong irregular menstrual cycle. RESULTS: During the 10-year follow-up, 1,790 women experienced natural menopause. A high physical activity level and a high intake of polyunsaturated fat were moderately but significantly associated with the earlier onset of menopause; the hazard ratios for the highest versus lowest quartile were 1.17 (95% CI, 1.02-1.34) for physical activity and 1.15 (95% CI, 1.01-1.31) for polyunsaturated fat intake. Total fat, other types of fat, dietary fiber, soy isoflavones, and alcohol were not associated with the onset of menopause. CONCLUSIONS: These data suggest that high levels of physical activity and polyunsaturated fat intake are associated with earlier onset of menopause.

Associations of birth weight and physical activity with sex steroids in preschool Japanese children.

PURPOSE: We aimed to assess the association of body size at birth or physical activity with sex steroid levels, independent of body mass among young children. METHODS: The cross-sectional study was conducted in 2006. Subjects were 230 boys and 198 girls, aged 3-6 years. Birth weight was based on parents' reports. Questions about physical activity focused on outdoor playtime. Urinary estrone, estradiol, testosterone, and 5-androstene-3ß,17α diol (3ß,17α-AED) levels were measured by liquid chromatography-electrospray ionization tandem mass spectrometry. Urinary dehydroepiandrosterone level was measured with a radioimmunoassay. RESULTS: After adjustments for age and BMI, girls with lower birth weight had higher testosterone (trend p = 0.038) and 3ß,17α-AED (trend p = 0.028). Girls with low birth weight and high birth weight had higher estrone (p = 0.014) and estradiol (p = 0.074) than those who had middle birth weight. Boys who were physically active had lower testosterone (p = 0.028) and 3ß,17α-AED (p = 0.003) than those who were not active. Girls who were physically active had lower estrone (p = 0.015). CONCLUSIONS: Sex steroid levels in childhood might be affected by body size at birth or by physical activity during childhood. These effects might differ by sex.