The quantity and quality of cardiovascular fat at mid-life and future cognitive performance among women: The SWAN cardiovascular fat ancillary study.

INTRODUCTION: Cardiovascular fat is a novel risk factor that may link to dementia. Fat volume and radiodensity are measurements of fat quantity and quality, respectively. Importantly, high fat radiodensity could indicate healthy or adverse metabolic processes. METHODS: The associations of cardiovascular fat (including epicardial, paracardial, and thoracic perivascular adipose tissue [PVAT]) quantity and quality assessed at mean age of 51 with subsequent cognitive performance measured repeatedly over 16 years of follow-up were examined using mixed models among 531 women. RESULTS: Higher thoracic PVAT volume was associated with a higher future episodic memory (ß[standard error (SE)] = 0.08 [0.04], P = 0.033), while higher thoracic PVAT radiodensity with lower future episodic (ß[SE] = -0.06 [0.03], P = 0.045) and working (ß[SE] = -0.24 [0.08], P = 0.003) memories. The latter association is prominent at higher volume of thoracic PVAT. DISCUSSION: Mid-life thoracic PVAT may have a distinct contribution to future cognition possibly due to its distinct adipose tissue type (brown fat) and anatomical proximity to the brain circulation. HIGHLIGHTS: Higher mid-life thoracic perivascular adipose tissue (thoracic PVAT) volume is related to a better future episodic memory in women. Higher mid-life thoracic PVAT radiodensity is related to worse future working and episodic memories. Negative association of high thoracic PVAT radiodensity with working memory is prominent at higher thoracic PVAT volume. Mid-life thoracic PVAT is linked to future memory loss, an early sign of Alzheimer's disease. Mid-life women's epicardial and paracardial fat are not related to future cognition.

Prediabetes and insulin resistance are associated with lower trabecular bone score (TBS): cross-sectional results from the Study of Women's Health Across the Nation TBS Study.

In pre- and early perimenopausal women, prediabetes (with blood glucose ≥ 110 mg/dL) and greater insulin resistance are associated with worse trabecular bone quality (as assessed by trabecular bone score). PURPOSE: Diabetes mellitus (DM) is associated with lower trabecular bone score (TBS) and fracture; less certain is whether the precursor states of prediabetes and increased insulin resistance are also related to adverse bone outcomes. We examined, in women who do not have DM, the associations of glycemic status (prediabetes vs. normal) and insulin resistance with TBS. METHODS: This was a cross-sectional analysis of baseline data collected from 42- to 52-year-old, pre- and perimenopausal participants in the Study of Women's Health Across the Nation (SWAN) TBS Study. Women with prediabetes were categorized as having either high prediabetes if their fasting glucose was between 110 and 125 mg/dL or low prediabetes if their fasting glucose was between 100 and 109 mg/dL. Normoglycemia was defined as a fasting glucose below 100 mg/dL. RESULTS: In multivariable linear regression, adjusted for age, race/ethnicity, menopause transition stage, cigarette use, calcium and vitamin D supplementation, lumbar spine bone mineral density, and study site, women with high prediabetes had 0.21 (p < 0.0001) standard deviations (SD) lower TBS than those with normoglycemia. Low prediabetes was not associated with lower TBS. When HOMA-IR levels were ≥ 1.62, each doubling of HOMA-IR was associated with a 0.11 SD decrement in TBS (p = 0.0001). CONCLUSION: Similar to diabetics, high prediabetics have lower TBS than normoglycemic individuals. Women with greater insulin resistance have lower TBS even in the absence of DM. Future studies should examine the associations of high prediabetes and insulin resistance with incident fracture.

Temporal increases in 25-hydroxyvitamin D in midlife women: Longitudinal results from the Study of Women's Health Across the Nation.

OBJECTIVE: 25-hydroxyvitamin D (25(OH)D) is critical for bone mineralization and may prevent fractures. Understanding vitamin D deficiency trends in midlife women is particularly important given their concurrent menopausal changes that increase risk for fracture. We aimed to evaluate changes in mean 25(OH)D over time and their determinants in a racially, ethnically and socioeconomically diverse cohort of midlife women. DESIGN: A multi-centre prospective cohort study. PATIENTS: 1585 women ages 42-52 years at baseline. MEASUREMENTS: We measured serum 25(OH)D at 2 time points (1998-2000 and 2009-2011). Between-visit change was assessed in the whole cohort and in socioeconomic and demographic subgroups. Among those with vitamin D deficiency (25(OH)D <30 nmol/L) at baseline, we evaluated determinants of persistent deficiency at follow-up. RESULTS: Mean 25(OH)D increased from 53.8 to 70.0 nmol/L (P < 0.001), and the prevalence of deficiency decreased from 20.4% to 9.7% (P < 0.001). While baseline 25(OH)D differed among subgroups, the changes in 25(OH)D were similar among groups. The proportion of women reporting dietary supplement use increased from 40.8% to 67.1% (P < 0.001), and the increase in 25(OH)D was significantly higher in supplement users. Among women with vitamin D deficiency at baseline, White women and supplement users were less likely to remain deficient at follow-up. CONCLUSIONS: Among midlife women, temporal increases in 25(OH)D concentrations are driven largely by increases in supplement use. The proportion of women with 25(OH)D <30 nmol/L and thus at high risk for skeletal consequences remains substantial. Targeted screening for vitamin D deficiency in populations at risk for fragility fracture may be advisable.

Social stratification and allostatic load: shapes of health differences in the MIDUS study in the United States.

Social stratification is an important mechanism of human organization that helps to explain health differences between demographic groups commonly associated with socioeconomic gradients. Individuals, or group of individuals, with similar health profiles may have had different stratification experiences. This is particularly true as social stratification is a significant non-measurable source of systematic unobservable differences in both SES indicators and health statuses of disadvantage. The goal of the present study was to expand the bulk of research that has traditionally treated socioeconomic and demographic characteristics as independent, additive influences on health by examining data from the United States. It is hypothesized that variation in an index of multi-system physiological dysregulation - allostatic load - is associated with social differentiation factors, sorting individuals with similar demographic and socioeconomic characteristics into mutually exclusive econo-demographic classes. The data were from the Longitudinal and Biomarker samples of the national Study of Midlife Development in the US (MIDUS) conducted in 1995 and 2004/2006. Latent class analyses and regression analyses revealed that physiological dysregulation linked to socioeconomic variation among black people, females and older adults are associated with forces of stratification that confound socioeconomic and demographic indicators. In the United States, racial stratification of health is intrinsically related to the degree to which black people in general, and black females in particular, as a group, share an isolated status in society. Findings present evidence that disparities in health emerge from group-differentiation processes to the degree that individuals are distinctly exposed to the ecological, political, social, economic and historical contexts in which social stratification is ingrained. Given that health policies and programmes emanate from said legal and political environments, interventions should target the structural conditions that expose different subgroups to different stress risks in the first place.

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 = 1720) from participants (n = 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 < 0.05). Condomless sex decreased with increasing age of the older partner when the age difference was 5-9 years (p = 0.004) or ≥10 years (p = 0.04), but not when <5 years. Condomless sex was less likely among older MSM when there was ≥5 years age difference between partners than <5 years difference. Both age and age discordance affect the likelihood of a sexual encounter between MSM being condomless.

Modeling Multisystem Physiological Dysregulation.

OBJECTIVES: The purposes of this study were to compare the relative fit of two alternative factor models of allostatic load (AL) and physiological systems, and to test factor invariance across age and sex. METHODS: Data were from the Midlife in the United States II Biomarker Project, a large (n = 1255) multisite study of adults aged 34 to 84 years (56.8% women). Specifically, 23 biomarkers were included, representing seven physiological systems: metabolic lipids, metabolic glucose, blood pressure, parasympathetic nervous system, sympathetic nervous system, hypothalamic-pituitary-adrenal axis, and inflammation. For factor invariance tests, age was categorized into three groups (≤45, 45-60, and >60 years). RESULTS: A bifactor model where biomarkers simultaneously load onto a common AL factor and seven unique system-specific factors provided the best fit to the biomarker data (comparative fit index = 0.967, root mean square error of approximation = 0.043, standardized root mean square residual = 0.028). Results from the bifactor model were consistent with invariance across age groups and sex. CONCLUSIONS: These results support the theory that represents and operationalizes AL as multisystem physiological dysregulation and operationalizing AL as the shared variance across biomarkers. Results also demonstrate that in addition to the variance in biomarkers accounted for by AL, individual physiological systems account for unique variance in system-specific biomarkers. A bifactor model allows researchers greater precision to examine both AL and the unique effects of specific systems.

Parental History of Diabetes, Positive Affect, and Diabetes Risk in Adults: Findings from MIDUS.

BACKGROUND: Family history of diabetes is one of the major risk factors for diabetes, but significant variability in this association remains unexplained, suggesting the presence of important effect modifiers. PURPOSE: To our knowledge, no previous work has examined whether psychological factors moderate the degree to which family history of diabetes increases diabetes risk. METHODS: We investigated the relationships among parental history of diabetes, affective states (positive affect, negative affect, and depressed affect), and diabetes in 978 adults from the MIDUS 2 national sample. RESULTS: As expected, parental history of diabetes was associated with an almost threefold increase in diabetes risk. We found a significant interaction between positive affect and parental history of diabetes on diabetes (p = .009): higher positive affect was associated with a statistically significant lower relative risk for diabetes in participants who reported having a parental history of diabetes (RR = .66 per unit increase in positive affect; 95 % CI = .47; .93), but it did not influence diabetes risk for participants who reported no parental history of diabetes (p = .34). This pattern persisted after adjusting for an extensive set of health and sociodemographic covariates and was independent of negative and depressed affect. CONCLUSIONS: These results suggest that psychological well-being may protect individuals at increased risk from developing diabetes. Understanding such interactions between non-modifiable risk factors and modifiable psychological resources is important for delineating biopsychosocial pathways to diabetes and informing theory-based, patient-centered interventions to prevent the development of diabetes.

Early life adversity and adult biological risk profiles.

OBJECTIVES: To determine whether there is a relationship between early life adversity (ELA) and biological parameters known to predict health risks and to examine the extent to which circumstances in midlife mediate this relationship. METHODS: We analyzed data on 1180 respondents from the biomarker subsample of the second wave of the National Survey of Midlife Development in the United States. ELA assessments were based on childhood socioeconomic disadvantage (i.e., on welfare, perceived low income, and less educated parents) and other stressors (e.g., parental death, parental divorce, and parental physical abuse). The outcome variable was cumulative allostatic load (AL), a marker of biological risk. We also incorporate information on adult circumstances, including than following: education, social relationships, and health behaviors. RESULTS: Childhood socioeconomic adversity and physical abuse were associated with increased AL (B = 0.094, standard error = 0.041, and B = 0.263, standard error = 0.091 respectively), with nonsignificant associations for parental divorce and death with AL. Adult education mediated the relationship between socioeconomic ELA and cumulative AL to the point of nonsignificance, with this factor alone explaining nearly 40% of the relationship. The association between childhood physical abuse and AL remained even after adjusting for adult educational attainments, social relationships, and health behaviors. These associations were most pronounced for secondary stress systems, including inflammation, cardiovascular function, and lipid metabolism. CONCLUSIONS: The physiological consequences of early life socioeconomic adversity are attenuated by achieving high levels of schooling later on. The adverse consequences of childhood physical abuse, on the other hand, persist in multivariable-adjusted analysis.

Menopause-Related Changes in Body Composition Are Associated With Subsequent Bone Mineral Density and Fractures: Study of Women's Health Across the Nation.

During the menopause transition (MT), lean mass decreases and fat mass increases. We examined the associations of these body composition changes during the MT (2 years before to 2 years after the final menstrual period) with bone mineral density (BMD) at the end of the MT and fracture after the MT. We included 539 participants from the Study of Women's Health Across the Nation who were not taking bone-beneficial or bone-detrimental medications before or during the MT. Using multivariable linear regression, we assessed the independent associations of % lean mass loss and % fat mass gain during the MT (mutually adjusted) with femoral neck (FN) and lumbar spine (LS) BMD at the end of the MT, adjusted for pre-MT BMD, pre-MT lean and fat mass, race/ethnicity, Study of Women's Health Across the Nation (SWAN) study site, age, and cigarette use. We used Cox proportional hazards regression to quantify the relations of % lean loss and % fat gain during the MT with fracture after the MT. The Cox model was adjusted for the covariates above plus post-MT use of bone-detrimental medications, and censored at the first use of bone-beneficial medications; we further controlled for FN or LS BMD at the end of the MT. Adjusted for covariates, each standard deviation (SD) (6.9%) increment in lean mass loss was associated with 0.010 g/cm2 lower FN BMD (p < 0.0001); each SD (19.9%) increment in fat mass gain was related to 0.026 g/cm2 greater FN (p = 0.009) and LS (p = 0.03) BMD. Each SD increment in lean mass loss and fat mass gain was associated with 63% (p = 0.001) and 28% (p = 0.05) greater fracture hazard after the MT; associations were essentially unchanged by BMD adjustment. MT-related lean mass loss and fat mass gain were associated differentially with BMD; both were independently related to more fractures. Mitigating MT-related body composition changes may reduce fracture risk. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Changes in collagen type I C-telopeptide and procollagen type I N-terminal propeptide during the menopause transition.

CONTEXT: Collagen type I C-telopeptide (CTX) and procollagen type I N-terminal propeptide (PINP) are reference bone resorption and formation markers, respectively. OBJECTIVE: To characterize CTX and PINP trajectories across the menopause transition (MT). DESIGN: 18-year longitudinal analysis from the Study of Women's Health Across the Nation. SETTING: Community-based cohort. PARTICIPANTS: 541 women (126 Black, 90 Chinese, 87 Japanese, 238 White) who transitioned from pre- to postmenopause. MAIN OUTCOME MEASURES: CTX and PINP. RESULTS: Multivariable mixed effects regression fit piecewise linear models of CTX or PINP relative to years from final menstrual period (FMP); covariates were race/ethnicity, body mass index (BMI), and age at FMP. In the referent participant (White, 52.46 years at FMP, BMI 27.12 kg/m2), CTX and PINP were stable until 3 years pre- FMP (premenopause). During the MT (3 years before to 3 years after the FMP), CTX and PINP increased 10.3% (p<0.0001) and 7.5% (p<0.0001) per year, respectively; MT-related gains totaled 61.9% for CTX and 45.2% for PINP. Starting 3 years post-FMP (postmenopause), CTX and PINP decreased 3.1% (p<0.0001) and 2.9% (p<0.0001) per year, respectively. Compared to White women, during the MT, Chinese participants had larger gains in CTX (p=0.01), and Japanese women experienced greater increases in CTX (p<0.0001) and PINP (p=0.02). In postmenopause, CTX (p=0.01) and PINP (p=0.01) rose more in Japanese relative to White women. CONCLUSIONS: CTX and PINP are stable in premenopause, increase during the MT, and decrease in postmenopause. During the MT and postmenopause, bone turnover change rates vary by race/ethnicity.

Prediabetes and Fracture Risk Among Midlife Women in the Study of Women's Health Across the Nation.

Importance: Whether prediabetes is associated with fracture is uncertain. Objective: To evaluate whether prediabetes before the menopause transition (MT) is associated with incident fracture during and after the MT. Design, Setting, and Participants: This cohort study used data collected between January 6, 1996, and February 28, 2018, in the Study of Women's Health Across the Nation cohort study, an ongoing, US-based, multicenter, longitudinal study of the MT in diverse ambulatory women. The study included 1690 midlife women in premenopause or early perimenopause at study inception (who have since transitioned to postmenopause) who did not have type 2 diabetes before the MT and who did not take bone-beneficial medications before the MT. Start of the MT was defined as the first visit in late perimenopause (or first postmenopausal visit if participants transitioned directly from premenopause or early perimenopause to postmenopause). Mean (SD) follow-up was 12 (6) years. Statistical analysis was conducted from January to May 2022. Exposure: Proportion of visits before the MT that women had prediabetes (fasting glucose, 100-125 mg/dL [to convert to millimoles per liter, multiply by 0.0555]), with values ranging from 0 (prediabetes at no visits) to 1 (prediabetes at all visits). Main Outcomes and Measures: Time to first fracture after the start of the MT, with censoring at first diagnosis of type 2 diabetes, initiation of bone-beneficial medication, or last follow-up. Cox proportional hazards regression was used to examine the association (before and after adjustment for bone mineral density) of prediabetes before the MT with fracture during the MT and after menopause. Results: This analysis included 1690 women (mean [SD] age, 49.7 [3.1] years; 437 Black women [25.9%], 197 Chinese women [11.7%], 215 Japanese women [12.7%], and 841 White women [49.8%]; mean [SD] body mass index [BMI] at the start of the MT, 27.6 [6.6]). A total of 225 women (13.3%) had prediabetes at 1 or more study visits before the MT, and 1465 women (86.7%) did not have prediabetes before the MT. Of the 225 women with prediabetes, 25 (11.1%) sustained a fracture, while 111 of the 1465 women without prediabetes (7.6%) sustained a fracture. After adjustment for age, BMI, and cigarette use at the start of the MT; fracture before the MT; use of bone-detrimental medications; race and ethnicity; and study site, prediabetes before the MT was associated with more subsequent fractures (hazard ratio for fracture with prediabetes at all vs no pre-MT visits, 2.20 [95% CI, 1.11-4.37]; P = .02). This association was essentially unchanged after controlling for BMD at the start of the MT. Conclusions and Relevance: This cohort study of midlife women suggests that prediabetes was associated with risk of fracture. Future research should determine whether treating prediabetes reduces fracture risk.

Dietary Inflammatory Index and Fractures in Midlife Women: Study of Women's Health Across the Nation.

CONTEXT: While evidence suggests that chronic, low-grade inflammation is a risk factor for bone loss and fractures, the potential relation between an inflammatory dietary profile and greater fracture risk is uncertain. OBJECTIVE: We examined whether a more inflammatory diet, consumed during pre- and early perimenopause, is associated with more incident fractures starting in the menopause transition (MT) and continuing into postmenopause. METHODS: Dietary inflammatory potential was quantified using 2 energy-adjusted dietary inflammatory index scores: one for diet only (E-DII), and one for diet plus supplements (E-DII-S). We included 1559 women from the Study of Women's Health Across the Nation, with E-DII and E-DII-S scores from the baseline visit (during pre- or early perimenopausal), and up to 20 years of follow-up. We excluded women using bone-beneficial medications at baseline; subsequent initiators were censored at first use. The associations of E-DII or E-DII-S (each tested as separate exposures) with incident fracture were examined using Cox proportional hazards regression. RESULTS: Adjusted for age, BMI, cigarette use, diabetes, MT stage, race/ethnicity, prior fracture, bone-detrimental medication use, aspirin or nonsteroidal anti-inflammatory drug use, and study site, greater E-DII and E-DII-S (tested separately) were associated with more future fractures. Each SD increment in E-DII and E-DII-S predicted 28% (P = .005) and 21% (P = .02) greater fracture hazard, respectively. Associations were essentially unchanged after controlling for bone mineral density. CONCLUSION: A more pro-inflammatory diet in pre- and early perimenopause is a risk factor for incident fracture. Future studies should consider whether reducing dietary inflammation in midlife diminishes fracture risk.

Leisure time physical activity and bone mineral density preservation during the menopause transition and postmenopause: a longitudinal cohort analysis from the Study of Women's Health Across the Nation (SWAN).

Background: Whether greater leisure time physical activity (LTPA) is associated with less bone mineral density (BMD) loss during the menopause transition (MT) remains an open question. We hypothesized that: 1) larger increases in LTPA from pre-/early perimenopause (period 1) to late perimenopause/postmenopause (period 2) would be associated with a slower period 2 BMD loss rate; and 2) greater entire-study LTPA levels would be associated with better final absolute BMD (g/cm2). Methods: Data were from of the Study of Women's Health Across the Nation (1996-2017). Exclusions were: bone beneficial medications, inability to identify start of the MT, and extreme BMD change rates. LTPA measures were a validated ordinal scale and number of metabolic equivalents per hour per week (MET hr wk-1) from sport/exercise. Multiply adjusted, linear regression models estimated: 1) BMD decline rate (annualized %) as a function of LTPA change; and 2) final BMD as a function of entire-study LTPA. Findings: Median [p25, p75] MET hr wk-1 were 4.2 [0.9, 10.1] and 4.9 [1.4, 11.2] in periods 1 and 2, respectively; walking was the commonest activity. In adjusted models (N = 875), greater increases in LTPA ordinal score and MET hr wk-1 were statistically significantly associated with a slower decline in femoral neck (FN) BMD. Larger entire-study averages of each LTPA measure were statistically significantly related to better final FN and lumbar spine BMD levels. Interpretation: Findings suggest that LTPA, at modest levels, mitigate MT-related BMD decline and even small increases in intensity, duration or frequency of common activities may lessen bone loss at the population level. Funding: US-NIH.

Longitudinal associations of insulin resistance with change in bone mineral density in midlife women.

BACKGROUNDThe effects of insulin resistance on bone mineral density (BMD) are unclear.METHODSIn Study of Women's Health Across the Nation (SWAN) participants, we used multivariable regression to test average insulin resistance (homeostatic model assessment of insulin resistance, HOMA-IR) and rate of change in insulin resistance as predictors of rate of change in lumbar spine (LS) and femoral neck (FN) BMD in 3 stages: premenopause (n = 861), menopause transition (MT) (n = 571), and postmenopause (n = 693). Models controlled for age, average BW, change in BW, cigarette use, race and ethnicity, and study site.RESULTSThe relation between HOMA-IR and BMD decline was biphasic. When average log2HOMA-IR was less than 1.5, greater HOMA-IR was associated with slower BMD decline; i.e., each doubling of average HOMA-IR in premenopause was associated with a 0.0032 (P = 0.01, LS) and 0.0041 (P = 0.004, FN) g/cm2 per year slower BMD loss. When greater than or equal to 1.5, average log2HOMA-IR was not associated with BMD change. In women in whom HOMA-IR decreased in premenopause, the association between the HOMA-IR change rate and BMD change rate was positive; i.e, slower HOMA-IR decline was associated with slower BMD loss. In women in whom insulin resistance increased in premenopause, the association was negative; i.e, faster HOMA-IR rise was associated with faster BMD decline. Associations of average HOMA-IR and HOMA-IR change rate with BMD change rate were similar in postmenopause, but weaker during the MT.CONCLUSIONWhen it decreases, insulin resistance is associated with BMD preservation; when it increases, insulin resistance is associated with BMD loss.FUNDINGThe SWAN has grant support from the NIH of the Department of Health and Human Services (DHHS) through the NIH National Institute on Aging (NIA), National Institute of Nursing Research (NINR), and Office of Research on Women's Health (ORWH) (grants U01NR004061, U01AG012505, U01AG012535, U01AG012531, U01AG012539, U01AG012546, U01AG012553, U01AG012554, U01AG012495, and U19AG063720).

Diurnal dynamic range as index of dysregulation of system dynamics. A cortisol examplar using data from the Study of Midlife in the United States.

We discuss the importance of including measures of dysregulated system dynamics in the operationalization of allostatic load. The concept of allostatic load, as originally proposed by McEwen and Stellar, included dysregulation not only in the resting state of physiological systems, but also in system dynamics. We describe previous work on cortisol diurnal dynamic range (peak to nadir spread) as an index of the health of the hypothalamic-pituitary-adrenal axis, with compression of dynamic range being a marker of dysregulation. In particular, we review the evidence for a) diurnal dynamic range compression in people from disadvantaged backgrounds, b) cross-sectional association of cortisol diurnal dynamic range compression with dysregulation in other systems' resting states, and c) cross-sectional association of cortisol diurnal dynamic range compression with lower scores on cognitive testing. Then, we present new data from the Study of Midlife in the United States (MIDUS) on longitudinal associations of cortisol dynamic range compression with subsequent cognitive decline and all-cause mortality. Briefly, each standard deviation decrement in cortisol diurnal dynamic range is associated with adjusted mortality hazard ratio of 1.35 (95% confidence interval: 1.19, 1.54). Among those who scored at median or lower in executive functioning at baseline and survive, each standard deviation decrement in cortisol dynamic range is associated with 1% greater decline in executive functioning over a decade (95% confidence interval: 0.4%, 2.0%). We conclude that including measures of system dynamics like diurnal dynamic range in the next generation of allostatic load measurement will likely advance understanding of the cumulative physiological burden of chronic stress and life experiences, and improve the prediction of future health consequences.

Associations of Age at Menopause With Postmenopausal Bone Mineral Density and Fracture Risk in Women.

CONTEXT: Menopause before age 45 is a risk factor for fractures, but menopause occurs at age ≥45 in ~90% of women. OBJECTIVE: To determine, in women with menopause at age ≥45, whether (1) years since the final menstrual period (FMP) is more strongly associated with postmenopausal bone mineral density (BMD) than chronological age and (2) lower age at FMP is related to more fractures. DESIGN AND SETTING: The Study of Women's Health Across the Nation, a longitudinal cohort study of the menopause transition (MT). PARTICIPANTS: A diverse cohort of ambulatory women (pre- or early perimenopausal at baseline, with 15 near-annual follow-up assessments). MAIN OUTCOME MEASURES: Postmenopausal lumbar spine (LS) or femoral neck (FN) BMD (n = 1038) and time to fracture (n = 1554). RESULTS: Adjusted for age, body mass index (BMI), cigarette use, alcohol intake, baseline LS or FN BMD, baseline MT stage, and study site using multivariable linear regression, each additional year after the FMP was associated with 0.006 g/cm2 (P < 0.0001) and 0.004 g/cm2 (P < 0.0001) lower postmenopausal LS and FN BMD, respectively. Age was not related to FN BMD independent of years since FMP. In Cox proportional hazards regression, accounting for race/ethnicity, BMI, cigarette use, alcohol intake, prior fracture, diabetes status, exposure to bone-modifying medications/supplements, and study site, the hazard for incident fracture was 5% greater for each 1-year decrement in age at FMP (P = 0.02). CONCLUSIONS: Years since the FMP is more strongly associated with postmenopausal BMD than chronological age, and earlier menopause is associated with more fractures.

Anti-Mullerian Hormone as Predictor of Future and Ongoing Bone Loss During the Menopause Transition.

The menopause transition in women is a period of significant bone loss, with rapid declines in bone mineral density (BMD) commencing a year before the final menstrual period (FMP). Changes in menstrual bleeding patterns cannot reliably tell us if this rapid bone loss has begun or is imminent. We hypothesized that low circulating levels of anti-Mullerian hormone (AMH), which decline as women approach the FMP, would be associated with future and ongoing rapid bone loss. We used data from The Study of Women's Health Across the Nation, a multisite, multi-ethnic, prospective cohort study of the menopause transition to test this hypothesis. Adjusted for age, body mass index, race/ethnicity, and study site, every 50% decrement in AMH level in premenopause and early perimenopause was associated with 0.14% per year faster decline over the following 3 to 4 years in lumbar spine BMD and 0.11% per year faster decline in femoral neck BMD (p < 0.001 for both). AMH in late perimenopause was not associated with the rate of future BMD decline. AMH was also associated with the magnitude of ongoing bone loss, measured as percent of peak BMD lost by the end of the next 2 to 3 years. Every 50% decrement in AMH level was associated with 0.22% additional loss in spine BMD in premenopause, 0.43% additional loss in early perimenopause, and 0.50% additional loss in late perimenopause (p < 0.001 for all three). If a woman will lose more of her peak BMD than the site-specific least significant change (LSC) at either the lumbar spine or femoral neck by the next 2 to 3 years, then AMH below 100 pg/mL will detect it with sensitivity of 50% in premenopause, 80% in early perimenopause, and 98% in late perimenopause. These findings suggest that AMH measurement can help flag women at the brink of significant bone loss for early intervention. © 2022 American Society for Bone and Mineral Research (ASBMR).

Pathways to resilience: maternal nurturance as a buffer against the effects of childhood poverty on metabolic syndrome at midlife.

Children raised in families with low socioeconomic status (SES) go on to have high rates of chronic illness in adulthood. However, a sizable minority of low-SES children remain healthy across the life course, which raises questions about the factors associated with, and potentially responsible for, such resilience. Using a sample of 1,205 middle-aged Americans, we explored whether two characteristics--upward socioeconomic mobility and early parental nurturance--were associated with resilience to the health effects of childhood disadvantage. The primary outcome in our analyses was the presence of metabolic syndrome in adulthood. Results revealed that low childhood SES was associated with higher prevalence of metabolic syndrome at midlife, independently of traditional risk factors. Despite this pattern, half the participants raised in low-SES households were free of metabolic syndrome at midlife. Upward social mobility was not associated with resilience to metabolic syndrome. However, results were consistent with a buffering scenario, in which high levels of maternal nurturance offset the metabolic consequences of childhood disadvantage.