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Objectives: Urinary sex hormones are investigated as potential biomarkers for the early detection of breast cancer, aiming to evaluate their relevance and applicability, in combination with supervised machine-learning data analysis, toward the ultimate goal of extensive screening., Methods: Sex hormones were determined on urine samples collected from 250 post-menopausal women (65 healthy - 185 with breast cancer, recruited among the clinical patients of Candiolo Cancer Institute FPO-IRCCS (Torino, Italy). Two analytical procedures based on UHPLC-MS/HRMS were developed and comprehensively validated to quantify 20 free and conjugated sex hormones from urine samples. The quantitative data were processed by seven machine learning algorithms. The efficiency of the resulting models was compared., Results: Among the tested models aimed to relate urinary estrogen and androgen levels and the occurrence of breast cancer, Random Forest (RF) proved to underscore all the other supervised classification approaches, including Partial Least Squares - Discriminant Analysis (PLS-DA), in terms of effectiveness and robustness. The final optimized model built on only five biomarkers (testosterone-sulphate, alpha-estradiol, 4-methoxyestradiol, DHEA-sulphate, and epitestosterone-sulphate) achieved an approximate 98% diagnostic accuracy on replicated validation sets. To balance the less-represented population of healthy women, a Synthetic Minority Oversampling TEchnique (SMOTE) data oversampling approach was applied., Conclusions: By means of tunable hyperparameters optimization, the RF algorithm showed great potential for early breast cancer detection, as it provides clear biomarkers ranking and their relative efficiency, allowing to ground the final diagnostic model on a restricted selection five steroid biomarkers only, as desirable for noninvasive tests with wide screening purposes., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Marco Vincenti reports financial support was provided by CRT Foundation. Marco Vincenti reports financial support was provided by Italian Ministry of Education, Universities, and Research. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Uropathogenic Escherichia coli (UPEC) is a typical cystitis-causing organism that can migrate from the vagina to the bladder and cause recurrent cystitis (RC). Few reports have compared the characteristics of urinary and vaginal UPEC in patients with RC. We carried out molecular biological analyses of Escherichia coli (E. coli) strains and their antimicrobial susceptibility to assess the association between urinary and vaginally UPEC. We included E. coli isolated from urinary and vaginal samples at the onset of cystitis in postmenopausal women with RC between 2014 and 2019 in our hospital. Pulsed-field gel electrophoresis (PFGE) was performed using a restriction enzyme (Xba I). These sequences were compared with 17 antimicrobial susceptibilities determined by a micro-liquid dilution method. Multilocus sequence typing (MLST) and classification of extended-spectrum β-lactamase (ESBL) genotypes by multiplex polymerase chain reaction (PCR) were performed on ESBL-producing E. coli. We analyzed 14 specimens (each seven urine and vaginal) from seven patients in total. On PFGE, the similarity of urinary and vaginal E. coli per patient ranged from 89.5 to 100 %, including four patients with 100 % matches. MLST demonstrated that 29 % (4/14 specimens) were strain sequence type 131. Two specimens contained ESBL-producing strains and identified the CTX-M-27 genotype for each specimen. For each patient, antimicrobial susceptibilities between urinary and vaginal E. coli were mostly identical. Thus, urinary- and vaginally-derived E. coli were identical in postmenopausal women with RC. Management targeting both urinary and vaginal UPEC is essential for RC, indicating the importance of a vagina-targeted approach., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Aims/introduction: Equol, which is produced by enteric bacteria from soybean isoflavones, has a chemical structure similar to estrogen. Both in vivo and in vitro studies have shown the beneficial metabolic effects of equol. However, its effects on type 2 diabetes remain unclear. We investigated the association between the equol producers/non-producers and type 2 diabetes., Materials and Methods: The participants included 147 patients with type diabetes mellitus aged 70-89 years, and 147 age- and sex-matched controls. To ascertain the equol producers or non-producers, we used the comparative logarithm between the urinary equol and daidzein concentrations (cut-off value -1.75)., Results: The urinary equol concentration was significantly lower in the diabetes group compared with the non-diabetes group (P = 0.01). A significant difference in the proportion of equol producers was observed among all participants (38.8% in the diabetes group and 53.1% in the non-diabetes group; P = 0.01). The proportion of equol producers among women was significantly lower in the diabetes group (31.4%) than in the non-diabetes group (52.8%; P < 0.01). Additionally, the frequency of dyslipidemia in female equol producers was significantly lower than that in female non-equol producers (P < 0.01). Among men, no such differences were observed. We found a significant positive correlation between the urinary equol and daidzein concentrations among equol producers (r = 0.55, P < 0.01)., Conclusions: Our study findings showed that postmenopausal women had a low proportion of equol producers with diabetes and dyslipidemia., (© 2023 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Postmenopausal women and renal transplant recipients are at increased risk of recurrent urinary tract infections (RUTI). Urine and vaginal microbiota of premenopausal controls (N = 18) and RUTI cases (18), and of postmenopausal controls (30) and RUTI cases (20) with and without a renal transplant, were characterized using 16S rRNA sequencing. Participants did not have UTI symptoms at the time of sampling. Gram-negative uropathobionts (predominantly Escherichia/Shigella, Pseudomonas, Klebsiella, and Acinetobacter) had a much higher mean relative abundance in urine than vaginal samples, especially in premenopausal women. No statistically significant differences in mean relative abundances of bacterial groups were found within the premenopausal group or within the postmenopausal group by RUTI or renal transplant status without chronic antibiotic use. Comparing postmenopausal to premenopausal women, mean relative abundances of lactobacilli (especially L. crispatus) in urine and vaginal samples and of Gram-negative uropathobionts in urine were lower, and of BV-anaerobes and Gram-positive uropathobionts in urine and vaginal samples were higher. While RUTI in premenopausal women is predominantly caused by Escherichia, the causative organisms in postmenopausal women are likely more diverse. The relative importance of individual organisms is currently unknown. We recommend that future studies, including intervention studies, include longitudinal microbiota assessments., (© 2022. The Author(s).)

Dietary guidance emphasizes healthy dietary patterns, but supporting evidence comes from self-reported dietary data, which are prone to measurement error. We explored whether nutritional biomarkers from the Women's Health Initiative Nutrition and Physical Activity Assessment Study Feeding Study (NPAAS-FS) (n = 153; 2010-2014) and the Women's Health Initiative Nutrition and Physical Activity Assessment Study Observational Study (NPAAS-OS) (n = 450; 2006-2009) could identify biomarker signatures of dietary patterns for development of corresponding regression calibration equations to help mitigate measurement error. Fasting blood samples were assayed for a specific panel of vitamins, carotenoids, and phospholipid fatty acids; 24-hour urine samples were assayed for nitrogen, sodium, and potassium levels. Intake records from the NPAAS-FS were used to calculate Healthy Eating Index 2010 (HEI-2010), Alternative Healthy Eating Index 2010 (AHEI-2010), alternative Mediterranean diet (aMED), and Dietary Approaches to Stop Hypertension (DASH) scores. Scores were regressed on blood and urine nutritional measures for discovery of dietary pattern biomarkers using a cross-validated model R2 ≥ 36% criterion (stage 1). Next, stepwise models (P ≤ 0.10 for entry/removal) using NPAAS-OS data were used to regress stage 1 dietary pattern biomarkers on NPAAS-OS self-reported dietary pattern scores using a food frequency questionnaire, a 4-day food record, and a 24-hour recall (stage 2). HEI-2010 and aMED analyses met the cross-validated R2 ≥ 36% criterion in stage 1, while AHEI-2010 and DASH analyses did not. The R2 values for HEI-2010 stage 2 calibration equations were as follows: food frequency questionnaire, 63.5%; 4-day food record, 83.1%; and 24-hour recall, 77.8%. Stage 2 aMED R2 values were 34.9%-46.8%. Dietary pattern biomarkers have potential for calibrating self-reports to enhance studies of diet-disease associations., (Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2021. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Clinical and preclinical studies have reported that Lactobacillus gasseri BNR17, a probiotic bacterial strain isolated from human breast milk, reduces body weight and white adipose tissue volume. In order to further explore the actions of L. gasseri BNR17, we investigated the anti-menopausal effects of L. gasseri BNR17 in an ovariectomized (OVX) rat model. The serum alanine aminotransferase levels of the rats in the OVX-BNR17 group were lower than those of the rats in the OVX-vehicle only (OVX-Veh) group. Upon administration of L. gasseri BNR17 after ovariectomy, calcitonin and Serotonin 2A levels increased significantly, whereas serum osteocalcin levels showed a decreasing tendency. Compared to the rats in the OVX-Veh group, those in the OVX-BNR17 group showed lower urine deoxypyridinoline levels, lower pain sensitivity, and improved vaginal cornification. Furthermore, L. gasseri BNR17 administration increased bone mineral density in the rats with OVX-induced femoral bone loss. These results suggest that L. gasseri BNR17 administration could alleviate menopausal symptoms, indicating that this bacterium could be a good functional probiotic for managing the health of older women.

Context: Phthalates are endocrine-disrupting chemicals that could disrupt normal physiologic function, triggering detrimental impacts on bone., Objective: We evaluated associations between urinary phthalate biomarkers and BMD in postmenopausal women participating in the prospective Women's Health Initiative (WHI)., Methods: We included WHI participants enrolled in the BMD substudy and selected for a nested case-control study of phthalates and breast cancer (N = 1255). We measured 13 phthalate biomarkers and creatinine in 2 to 3 urine samples per participant collected over 3 years, when all participants were cancer free. Total hip and femoral neck BMD were measured at baseline and year 3, concurrent with urine collection, via dual-energy x-ray absorptiometry. We fit multivariable generalized estimating equation models and linear mixed-effects models to estimate cross-sectional and longitudinal associations, respectively, with stratification on postmenopausal hormone therapy (HT) use., Results: In cross-sectional analyses, mono-3-carboxypropyl phthalate and the sum of di-isobutyl phthalate metabolites were inversely associated with total hip BMD among HT nonusers, but not among HT users. Longitudinal analyses showed greater declines in total hip BMD among HT nonusers and with highest concentrations of mono-3-carboxyoctyl phthalate (-1.80%; 95% CI, -2.81% to -0.78%) or monocarboxynonyl phthalate (-1.84%; 95% CI, -2.80% to -0.89%); similar associations were observed with femoral neck BMD. Among HT users, phthalate biomarkers were not associated with total hip or femoral neck BMD change., Conclusion: Certain phthalate biomarkers are associated with greater percentage decreases in total hip and femoral neck BMD. These findings suggest that phthalate exposure may have clinically important effects on BMD, and potentially fracture risk., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Recent studies suggest that alterations in the female urinary microbiota is associated to development of bladder disease. However, the normal microbiota composition and variation in healthy women are poorly described. Moreover, the effects of hormonal changes on microbiota during menopause is not well understood. The aim of our study was to investigate the urinary microbiota in healthy pre- and postmenopausal women without urinary tract symptoms. Microbiota composition in catheterized urine samples was mapped using 16S rRNA gene sequencing. In total, 41 premenopausal and 42 postmenopausal women were initially included. Samples with first PCR amplification concentration below level of the negative control were excluded, resulting in 34 premenopausal and 20 postmenopausal women included in data analysis. Urine from postmenopausal women showed significantly higher alpha diversity compared to premenopausal women. Lactobacillus was the most abundant bacteria in both groups, however the relative abundance of Lactobacillus accounted for 77.8% in premenopausal versus 42.0% in postmenopausal women. In conclusion, urine from premenopausal mostly presented with Lactobacillus dominated urotypes, whereas urine from postmenopausal women presented a more diverse urinary microbiota with higher abundance of the genera Gardnerella and Prevotella. The clinical and pathophysiological implications of this difference remain to be elucidated.

Background & Aims: Nutrition is one of the most important environmental factors affecting the formation of osteopenia. The purpose of this study was to investigate the effects of dietary changes on bone formation and bone resorption markers of postmenopausal women with vertebral osteopenia., Methods: In this study, 108 women with postmenopausal vertebral osteopenia were included. Patients were observed for a month to identify their regular nutritional status. Before intervention, blood and urine samples were taken from all patients. Then, 2-day food consumption records were taken and the patients were divided into 4 groups. Different types of diets (opposite of their regular diets) were prepared for these groups (1: control, 2: reduced-carbohydrate, 3: reduced-protein, 4: reduced-sodium) and followed for 3 months. At the end of follow-ups, blood and urine samples were taken again and changes in osteocalcin (OC) and N-terminal telopeptide (NTX) levels were examined., Results: According to biochemical analysis, there was a significant decrease (p < 0,001) in OC levels in reduced protein group and an increase (p > 0,05) in reduced carbohydrate group. When NTX levels were assessed, a significant decrease (p < 0.001) in the reduced carbohydrate group and a significant increase in the reduced protein group (p < 0.05) were found., Conclusion: Our findings show that reduced carbohydrate diet protected whereas, reduced protein diet negatively affected bone health. Osteopenic individuals were thought to be able to improve bone health and their quality of life by early dietary intervention., Competing Interests: Conflict of interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Chronic insomnia is the most common sleep disorder in the elderly population. From 9 to 50% of patients suffer of paradoxical insomnia, with the same symptoms and ailments, though characterized by normal sleep patterns. We have investigated the level of parameters related to stress in a group of post-menopausal female patients (age range 55-70 years) suffering by either objective or paradoxical insomnia, in particular we have measured 24-hours urinary cortisol, allostatic load index, Perceived Stress Scale (PSS) score, and, for the first time, mitokines (mitochondrial stress response molecules) such as FGF21, GDF15 and Humanin (HN). Results show that the two groups are different as far as sleep efficiency score, as expected, but not for stress parameters, that in some cases resulted within the normality range, although quite close to the top threshold (such as cortisol) or much higher with respect to normality ranges (such as PSS). Therefore, the consequences of paradoxical insomnia on the expression of these parameters are the same as objective insomnia. As far as the level of mitokines, we showed that FGF21 and HN in particular resulted altered (decreased and increased, respectively) with respect to control population, however with no difference between the two groups of patients.

Purpose: Bone turnover markers (BTMs) are not widely used in clinical decision-making partly due to the wide variation of the reference values. This paper describes the geographical variation in BTMs reported from Asian countries., Method: A systematic search was conducted using the PubMed, EMBASE, and Ovid. We searched for BTMs or individual BTMs in Asia or different countries in the Asian region. Original research which published BTM values were included while reviews, comments, and meta-analyses were excluded., Results: Of 650 articles, 23 fulfilled the selection criteria and were considered for this study. Among premenopausal women, mean intact OC ranged from 3.35 in Japan to 7.38 ng/mL (55%) in Thailand while it ranged between 3.35 and 5.8 ng/mL (42%) within Japan. Mean BALP varied from 15.9 in India to 41.2 U/L (61%) in Japan whereas in India, it ranged between 15.9 and 53.7 U/L (70%). Mean sP1NP ranged from 29.5 in Japan to 38.02 ng/mL in China (22%) whereas sCTX varied from 0.26 in Thailand to 0.099 ng/mL (62%) in Japan. Among postmenopausal women, mean total OC ranged from 10.02 in India to 29.8 ng/mL (66%) in Japan and intact OC ranged between 2.69 and 9.49 ng/mL (72%) within China. Mean BALP ranged from 20.9 in Japan to 60.28 U/L (65%) in China, and within China, it ranged from 28.2 to 60.28 U/L (53%). Mean sP1NP ranged from 40.11 in China to 56.4 ng/mL (29%) in Japan whereas it ranged within China from 40.11 to 53.76 ng/mL (25%). Mean sCTX varied from 0.25 to 0.433 ng/mL (42%) between the same countries respectively while within China, it varied from 0.25 to 0.395 ng/mL (37%). Urinary BTMs showed a lesser variation., Conclusion: A wide inter-country and intra-country variation of serum BTMs was observed among pre and postmenopausal women in Asia. Differences in selection criteria of subjects and those inherited to analytical methods may have contributed to these differences.

Background: Primary hyperparathyroidism (PHPT) is a common cause of secondary osteoporosis in postmenopausal women. Th17 lymphocytes and the released cytokine IL-17A play an important role in bone metabolism. Th17 cells have been shown to be activated by PTH, and peripheral blood T cells from patients affected with PHPT express higher levels of IL-17A mRNA than controls., Aim: To investigate circulating levels of IL-17A and the ratio RANKL/OPG, as markers of osteoclastogenesis, in 50 postmenopausal PHPT women compared with postmenopausal osteoporotic non-PHPT women ( n = 20)., Results: Circulating levels of IL-17A were similarly detectable in most PHPT and non-PHPT osteoporotic women (12.9 (8.4-23.1) vs. 11.3 (8.3-14.3) pg/ml, median (range interquartile), P = 0.759), at variance with premenopausal women where IL-17A was undetectable. In PHPT women, any significant correlations could be detected between circulating IL-17A levels and PTH levels. Nonetheless, significant negative correlations between circulating IL-17A and ionized calcium levels ( r = -0.294, P = 0.047) and urine calcium excretions ( r = -0.300, P = 0.045) were found. Moreover, PHPT women were characterized by positive correlations between IL-17A levels and femur neck ( r = 0.364, P = 0.021) and total hip ( r = 0.353, P = 0.015) T -scores. Circulating IL-17A levels did not show any significant correlation with sRANKL, OPG, and sRANKL/OPG ratio in PHPT women., Conclusions: In postmenopausal PHPT women, circulating IL-17A levels were similar to those detected in postmenopausal non-PHPT women, showing a disruption of the relationship observed in postmenopausal osteoporosis among circulating PTH, sRANKL, OPG, IL-17A, and bone demineralization in postmenopausal PHPT women. The data support an osteogenic effect of IL-17A in postmenopausal PHPT women., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 E. Dozio et al.)

The aim of this study was to investigate the effect of the ingestion of tomato before bed on obese postmenopausal women's urinary 6-sulphatoxymelatonin (aMT6s) level and sleep quality. We quantified melatonin concentrations in beefsteak tomato, black tomato, and two commercial tomato juices and found that beefsteak tomato contained the highest level of melatonin. In this 8-week open-label, randomized controlled dietary intervention trial, 36 subjects completed the entire trial. The tomato group ate 250 g of beefsteak tomatoes 2 h before sleep for 8 weeks. Blood and urine samples were collected at the baseline and in the 8th week and were analyzed. The Pittsburgh Sleep Quality Index (PSQI) in the tomato group significantly decreased with time (p for trend = 0.0297). After 8 weeks of the beefsteak intervention, all components of the PSQI in tomato group had significantly improved, and their aMT6s level was 10-fold significantly higher than that of the control group. Therefore, supplementation with beefsteak tomato before sleep can increase circulating melatonin and improve sleep quality in obese postmenopausal women., (Copyright © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Objective: Kidney involvement is a common complication in primary hyperparathyroidism (PHPT). No study so far has assessed the prevalence of kidney injury developing before the reduction in glomerular filtration rate (GFR) in PHPT. The study was aimed at establishing the potential role of biomarkers of kidney injury in detecting subtle renal damage in patients with PHPT., Design: Cross-sectional study., Patients: A total of 69 postmenopausal patients with PHPT and 41 healthy age- and sex-matched subjects were studied. Exclusion criteria were as follows: GFR < 30 mL/min, chronic inflammatory disease, nephrotic syndrome, infection, malignancy, heart failure, recent exposure to iodinated contrast media or nonsteroidal anti-inflammatory drugs., Measurements: We measured a panel of sensitive biomarkers of kidney injury in PHPT vs controls., Results: Mean FGF23 and Klotho were higher in PHPT (72 ± 48 and 811 ± 366 pg/mL, respectively) than controls (53 ± 23.5 and 668.6 ± 17; P < .02 and P < .05). Urine KIM-1/uCr was significantly higher in PHPT (1.4 -6  ± 1.3 -6 ) than controls (9.2 -7  ± 7 -7 ; P < .05); this was particularly evident in the CrCl 60-89 mL/min category (1.3 6  ± 9 7 vs 8.2 -7  ± 3.6 -7 ; P < .02). Mean values of urine NGAL/uCr were higher in PHPT with (n = 28) compared to those without kidney stones (n = 35; 1.8 -5  ± 1.4 -5 and 1 -5  ± 8 -6 ; P < .0001). We found significant positive associations between urine NGAL/uCr and Ca (R = .292, P < .02) and urine KIM1/uCr and PTH (R = .329, P < .01)., Conclusions: We propose the utilization of these molecules, particularly urine KIM-1/uCr and urine NGAL/uCr ratios for the assessment of subtle kidney injury in patients with PHPT. These molecules are elevated in tubular necrosis and have potential role in the development of kidney damage in PHPT, according to the severity of the disease., (© 2019 John Wiley & Sons Ltd.)

Objective: We aimed to establish correlations for the levels of follicle-stimulating hormone (FSH), estrone (E1) and estradiol (E2) between urine and serum in premenopausal and postmenopausal women using immunoassays., Methods: In this study of 92 women (61 postmenopausal, 31 premenopausal), both urine and blood specimens were collected on the same day and stored at 4 °C for analysis by chemiluminescent immunoassay, radioimmunoassay and/or electrochemiluminescent immunoassay., Results: There were correlations in the levels of FSH, E1 and E2 between urine and serum in both postmenopausal (r = 0.96 for FSH, r = 0.91 for E1, r = 0.80 for E2) and premenopausal (r = 0.98 for FSH, r = 0.92 for E1, r = 0.90 for E2) women. It is indicated that the correlations were stronger in the premenopausal group compared with the postmenopausal group, especially for FSH., Conclusion: The levels of FSH, E1 and E2 in urine correlated with those in the serum in premenopausal and postmenopausal women. Urine samples could be used instead of serum samples to measure hormone levels, which would reduce the difficulty of conducting large survey studies., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Breast density, as estimated by mammography, is a strong risk factor for breast cancer in pre- and postmenopausal women, but the determinants of breast density have not yet been established. The aim of this study was to assess if urinary estrogens or gut microbiota alterations are associated with mammographic density in postmenopausal women., Methods: Among 54 cancer-free, postmenopausal controls in the Breast and Colon Health study, we classified low- versus high-density women with Breast Imaging Reporting and Data System (BI-RADS, 5th edition) mammographic screening data, then assessed associations with urinary estrogens and estrogen metabolites (determined by liquid chromatography/tandem mass spectrometry), and fecal microbiota alpha and beta diversity (using Illumina sequencing of 16S rRNA amplicons)., Results: Multiple logistic regression revealed no significant association between breast density and fecal microbiota metrics (PD&#95;tree P-value = 0.82; un-weighted and weighted UniFrac P = 0.92 and 0.83, respectively, both by MiRKAT). In contrast, total urinary estrogens (and all 15 estrogens/estrogen metabolites) were strongly and inversely associated with breast density (P = 0.01) after adjustment for age and body mass index., Conclusion: Mammographic density was not associated with the gut microbiota, but it was inversely associated with urinary estrogen levels., Impact: The finding of an inverse association between urinary estrogens and breast density in cancer-free women adds to the growing breast cancer literature on understanding the relationship between endogenous estrogens and mammographic density., Competing Interests: The authors have declared that no competing interests exist.

Background/aim: This study was designed to evaluate the relationship between urinary phytate concentration and risk of fracture at 10 years, determined by using the FRAX model, in women who had undergone menopause within 5 years of the time of enrollment., Materials and Methods: Of the 212 postmenopausal women evaluated, 69 were excluded because they had urinary phytate concentrations between 0.51 and 0.99 mg/L. Of the remaining 143 women, 91 had low (≤0.50 mg/L) and 52 had high (≥1.0 mg/L) urinary phytate concentrations. The 10-year risk of fracture was calculated by using the FRAX model., Results: The risks of major osteoporotic fracture and hip fracture were higher in women with low urinary phytate levels (P < 0.001 in both cases). Evaluation of the risk of hip fracture in women with and without risk factors for osteoporosis (e.g., tobacco, alcohol, and drug consumption) and according to urinary phytate concentrations indicated that, among women with no risk factors, those with low and high urinary phytate levels had a range of risks of 0%–0.6% and 0%–0.3%, respectively (P = 0.098). Moreover, among women with at least one risk factor, those with low and high urinary phytate had a range of risks of 0.1%–0.8% and 0.1%–0.4%, respectively (P = 0.002). Similar results were observed when the risks of major osteoporotic fracture were analyzed., Conclusion: These results indicate the relationship of phytate with the risks of major osteoporotic fracture and hip fracture, with these differences being more marked in women with risk factors for osteoporosis. From this study follows the importance of the consumption of phytate-rich products (nuts, legumes, whole cereals) to protect against the risk of fracture in 10 years, mainly in women with risk factors for osteoporosis.

Background: Some phthalates are endocrine disrupting chemicals used as plasticizers in consumer products, and have been associated with obesity in cross-sectional studies, yet prospective evaluations of weight change are lacking. Our objective was to evaluate associations between phthalate biomarker concentrations and weight and weight change among postmenopausal women., Methods: We performed cross-sectional (N = 997) and longitudinal analyses (N = 660) among postmenopausal Women's Health Initiative participants. We measured 13 phthalate metabolites and creatinine in spot urine samples provided at baseline. Participants' weight and height measured at in-person clinic visits at baseline, year 3, and year 6 were used to calculate body mass index (BMI). We fit multivariable multinomial logistic regression models to explore cross-sectional associations between each phthalate biomarker and baseline BMI category. We evaluated longitudinal associations between each biomarker and weight change using mixed effects linear regression models., Results: In cross-sectional analyses, urinary concentrations of some biomarkers were positively associated with obesity prevalence (e.g. sum of di (2-ethylhexyl) phthalate metabolites [ΣDEHP] 4th vs 1st quartile OR = 3.29, 95% CI 1.80-6.03 [p trend< 0.001] vs normal). In longitudinal analyses, positive trends with weight gain between baseline and year 3 were observed for mono-(2-ethyl-5-oxohexyl) phthalate, monoethyl phthalate (MEP), mono-hydroxybutyl phthalate, and mono-hydroxyisobutyl phthalate (e.g. + 2.32 kg [95% CI 0.93-3.72] for 4th vs 1st quartile of MEP; p trend < 0.001). No statistically significant associations were observed between biomarkers and weight gain over 6 years., Conclusions: Certain phthalates may contribute to short-term weight gain among postmenopausal women.

Results of studies on the associations of soy food intake with urinary estrogen levels in premenopausal women and in postmenopausal women have been inconsistent. We examined the associations of urinary isoflavone levels as well as soy food intake with estrone (E1) and estradiol (E2) in pre- and postmenopausal women. In addition, we compared the levels of isoflavones, E1 and E2 across current hormone users such as those receiving hormone replacement therapy and those using oral contraceptives and non-users among both pre- and postmenopausal women. Urinary levels of isoflavones, E1 and E2 in 498 women (36 hormone users and 462 non-users) were analyzed. Premenopausal women with a higher frequency of soy food intake had higher urinary isoflavone levels, but there were no significant associations between E1 and E2 levels and urinary isoflavone levels. Levels of E1 and E2 in hormone users were significantly lower than those in hormone non-users among premenopausal women, but levels of E1 and E2 in hormone users were significantly higher than those in hormone non-users among postmenopausal women. Postmenopausal women with a higher frequency of soy food intake had higher urinary isoflavone levels, and postmenopausal women with high urinary isoflavone levels had significantly higher E1 and E2 levels. In conclusion, the associations of urinary isoflavone levels with urinary estrogen levels differed with menopausal status. Urinary levels of E1 and E2 were high in postmenopausal women with high urinary isoflavone levels but not in premenopausal women with high urinary isoflavone levels., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: To explore the differences of 24-hour urine compositions associated with urolithiasis between non- and postmenopausal females., Methods: The 24-hour urine samples of female participants were collected from May 2013 to July 2014 along with national cross-sectional study of urolithiasis among adults aged ≥18 years in China. The exclusion criteria for the participants were: serum creatinine > 133μmol/L, with urinary tract infection, gout, hyperthyroidism, malignancy, had a history of cancer, kidney stones, enterectomy, had taken thiazide diuretics, allopurinol, vitamin supplement, potassium citrate or calcium supplements during the past two weeks. The compositions associated with urinary stone in 24-hour urine were measured and compared between non-and postmenopausal women., Results: A total of 603 24-hour urine samples of female participants were analyzed. 354 women with a mean age of 52.5± 14.03 (range 19-84) years met the criteria, including 160 non-menopausal women and 194 postmenopausal women. Compared to the non-menopausal women, postmenopausal women had a lower secretion of citrate (p = 0.043), magnesium (p = 0.001) and creatinine (p = 0.001) in 24h urine. Multivariate linear regression analysis showed that the menopause status was associated with the changes in magnesium (p = 0.003) and creatinine (p = 0.002) secretion, whereas not with the changes in citrate (p = 0.402) secretion., Conclusions: Postmenopausal women have a significant lower secretion of magnesium in their 24-hour urine than non-menopausal ones. We suppose that might be associated with increased risk of urinary stone formation among postmenopausal women., Competing Interests: The authors have declared that no competing interests exist.

Objective: In the present study, we aimed to characterize the pathological development of menopausal osteoporosis, as well as to explore potential biomarkers and metabolic pathways involved in osteoporosis., Methods: Urine samples from 322 female participants categorized by menopause status and different bone conditions were collected and analyzed based on a gas chromatography-mass spectrometry (GC-MS) approach. Multivariate and univariate statistical analyses were carried out for urinary metabolomic profile characterization and comparison., Results: Seventeen metabolites in the low bone mineral density (BMD) groups were clearly differentiated from those in normal BMD groups. Among these 17 differentiating metabolites, taurine, β-alanine, and 5-hydroxycaproic acid were found to be potential biomarkers of osteoporosis. The taurine metabolic pathway and the β-alanine metabolic pathway were found to be related to menopause and bone loss., Conclusions: Based on the GC-MS metabolomic platform, four typical pathological phases during the progression of postmenopausal osteoporosis were described. Several differentiating metabolites and metabolic pathways were found to be closely related to the pathology of postmenopausal osteoporosis. Our results provided a solid foundation for further studies on early diagnosis and pathomechanistic evaluation.

Background and Objectives: In-vitro data suggest that clearance of vilaprisan is mediated by cytochrome P450 3A4 (oxidation) and aldoketoreductases (reduction). To fully understand the elimination and biotransformation pathways of vilaprisan, a selective progesterone receptor modulator, and to quantify the impact of cytochrome P450 3A4 inhibition on the pharmacokinetics of vilaprisan, two clinical studies in healthy postmenopausal women were conducted., Methods: In study 1, pharmacokinetics, mass balance, and metabolite patterns were determined after single oral administration of 5 mg of [ 14 C]-labeled vilaprisan in six subjects. In study 2, pharmacokinetics were determined after single oral administration of 4 mg of vilaprisan without and with concomitant administration of the strong cytochrome P450 3A4 inhibitor itraconazole (200 mg/day) in 14 subjects. In addition, a microtracer dose of vilaprisan was given intravenously to determine absolute bioavailability, clearance, and volume of distribution., Results: The dominant single compound in plasma was vilaprisan. No plasma metabolites exceeding 10% of total drug-related area under the concentration-time curve were detected. The absolute oral bioavailability of vilaprisan was ~ 60%. The mean clearance was ~ 7 L/h and the volume of distribution at steady state was ~ 360 L. Excretion occurred primarily via feces (73.5 ± 3.70% of dose; urine: 13.1 ± 1.71%; total recovery: 86.6 ± 2.81%), mostly in a metabolized form. Only small amounts of the parent drug were found in excreta. When vilaprisan was administered together with itraconazole, exposure to vilaprisan was increased 6.2-fold (90% confidence interval 5.4-7.2)., Conclusions: Vilaprisan is predominantly metabolized in the liver to a complex variety of metabolites, which are mainly excreted with feces. The pivotal role of cytochrome P450 3A4 in the metabolism of vilaprisan was confirmed., Clinical Trial Registration: EudraCT numbers 2013-000707-16 (mass balance study) and 2014-004929-41 (drug-drug interaction/microtracer study); NCT02456129 (drug-drug interaction/microtracer study).

Laboratory studies indicate that melatonin has beneficial vascular effects. However, epidemiologic studies on the relationship between endogenous levels of melatonin and hypertension in humans are limited. We examined the association of quartile levels of 6-sulfatoxymelatonin (aMT6s) in first morning urines with prevalent and incident hypertension in 777 postmenopausal women who were originally part of a case-control study of breast cancer nested in the Women's Health Initiative Observational Study. A total of 321 prevalent and 172 incident cases of hypertension were studied. In cross-sectional analyses, higher quartile level of aMT6s was associated with lower odds of hypertension (Q4 versus Q1; odds ratio = 0.57; 95% confidence interval [CI]: 0.3-0.9), after adjustment for age, body mass index and other risk factors. We also examined the association between baseline aMT6s levels and risk of incident hypertension. Compared to women in the lowest quartile of urinary aMT6s, the multivariable-adjusted hazard ratios and 95% CIs of incident hypertension for women in the second, third and highest quartile were 1.16 (0.8-1.8), 0.96 (0.6-1.5) and 1.02 (0.6-1.6), respectively. The mean change in systolic and diastolic blood pressure over 3 years also did not vary by baseline quartile levels of aMT6s. Although we found no evidence of a prospective association between urinary levels of aMT6s and risk of incident hypertension in postmenopausal women, our cross-sectional results provide some possible evidence of a role for physiologic levels of melatonin in hypertension. Additional larger studies are warranted, preferably with a wider range of ages, both genders and multiple melatonin measurements.

Arsenic is a risk factor for several noncommunicable diseases, even at low doses. Urinary arsenic (UAs) concentration is a good biomarker for internal dose, and demographic, dietary, and lifestyle factors are proposed predictors in nonoccupationally exposed populations. However, most predictor studies are limited in terms of size and number of predictors. We investigated demographic, dietary, and lifestyle determinants of UAs concentrations in 744 postmenopausal Danish women who had UAs measurements and questionnaire data on potential predictors. UAs concentrations were determined using mass spectrometry (ICP-MS), and determinants of the concentration were investigated using univariate and multivariate regression models. We used a forward selection procedure for model optimization. In all models, fish, alcohol, and poultry intake were associated with higher UAs concentration, and tap water, fruit, potato, and dairy intake with lower concentration. A forward regression model explained 35% ( R ²) of the variation in concentrations. Age, smoking, education, and area of residence did not predict concentration. The results were relatively robust across sensitivity analyses. The study suggested that UAs concentration in postmenopausal women was primarily determined by dietary factors, with fish consumption showing the strongest direct association. However, the majority of variation in UAs concentration in this study population is still unexplained.

Objective: To assess the relationship of constipation and diarrhea severity during the menopause transition (MT) with age, MT stage, reproductive biomarkers, stress-related biomarkers, and stress-related perceptions., Methods: From 1990 to 1992, women aged 35 to 55 years were recruited from the greater Seattle area; 291 of them consented to ongoing (1990-2013) annual data collection by daily menstrual calendar, health diary, and annual health questionnaire. A subset (n = 131) provided a first morning voided urine specimen (1997-2013). These were assayed for levels of E1G, follicle-stimulating hormone, testosterone, cortisol, norepinephrine, and epinephrine. Mixed-effects modeling was used to identify how changes in constipation and diarrhea severity over time related to age, MT stage, reproductive biomarkers, stress-related biomarkers, and stress-related perceptions., Results: In a univariate model, age, late reproductive (LR) stage, tension, and anxiety were all significantly and positively related to constipation severity, whereas cortisol was significantly and negatively associated. In a multivariate model, only tension and cortisol remained significant predictors of constipation severity (P < 0.05). In a univariate model, age, LR stage, and estrone glucuronide were significantly and negatively associated with diarrhea severity, whereas tension, anxiety, and perceived stress were significantly and positively related. In a multivariate model, only tension and age remained significant predictors of diarrhea severity., Conclusions: Key reproductive hormones do not play a significant role in constipation or diarrhea severity in the MT. In contrast, stress perception, tension, anxiety, and cortisol do. These factors should be evaluated in further research involving constipation and diarrhea.

Background: The diversity and composition of the gut microbiota may affect breast cancer risk by modulating systemic levels of oestrogens and inflammation. The current investigation tested this hypothesis in postmenopausal women by identifying breast cancer associations with an inflammation marker, oestrogen levels, and faecal microbes that were or were not coated with mucosal immunoglobulin A (IgA)., Methods: In this population-based study, we compared 48 postmenopausal breast cancer cases (75% stage 0-1, 88% oestrogen-receptor positive) to 48 contemporaneous, postmenopausal, normal-mammogram, age-matched controls. Microbiota metrics employed 16S rRNA gene amplicon sequencing from IgA-coated and -noncoated faecal microbes. High-performance liquid chromatography/mass spectrometry (HPLC/MS) and radioimmunoassay were used to quantify urine prostaglandin E metabolite (PGE-M), a possible marker of inflammation; urine oestrogens and oestrogen metabolites were quantified by HPLC/MS-MS., Results: Women with pre-treatment breast cancer had non-significantly elevated oestrogen levels; controls' (but not cases') oestrogens were directly correlated with their IgA-negative microbiota alpha diversity (P=0.012). Prostaglandin E metabolite levels were not associated with case status, oestrogen levels, or alpha diversity. Adjusted for oestrogens and other variables, cases had significantly reduced alpha diversity and altered composition of both their IgA-positive and IgA-negative faecal microbiota. Cases' faecal microbial IgA-positive imputed Immune System Diseases metabolic pathway genes were increased; also, cases' IgA-positive and IgA-negative imputed Genetic Information Processing pathway genes were decreased (P⩽0.01)., Conclusions: Compared to controls, breast cancer cases had significant oestrogen-independent associations with the IgA-positive and IgA-negative gut microbiota. These suggest that the gut microbiota may influence breast cancer risk by altered metabolism, oestrogen recycling, and immune pressure.

We investigated whether the phosphate (Pi) load in the circulation causes renal damage in non-CKD women. This cross-sectional study included 1,094 non-CKD Japanese women. Fibroblast growth factor (FGF)-23 as a parameter for the Pi load, bone alkaline phosphatase (BAP) as a bone metabolic marker, and the urinary albumin-to-creatinine ratio (UACR) as an early marker for renal damage were measured. Postmenopausal women exhibited significantly higher levels of serum Pi, FGF-23, BAP, and UACR and significantly lower eGFR than premenopausal women. In postmenopausal women, a multiple regression analysis confirmed a correlation between serum BAP and log UACR. In premenopausal women, although serum FGF-23 did not correlate with log UACR, a multiple regression analysis revealed that FGF-23 correlated with log UACR. Based on the i ncrease observed in BAP and its close relationship with log UACR in postmenopausal women, the release of Pi from bone may be linked to the systemic circulation of Pi, which has the potential to induce renal and vascular damage. Therefore, serum FGF-23 may be a useful marker for renal and vascular damage in premenopausal women; however, it currently remains unclear whether FGF-23 by itself or as a surrogate marker for the Pi load induces damage in the kidney and/or vasculature.

Studies of the associations of sodium and potassium intakes with cardiovascular disease incidence often rely on self-reported dietary data. In the present study, self-reported intakes from postmenopausal women at 40 participating US clinical centers are calibrated using 24-hour urinary excretion measures in cohorts from the Women's Health Initiative, with follow-up from 1993 to 2010. The incidence of hypertension was positively related to (calibrated) sodium intake and to the ratio of sodium to potassium. The sodium-to-potassium ratio was associated with cardiovascular disease incidence during an average follow-up period of 12 years. The estimated hazard ratio for a 20% increase in the sodium-to-potassium ratio was 1.13 (95% confidence interval (CI): 1.04, 1.22) for coronary heart disease, 1.20 (95% CI: 1.01, 1.42) for heart failure, and 1.11 (95% CI: 1.04, 1.19) for a composite cardiovascular disease outcome. The association with total stroke was not significant, but it was positive for ischemic stroke and inverse for hemorrhagic stroke. Aside from hemorrhagic stroke, corresponding associations of cardiovascular disease with sodium and potassium jointly were positive for sodium and inverse for potassium, although some were not statistically significant. Specifically, for coronary heart disease, the hazard ratios for 20% increases were 1.11 (95% CI: 0.95, 1.30) for sodium and 0.85 (95% CI: 0.73, 0.99) for potassium; and corresponding values for heart failure were 1.36 (95% CI: 1.02, 1.82) for sodium and 0.90 (95% CI: 0.69, 1.18) for potassium., (© The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Elevated concentrations of polyamines have been found in urine of patients with malignant tumors, including ovarian cancer. Previous research has suffered from poorly standardized detection methods. Our liquid chromatography-tandem mass spectrometry (LC-MS/MS) method is capable of simultaneous standardized analysis of most known polyamines. Liquid chromatography-tandem mass spectrometry has not previously been used in the differential diagnostics of ovarian tumors in postmenopausal women., Materials and Methods: In this prospective study, postmenopausal women (n = 71) presenting with an adnexal mass and, as controls, women with genital prolapse or urinary incontinence scheduled for surgery (n = 22) were recruited in the study. For analysis of the polyamines, a morning urine sample was obtained before surgery. Preoperative serum CA125 concentrations were determined in the study group., Results: Twenty-three women with benign and 37 with malignant ovarian tumors were eligible. Of all analyzed polyamines, only urinary N,N-diacetylspermine showed statistically significant differences between all groups except controls versus benign tumors. N,N-diacetylspermine was elevated in malignant versus benign tumors (P < 0.001), in high-grade versus low malignant potential tumors (P < 0.001), in stage III to IV versus stage I to II cancers (P < 0.001), and even in early-stage cancer (stage I-II) versus benign tumors (P = 0.017). N,N-diacetylspermine had better sensitivity (86.5%) but lower specificity (65.2%) for distinguishing benign and malignant ovarian tumors than CA125 with a cut-off value of 35 kU/L (sensitivity, 75.7%; specificity, 69.6%)., Conclusions: Urinary N,N-diacetylspermine seems to be able to distinguish benign and malignant ovarian tumors as well as early and advanced stage, and low malignant potential and high-grade ovarian cancers from each other, respectively.

Determination of whether magnesium (Mg) is a nutrient of public health concern has been hindered by questionable Dietary Recommended Intakes (DRIs) and problematic status indicators that make Mg deficiency assessment formidable. Balance data obtained since 1997 indicate that the EAR and RDA for 70-kg healthy individuals are about 175 and 250 mg/day, respectively, and these DRIs decrease or increase based on body weight. These DRIs are less than those established for the USA and Canada. Urinary excretion data from tightly controlled metabolic unit balance studies indicate that urinary Mg excretion is 40 to 80 mg (1.65 to 3.29 mmol)/day when Mg intakes are <250 mg (10.28 mmol)/day, and 80 to 160 mg (3.29 to 6.58 mmol)/day when intakes are >250 mg (10.28 mmol)/day. However, changing from low to high urinary excretion with an increase in dietary intake occurs within a few days and vice versa. Thus, urinary Mg as a stand-alone status indicator would be most useful for population studies and not useful for individual status assessment. Tightly controlled metabolic unit depletion/repletion experiments indicate that serum Mg concentrations decrease only after a prolonged depletion if an individual has good Mg reserves. These experiments also found that, although individuals had serum Mg concentrations approaching 0.85 mmol/L (2.06 mg/dL), they had physiological changes that respond to Mg supplementation. Thus, metabolic unit findings suggest that individuals with serum Mg concentrations >0.75 mmol/L (1.82 mg/L), or as high as 0.85 mmol/L (2.06 mg/dL), could have a deficit in Mg such that they respond to Mg supplementation, especially if they have a dietary intake history showing <250 mg (10.28 mmol)/day and a urinary excretion of <80 mg (3.29 mmol)/day.

Iodine and selenium are required for thyroid function. This study investigated iodine and selenium intakes in healthy, women aged 50-70 years ( n = 97) from three cities in the North Island of New Zealand, after mandatory fortification of bread with iodised salt. Iodine and selenium concentrations were determined in 24-h urine samples; daily intakes were extrapolated from amounts in urine (90% and 55% of daily intake, respectively). Three day diet diaries (3DDD) also estimated selenium and iodine (excluding iodised salt) intake. Median urinary iodine concentration (UIC) was 57 (41, 78) µg/L, indicating mild iodine deficiency. Estimated median iodine intake based on urine was 138 (100, 172) µg/day, below Recommended Dietary Intake (RDI) (150 µg/day) with 25% below Estimated Average Requirement (EAR) (100 µg/day). Estimated median selenium intake was 50 (36, 71) µg/day based on urine and 45 (36, 68) µg/day using 3DDD, below RDI (60 µg/day) with 49%-55% below EAR (50 µg/day). Median bread intakes were low at 1.8 (1.1, 2.7) serves/day; 25% consumed ≤1 serve/day. Although population iodine intakes improved following mandatory fortification, some had low intakes. Selenium intakes remain low. Further research should investigate thyroid function of low consumers of iodine fortified bread and/or selenium in New Zealand.

Aims: The aim of this study was to compare the expression of urinary nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), substance P (SP), and calcitonin-gene related peptide (CGRP) in women with and without overactive bladder (OAB). We sought to determine factors associated with higher expression of these neuropeptides., Methods: Participants with OAB and age-matched controls were enrolled. Symptom severity was assessed with validated questionnaires. Urinary neurotrophin levels, symptom scores, and clinical data were compared between the groups. Multivariate analysis determined independent factors associated with urinary neurotrophin levels., Results: Sixty-seven women (38 OAB, 29 controls) were included. Women with OAB and controls were similar in age, race, body mass index, parity, and smoking status. Women with OAB were more likely to report a history of pelvic pain and pelvic surgery. Neurotrophic factor levels normalized to urinary creatinine did not differ between the groups. Increasing age was associated with greater urinary levels of BDNF and NGF (β = 0.23, 95%CI 0.11-0.34 and 0.75, 95%CI 0.17-1.33, respectively, P < 0.02). Higher urinary NGF was associated with increasing BMI (β = 0.81, 95%CI 0.05-1.57, P = 0.04) while pain was associated with elevated urinary SP (β = 0.21, 95%CI 0.09-0.33, P = 0.001)., Conclusions: Our data does not support a relationship between urinary neurotrophin levels and OAB in age-matched postmenopausal women. Further research is necessary to elucidate the role of urinary neurotrophins in the diagnosis and management of OAB. Neurourol. Urodynam. 36:740-744, 2017. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Background: Prostaglandin E 2 (PGE 2 ) induces aromatase expression in adipose tissue, leading to increased estrogen production that may promote the development and progression of breast cancer. However, few studies have simultaneously investigated systemic levels of PGE 2 and estrogen in relation to postmenopausal breast cancer risk. Methods: Here, we determined urinary estrogen metabolites (EM) using mass spectrometry in a case-cohort study (295 incident breast cancer cases and 294 subcohort members), and using linear regression estimated the effect of urinary levels of a major PGE 2 metabolite (PGE-M) on EMs. HRs for the risk of developing breast cancer in relation to PGE-M and EMs were compared between Cox regression models with and without mutual adjustment. Results: PGE-M was a significant predictor of estrone (E1), but not estradiol (E2) levels in multivariable analysis. Elevated E2 levels were associated with an increased risk of developing breast cancer [HR Q5vs.Q1 , 1.54; 95% confidence interval (CI), 1.01-2.35], and this association remained unchanged after adjustment for PGE-M (HR Q5vs.Q1 , 1.52; 95% CI, 0.99-2.33). Similarly, elevated levels of PGE-M were associated with increased risk of developing breast cancer (HR Q4vs.Q1 , 2.01; 95% CI, 1.01-4.29), and this association was only nominally changed after consideration of E1 or E2 levels. Conclusions: Urinary levels of PGE-M and estrogens were independently associated with future risk of developing breast cancer among these postmenopausal women. Impact: Increased breast cancer risk associated with PGE-M might not be fully explained by the estrogens-breast cancer association alone but also by additional effects related to inflammation. Cancer Epidemiol Biomarkers Prev; 26(3); 383-8. ©2016 AACR ., (©2016 American Association for Cancer Research.)

Background: Urinary melatonin levels have been associated with a reduced risk of breast cancer in postmenopausal women, but this association might vary according to tumor melatonin 1 receptor (MT1R) expression. Methods: We conducted a nested case-control study among 1,354 postmenopausal women in the Nurses' Health Study, who were cancer free when they provided first-morning spot urine samples in 2000 to 2002; urine samples were assayed for 6-sulfatoxymelatonin (aMT6s, a major metabolite of melatonin). Five-hundred fifty-five of these women developed breast cancer before May 31, 2012, and were matched to 799 control subjects. In a subset of cases, immunohistochemistry was used to determine MT1R status of tumor tissue. We used multivariable-adjusted conditional logistic regression to estimate the relative risk (RR) of breast cancer [with 95% confidence intervals (CI)] across quartiles of creatinine-standardized urinary aMT6s level, including by MT1R subtype. Results: Higher urinary melatonin levels were suggestively associated with a lower overall risk of breast cancer (multivariable-adjusted RR = 0.78; 95% CI = 0.61-0.99, comparing quartile 4 vs. quartile 1; P trend = 0.08); this association was similar for invasive vs. in situ tumors ( P heterogeneity = 0.12). There was no evidence that associations differed according to MT1R status of the tumor (e.g., P heterogeneity for overall breast cancer = 0.88). Conclusions: Higher urinary melatonin levels were associated with reduced breast cancer risk in this cohort of postmenopausal women, and the association was not modified by MT1R subtype. Impact: Urinary melatonin levels appear to predict the risk of breast cancer in postmenopausal women. However, future research should evaluate these associations with longer-term follow-up and among premenopausal women. Cancer Epidemiol Biomarkers Prev; 26(3); 413-9. ©2016 AACR ., (©2016 American Association for Cancer Research.)

Increased abdominal obesity is associated with increased cardiovascular risk, especially in African American women. The adipocyte is documented to produce a number of inflammatory factors including the hormone aldosterone. There are very few data documenting aldosterone production from adipocytes of postmenopausal women as well as data demonstrating the effects of angiotensin receptor blockade (ARB) on its production in predominately African American women. The authors hypothesize that increased central adipocyte mass in obese postmenopausal women contributes to increased production of aldosterone that is suppressed with the ARB azilsartan medoxomil. The authors tested this hypothesis in a double-blind, placebo-controlled pilot study of 34 hypertensive postmenopausal women (mean age 57.5±7.5 years), 91% of whom were African American. Patients had a mean 24-hour ambulatory systolic blood pressure of 127±13 mm Hg off any blocker of the renin-angiotensin system but while taking other antihypertensive medications. The authors further validated aldosterone production in a nested cohort of women using fat cells from a fat pad biopsy. Azilsartan reduced 24-hour urinary aldosterone by 47.3% from baseline (P=.03), with between-groups differences in urine aldosterone of -5.3±52.3% placebo vs -47.3±32.9% azilsartan (P=.07) at 6 months. An adrenal cell line treated with adipocyte-conditioned media from subcutaneous abdominal adipocytes of postmenopausal women (n=3) showed an increase in aldosterone production blocked by an ARB (1948±1297 pg/mL fat alone vs 894±438 pg/mL fat + ARB; P=.022). The authors conclude that aldosterone is produced from subcutaneous adipocytes of obese postmenopausal women. Moreover, use of an ARB significantly reduces aldosterone production within 6 months of use in these women as well as in cells exposed to their adipocytes., (© 2016 Wiley Periodicals, Inc.)

The purpose of this study was to assess the ability of urinary N-telopeptide (U-NTX) to gauge rate of bone loss across and after the menopause transition (MT). U-NTX measurement was measured in early postmenopause in 604 participants from the Study of Women's Health Across the Nation (SWAN). We examined the association between U-NTX and annualized rates of decline in lumbar spine and femoral neck bone mineral density (BMD) across the MT (1 year before the final menstrual period [FMP] to time of U-NTX measurement), after the MT (from time of U-NTX measurement to 2 to 4 years later), and over the combined period (from 1 year before FMP to 2 to 4 years after U-NTX measurement). Adjusted for covariates in multivariable linear regression, every standard deviation (SD) increase in U-NTX was associated with 0.6% and 0.4% per year faster declines in lumbar spine and femoral neck BMD across the MT; and 0.3% (lumbar spine) and 0.2% (femoral neck) per year faster declines over the combined period (across and after the MT) (all p < 0.01). Each SD increase in U-NTX was also associated with 44% and 50% greater risk of fast bone loss in the lumbar spine (defined as BMD decline in the fastest 16% of the distribution) across the MT (p < 0.001, c-statistic = 0.80) and over the combined period (across and after the MT) (p = 0.001, c-statistic = 0.80), respectively. U-NTX measured in early postmenopause is most strongly associated with rates of bone loss across the MT, and may aid early identification of women who have experienced fast bone loss during this critical period. © 2016 American Society for Bone and Mineral Research., (© 2016 American Society for Bone and Mineral Research.)

Background: Exposure to cadmium has been suspected as a risk factor for breast cancer. The present study examined the associations between urinary cadmium levels and circulating sex hormone levels that are linked to breast cancer risk in healthy women., Methods: The study subjects were 396 premenopausal Japanese women who had regular menstrual cycles less than 40 days long and 207 postmenopausal Japanese women. Urinary cadmium was measured using spot urine samples. Plasma estradiol, testosterone, and dehydroepiandrosterone sulfate were measured. Additionally, the follicle-stimulating hormone, luteinizing hormone, and sex hormone-binding globulin were measured for premenopausal women., Results: In premenopausal women, the urinary cadmium level either expressed in μg per liter or per g of urine creatinine was significantly inversely associated with total and free testosterone levels after controlling for age, body mass index, smoking status, alcohol intake, and the phase of the menstrual cycle. Total and free testosterone levels were 14.6% and 15.0% lower, respectively, in women in the highest quartile of urinary cadmium per g creatinine in those in the lowest quartile. In postmenopausal women, the urinary cadmium in μg per liter as well as per g creatinine was significantly inversely associated with the estradiol level after controlling for covariates. The estradiol level was 25.8% lower in women in the highest tertile of urinary cadmium per g creatinine than in those in the lowest tertile., Conclusions: The data suggest inverse associations between urinary cadmium and the plasma estradiol or testosterone level in Japanese women., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: This study examined the cross-sectional association between phytoestrogens and speed of processing. We hypothesized that higher levels of phytoestrogens would be related to better cognitive performance among older women., Methods: Participants were from the National Health and Nutrition Examination Survey and consisted of 200 older women (M = 74.4 y). Stepwise regressions examined indicators of speed of processing, measured by the Digit Symbol Substitution Test. Isoflavones, lignans, and individual phytoestrogens were added to the regression after including covariates of age, education, race, smoking, and creatinine. Isoflavones were further broken into quartiles among the sample to further evaluate the nature of the curvilinear association., Results: Results showed a relationship between cognition and lignans, explaining 3.8% of the variance after including the covariates, indicating fewer lignans were associated with better speed of processing (P < 0.001). A significant curvilinear relationship with isoflavones explained 1.3% additional variance (P < 0.001). The moderate-high, low-moderate, and the lowest quartile of isoflavones were associated with better cognition, whereas the highest amount was associated with worse speed of processing. Among the individual phytoestrogens, only enterodiol accounted for 4.4% additional variance after taking into account covariates and indicated a negative association with cognition (P = 0.03)., Conclusions: Results suggest that moderate levels of isoflavones, but not lignans, may be associated with better speed of processing. Caution must remain for high isoflavone amounts due to the negative association with cognition. Given the results, phytoestrogens have the potential to be an intervention target for older females' cognition. To become a viable intervention, further research is needed.

Studying microbiota of different urogenital tract habitats in healthy postmenopausal women is of practical importance in deciding on the appropriateness of correction of dysbiotic disorders. The aim of this study was to examine the vaginal and urine microbiota of healthy postmenopausal women. The study included 20 healthy postmenopausal women (mean age 59,0+/-2,1 years). Duration of menopause in all subjects was more than 8 years. Bacteriological testing of urine and vaginal specimen was carried out on the extended media (15) for cultivating facultative anaerobic bacteria (FAB) and nonclostridial anaerobic bacteria (NAB) and included PCR of midstream morning urine. Among FAB in the urine and vagina dominated coagulase-negative staphylococci and NAB. Bacterial patterns of studied habitats turned out to be similar in many respects. In the urine Megasphaera spp., Veillonella spp., Prevotella spp., Mobiluncus spp., Fusobacterium spp. were found, whereas in the vagina these microorganisms were not present. Cluster analysis revealed no significant differences in the concentration of the same microorganisms isolated from the urine and vagina. When comparing the frequency of microorganism detection in urine by bacteriological method and by PCR, bacterial patterns were identical in 56% of cases.

Objective: This study measured the differences in bone mineral density and content in relation to changes in serum hormone and bone marker levels during the perimenopausal transition in naturally menopausal cynomolgus monkeys., Methods: The bone mineral density and content of premenopausal, perimenopausal, and early (0-< 5 y), mid (5-10 y), and late (> 10 y) postmenopausal monkeys were measured at the distal radius and proximal tibia in both metaphysis and diaphysis. Hormonal and bone marker levels were also measured., Results: The serum 17β-estradiol level significantly decreased during late postmenopause, whereas the serum follicle-stimulating hormone levels significantly increased from early postmenopause before declining at late postmenopause. Trabecular bone loss at metaphysis occurred once the animals entered into the perimenopausal period, whereas cortical bone loss gradually and continuously decreased, dependent on the time-course after perimenopause, and was greatest in the late postmenopausal period. Serum bone-specific alkaline phosphatase and urinary N-telopeptide of bone type-1 collagen levels were negatively correlated with the trabecular bone mineral content at metaphysis, whereas serum osteocalcin levels showed a negative correlation with the cortical bone mineral density at the diaphysis. The only positive linear correlation observed was between serum follicle-stimulating hormone and urinary N-telopeptide of bone type-1 collagen levels., Conclusions: Unlike the ovariectomized monkey models that do not retain the perimenopausal transition, naturally menopausal monkeys elicit different patterns of bone loss during the transition-an abrupt decline in the trabecular metaphysis and a gradual decline in the cortical diaphysis. Naturally menopausal cynomolgus monkeys offer an alternative model for osteoporosis research for postmenopausal women.

Relationships between the plasma concentration of a cathepsin K inhibitor (ONO-5334) and inhibition of bone resorption markers N-telopeptide of type I collagen (NTX) and C-telopeptide of type I collagen (CTX) in serum and urinary NTX/creatinine and CTX/creatinine were examined in 10 postmenopausal women. The subjects received slow-release tablets of 100mg ONO-5534 under fasted or fed conditions in a study with a crossover design. Inhibition of serum NTX and CTX levels and plasma concentrations of ONO-5334 were monitored at 0, 24, 48 and 168 h after dosing. Changes in urinary NTX/creatinine and CTX/creatinine levels in second morning urine were evaluated on 0, 1, 2 and 7 days after dosing. Data were analyzed using sigmoid maximal drug effect (Emax) models. The maximal inhibition, estimated Emax values, were -31.8% for serum NTX, -53.1% for serum CTX, -67.2% for urinary NTX/creatinine, and -95.2% for urinary CTX/creatinine. The estimated half maximal effective plasma concentrations (EC50) of ONO-5334 and confidence intervals were 1.79 (1.01 to 3.16) ng/mL for serum NTX, 2.07 (1.63 to 2.62) ng/mL for serum CTX, 1.85 (1.30 to 2.61) ng/mL for urinary NTX/creatinine, and 1.98 (0.94 to 3.76) ng/mL for urinary CTX/creatinine. EC50 values for the four crosslinks did not significantly differ, as indicated by the overlapping 95% confidence intervals. The highest signal-to-noise ratio was achieved with serum CTX, and was 2-fold higher than that on serum NTX. Inhibition for serum NTX and CTX, and urinary NTX/creatinine and CTX/creatinine by ONO-5334 were all correlated with correlation coefficients ranging from 0.55 to 0.80. In conclusion, data of ONO-5334 slow-releasing tablets in postmenopausal women were well fitted in Emax model. In all measured telopeptides, the maximal inhibition was obtained at urinary CTX/creatinine level, but serum CTX had the highest signal-to-noise ratio. Inhibition for all measured telopeptides by ONO-5334 were all correlated. The estimated half maximal effective plasma concentrations were not significantly different between all measured telopeptides., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To examine the association between urinary phytoestrogens and self-reported urinary incontinence in postmenopausal women in the United States using a large, cross-sectional, population-based cohort survey., Methods: Data were analyzed for 1789 postmenopausal women aged 50 years or older who participated in one of the 2001-2010 cycles of National Health and Nutrition Examination Survey and underwent measurement of 4 isoflavone (soy derived) and 2 lignan (flax derived) phytoestrogens in their urine. Incontinence was defined as self-reported stress, urge, other, or mixed incontinence. Urine phytoestrogen concentrations were examined in weighted, multivariate logistic regression models for association with each of the lower urinary tract symptoms. All models were adjusted for age, body mass index, diabetes, race, smoking, and parity., Results: Increasing urine concentrations of the lignan phytoestrogen enterodiol was associated with decreased likelihood of urge (odds ratio [OR], 0.92; 95% confidence interval [CI], 0.85-0.99), mixed (OR, 0.90; 95% CI, 0.82-0.98), and other (OR, 0.90; 95% CI, 0.81-0.99) incontinence, whereas increasing urine concentrations of the lignan phytoestrogen enterolactone was associated with decreased likelihood of urge (OR, 0.92; 95% CI, 0.86-0.99) and mixed (OR, 0.91; 95% CI, 0.84-0.99) incontinence. No association was observed between any isoflavone phytoestrogens and types of incontinence., Conclusion: This study demonstrates that lignan phytoestrogens may have a protective effect against incontinence in postmenopausal women. Prospective clinical and laboratory studies are warranted to investigate the mechanism of this relationship., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Cadmium is a known carcinogen that can disrupt endocrine signalling. Cigarette smoking and food are the most common routes of non-occupational exposure to cadmium. Cadmium accumulates in the kidney and can be measured in urine, making urine cadmium (U-Cd) a biomarker of long-term exposure. However dietary-cadmium (D-Cd) intake estimates are often used as surrogate indicator of cadmium exposure in non-smoking subjects. It is therefore important to investigate the concordance between D-Cd estimates obtained with Food Frequency Questionnaires and U-Cd., Methods: U-Cd levels were compared with estimated dietary-cadmium (D-Cd) intake in 1764 post-menopausal women from the Danish Diet, Cancer and Health cohort. For each participant, a food frequency questionnaire, and measures of cadmium content in standard recipes were used to judge the daily intake of cadmium, normalized by daily caloric intake. Cadmium was measured by ICP-MS in spot urine sampled at baseline and normalized by urinary creatinine. Information on diet, socio-demographics and smoking were self-reported at baseline., Results: Linear regressions between U-Cd and D-Cd alone revealed minimal but significant positive correlation in never smokers (R2 = 0.0076, β = 1.5% increase per 1 ng Cd kcal(-1), p = 0.0085, n = 782), and negative correlation in current smokers (R2 = 0.0184, β = 7.1% decrease per 1 ng Cd kcal(-1) change, p = 0.0006, n = 584). In the full study population, most of the variability in U-Cd was explained by smoking status (R2 = 0.2450, n = 1764). A forward selection model revealed that the strongest predictors of U-Cd were age in never smokers (Δ R2 = 0.04), smoking duration in former smokers (Δ R2 = 0.06) and pack-years in current smokers (Δ R2 = 0.07). Food items that contributed to U-Cd were leafy vegetables and soy-based products, but explained very little of the variance in U-Cd., Conclusions: Dietary-Cd intake estimated from food frequency questionnaires correlates only minimally with U-Cd biomarker, and its use as a Cd exposure indicator may be of limited utility in epidemiologic studies.

Aim: The objective of this study was to develop a reference range for urine calcium excretion (both 24-hour and fasting) for African American women compared to White women. In addition, the variables that determine urine calcium excretion were identified., Material: Data were analyzed for baseline studies of healthy postmenopausal volunteers who participated in seven separate studies conducted at one site., Methods: Some studies included fasting urine Ca/Cr and others 24-hour urine calcium excretion. 24-hour urine calcium was considered with and without correction for urinary creatinine excretion. Calcium was measured initially by atomic absorption spectrophotometry and more recently by an automated method (ADVIA 2400 Chemistry System)., Results: Participants were considered healthy based on history and physical and routine laboratory studies. Those screened who had a history of nephrolithiasis were excluded. A reference range for 24-hour urine calcium and fasting urine calcium/ creatinine was developed. Reference intervals of 11 - 197 mg/24-hour urine calcium excretion and of 0.007 - 0.222 of fasting Ca/Cr were found for African American women compared to 21 - 221 mg/24 hours and 0.019 - 0.264 in White women, respectively. Urine creatinine excretion was higher in African Americans consistent with their higher muscle mass., Conclusion: Urine calcium excretion is lower in postmenopausal African American than White women. The reference range developed should be considered in the diagnosis of hypocalciuric states and may also be useful in the diagnosis of hypercalciuria.

Purpose: Two main estradiol metabolites have different biological behavior with tumorigenic features of 16-OHE1 and antiproliferative characteristics of 2-OHE1. We investigated the ratio of these estradiol metabolites in pre- and postmenopausal patients with breast cancer (BC) within two case-control studies., Methods: From 41 premenopausal patients with (cases) and without (controls N = 211) BC and 207 postmenopausal patients with and without BC (N = 206), urine samples were collected. Urine samples were collected prior to surgery and stored at -20 °C until measurement by ELISA. The multiple linear regression test with two interactions was performed to evaluate the influence of different factors on the metabolic ratio., Results: In premenopausal patients, log ratio of 2-OHE1/16-OHE1 was 0.25 (CI 0.20;0.29) and 0.21 (CI 0.11;0.31) for controls and cases without significant difference. In postmenopausal patients, log ratio was 0.22 (CI 0.17;0.26) and 0.11 (CI 0.07;0.15) in controls and cases, respectively, and was statistically significantly lower (p = 0.0002). Log ratio was significantly influenced by BMI, but only in postmenopausal patients, an increased BMI resulted in a significantly (p < 0.042) decreased ratio., Conclusions: Our case control studies suggest that in postmenopausal women a different metabolism of estrogens may play a role in the tumorigenesis of breast cancer. This genetically determined metabolism could be influenced by the exogenic factor BMI. In premenopausal women different hormone levels at different time points of the menstrual cycle may be an explanation that why we could not find an influence of estrogen metabolism.

Objectives: The frequent prescription of calcium supplements with vitamin D by health practitioners is a topic of concern globally. The present study was designed to find out whether the calcium supplements with vitamin D really affect serum and urinary calcium levels in post-menopausal women., Design, Settings and Participants: The age-matched comparative study was performed among postmenopausal women who were already on and those who were not on calcium supplements with vitamin D for a period of time in relation to the estimation of the serum calcium and the urine calcium levels. Sixty healthy postmenopausal women were enrolled, with thirty among them forming the study group (SG) - who were on calcium supplements with vitamin D for a period of a month, three months, and up to twelve months - were studied and compared the results obtained with the age-matched control group (CG) of thirty post-menopausal women who were not on calcium supplements., Measurements: The serum and the urinary calcium levels were estimated by using appropriate biochemical methods and the data were analysed using relevant statistical methods., Results: The serum calcium levels did not vary significantly in SG in spite of consuming calcium supplements over a period of time, whereas the urinary calcium levels increased progressively (p value < 0.005) in those who have taken calcium supplements for a year compared to those who have taken for a month., Conclusion: Thus, the calcium supplements were of little significance on the serum calcium levels, but have a significant effect on the urinary calcium levels in post-menopausal women.

Osteoporosis is the most important metabolic bone disease in patients with diabetes mellitus. Several studies have documented that metformin is osteogenic in vitro. In contrast, others showed no effect of metformin on the osteogenic differentiation of bone marrow-derived mesenchymal stem cells. Incretin hormones have received much attention because of their beneficial effects beyond glycemia, including on bone health. The study evaluated the anti-osteoporotic effect of metformin and sitagliptin in postmenopausal diabetic women. Forty postmenopausal diabetic women were randomly divided into two equal groups. Group 1 received metformin (Glucophage(®) 500 mg) 1 tablet twice daily, and group 2 received sitagliptin (Januvia(®) 100 mg) 1 tablet/day, for 12 weeks. Fasting blood and urine samples were collected for measurement of serum total alkaline phosphatase (ALP), osteocalcin, and urinary deoxypyridinoline (DPD). Laboratory tests were measured at baseline, after 4 and 8 weeks, and at the end of the study. Bone mineral density of the anterior posterior lumbar spine was measured by dual energy X-ray absorptiometry at baseline and after 12 weeks of the intervention. In the metformin-treated group, the mean values for all markers of bone turnover at 12 weeks of treatment were not significantly different from baseline. In group 2, the mean serum total ALP was significantly decreased, serum osteocalcin levels were non-significantly decreased gradually by 10% at 12 weeks, while urinary DPD decreased significantly and was then maintained at 28% decrease at 12 weeks. In conclusion, metformin is neither osteogenic nor has anti-osteoporotic effect, while sitagliptin could positively regulate bone metabolism.

Inhibition of sclerostin, a glycoprotein secreted by osteocytes, offers a new therapeutic paradigm for treatment of osteoporosis (OP) through its critical role as Wnt/catenin signaling regulator. This study describes the epigenetic regulation of SOST expression in bone biopsies of postmenopausal women. We correlated serum sclerostin to bone mineral density (BMD), fractures, and bone remodeling parameters, and related these findings to epigenetic and genetic disease mechanisms. Serum sclerostin and bone remodeling biomarkers were measured in two postmenopausal groups: healthy (BMD T-score > -1) and established OP (BMD T-score < -2.5, with at least one low-energy fracture). Bone specimens were used to analyze SOST mRNAs, single nucleotide polymorphisms (SNPs), and DNA methylation changes. The SOST gene promoter region showed increased CpG methylation in OP patients (n = 4) compared to age and body mass index (BMI) balanced controls (n = 4) (80.5% versus 63.2%, p = 0.0001) with replication in independent cohorts (n = 27 and n = 36, respectively). Serum sclerostin and bone SOST mRNA expression correlated positively with age-adjusted and BMI-adjusted total hip BMD (r = 0.47 and r = 0.43, respectively; both p < 0.0005), and inversely to serum bone turnover markers. Five SNPs, one of which replicates in an independent population-based genomewide association study (GWAS), showed association with serum sclerostin or SOST mRNA levels under an additive model (p = 0.0016 to 0.0079). Genetic and epigenetic changes in SOST influence its bone mRNA expression and serum sclerostin levels in postmenopausal women. The observations suggest that increased SOST promoter methylation seen in OP is a compensatory counteracting mechanism, which lowers serum sclerostin concentrations and reduces inhibition of Wnt signaling in an attempt to promote bone formation., (© 2014 American Society for Bone and Mineral Research.)

Prostaglandin E2 (PGE2) is an inflammatory mediator that plays key roles in promoting tumor development and progression. Urinary concentration of a major PGE2 metabolite (PGE-M) has been recently proposed as a promising cancer biomarker. Using dietary intake data from 600 postmenopausal women aged 50-74 years, we examined cross-sectional relationships between fruit and vegetable intake and urinary levels of PGE-M, determined using liquid chromatography/tandem mass spectrometry. After multivariable adjustment, increasing consumption of fruits, but not vegetables, was associated with reduced levels of urinary PGE-M (P for linear trend = 0.02), with geometric means of 5.8 [95% confidence interval (CI): 5.2-6.6] in the lowest quintile versus 4.8 (95% CI: 4.3-5.4) in the highest quintile (Q5) of fruit consumption. A better quality diet, indicated by higher scores on the Healthy Eating Index, was also associated with decreased PGE-M (P for linear trend <0.01). The lack of association with vegetable intake may be related to variation in antioxidant capacities of the major dietary sources of fruits and vegetables for the study participants. Our findings suggest that urinary PGE-M may be modifiable by a healthy diet that follows current national dietary guideline. Further studies are warranted to assess potential utility of urinary PGE-M in assessing cancer prevention efficacy.

Aim: The aim of this study was to assess the effect of body iodine status on hot flashes and cardiovascular disease risk in postmenopausal women., Methods: Two hundred and ten consecutive postmenopausal women without known any risk factor for cardiovascular disease risk or systemic disorder were recruited for the study. All participants underwent serum screening consisted of lipid profile including lipoprotein-a (Lp(a)) and urinary iodine excretion. Participants were also asked for the frequency and the duration of hot flashes. All parameters were assessed for the association between urine iodine excretion and other parameters., Results: Urine spot iodine level was significantly correlated with Lp(a) (r = -0.287, p < 0.001), low-density lipoprotein cholesterol (LDL-C) (r = -0.187, p = 0.006), cholesterol level (r = -0.573, p < 0.001), TG level (r = -0.211, p = 0.02), frequency of hot flashes per a day (r = -0.467, p < 0.001), durations of hot flashes (r = -0.424, p < 0.001), fasting glucose level (r = 0.331, p < 0.001), and fT3 level (r = 0.475, p < 0.001). In multivariate analysis, Lp(a) levels were significantly associated with the urine iodine level (beta coefficient = -0.342, p < 0.001) after adjustment for LDL-C (beta coefficient = 0.225, p < 0.001), glucose (beta coefficient = 0.303, p < 0.001), and age (beta coefficient = 0.146, p < 0.017)., Conclusion: Body iodine status during postmenopausal period is associated with the menopausal symptoms and lipid profile including Lp(a).