Urinary Nâ Telopeptide as Predictor of Onset of Menopauseâ Related Bone Loss in Preâ and Perimenopausal Women

The menopause transition (MT) is a period of rapid bone loss and has been proposed to be a timeâ limited window for early intervention to prevent permanent microarchitectural damage and reduce the risk of subsequent fracture. To intervene early, however, we first need to be able to determine whether menopauseâ related bone loss is about to begin, in advance of substantial bone loss. The objective of this study was, therefore, to assess whether urinary Nâ telopeptide (Uâ NTX) in preâ or early perimenopause can predict the onset of menopauseâ related bone loss. Repeated Uâ NTX measurements were obtained during preâ and early perimenopause in 1243 participants from the Study of Women’s Health Across the Nation (SWAN). We examined the ability of Uâ NTX to predict the onset of significant menopauseâ related bone loss (categorical outcome, yes versus no) at the lumbar spine (LS) and femoral neck (FN), defined as annualized bone mineral density (BMD) decline at a rate faster than the smallest detectable change in BMD over the 3 to 4 years from the time of Uâ NTX measurement. Adjusting for age, race/ethnicity, body mass index, urine collection time, starting BMD, and study site in multivariable, modified Poisson regression, every standard deviation increment in Uâ NTX, measured at baseline in early perimenopausal women, was associated with an 18% and 22% greater risk of significant bone loss at the LS (pâ =â 0.003) and FN (pâ =â 0.003), respectively. The area under the receiverâ operator curve for predicting LS and FN bone loss was 0.72 and 0.72, respectively. In mixedâ effects analysis of all repeated measures of early perimenopausal Uâ NTX over followâ up, Uâ NTX predicted onset of bone loss at the LS (pâ =â 0.002) but not at the FN. We conclude that Uâ NTX can be used early in the MT to determine if a woman is about to experience significant LS bone loss before there has been substantial skeletal deterioration. © 2018 The Authors. JBMR Plus is published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149249/1/jbm410116_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149249/2/jbm410116.pd

Estradiol and Follicleâ Stimulating Hormone as Predictors of Onset of Menopause Transitionâ Related Bone Loss in Preâ and Perimenopausal Women

The menopause transition (MT) may be an opportunity for early intervention to prevent rapid bone loss. To intervene early, we need to be able to prospectively identify preâ and perimenopausal women who are beginning to lose bone. This study examined whether estradiol (E2), or follicleâ stimulating hormone (FSH), measured in preâ and perimenopausal women, can predict significant bone loss by the next year. Bone loss was considered significant if bone mineral density (BMD) decline at the lumbar spine (LS) or femoral neck (FN) from a preâ or early perimenopausal baseline to 1â year after the E2 or FSH measurement was greater than the least detectable change. We used data from 1559 participants in the Study of Women’s Health Across the Nation and tested E2 and FSH as separate predictors using repeated measures modified Poisson regression. Adjusted for MT stage, age, race/ethnicity, and body mass index, women with lower E2 (and higher FSH) were more likely to lose BMD: At the LS, each halving of E2 and each doubling of FSH were associated with 10% and 39% greater risk of significant bone loss, respectively (pâ <â 0.0001 for each). At the FN, each halving of E2 and each doubling of FSH were associated with 12% (p = 0.01) and 27% (pâ <â 0.001) greater risk of significant bone loss. FSH was more informative than E2 (assessed by the area under the receiverâ operator curve) at identifying women who were more versus less likely to begin losing bone, especially at the LS. Prediction was better when hormones were measured in preâ or early perimenopause than in late perimenopause. Tracking withinâ individual change in either hormone did not predict onset of bone loss better than a single measure. We conclude that measuring FSH in the MT can help prospectively identify women with imminent or ongoing bone loss at the LS. © 2019 American Society for Bone and Mineral Research.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153118/1/jbmr3856_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153118/2/jbmr3856.pd

Melatonin Patterns and Levels During the Human Menstrual Cycle and After Menopause

Context: Melatonin may play a role in the regulation of the human menstrual cycle and may decline with menopause and/or aging. Objective: The objective of this work is to investigate the relations between melatonin and the menstrual cycle, menopause, and aging. Methods: This was a cross-sectional and longitudinal analysis of 20 participants from the Study of Women\u27s Health Across the Nation (SWAN) Daily Hormone Study (DHS). The outcome measure was first-morning urine assay of 6-sulfatoxymelatonin (aMT6s), a gauge of melatonin. For each participant, aMT6s was measured daily during one premenopausal cycle with evidence of luteal activity (ELA) and one postmenopausal collection with no evidence of luteal activity (NELA). Results: In addition to the organized patterns of hormone metabolites (estrone conjugates [E1c], and pregnanediol glucuronide [PdG]) and gonadotropins that characterized ovulatory menstrual cycles, there was a late luteal rise in aMT6s. In NELA collections, there was no periodicity of E1c, PdG, gonadotropins, or aMT6s. The strongest predictors of aMT6s levels were PdG values 11 to 12 days prior to aMT6s (beta = 1.46, P = .001 and beta = 1.44, P = .001, respectively). E1c and gonadotropins were not statistically significantly associated with aMT6s. Mean aMT6s in premenopause was 53.5 ng/mL, greater than the mean of 37.4 ng/mL in postmenopausal samples from the same women (P = .0002). Conclusions: This study confirms a late luteal melatonin rise, likely signaled by progesterone, which may influence menstrual cycle pacemaker control. Melatonin declined from premenopause to postmenopause. A high correlation between menopause transition stage and age precludes distinction between the influences of ovarian and chronological aging

Sarcopenia Exacerbates Obesity-Associated Insulin Resistance and Dysglycemia: Findings from the National Health and Nutrition Examination Survey III

Sarcopenia often co-exists with obesity, and may have additive effects on insulin resistance. Sarcopenic obese individuals could be at increased risk for type 2 diabetes. We performed a study to determine whether sarcopenia is associated with impairment in insulin sensitivity and glucose homeostasis in obese and non-obese individuals.We performed a cross-sectional analysis of National Health and Nutrition Examination Survey III data utilizing subjects of 20 years or older, non-pregnant (N = 14,528). Sarcopenia was identified from bioelectrical impedance measurement of muscle mass. Obesity was identified from body mass index. Outcomes were homeostasis model assessment of insulin resistance (HOMA IR), glycosylated hemoglobin level (HbA1C), and prevalence of pre-diabetes (6.0≤ HbA1C<6.5 and not on medication) and type 2 diabetes. Covariates in multiple regression were age, educational level, ethnicity and sex.Sarcopenia was associated with insulin resistance in non-obese (HOMA IR ratio 1.39, 95% confidence interval (CI) 1.26 to 1.52) and obese individuals (HOMA-IR ratio 1.16, 95% CI 1.12 to 1.18). Sarcopenia was associated with dysglycemia in obese individuals (HbA1C ratio 1.021, 95% CI 1.011 to 1.043) but not in non-obese individuals. Associations were stronger in those under 60 years of age. We acknowledge that the cross-sectional study design limits our ability to draw causal inferences.Sarcopenia, independent of obesity, is associated with adverse glucose metabolism, and the association is strongest in individuals under 60 years of age, which suggests that low muscle mass may be an early predictor of diabetes susceptibility. Given the increasing prevalence of obesity, further research is urgently needed to develop interventions to prevent sarcopenic obesity and its metabolic consequences

Gender, Obesity and Repeated Elevation of C-Reactive Protein: Data from the CARDIA Cohort

C-reactive Protein (CRP) measurements above 10 mg/L have been conventionally treated as acute inflammation and excluded from epidemiologic studies of chronic inflammation. However, recent evidence suggest that such CRP elevations can be seen even with chronic inflammation. The authors assessed 3,300 participants in The Coronary Artery Risk Development in Young Adults study, who had two or more CRP measurements between 1992/3 and 2005/6 to a) investigate characteristics associated with repeated CRP elevation above 10 mg/L; b) identify subgroups at high risk of repeated elevation; and c) investigate the effect of different CRP thresholds on the probability of an elevation being one-time rather than repeated. 225 participants (6.8%) had one-time and 103 (3.1%) had repeated CRP elevation above 10 mg/L. Repeated elevation was associated with obesity, female gender, low income, and sex hormone use. The probability of an elevation above 10 mg/L being one-time rather than repeated was lowest (51%) in women with body mass index above 31 kg/m2, compared to 82% in others. These findings suggest that CRP elevations above 10 mg/L in obese women are likely to be from chronic rather than acute inflammation, and that CRP thresholds above 10 mg/L may be warranted to distinguish acute from chronic inflammation in obese women

Age and Age Discordance Associations with Condomless Sex Among Men Who Have Sex with Men

We explored the effect of older partner's age and age difference between partners on condomless sex among men who have sex with men (MSM). We analyzed dyads (n&nbsp;=&nbsp;1720) from participants (n&nbsp;=&nbsp;969) in the Sexual Acquisition Transmission of HIV Cooperative Agreement Program. We used modified Poisson regression to model the probability of a sexual encounter's being condomless as a function of older partner's age and age difference between partners adjusting for HIV status, substance use, race/ethnicity, and partner type. We found an interaction between older partner's age and age difference (p&nbsp;&lt;&nbsp;0.05). Condomless sex decreased with increasing age of the older partner when the age difference was 5-9&nbsp;years (p&nbsp;=&nbsp;0.004) or ≥10&nbsp;years (p&nbsp;=&nbsp;0.04), but not when &lt;5&nbsp;years. Condomless sex was less likely among older MSM when there was ≥5&nbsp;years age difference between partners than &lt;5&nbsp;years difference. Both age and age discordance affect the likelihood of a sexual encounter between MSM being condomless

Gut permeability, inflammation, and bone density across the menopause transition

BACKGROUNDInflammation is implicated in many aging-related disorders. In animal models, menopause leads to increased gut permeability and inflammation. Our primary objective was to determine if gut permeability increases during the menopause transition (MT) in women. Our exploratory objectives were to examine whether greater gut permeability is associated with more inflammation and lower bone mineral density (BMD).METHODSWe included 65 women from the Study of Women's Health Across the Nation (SWAN). Key measures were markers of gut permeability (gut barrier dysfunction, fatty acid binding protein 2 [FABP2]) and immune activation secondary to gut microbial translocation (LPS binding protein [LBP], soluble CD14 [sCD14]), inflammation (high-sensitivity CRP), and lumbar spine (LS) or total hip (TH) BMD.RESULTSIn our primary analysis, FABP2, LBP, and sCD14 increased by 22.8% (P = 0.001), 3.7% (P = 0.05), and 8.9% (P = 0.0002), respectively, from pre- to postmenopause. In exploratory, repeated measures, mixed-effects linear regression (adjusted for BMI, age at the premenopausal visit, race/ethnicity, and study site), greater gut permeability was associated with greater inflammation, along with lower LS and TH BMD.CONCLUSIONGut permeability increases during the MT. Greater gut permeability is associated with more inflammation and lower BMD. Future studies should examine the longitudinal associations of gut permeability, inflammation, and BMD.FUNDINGFunding for this research was provided by NIH, Department of Health and Human Services, through the National Institute on Aging, National Institute of Nursing Research, and NIH Office of Research on Women's Health (U01NR004061, U01AG012505, U01AG012535, U01AG012531, U01AG012539, U01AG012546, U01AG012553, U01AG012554, and U01AG012495)

Associations of insulin resistance and dysglycemia with sarcopenia, obesity, and sarcopenic obesity, adjusted for age, sex, race, and education.

1<p>Ratio of HOMA IR in sarcopenic obese group to HOMA IR in reference group (neither sarcopenic nor obese) where HOMA IR is the Homeostatic Model Assessment of Insulin Resistance.</p>2<p>Ratio of HbA1C in sarcopenic obese group to HbA1C in reference group (neither sarcopenic nor obese) where HbA1C is the blood level of glycosylated hemoglobin.</p>3<p>Pre-diabetes is defined as a 1) HbA1C ≥6% but <6.5%, OR fasting glucose ≥5.5 but <7 mmol/L, 2)no self-reported DM, <b><u>and</u></b> 3) absence of DM medications.</p

Descriptive statistics (median with inter-quartile range, or percentage).

<p>*Those in the NHANES III sample who were older than 20 years and not pregnant, but were excluded because they were missing bioelectrical impedance or body mass index measurement.</p