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Background: Hormones are linked to cardiometabolic diseases and may be impacted by acculturation though multiple mechanisms. We evaluated associations of Hispanic/Latino background and acculturation with levels of sex- and thyroid-related hormones and the potential mediating effect of adiposity, lifestyle factors, and sleep apnea syndrome on these associations., Methods: We studied 1789 adults, aged 45-74, from a sub-cohort of the Hispanic Community Health Survey/Study of Latinos. Peri/pre-menopausal women and individuals on medications related to hormones were excluded. Our study assessed eleven sex- and thyroid-related hormones, Hispanic/Latino background, and five acculturation measures. Associations were assessed using multivariable linear and logistic regression adjusted for survey design and confounding variables. We explored potential mediation using a path analysis., Results: In postmenopausal women, acculturation score-MESA was associated with decreased thyroid-stimulating hormone (β = - 0.13;95%CI = - 0.22, - 0.03) while age at immigration greater than the median (vs US-born) was associated with decreased (β = - 14.6; 95%CI = - 28.2, - 0.99) triiodothyronine (T3). In men, language acculturation and acculturation score-MESA were associated with increased estradiol and sex hormone-binding globulin (SHBG) while age at immigration greater and lesser than the median (vs US-born) was associated with decreased SHBG. Hispanic/Latino background (Mexicans as reference) were selectively associated with sex- and thyroid-related hormone levels in both sexes. Current smoking and sleep apnea syndrome partially mediated the association of Cuban and Puerto Rican heritage (vs Mexican) with T3 levels in men and postmenopausal women, respectively., Conclusion: Selected acculturation measures were associated with thyroid-related hormones in postmenopausal women and sex-related hormones in men. Understanding the mechanisms involved in the relationship of acculturation and Hispanic/Latino background with hormones warrants additional investigation., (© 2023. W. Montague Cobb-NMA Health Institute.)

Using 1998-2022 Women's Health Initiative (WHI) data, our study provides contemporary fracture data by race and ethnicity, specifically focusing on Hispanic and Asian women. Fractures of interest included any clinical, hip, and major osteoporotic fractures (MOFs). We utilized the updated race and ethnicity information collected in 2003, which included seven Asian and five Hispanic origin groups. We computed crude and age-standardized fracture incidence rates per 10 000 woman-years across race and ethnic categories and by Asian and Hispanic origin. We used Cox proportional hazards model, adjusting for age and WHI clinical trial arm, to evaluate the risk of fracture (1) by race compared to White women, (2) Asian origin compared to White women, (3) Hispanic compared to non-Hispanic women, and (4) Asian and Hispanic origins compared the most prevalent origin group. Over a median (interquartile range) follow-up of 19.4 (9.2-24.2) years, 44.2% of the 160 824 women experienced any clinical fracture, including 36 278 MOFs and 8962 hip fractures. Compared to White women, Black, Pacific Islander, Asian, and multiracial women had significantly lower risk of any clinical and MOFs, while only Black and Asian women had significantly lower hip fracture risk. Within Asian women, Filipina women had 24% lower risk of any clinical fracture compared to Japanese women. Hispanic women had significantly lower risk of any clinical, hip, and MOF fractures compared to non-Hispanic women, with no differences in fracture risk observed within Hispanic origin groups. In this diverse sample of postmenopausal women, we confirmed racial and ethnic differences in fracture rates and risk, with novel findings among within Asian and Hispanic subgroups. These data can aid in future longitudinal studies evaluate contributors to racial and ethnic differences in fractures., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.)

In this study of postmenopausal women in Malaysia, total adiposity was inversely associated with total BMD, while regional associations varied. No differences were detected across Malay, Chinese, and Indian ethnicities. Low BMD contributes substantially to morbidity and mortality, and increasing adiposity levels globally may be contributing to this., Purpose: To investigate associations of total and regional adiposity with bone mineral density (BMD) among a multi-ethnic cohort of postmenopausal women., Methods: Dual X-ray absorptiometry (DXA) imaging was undertaken for 1990 postmenopausal women without prior chronic diseases (30% Malay, 53% Chinese, and 17% Indian) from The Malaysian Cohort (TMC). The strength of the associations between standardized total and regional body fat percentages with total and regional BMD was examined using linear regression models adjusted for age, height, lean mass, ethnicity, education, and diabetes. Effect modification was assessed for ethnicity., Results: Women with a higher total body fat percentage were more likely to be Indian or Malay. Mean (SD) BMD for the whole-body total, lumbar spine, leg, and arm were 1.08 (0.11), 0.96 (0.15), 2.21 (0.22), and 1.36 (0.12) g/cm 2 , respectively. Total body and visceral fat percentage were inversely associated with total BMD (- 0.02 [95% CI - 0.03, - 0.01] and - 0.01 [- 0.02, - 0.006] g/cm 2 per 1 SD, respectively). In contrast, subcutaneous and gynoid fat percentages were positively associated with BMD (0.007 [0.002, 0.01] and 0.01 [0.006, 0.02] g/cm 2 , respectively). Total body fat percentage showed a weak positive association with lumbar BMD (0.01 [0.004, 0.02]) and inverse associations with leg (- 0.04 [- 0.06, - 0.03]) and arm (- 0.02 [- 0.03, - 0.02]) BMD in the highest four quintiles. There was no effect modification by ethnicity (p hetero  > 0.05)., Conclusion: Total adiposity was inversely associated with total BMD, although regional associations varied. There was no heterogeneity across ethnic groups suggesting adiposity may be a risk factor for low BMD across diverse populations., (© 2024. The Author(s).)

There are racial/ethnic differences in the incidence of hormone receptor positive and negative breast cancer. To understand why these differences exist, we investigated associations between hormone-related factors and breast cancer risk by race/ethnicity in the Multiethnic Cohort (MEC) Study. Among 81 511 MEC participants (Native Hawaiian, Japanese American, Latina, African American and White women), 3806 estrogen receptor positive (ER+) and 828 ER- incident invasive breast cancers were diagnosed during a median of 21 years of follow-up. We used Cox proportional hazards regression models to calculate associations between race/ethnicity and breast cancer risk, and associations between hormone-related factors and breast cancer risk by race/ethnicity. Relative to White women, ER+ breast cancer risk was higher in Native Hawaiians and lower in Latinas and African Americans; ER- disease risk was higher in African Americans. We observed interaction with race/ethnicity in associations between oral contraceptive use (OC; P int .03) and body mass index (BMI; P int .05) with ER+ disease risk; ever versus never OC use increased risk only in Latinas and positive associations for obese versus lean BMI were strongest in Japanese Americans. For ER- disease risk, associations for OC use, particularly duration of use, were strongest for African Americans (P int .04). Our study shows that associations of OC use and obesity with ER+ and ER- breast cancer risk differ by race/ethnicity, but established risk factors do not fully explain racial/ethnic differences in risk. Further studies are needed to identify factors to explain observed racial/ethnic differences in breast cancer incidence., (© 2021 UICC.)

Background: Literature assessing the effect of marital status on mortality has underrepresented, or altogether omitted Hispanics and the potential moderating effect of Hispanic ethnicity on these relationships. Given cultural and network dynamics, marital advantages in older Hispanic women may be greater than other groups given their family-focused, collectivist orientation., Purpose: The purpose of this study was to understand whether older Hispanic women exhibited a more pronounced marital advantage as compared with non-Hispanic Whites., Methods: We used longitudinal data from the Women's Health Initiative (WHI) Observational Study and Clinical Trials (N = 161,808) collected initially from 1993 to 1998 and followed until 2018. Our sample excluded those respondents indicating "other" as their race-ethnicity and those missing marital status and race-ethnicity variables (N = 158,814). We used Cox-proportional hazards models to assess the association between race-ethnicity, marital status, and the interactive effect of race-ethnicity and marital status on survival., Results: After controlling for socioeconomic status (SES) and health controls, we found a Hispanic survival advantage when compared with non-Hispanic Whites and all other racial-ethnic groups with the exception of Asian/Pacific Islander women (all significant HRs < 0.78, all ps ≤ 0.001). Hispanics had a higher rate of divorce when compared with non-Hispanic Whites. The interactive effect of race-ethnicity and marital status was not significant., Conclusions: U.S. Hispanic, postmenopausal women exhibit a mortality advantage over and above marital status despite their high rates of divorce. Implications and potential explanations are discussed., Clinical Trial Registration: NCT00000611., (© Society of Behavioral Medicine 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: A previous survey investigated postmenopausal vaginal atrophy in a sample of women across Latin America. To help implement a tailored approach to improve postmenopausal care and outcomes in Brazil, we consider results from the survey for this country., Methods: A total of 2509 postmenopausal women resident in Argentina, Brazil, Chile, Colombia, or Mexico completed an online questionnaire. The Brazilian cohort comprised 504 women., Results: Over half of the Brazilian cohort (56%) reported experiencing symptoms of vaginal atrophy; most described them as moderate or severe (76%), and almost half (48%) experienced symptoms for at least 1 year. Three-quarters of the Brazilian cohort (75%) were unaware of the chronic nature of the condition. Upon experiencing symptoms of vaginal atrophy, 92% had visited a health-care provider to discuss treatment options. Overall, 56% were aware of some form of local hormone therapy and 40% of those affected by vaginal atrophy had used such treatment., Conclusion: Postmenopausal women in Brazil are likely to benefit from increased awareness of the symptoms of vaginal atrophy. Health-care providers can potentially improve outcomes by helping women to understand the chronic nature of the condition and available treatment options. Women may be open to education pre menopause, before symptoms occur.

Vitamin D plays an important role in bone metabolism and is important for the prevention of multifactorial pathologies, including osteoporosis (OP). The biological action of vitamin is realized through its receptor, which is coded by the VDR gene. VDR gene polymorphism can influence individual predisposition to OP and response to vitamin D supplementation. The aim of this work was to reveal the effects of VDR gene ApaI rs7975232, BsmI rs1544410, TaqI rs731236, FokI rs2228570, and Cdx2 rs11568820 variants on bone mineral density (BMD), 25-hydroxyvitamin D level, and OP risk in Belarusian women., Methods: The case group included 355 women with postmenopausal OP, and the control group comprised 247 women who met the inclusion criteria. TaqMan genotyping assay was used to determine VDR gene variants., Results: Rs7975232 A/A, rs1544410 T/T, and rs731236 G/G single variants and their A-T-G haplotype showed a significant association with increased OP risk (for A-T-G, OR = 1.8, p = 0.0001) and decreased BMD (A-T-G, -0.09 g/cm 2 , p = 0.0001). The rs11568820 A-allele showed a protective effect on BMD (+0.22 g/cm 2 , p = 0.027). A significant dose effect with 25(OH)D was found for rs1544410, rs731236, and rs11568820 genotypes. Rs731236 A/A was associated with the 25(OH)D deficiency state., Conclusion: Our novel data on the relationship between VDR gene variants and BMD, 25(OH)D level, and OP risk highlights the importance of genetic markers for personalized medicine strategy.

Objectives: To determine how baseline weight status contributes to differences in postmenopausal weight gain among non-Hispanic Blacks (NHBs) and non-Hispanic Whites (NHWs)., Methods: Data were included from 70,750 NHW and NHB postmenopausal women from the Women's Health Initiative Observational Study (WHI OS). Body Mass Index (BMI) at baseline was used to classify women as having normal weight, overweight, obese class I, obese class II or obese class III. Cox proportional hazards was used to estimate the hazard of a 10% or more increase in weight from baseline., Results: In both crude and adjusted models, NHBs were more likely to experience ≥10% weight gain than NHWs within the same category of baseline weight status. Moreover, NHBs who were normal weight at baseline were most likely to experience ≥10% weight gain in both crude and adjusted models. Age-stratified results were consistent with overall findings. In all age categories, NHBs who were normal weight at baseline were most likely to experience ≥10% weight gain. Based on the results of adjusted models, the joint influence of NHB race/ethnicity and weight status on risk of postmenopausal weight gain was both sub-additive and sub-multiplicative., Conclusion: NHBs are more likely to experience postmenopausal weight gain than NHWs, and the disparity in risk is most pronounced among those who are normal weight at baseline. To address the disparity in postmenopausal obesity, future studies should focus on identifying and modifying factors that promote weight gain among normal weight NHBs., Competing Interests: CEB is employed by the RAND Corporation. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: The prevalence and intensity of menopausal symptoms differ depending on ethnicity, culture, and country. Epidemiological data from China are scarce., Objective: To compare the prevalence and severity of menopausal symptoms in peri- and postmenopausal Chinese women., Methods: This was a prospective two year cohort study that included all eligible women from 31 Chinese provinces attending our 'Menopause Clinic', the first official specialized center in China. Structured questionnaires containing seven domains with 41 items in total were used to assess the following menopausal symptoms using descriptive analysis: negative mood, cognitive symptoms, sleep disorder, vasomotor symptoms (VMS), urogenital symptoms, autonomic nervous disorder, and limb pain/paresthesia., Results: A total of 4063 women with a mean age of 50.53 ± 6.57 ( n  = 2107 perimenopausal and 1956 postmenopausal) participated. All menopausal symptoms were more severe in postmenopausal women ( p <.05). Independent of menopausal status, urogenital symptoms, often combined with sexual problems, were the most common complaints (in prevalence and severity), followed by sleep disorder, cognitive symptoms (especially hypomnesia), negative mood, autonomic nervous disorder, limb pain/paresthesia and, as the rarest complaint, VMS., Conclusions: Urogenital symptoms among midlife Chinese women are common, frequently also in combination with sexual dysfunction, although many do not often complain about these in the first place. Postmenopausal women presented more prevalent and severe menopausal symptoms. In contrast to Western countries, VMS are rare among our population. A multidisciplinary approach and use of hormonal and non-hormonal therapies should be considered for these women.

The present study investigated the concomitants of menopause-specific quality of life among premenopausal and postmenopausal women. Based on the Wilson and Cleary model of quality of life, this cross-sectional study recruited 329 women of age 40-65 years following operational convenience. The study was conducted in the office of the Korea Population, Health and Welfare Association (KPHWA) in Incheon, South Korea. Data collected on sociodemographic characteristics, social support, biological/physiological characteristics, the Pittsburgh Sleep Quality Index (PSQI-K), and self-rated health. Menopause-specific quality of life questionnaire (MENQOL) was used in this study. Hierarchical multiple linear regression analysis was performed. The study found that social support and self-rated health were negatively correlated with MENQOL in premenopausal women, while the income level and self-rated health were negatively associated with MENQOL in postmenopausal women. Sleep quality was positively correlated with MENQOL in both premenopausal and postmenopausal women. The study results indicate the need for tailored approaches based on menopausal status. Especially, social support may help improve the MENQOL of premenopausal women, while in postmenopausal women, improved sleep quality may enhance their menopause-specific quality of life.

Background: Growth differentiation factor 15 (GDF15), is a newly identified member of the transforming growth factor-beta (TGF-β) family. It circulates as a 24.5-kDa homodimer. However, the function of GDF15 in bone metabolism remains unclear. In this study, we investigated the function of GDF15 in postmenopausal Chinese women. Methods: We measured serum GDF15 levels, bone mineral density (BMD), and bone turnover markers in 201 postmenopausal Chinese women ranging in age from 47 to 80 years. Results: The concentration of serum GDF15 increased with age. Growth differentiation factor 15 levels displayed a negative correlation with lumbar spine, femoral neck, and total hip BMD. After adjusting for age, this association still existed and was significant. We identified age, GDF15, body mass index (BMI), and estradiol to be associated with BMD. Furthermore, we found that GDF15 levels had a significant negative relationship with bone alkaline phosphatase (BAP) levels; this relationship remained significant after adjustment. However, there was no significant correlation between levels of GDF15 and N-terminal telopeptide of type I collagen (NTX). Conclusions: For postmenopausal Chinese women, GDF15 is a negative predictor of BMD and has a negative correlation with bone formation biomarker BAP. In other words, GDF15 exerts negative regulation on bone mass by inhibiting bone formation.

To evaluate the association between thyroid hormones (TH) and metabolic syndrome (MS) in postmenopausal women (PmW), a cross-sectional study was conducted with a sample of 1000 participants of PmW (40-65 years). Thyroid stimulating hormone (TSH) and free thyroxine (fT4) were evaluated. The MS was defined using the International Diabetes Federation (IDF) ethnicity-specific definitions for Asian. Participants were classified into three groups according to the TSH reference range: high-TSH (≥4.2 mU/L), low-TSH (<0.1mU/L), and normal-TSH (0.1-4.2 mU/L) group. Serum triglycerides (TG) levels were higher in low-TSH group and high-TSH group compared with normal-TSH group ( p  < .05). The whole sample was stratified into <60 and ≥60 years subgroups. In the ≥60 years group, fT4 was negatively correlated with waist circumference (WC) ( p  = .028) and positively correlated with fasting blood glucose (FBG) ( p  = .043), meanwhile TSH was positively correlated with WC only in the control subjects ( p  = .014). No difference was found between TH and the number of MS components. It was demonstrated that serum fT4 levels were associated with FBG and WC, while TSH was associated with WC in elderly PmW without MS.

Foreign and native populations differ in terms of breast cancer outcomes. Studies rarely distinguish between premenopausal and postmenopausal breast cancer, although the risk profile is different; nor between migrants of the first and second generation (FG and SG), which is crucial to examine genetic and environmental influences on breast cancer. This research fills these gaps by investigating patterns in breast cancer incidence and survival in different migrant groups by menopausal and migrant generational status, taking various risk factors into account. To this end, individually linked data from the 2001 census, the Belgian Cancer Registry and the Crossroads Bank for Social Security are used. Age-standardised incidence rates and incidence rate ratios are calculated by migrant background group, stratified according to ages 30-50 (premenopausal) and 50-70 (postmenopausal). Incidence rate ratios are examined with and without taking reproductive factors and socioeconomic position (SEP) into account. Relative survival percentages and relative excess risks of dying among premenopausal and postmenopausal patients are computed with and without controlling for the stage at diagnosis and SEP. Premenopausal breast cancer is further examined by migrant generational status. Breast cancer incidence is lower among non-European migrants compared to Belgians. Keeping SEP and known risk factors constant reduces much, but not all of the observed discrepancies. A risk convergence between SG migrants and Belgians for the development of premenopausal breast cancer is observed. Premenopausal breast cancer survival is worse among Moroccan patients due to a higher stage at diagnosis. This disadvantage is concentrated in the FG., (© 2019 UICC.)

After reports from the Women's Health Initiative randomized trial evaluating estrogen plus progestin, there was a sudden, substantial, and sustained decrease in all categories of menopausal hormone therapy, and the first reduction in age-adjusted breast cancer incidence in more than 20 years was seen in 2003-2004 among US women 50 years of age or older. Subsequent trends in breast cancer incidence have been described, but most reports have not focused on the postmenopausal age group or fully engaged the potential influence of reduced hormone therapy on breast cancer incidence trends by race/ethnicity. To address this gap, this commentary examines trends for annual age-adjusted breast cancer incidence over a 40-year period from 1975 to 2015 for white and black women on the basis of findings from the Surveillance, Epidemiology, and End Results 9 registries. Overall, the sharp decline in breast cancer incidence seen in 2003-2004 was followed in the subsequent decade by a continued low breast cancer incidence plateau in white women that has largely persisted. In contrast, a new discordance between breast cancer incidence trends in black and white women has emerged. In the 2005-2015 decade, a sustained increase in breast cancer incidence in black women has resulted in annual incidence rates comparable, for the first time, to those in white women. This commentary explores the hypothesis that the over-decade-long and discordant changes in breast cancer incidence rates in postmenopausal black and white women are, to a large extent, associated with changes in hormone therapy use in these 2 groups., (© 2020 American Cancer Society.)

Purpose: Vitamin D deficiency (VDD) and polymorphisms in the group-specific component (GC) gene are known to be associated in different populations. However, the effects of such genetic variants may vary across different populations. Thus, the objective of this study was to estimate the association between Vitamin D-Binding Protein (VDBP) haplotypes and VDD in mestizo postmenopausal women and Mexican Amerindian ethnic groups., Methods: This was a cross-sectional study of 726 postmenopausal Mexican women from the Health Workers Cohort Study (HWCS) and 166 postmenopausal women from the Metabolic Analysis in an Indigenous Sample (MAIS) cohort in Mexico. GC polymorphisms (rs7045 and rs4588) were analyzed by TaqMan probes. Serum 25-hydroxyvitamin D [25(OH)D] levels were measured by Chemiluminescent Microparticle Immuno Assay., Results: The prevalence of VDD serum 25(OH)D < 20 ng/mL was 43.7% in mestizo women and 44.6% in indigenous women. In HWCS, the single nucleotide polymorphisms (SNPs) rs7041 and rs4588 were associated with VDD. In addition, women from the HWCS, carrying the haplotypes GC2/2 and GC1f/2 had higher odds of VDD (OR = 2.83, 95% CI 1.14, 7.02; and OR = 2.30, 95% CI 1.40, 3.78, respectively) compared to women with haplotype 1f/1 s. These associations were not statistically significant in the MAIS cohort., Conclusions: Our results show genetic association of the analyzed SNPs and related haplotypes, on the GC gene, with VDD in mestizo Mexican postmenopausal women. Moreover, a high prevalence of VDD with high genetic variability within the country was observed. Our results support the need for national policies for preventing VDD.

Background: Quality of life (QoL) after menopause could be influenced by a host of personal and social factors. This study aimed to determine the factors associated with quality of life among postmenopausal women., Methods: This cross-sectional study was conducted among 405 postmenopausal women selected using a multi-stage randomized sampling. The data-collection tools were the WHO Quality of Life-BREF (WHOQOL-BREF), the Menopause Rating Scale (MRS), and a researcher-designed questionnaire. The relationship between QoL and its potentially correlated factors was examined using t-test, ANOVA, Pearson's correlation, Spearman's correlation coefficient, and multiple linear regression., Results: A negative correlation was found between the scores of QoL (total and all subscales) and the MRS total scores. The total scores of QoL were negatively correlated with duration of menopause (r = - 0.127, P = 0.010), gravida (r = - 0.177, P < 0.001), parity (r = - 0.165, P = 0.001), frequency of stillbirth (r = - 0.104, P = 0.037), vaginal delivery (r = - 0.161, P = 0.001), and waist-to-hip ratio (r = - 0.195, P < 0.001). The QoL total scores were positively correlated with the educational level of the participants (r = 0.207, P < 0.001) and that of their spouses (r = 0.160, P = 0.001) along with their level of monthly family income (r = 0.218, P < 0.001). Multiple-linear-regression analysis showed that the total score of QoL decreased with inadequate income, waist-to-hip ratio, and the total score of MRS., Conclusions: Personal and social factors along with the severity of menopausal symptoms affect QoL post-menopause. These factors need to have a bearing on any effort to improve QoL among postmenopausal women.

Background: Obesity disproportionately affects more women than men. The loss of ovarian function during the menopause transition coincides with weight gain, increases in abdominal adiposity, and impaired metabolic health. Racial differences in obesity prevalence that results from the menopause transition are not well understood., Objective: The purpose of the study was to assess longitudinal changes in body composition and cardiometabolic risk among black and white women during the menopausal transition., Study Design: In a secondary analysis of a prospective, observational cohort study (the Healthy Transitions study), 161 women ≥43 years old with a body mass index of 20-40 kg/m 2 and who had not yet transitioned through menopause were enrolled at Pennington Biomedical Research Center. Women were seen annually for body composition by dual-energy X-ray absorptiometry, for abdominal adipose tissue distribution by computed tomography, for sex steroid hormones, and for cardiometabolic risk factors that include fasting glucose, insulin, and lipids. Surrogate measures of insulin sensitivity were also calculated., Results: Ninety-four women (25 black, 69 white) transitioned through menopause and were included within the analyses. At menopause onset, black women weighed more (77.8±3.0 vs 70.8±1.8 kg) and had a higher systolic (125±16 vs 118±14 mm Hg) and diastolic (80±8 vs 74±7 mm Hg) blood pressure compared with white women (all P≤.05). No other differences in body composition, sex steroid hormones, or cardiometabolic risk factors were observed at menopause onset. Before menopause, white women gained significant weight (3 kg), total body adiposity (6% percent body fat, 9% fat mass, 12% trunk fat mass) and abdominal adipose tissue (19% subcutaneous fat, 15% visceral fat, 19% total adipose tissue), which coincided with significant decreases in estradiol, sex hormone-binding globulin, and estrone sulfate and increases in follicle-stimulating hormone, total cholesterol, and low-density lipoprotein cholesterol. Conversely, black women had more abdominal adipose tissue before menopause, which was maintained across the menopause transition. Black women also had significant decreases in estrone sulfate and total testosterone and increases in follicle-stimulating hormone before menopause. In the postmenopausal years, abdominal subcutaneous adipose tissue, total adipose tissue, follicle-stimulating hormone, total cholesterol, and low-density and high-density lipoprotein cholesterol increased only in white women., Conclusion: White women gained more abdominal adiposity during the menopause transition compared with black women, which, in part, may be due to differences in the pattern of sex steroid hormone changes between women of different racial backgrounds. The gains in abdominal adiposity in white women were observed in tandem with increased cardiometabolic risk factors. Future studies should consider comprehensive lifestyle approaches to target these increased gains in abdominal adiposity (ie, nutrition and physical activity coaching), while taking into account the potential interactions of race, body adiposity, sex steroid hormones, and their influence on cardiometabolic risk., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background Sedentary behavior is pervasive, especially in older adults, and is associated with cardiometabolic disease and mortality. Relationships between cardiometabolic biomarkers and sitting time are unexplored in older women, as are possible ethnic differences. Methods and Results Ethnic differences in sitting behavior and associations with cardiometabolic risk were explored in overweight/obese postmenopausal women (n=518; mean±SD age 63±6 years; mean body mass index 31.4±4.8 kg/m 2 ). Accelerometer data were processed using validated machine-learned algorithms to measure total daily sitting time and mean sitting bout duration (an indicator of sitting behavior pattern). Multivariable linear regression was used to compare sitting among Hispanic women (n=102) and non-Hispanic women (n=416) and tested associations with cardiometabolic risk biomarkers. Hispanic women sat, on average, 50.3 minutes less/day than non-Hispanic women ( P <0.001) and had shorter (3.6 minutes less, P =0.02) mean sitting bout duration. Among all women, longer total sitting time was deleteriously associated with fasting insulin and triglyceride concentrations, insulin resistance, body mass index and waist circumference; longer mean sitting bout duration was deleteriously associated with fasting glucose and insulin concentrations, insulin resistance, body mass index and waist circumference. Exploratory interaction analysis showed that the association between mean sitting bout duration and fasting glucose concentration was significantly stronger among Hispanic women than non-Hispanic women ( P -interaction=0.03). Conclusions Ethnic differences in 2 objectively measured parameters of sitting behavior, as well as detrimental associations between parameters and cardiometabolic biomarkers were observed in overweight/obese older women. The detrimental association between mean sitting bout duration and fasting glucose may be greater in Hispanic women than in non-Hispanic women. Corroboration in larger studies is warranted.

Importance: Hormone therapy (HT) has been suggested for protection against age-related muscle weakness in women. However, the potential for HT-associated health risks necessitates a better understanding of the direction and magnitude of the association between HT and health outcomes, such as lean body mass (LBM)., Objective: To determine whether HT was associated with reduced LBM loss compared with not receiving HT among postmenopausal women aged 50 years and older., Data Sources: MEDLINE, Embase, AgeLine, CINAHL, and SportDiscus (searched from inception until April 25, 2018)., Study Selection: For this systematic review and meta-analysis, randomized clinical trials including postmenopausal women undergoing HT and control groups of women not receiving HT were selected by 2 reviewers. Studies were included if LBM or fat-free mass were measured as an outcome. Studies with participants from hospitals, long-term care facilities, or with specific diseases were excluded., Data Extraction and Synthesis: Information regarding study characteristics and outcome measures were extracted by 1 reviewer and verified by another. Risk of bias was evaluated. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were used to abstract data and assess data quality/validity. Data were pooled using a fixed-effects model., Main Outcomes and Measures: The primary study outcome was the overall absolute change in LBM (measured in kilograms), captured by dual-energy x-ray absorptiometry, dual-photon absorptiometry, or bioelectrical impedance analysis imaging., Results: Of 8961 studies that met selection criteria, 12 were included, with a total of 4474 recruited participants. Of the participants, mean (SD) age was 59.0 (6.1) years. Data on ethnicity were collected by 2 of the studies. Of the 22 HT intervention arms, 15 used estrogen-progesterone combination HT and 7 used estrogen-only HT. Control participants were women who received no HT at all or who received placebo. The median follow-up duration was 2 years (range, 6 months to 6 years). Seven treatment arms showed a loss of LBM, and 14 were protective. Overall, HT users lost 0.06 kg (95% CI, -0.05 to 0.18) less LBM compared with control participants, but the difference was not statistically significant (P = .26). The results were unchanged when stratified based on treatment type and dosage, duration of follow-up, time since menopause, study quality, and type of LBM measurement, with HT users losing between 0.06 kg more to 0.20 kg less LBM compared with control participants for all strata. The quality of evidence based on GRADE was low., Conclusions and Relevance: This systematic review and meta-analysis did not show a significant beneficial or detrimental association of HT with muscle mass. Although muscle retention in aging women is of crucial importance, these findings suggest that interventions other than HT should be explored.

Postmenopausal African American women are at elevated risk for metabolic syndrome (MetS), which predisposes them to cardiovascular disease and other chronic diseases. Circulating microRNAs (ci-miR) are potential mediators of cardiometabolic diseases also impacted by cardiorespiratory fitness (CRF) level. Using real-time quantitative PCR, we compared the expression of vascular-related ci-miRs (miR-21-5p, miR-92a-3p, miR-126-5p, miR-146a-5p, miR-150-5p, miR-221-3p) in sedentary, overweight/obese, postmenopausal African American women based on 1) presence (n = 31) or absence (n = 42) of MetS and 2) CRF level (VO 2peak ) (Very Low < 18.0 mL·kg -1 ·min -1 [n = 31], Low = 18.0-22.0 mL·kg -1 ·min -1 [n = 24], or Moderate >22.0 mL·kg -1 ·min -1 [n = 18]). Endothelial migration rate in response to subjects' serum was assessed to determine the effect of circulating blood-borne factors on endothelial repair. Ci-miR-21-5p was the only ci-miR that differed between women with MetS compared to those without MetS (0.93 ± 0.43 vs. 1.28 ± 0.71, P = 0.03). There were borderline significant differences (P = 0.06-0.09) in ci-miR-21-5p, 126-5p, and 221-3p levels between the CRF groups, and these three ci-miRs correlated with VO 2peak (r = -0.25 to -0.28, P < 0.05). Endothelial migration rate was impaired in response to serum from women with MetS compared to those without after 16-24 h. Serum from women with Moderate CRF induced greater endothelial migration than the Very Low and Low CRF groups after 4 and 16-24 h, that was also not different from a young, healthy reference group. Ci-miR-21-5p is lower in postmenopausal African American women with MetS, while ci-miRs-21-5p, 126-5p, and 221-3p are associated with CRF. Factors which impair endothelial cell migration rate are present in serum of women with MetS, though having Moderate CRF may be protective., (© 2019 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Study Objectives: To describe racial/ethnic differences in sleep duration, continuity, and perceived sleep quality in postmenopausal women and to identify statistical mediators of differences in sleep characteristics., Methods: Recruited from the observational Study of Women's Health Across the Nation (SWAN), 1,203 (548 white, 303 black, 147 Chinese, 132 Japanese, and 73 Hispanic; mean age 65 years, 97% postmenopausal) women participated in a week-long actigraphy and daily diary study in 2013-2015. Actigraphic measures of sleep duration and wake after sleep onset (WASO), and diary-rated sleep quality were averaged across the week. Candidate mediators included health-related variables; stress; and emotional well-being assessed up to 13 times across 18 years from baseline to sleep study., Results: Whites slept longer than other groups; the significant mediators were concurrent financial hardship and increasing number of stressors for Hispanics or Japanese versus whites. Whites had less WASO than blacks and Hispanics; significant mediators were concurrent number of health problems, physical inactivity, waist circumference, vasomotor symptoms, number of life stressors, and financial hardship, and increasing number of health problems from baseline to sleep study. Whites reported better sleep quality than blacks, Chinese, and Japanese; significant mediators were concurrent physical inactivity, vasomotor symptoms, positive affect, and depressive symptoms., Conclusions: Sleep differences between blacks or Hispanics versus whites were mediated by health problems, number of stressors, and financial hardship, whereas sleep differences between Chinese or Japanese versus whites were mediated by emotional well-being. This is the first study using formal mediational approaches., (© Sleep Research Society 2019. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Objectives: To estimate the efficacy of vitamin D supplementation to reduce urgency urinary incontinence (UUI) episodes., Design: Pilot, two-arm, randomized trial conducted from 2013 to 2017. Interventions were 12 weeks of weekly oral 50,000 IU vitamin D3 or placebo., Setting: Academic, university-based outpatient clinic., Participants: Community-dwelling postmenopausal women, 50 years or older, with at least three UUI episodes on 7-day bladder diary and serum vitamin 25-hydroxyvitamin D (25[OH]D) of 30 ng/mL or less., Measurements: The primary efficacy estimate was the percentage change in UUI episodes. Secondary estimates included changes in other lower urinary tract symptoms, along with exploratory subgroup analysis by race/ethnicity and obesity., Results: We randomized 56 women (aged 50-84 years; mean = 60.5 ± 8.2 years), 28 to vitamin D and 28 to placebo; 51 completed treatments. Mean serum 25(OH)D at baseline (21.2 ± 5.2 and 18.2 ± 5.6, P = .30) improved to 57.9 ± 16.3 ng/mL with vitamin D3 and 21.9 ± 8.2 ng/mL with placebo (P < .001). UUI episodes per 24-hour day decreased by 43.0% with vitamin D3 compared to 27.6% with placebo (P = .22). Among black women (n = 33), UUI episodes decreased by 63.2% with vitamin D3 compared to 22.9% with placebo (P = .03). Among obese women, UUI episodes decreased by 54.1% with vitamin D compared to 32.7% with placebo (P = .29). For all women, changes in voiding frequency (P = .40), nocturia (P = .40), urgency (P = .90), incontinence severity (P = .81), and overactive bladder symptom severity (P = .47) were not different between arms., Conclusions: Postmenopausal women with UUI and vitamin D insufficiency demonstrated a greater than 40% decrease in UUI episodes, which did not reach statistical significance compared to placebo, except in the subset of black women. The results of this pilot study support further investigation of vitamin D3 alone or in combination with other treatments for UUI, particularly for women in higher-risk subgroups. J Am Geriatr Soc 67:570-575, 2019., (Published 2018. This article is a U.S. Government work and is in the public domain in the USA.)

Cultural *YZ and XZ contributed equally. background has been shown to influence climacteric symptoms of women. This study compares various characteristics of climacteric symptoms, illness conception, health-seeking behavior, and attitude towards menopause of Mosuo women, a Chinese ethnic minority with a matriarchal structure, and Han Chinese women, the majority ethnic group of China with a patriarchal structure. Through convenience sampling, 51 Mosuo and 47 Han women ages 40 to 60 completed a sociodemographic questionnaire, the modified Kupperman Menopause Index (KMI), the Self-Rating Scale of Illness Conception and Health Seeking Behavior (SSICHSB) and the Menopause Attitude Questionnaire (MAQ). The Mosuo and Han Chinese women are comparable with regard to their age, educational levels and menstrual status. During climacteric, Mosuo women showed less severe melancholia ( p = .009), reported less health-seeking behavior ( p = .009), and displayed more positive attitudes towards menopause than their Han Chinese counterparts ( p < .001). One predictive variable of the melancholia severity in Mosuo was "menarche age", while that in the Han group was "social view on the menopause". Future research with a larger sample is needed to deepen our understanding about the interaction between culture and climacteric symptoms.

Background: Sex differences in the incidence and manifestation of cardiovascular disease (CVD) suggest the involvement of sex hormones in disease pathogenesis. Coronary artery calcium (CAC) and its progression, measured by non-contrast cardiac computed tomography, are markers of subclinical atherosclerosis and predict CVD, even among low-risk women. We hypothesized that sex hormone levels were associated with CAC progression among women in the Multi-Ethnic Study of Atherosclerosis., Methods: We studied 2759 post-menopausal women (age 65 ± 9 years), free of baseline CVD, with baseline serum sex hormones and CAC measured at Exam 1 (2000-2002). Of this sample, 2427 had ≥1 follow-up CAC measurement through Exam 5 (2010-2012). Using mixed effects linear regression methods, we tested change in log[CAC+1] score by log[sex hormone] levels (continuous, comparing the 90th versus 10th percentiles). Models adjusted for demographics, lifestyle factors, cardiovascular risk factors, hormone therapy, and years since menopause., Results: At baseline, we found no associations between sex hormones and prevalent CAC. Over a median of 4.7 years, in fully-adjusted models, women with higher free testosterone levels had relatively greater CAC progression [Ratio 1.26 (95% CI 1.01-1.56)], whereas higher sex hormone binding globulin (SHBG) was associated with lower progression risk [0.80 (0.64-0.99). No associations were seen for total testosterone, estradiol, or dehydroepiandrosterone., Conclusion: A more androgenic hormone profile of higher free testosterone and lower SHBG is associated with a greater CAC progression up to 10-years in post-menopausal women. Sex hormone levels may help identify women at increased risk for CVD who may benefit from additional risk-reducing strategies., (Copyright © 2018. Published by Elsevier Inc.)

Odanacatib (ODN), an oral selective inhibitor of cathepsin K, was an investigational agent previously in development for the treatment of osteoporosis. In this phase 1 open-label study, 12 healthy Chinese postmenopausal women received single-dose ODN 50 mg on day 1 and multiple-dose ODN 50 mg once weekly on days 15, 22, 29, and 36 under fasted conditions. Pharmacokinetic (PK) parameters were evaluated on days 1 and 36. Multiple-dose area under the concentration-time profile (AUC 0-168h ) and maximum plasma concentration (C max ) were compared with historical data from 9 non-Chinese postmenopausal women who also received ODN 50 mg once weekly for 4 weeks. Median time to C max (t max ) was 3 and 4 hours following single- and multiple-dose administration, respectively. The arithmetic mean ± SD terminal half-life was 81.0 ± 14.0 and 106.7 ± 14.4 hours following single- and multiple-dose administration, respectively. Comparison of multiple-dose PK parameters showed that the geometric mean ratios (Chinese/non-Chinese) and 95%CIs for AUC 0-168h and C max were 0.81 (0.55-1.19) and 0.87 (0.69-1.11), respectively. All adverse events were mild, none were serious, and none led to discontinuation. Single- and multiple-dose PKs of ODN 50 mg in Chinese postmenopausal women were generally similar to those previously reported in non-Chinese postmenopausal women., (© 2018, The American College of Clinical Pharmacology.)

Aims: This study explored the impact of menopause on sexual health and marital relationships, the associated factors and the support needed among middle-aged and older women., Background: Although women experiencing menopause are more vulnerable to sexual health and marital problems, few studies have addressed this topic., Design: A mixed methods design was used, comprising primarily quantitative methods with a qualitative component to evaluate the impact of menopause on sexual health., Methods: Eligible women from community-based women centre in Hong Kong were recruited for a survey. The Female Sexual Function Index (FSFI) was used to evaluate sexual function and risk factors for developing sexual dysfunction. Purposively selected women were invited to participate in in-depth individual interviews to explore the impact of menopause on sexual health, the barriers encountered and the desired support., Findings: In total, 540 respondents completed the survey with response rate of 59.7% where 30 respondents participated in the in-depth individual interview. The prevalence of sexual dysfunction in the overall respondents and postmenopause were 85.1% and 91.2% respectively. Depression was found as a strong factor associated with sexual dysfunction. The qualitative data showed that menopause had a considerable negative impact on women's sexual lives. Vaginal dryness and low sexual desire were most commonly reported. Knowledge, financial support and family understanding were important to helping women manage menopause., Conclusion: This study gives further knowledge for healthcare providers and policy makers to develop appropriate strategies and deliver suitable services to improve the quality of sexual health of menopausal women., (© 2018 John Wiley & Sons Ltd.)

Objective: To investigate the differential protein expression before and after menopause in women with nonalcoholic fatty liver disease (NAFLD) and to explore novel markers for menopausal NAFLD., Methods: Eight serum samples collected from pre- or post-menopausal women with NAFLD were analysed by iTRAQ 2D-LC-MS/MS. Two protein candidates were selected and verified by enzyme-linked immunosorbent assay (ELISA) in serum samples collected from a one hundred and fifty-three female population subsequently, including 51 in post-menopausal status with NAFLD, 41 in pre-menopausal with NAFLD, 19 healthy individuals in post-menopausal status and 42 healthy pre-menopausal women., Results: A total of one hundred and sixty-seven proteins exhibiting significant changes were characterized, among which sixty-five were up-regulated and one hundred and two were down-regulated. Of those altered proteins, the expression of serum retinol binding protein 4 (RBP4) and galectin-3 binding protein (LGALS3BP) was obviously increased in the post-menopausal patient group compared to the other. ELISA validations for the two proteins were consistent with the proteomic profiling., Conclusions: Serum RBP4 and LGAL3BP were up-regulated after menopause under NAFLD conditions, which suggested the two proteins may be potential markers as NAFLD in postmenopausal population., (Copyright © 2018 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Background: Sex hormones are implicated in the development of diabetes. However, whether genetic variations in sex hormone pathways (SHPs) contribute to the risk of type 2 diabetes mellitus (T2DM) remains to be determined. This study investigated associations between genetic variations in all candidate genes in SHPs and T2DM risk among a cohort of women participating in the Women's Health Initiative (WHI)., Methods: Single nucleotide polymorphisms (SNPs) located within 30 kb upstream and downstream of SHP genes were comprehensively examined in 8180 African American, 3498 Hispanic American, and 3147 European American women in the WHI. In addition, whether significant SNPs would be replicated in independent populations was examined., Results: After adjusting for age, region, and ancestry estimates and correcting for multiple testing, seven SNPs were significantly associated with the risk of T2DM among Hispanic American women were identified in the progesterone receptor (PGR) gene, with rs948516 showing the greatest significance (odds ratio 0.67; 95% confidence interval 0.57-0.78; P = 8.8 × 10 -7 ; false discovery rate, Q = 7.8 × 10 -4 ). These findings were not replicated in other ethnic groups in the WHI or in sex-combined analyses in replication studies., Conclusion: Significant signals were identified implicating the PGR gene in T2DM development in Hispanic American women in the WHI, which are consistent with genome-wide association studies findings linking PGR to glucose homeostasis. Nevertheless, the PGR SNPs-T2DM association was not statistically significant in other ethnic populations. Further studies, especially sex-specific analyses, are needed to confirm the findings and clarify the role of SHPs in T2DM., (© 2018 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Background: Sex hormones may play important roles in sex-specific biological aging. In the study, we specifically examined associations between circulating sex hormone concentrations and leukocyte telomere length (TL)., Methods: A cross-sectional study was conducted among 1124 Black, 444 Hispanic, and 289 Asian/Pacific Islander women in the Women's Health Initiative Observational Cohort. Estradiol and testosterone concentrations were measured using electrochemiluminescence immunoassays; TL was measured using quantitative polymerase chain reaction., Results: Women in the study were aged 50-79 years. Estradiol concentrations were not significantly associated with TL in this sample. The associations between total and free testosterone and TL differed by race/ethnicity (P interaction  = 0.03 and 0.05 for total and free testosterone, respectively). Total and free testosterone concentrations were not associated with TL in Black and Hispanic women, whereas in Asian/Pacific Islander women their concentrations were inversely associated with TL (P trend  = 0.003 for both). These associations appeared robust in multiple subgroup analyses and multivariable models adjusted for potential confounding factors. In Asian/Pacific Islander women, a doubling of serum free and total testosterone concentrations was associated with a 202-bp shorter TL (95% confidence interval [CI] 51-353 bp) and 203-bp shorter TL (95% CI 50-355 bp), respectively., Conclusions: Serum estradiol concentrations were not associated with leukocyte TL in this large sample of postmenopausal women. Total and free testosterone concentrations were inversely associated with TL in Asian/Pacific Islander women, but not in Black and Hispanic women, although future studies to replicate our observations are warranted particularly to address potential ethnicity-specific relationships., (© 2017 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Background: The relationship between physical activity (PA) and bone health is well known, but the role of lean mass (LM) and fat mass (FM) in this relationship remains uncertain. Therefore, the aim of this study was to examine the mediating effect of LM and FM on the relationship between PA and bone mineral density (BMD) in postmenopausal women., Materials and Methods: This cross-sectional study involved 282 postmenopausal women aged between 50 and 65 year, who were randomly selected from Hongqi community of Harbin City in China. PA was measured using an International PA Questionnaire. Body composition, BMD of the lumbar spine, hip, and total body were measured using dual-energy X-ray absorptiometry. Mediation analysis was performed to investigate the mediating effect of LM and FM on the relationship between PA and BMD., Results: In partial correlation analysis, PA, LM, and FM were positively related to BMD. Positive correlation was found between PA and LM. There were significant differences in BMD between different categories of PA, but the differences disappeared after adjusting for LM. Mediation analysis showed that LM and FM played a mediating role in the relationship between PA and BMD. LM appeared to mediate the effect of BMD in the spine, hip, and total body by 26.91%, 19.55% and 47.98%, respectively; and FM was 22.23%, 27.97%, and 33.02%, respectively., Conclusion: LM and FM affected the relationship between PA and BMD as mediator. Postmenopausal women with high LM and FM had more BMD.

Purpose: To investigate the perceptions of postmenopausal symptoms and treatment options among middle-aged Korean women., Materials and Methods: This cross-sectional study included 2330 Korean women. The women were administered a structured questionnaire to collect sociodemographic data and information regarding menopause and its treatment., Results: More than half (65%) of the participants perceived menopause as a disease, and 66.8% knew hormone therapy (HT) is available for menopausal symptom treatment. However, only 19.7% of participants visited clinics for HT. The most common reasons for having negative views about HT were its adverse reactions (47.3%) and concerns about developing cancer (41.1%). For symptom management, 36.5% of the participants tried lifestyle modification instead of HT., Conclusion: The majority of Korean women regarded menopause as a disease. They were aware of HT for menopausal symptom treatment, but the use of HT was relatively low. Education about the safety and positive effects of HT and the importance of professional healthcare should be provided., Competing Interests: The authors have no financial conflicts of interest., (© Copyright: Yonsei University College of Medicine 2017)

Objective: The aim of the study was to identify whether there is a decline in sexual functioning related to the menopausal transition or to hysterectomy., Methods: In a cohort of 1,390 women aged 42 to 52, with intact uterus and at least one ovary, not using hormone therapy, and pre- or early perimenopausal at baseline, we fit piecewise linear growth curves to 5,798 repeated measurements (seven visits spanning 14.5 y) of a sexual functioning score (range, 5-25) as a function of time relative to date of final menstrual period (FMP) or hysterectomy., Results: Mean sexual functioning at baseline in women with a dateable FMP was 18.0 (SD, 3.4). There was no change in sexual function until 20 months before the FMP. From 20 months before until 1 year after the FMP, sexual function decreased by 0.35 annually (95% CI, -0.44 to -0.26) and continued to decline more than 1 year after the FMP, but at a slower rate (-0.13 annually, 95% CI, -0.17 to -0.10). The decline was smaller in African Americans and larger in Japanese than whites. Vaginal dryness, lubricant use, depressive symptoms, or anxiety did not explain decline in sexual function. Women who had a hysterectomy before the FMP did not show a decline in sexual function before hysterectomy, but scores declined afterward (0.21 annually, 95% CI, -0.28 to -0.14)., Conclusions: Decline in sexual function became apparent 20 months before FMP and slowed 1 year after FMP through 5 years afterward. A decline in sexual function was observed immediately after hysterectomy and persisted for the 5 years of observation.

Objective: Bioavailable insulin-like growth factor-I (IGF-I) interacts with obesity and exogenous estrogen (E) in a racial disparity in obesity-related cancer risk, yet their interconnected pathways are not fully characterized. We investigated whether circulating bioavailable IGF-I acted as a mediator of the racial disparity in obesity-related cancers such as breast and colorectal (CR) cancers and how obesity and E use regulate this relationship., Methods: A total of 2,425 white and 164 African American (AA) postmenopausal women from the Women's Health Initiative Observational Study were followed from October 1, 1993 through August 29, 2014. To assess bioactive IGF-I as a mediator of race-cancer relationship, we used the Baron-Kenny method and quantitative estimation of the mediation effect., Results: Compared with white women, AA women had higher IGF-I levels; their higher risk of CR cancer, after accounting for IGF-I, was no longer significant. IGF-I was associated with breast and CR cancers even after controlling for race. Among viscerally obese (waist/hip ratio >0.85) and overall nonobese women (body mass index <30), IGF-I was a strong mediator, reducing the racial disparity in both cancers by 30% and 60%, respectively. In E-only users and nonusers, IGF-I explained the racial disparity in CR cancer only modestly., Conclusions: Bioavailable IGF-I is potentially important in racial disparities in obesity-related breast and CR cancer risk between postmenopausal AA and white women. Body fat distribution and E use may be part of the interconnected hormonal pathways related to racial difference in IGF-I levels and obesity-related cancer risk.

Objective: Vasomotor symptoms (VMS, ie, hot flashes or night sweats) are reported by many, but not all, women. The extent to which VMS are genetically determined is unknown. We evaluated the relationship of genetic variation and VMS., Methods: In this observational study, we accessed data from three genome-wide association studies (GWAS) (SNP Health Association Resource cohort [SHARe], WHI Memory Study cohort [WHIMS+], and Genome-Wide Association Studies of Treatment Response in Randomized Clinical Trials [GARNET] studies, total n = 17,695) of European American, African American, and Hispanic American postmenopausal women aged 50 to 79 years at baseline in the Women's Health Initiative Study. We examined genetic variation in relation to VMS (yes/no) in each study and using trans-ethnic inverse variance fixed-effects meta-analysis. A total of 11,078,977 single-nucleotide polymorphisms (SNPs) met the quality criteria., Results: After adjustment for covariates and population structure, three SNPs (on chromosomes 3 and 11) were associated with VMS at the genome-wide threshold of 5 × 10 in the African American SHARe GWAS, but were not associated in the other cohorts. In the meta-analysis, 14 SNPs, all located on chromosome 4 in the tachykinin receptor 3 (TACR3) locus, however, had P < 5 × 10. These SNPs' effect sizes were similar across studies/participants' ancestry (odds ratio ∼1.5)., Conclusions: Genetic variation in TACR3 may contribute to the risk of VMS. To our knowledge, this is the first GWAS to examine SNPs associated with VMS. These results support the biological hypothesis of a role for TACR3 in VMS, which was previously hypothesized from animal and human studies. Further study of these variants may lead to new insights into the biological pathways involved in VMS, which are poorly understood.

Recent studies have shown that circulating serotonin plays a potential role in bone metabolism. However, conflicting results have been reported for the relationship between serum serotonin concentrations and bone mineral density (BMD). We investigated whether the serum serotonin concentrations related to BMD in Chinese postmenopausal women. Serum serotonin and bone turnover concentrations of 117 premenopausal women and 262 asymptomatic postmenopausal women were analyzed by enzyme-linked immunosorbent assay. BMD at the lumbar spine and femoral neck was measured by dual energy X-ray absorptiometry. The relationship between serotonin and BMD was investigated. The postmenopausal women had lower mean serum serotonin concentrations compared to the premenopausal women. Serotonin concentrations were negatively associated with age, weight, BMI, fat mass, and β-CTX concentrations in postmenopausal women. No significant correlations were found between serotonin and these parameters in premenopausal women. In postmenopausal women, age- and BMI-adjusted serotonin concentrations were positively correlated with BMD of the lumbar spine and femoral neck. Multiple regression analyses showed serum serotonin and β-CTX were the predictors for lumbar spine BMD. Only serum serotonin was the determinant for femoral neck BMD. In conclusion, lower serum serotonin concentrations are linked to low lumbar spine and femoral neck BMD in postmenopausal women.

The South Asian population suffers from a high prevalence of type 2 diabetes and cardiovascular disease (CVD). A unique obesity phenotype of elevated visceral adipose tissue (VAT) is associated with CVD risk among South Asians. Exercise-induced reduction in VAT and body fat is an effective mechanism to improve cardiometabolic risk factors but this has not been shown in South Asians. Whether exercise-induced changes in measurements such as waist circumference (WC) are independently related to changes in cardiometabolic risk factors in South Asians is unknown. Multi-slice computed tomography scanning was used to assess VAT, cardiometabolic risk factors through a fasting blood sample, and body fat using dual-energy X-ray absorptiometry. Forty- nine postmenopausal South Asian women who participated in two 12-week aerobic exercise programs were included. Bivariate correlations were used to assess associations between change in cardiometabolic risk factors and change in body composition. Regression analyses were conducted with change in glucose, insulin, and homeostatic model assessment of insulin resistance (HOMA-IR) as dependent variables and change in body composition as independent variables of interest. There were significant associations between changes in fasting insulin, glucose, and HOMA-IR with change in VAT. The association between change in VAT and these cardiometabolic risk factors was independent of change in other body composition variables of interest. South Asian women should be encouraged to engage in aerobic activity to reduce their risk of type 2 diabetes and CVD, and physicians should be aware of improvements in glucose regulation with exercise training not observed through reductions in WC.

Purpose: Hormonal changes after menopause can cause dyslipidemia by the cessation of endogenous estrogen. We analyzed the lipid profile of the Korean healthy menopausal women according to the use of hormone replacement therapy (HRT)., Methods: Data obtained from the Korea National Health and Nutrition Examination Survey (KNHANES) 2010-2012 were analyzed. The study included 428 healthy postmenopausal women with HRT (HRT group) and 1804 healthy postmenopausal women without HRT (NHRT group)., Results: After adjustment for confounding factors, total cholesterol (TC) and low-density lipoprotein (LDL) were lower in the HRT group than in the NHRT group (TC: 200.1 ± 2.0 vs. 204.9 ± 1.1, P = 0.04; LDL: 120.3 ± 1.0 vs. 124.5 ± 1.0 mg/ml, P = 0.033). Triglycerides (TG) were lower in the HRT group than in the NHRT group [106.8, (95 % CI 99.8-114.3) vs. 115.1 (95 % CI 111.8-118.5), P = 0.04]. Non-high-density lipoprotein (HDL) was lower in the HRT group than in the NHRT group (145.4 ± 1.9 vs. 151.2 ± 1.0 mg/ml, P = 0.008). Patients with HRT were lower in the LDL cholesterol level (OR 0.601, 95 % CI 0.397-0.917, P = 0.018), the total cholesterol to high-density lipoprotein ratio (OR 0.787, 95 % CI 0.617-0.997, P = 0.016), and the non-HDL level (OR 0.68, 95 % CI 0.509-0.907, P = 0.009)., Conclusion: The results of this study suggest that the use of HRT may have a positive effect on dyslipidemia in postmenopausal women.

Background: The incidence of atrial fibrillation (AF) is higher in non-Hispanic whites (NHWs) compared with other race-ethnic groups, despite more favorable cardiovascular risk profiles. To explore reasons for this paradox, we compared the hazards of AF from traditional and other risk factors between 4 race-ethnic groups in a large cohort of postmenopausal women., Methods: We included 114,083 NHWs, 11,876 African Americans, 5,174 Hispanics, and 3,803 Asians from the Women's Health Initiative free of AF at baseline. Women, averaging 63 years old, were followed up for incident AF using hospitalization records and diagnostic codes from Medicare claims., Results: Over a mean of 13.7 years, 19,712 incident cases of AF were recorded. Despite a higher burden of hypertension, diabetes, and obesity, annual AF incidence was lower among nonwhites (0.7%, 0.4%, and 0.4% for African American, Hispanic, and Asian participants, respectively, compared with 1.2% for NHWs). The hazards of AF from hypertension, diabetes, obesity, heart failure, and coronary artery disease were similar across race-ethnic groups. Major risk factors, including hypertension, obesity, diabetes, smoking, peripheral arterial disease, coronary artery disease, and heart failure, accounted for an attributable risk of 50.3% in NHWs, 83.1% in African Americans, 65.6% in Hispanics, and 37.4% in Asians. Established AF prediction models performed comparably across race-ethnic groups., Conclusions: In this large study of postmenopausal women, traditional cardiovascular risk factors conferred a similar degree of individual risk of AF among 4 race-ethnic groups. However, major AF risk factors conferred a higher-attributable risk in African Americans and Hispanics compared with NHWs and Asians., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objectives: The objective of this study was to explore the trend and risk factors of the prevalence of hyperuricemia among post-menopausal women in Beijing over a ten years period., Method: This research was based on two cross-sectional surveys in post-menopausal women in Beijing. A total of 1881 post-menopausal women were included. Subjects answered a questionnaire and underwent a physical examination and blood test. Serum uric acid >357 μmol/L was diagnosed as hyperuricemia, and another diagnosis criterion (serum uric acid >416 μmol/L) was applied in these women., Results: Serum uric acid levels and hyperuricemia prevalence increased remarkably in the 10-year period. The prevalence of hyperuricemia increased more than 2-fold after being adjusted by age. Multivariate logistic regression models revealed hyperuricemia associated with age, education level, urban residents, alcohol consumption, hypertension, obesity, and dyslipidemia. With the increasing number of traditional cardiovascular risk factors (including hypertension, obesity, diabetes, and dyslipidemia), the risk of hyperuricemia increased significantly, and the accumulative effect of the factors on the risk of hyperuricemia was determined., Conclusion: The prevalence of hyperuricemia was high and exhibited a remarkable, increasing trend in Beijing community-based, post-menopausal women. Better management of relative factors could help to prevent further increases in the burden of hyperuricemia in post-menopausal women in this region., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Kidney disease disproportionately affects minority populations, including African Americans and Hispanics; therefore, understanding the relationship of kidney function to cardiovascular (CV) outcomes within different racial/ethnic groups is of considerable interest. We investigated the relationship between kidney function and CV events and assessed effect modification by race/ethnicity in the Women's Health Initiative., Study Design: Prospective cohort study., Setting & Participants: Baseline serum creatinine concentrations (assay traceable to isotope-dilution mass spectrometry standard) of 19,411 postmenopausal women aged 50 to 79 years who self-identified as either non-Hispanic white (n=8,921), African American (n=7,436), or Hispanic (n=3,054) were used to calculate estimated glomerular filtration rates (eGFRs)., Predictors: Categories of eGFR (exposure); race/ethnicity (effect modifier)., Outcomes: The primary outcome was the composite of 3 physician-adjudicated CV events: myocardial infarction, stroke, or CV-related death., Measurements: We evaluated the multivariable-adjusted associations between categories of eGFR and CV events using proportional hazards regression and formally tested for effect modification by race/ethnicity., Results: During a mean follow-up of 7.6 years, 1,424 CV events (653 myocardial infarctions, 627 strokes, and 297 CV-related deaths) were observed. The association between eGFR and CV events was curvilinear; however, the association of eGFR with CV outcomes differed by race (P=0.006). In stratified analyses, we observed that the U-shaped association was present in non-Hispanic whites, whereas African American participants had a rather curvilinear relationship, with lower eGFR being associated with higher CV risk, and higher eGFR, with reduced CV risk. Analyses among Hispanic women were inconclusive owing to few Hispanic women having very low or high eGFRs and very few events occurring in these categories., Limitations: Lack of urinary albumin measurements; residual confounding by unmeasured or imprecisely measured characteristics., Conclusions: In postmenopausal women, the patterns of association between eGFR and CV risk differed between non-Hispanic whites and African American women., (Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

The current investigation aimed to assess levels of knowledge about risk factors for heart disease among midlife Israeli women, and to evaluate the relationship of knowledge to personal risk factors and vulnerability to heart disease. Face-to-face interviews with women aged 45-64 years were conducted during 2004-2006 within three population groups: long-term Jewish residents (LTR), immigrants from the former Soviet Union, and Arab women. The survey instrument included six knowledge statements relating to: the risk after menopause, family history, elevated cholesterol level, diabetes, obesity, and warning signs of a heart attack. The findings showed wide disparities in knowledge by educational level and between immigrants and LTR, after taking into account personal risk factors and education. Personal risk factors were not significantly related to the knowledge items, except for personal history of cardiovascular disease, which was associated with knowledge about "warning signs of a heart attack" and "family history." Women who perceived themselves as more vulnerable to heart disease were more likely to identify several risk factors correctly. These findings stress the need to increase knowledge about heart disease, especially among less educated and minority women, and to emphasize the risk of patients' personal status by health providers.

Objectives: The goal of this study was to evaluate the frequency of Sp1 +1245G>T (rs 1800012) and -199 7G>T (rs 1107946) COL1A1 gene polymorphisms in postmenopausal women with osteoporosis and osteopenia as well as assessing their relations with the clinical parameters and parameters of bone turnover., Study Design: The study included 538 (236 postmenopausal and 302 healthy reproductive) Polish women. The postmenopausal group included women with osteoporosis (n = 90), osteopenia (n = 90), as well as healthy individuals (n = 56). All women of reproductive age were healthy BMD was marked in the L2-L4 lumbar region of the spine using dual energy X-ray absorptiometry (DXA). Genomic DNA was isolated from peripheral blood, the genotype frequency of investigated polymorphisms was determined by PCR-RFLP technique., Results: The frequency of Sp1 +1245G>T and -1997G>T polymorphisms of COL1A1 gene showed no statistically significant differences between group with osteoporosis, osteopenia and correct T-score and women of reproductive age. In postmenopausal women it was found that osteopenia and osteoporosis were correlated with age, birth weight, age of last menses occurrence, height, body weight and BMI value. Clinical parameters in all groups of women did not show any statistically significant correlation with frequency of Sp1 +1245G>T and -1997G>T COL1A1 polymorphisms., Conclusions: An evaluation of Sp1 +1245G>T (rs1800012) and -1997G>T(rs 1107946) COL1A1 polymorphisms showed any influence of these genetic variants on osteoporosis development in Polish postmenopausal women. The presented correlation between osteoporosis and age, birth weight, age of last menses occurrence, height, body weight and BMI value confirms the important role of environmental factors in disease etiology.

Objective: Telomeres are regions at the ends of chromosomes that maintain chromosomal structural integrity and genomic stability. In studies of mainly older, white populations, shorter leukocyte telomere length (LTL) is associated with cardiometabolic risk factors and increased risks of mortality and coronary heart disease (CHD). On average, African Americans (AfAm) have longer LTL than whites, but the LTL-CHD relationship in AfAm is unknown. We investigated the relationship of LTL with CHD and mortality among AfAm., Approach and Results: Using a case-cohort design, 1525 postmenopausal women (667 AfAm and 858 whites) from the Women's Health Initiative had LTL measured in baseline blood samples by Southern blotting. CHD or mortality hazards ratios were estimated using race-stratified and risk factor-adjusted Cox proportional hazards models. There were 367 incident CHD (226 mortality) events in whites, whereas AfAm experienced 269 incident CHD (216 mortality) events during median follow-up of 13 years. Shorter LTL was associated with older age, current smoking, and white race/ethnicity. In whites, each 1 kilobase decrease in LTL was associated with 50% increased hazard of CHD, hazard ratio=1.50 (95% confidence interval, 1.08-2.10), P=0.017. There was no association between CHD and LTL in AfAm. White women with shorter LTL had higher risks of mortality. In contrast, shorter LTL was weakly associated with decreased mortality hazard in AfAm., Conclusions: As one of the largest prospective studies of LTL associations with incident CHD and mortality in a racially diverse sample, our study suggests differences in LTL associations with CHD and mortality between white and AfAm postmenopausal women., (© 2015 American Heart Association, Inc.)

Background: A low serum osteocalcin level, visceral obesity and postmenopausal status are recognized risk factors for cardiovascular disease., Objective: We investigated the relationship between the serum osteocalcin level and visceral fat content in a population of Chinese postmenopausal women., Design and Patients: In total, 1481 postmenopausal women (mean age ± standard deviation, 57·1 ± 4·8 years) were selected from the Shanghai Obesity Study., Measurements: Abdominal fat accumulation was quantified using magnetic resonance imaging. Subjects with a visceral fat area (VFA) of ≥80 cm(2) were classified as abdominally obese. The total serum osteocalcin level was measured by electrochemiluminescence immunoassay., Results: The median serum osteocalcin level was 20·66 μg/l (interquartile range, 16·88-25·42 μg/l). The overall prevalence of abdominal obesity was 49·1% (n = 727). Abdominally obese subjects had lower serum osteocalcin levels than did nonabdominally obese subjects [19·14 (16·02-23·82) vs 21·97 (18·14-26·77) μg/l, respectively; P < 0·001]. Partial correlation analysis showed that the serum osteocalcin level was still negatively correlated with VFA after adjusting for age, years since menopause and body mass index (P < 0·01). Moreover, VFA was independently associated with the serum osteocalcin level after adjustment for confounding factors (P < 0·05). A low serum osteocalcin level was an independent risk factor for abdominal obesity (odds ratio, 0·972; 95% confidence interval, 0·953-0·991; P = 0·004)., Conclusion: The serum osteocalcin level was inversely correlated with the visceral fat content in these Chinese postmenopausal women., (© 2015 John Wiley & Sons Ltd.)

Background: It is unclear whether obesity unaccompanied by metabolic abnormalities is associated with increased cardiovascular disease risk across racial and ethnic subgroups., Methods and Results: We identified 14 364 postmenopausal women from the Women's Health Initiative who had data on fasting serum lipids and serum glucose and no history of cardiovascular disease or diabetes at baseline. We categorized women by body mass index (in kg/m(2)) as normal weight (body mass index 18.5 to <25), overweight (body mass index 25 to <30), or obese (body mass index ≥30) and by metabolic health, defined first as the metabolic syndrome (metabolically unhealthy: ≥3 metabolic abnormalities) and second as the number of metabolic abnormalities. We used Cox proportional hazards regression to assess associations between baseline characteristics and cardiovascular risk. Over 13 years of follow-up, 1101 women had a first cardiovascular disease event (coronary heart disease or ischemic stroke). Among black women without metabolic syndrome, overweight women had higher adjusted cardiovascular risk than normal weight women (hazard ratio [HR] 1.49), whereas among white women without metabolic syndrome, overweight women had similar risk to normal weight women (HR 0.92, interaction P=0.05). Obese black women without metabolic syndrome had higher adjusted risk (HR 1.95) than obese white women (HR 1.07; interaction P=0.02). Among women with only 2 metabolic abnormalities, cardiovascular risk was increased in black women who were overweight (HR 1.77) or obese (HR 2.17) but not in white women who were overweight (HR 0.98) or obese (HR 1.06). Overweight and obese women with ≤1 metabolic abnormality did not have increased cardiovascular risk, regardless of race or ethnicity., Conclusions: Metabolic abnormalities appeared to convey more cardiovascular risk among black women., (© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Purpose: We performed a case-control study to evaluate the association of genetic polymorphisms of estrogen-metabolizing enzyme genes and estrogen receptor genes with breast cancer risk according to age group and subtypes in Korean women., Methods: Breast cancer patients (n = 830) and the hospital healthy controls (n = 390) with both clinical information and SNP data were included in the study. Age was divided into three groups: premenopausal under 35 years (n = 64), premenopausal over 35 years (n = 456), and postmenopausal women (n = 310), respectively. Tumor subtype was classified into four subtypes: luminal A, luminal B, HER2-overexpressing, and triple-negative, respectively. Genotyping of the selected SNPs in ESR1, ESR2, CYP1A1, CYP1B1, and COMT was conducted using the VeraCode Golden Gate Genotyping Assay Technology. Multiple logistic regression models (dominant, recessive, and additive) were applied to determine the odds ratio, 95% confidence interval, and p value., Results: ESR1, rs2881766, rs2077647, rs926778, and rs2273206 polymorphisms increased breast cancer risk, and rs3798377 decreased the risk in overall patients. The association between SNP genotype and breast cancer risk was varied according to age groups and tumor subtypes. For age subgroups, rs2881766 increased breast cancer risk in the all three age groups, and rs926778 increased the risk in premenopausal over 35 years women and in postmenopausal women. For the tumor subtypes, rs2881766 increased breast cancer risk manly in luminal A, HER2-overexpressing, and triple-negative subtypes except for luminal B subtype, and rs926778 increased the risk in luminal A and triple-negative subtypes. Rs3798577 decreased the risk in luminal B and triple-negative subtypes., Conclusion: The results showed that ESR1 rs2881766 polymorphism increased breast cancer risk and rs3798377 decreased the risk in Korean women. Because of wide variation of the association between SNP genotype and breast cancer risk according to age group and tumor subtypes, further studies such as a large-scale cohort study need for validation and test of biologic significance.

Background: The role of exogenous estrogen use in racial differences in insulin-like growth factor-I (IGF-I) levels which affect cancer risk is unclear. We investigated whether the relationship between race and circulating bioactive IGF-I proteins was mediated by exogenous estrogen and the extent to which exogenous estrogen influenced the race-IGF-I relationship in postmenopausal women., Methods: This cross-sectional study included 636 white and 133 African American postmenopausal women enrolled in an ancillary study of the Women's Health Initiative Observational Study. To assess exogenous estrogen use (nonusers [n = 262] vs users [n = 507]) as a mediator of the race-IGF-I relationship, we used the Baron-Kenny method and an estimation of the proportional change in the odd ratios for IGF-I levels on race plus a bootstrapping test for the significance of the mediation effect., Results: Compared with white women, African American women were more likely to have high IGF-I levels and less likely to use exogenous estrogen. After accounting for race, estrogen nonusers had higher IGF-I levels than estrogen users did. Among oral contraceptive ever users, exogenous estrogen had a strong mediation effect (67%; p = .018) in the race-IGF-I relationship. In the women with a history of hypertension, exogenous estrogen explained racial differences in IGF-I levels to a modest degree (23%; p = .029)., Conclusions: Exogenous estrogen use has a potentially important role in disparities in IGF-I bioactivity between postmenopausal African American and white women. A history of oral contraceptive use and hypertension may be part of the interconnected hormonal pathways related to racial differences in IGF-I levels., (© The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)