Carolyn J. Crandall

History of socioeconomic disadvantage and allostatic load in later life.

There is a growing interest in understanding how the experience of socioeconomic status (SES) adversity across the life course may accumulate to negatively affect the functioning of biological regulatory systems important to functioning and health in later adulthood. The goal of the present analyses was to examine whether greater life course SES adversity experience would be associated with higher scores on a multi-system allostatic load (AL) index of physiological function in adulthood. Data for these analyses are from 1008 participants (92.2% White) from the Biomarker Substudy of the Study of Midlife in the US (MIDUS). Multiple indicators of SES adversity in childhood (parent educational attainment, welfare status, financial situation) and two points in adulthood (educational attainment, household income, difficulty paying bills, availability of money to meet basic needs, current financial situation) were used to construct SES adversity measures for each life course phase. An AL score was constructed using information on 24 biomarkers from 7 different physiological systems (sympathetic and parasympathetic nervous systems, hypothalamic-pituitary-adrenal axis, cardiovascular, lipid metabolism, glucose metabolism, inflammatory immune activity). Analyses indicate higher AL as a function of greater SES adversity at each phase of, and cumulatively across, the life course. Associations were only moderately attenuated when accounting for a wide array of health status, behavioral and psychosocial factors. Findings suggest that SES adversity experience may cumulate across the life course to have a negative impact on multiple biological systems in adulthood. An important aim of future research is the replication of current findings in this predominantly White sample in more ethnically diverse populations.

Factors Related to Age at Natural Menopause: Longitudinal Analyses From SWAN

Early age at the natural final menstrual period (FMP) or menopause has been associated with numerous health outcomes and might be a marker of future ill health. However, potentially modifiable factors affecting age at menopause have not been examined longitudinally in large, diverse populations. The Study of Womens Health Across the Nation (SWAN) followed 3,302 initially premenopausal and early perimenopausal women from 7 US sites and 5 racial/ethnic groups, using annual data (1996-2007) and Cox proportional hazards models to assess the relation of time-invariant and time-varying sociodemographic, lifestyle, and health factors to age at natural FMP. Median age at the FMP was 52.54 years (n = 1,483 observed natural FMPs). Controlling for sociodemographic, lifestyle, and health factors, we found that racial/ethnic groups did not differ in age at the FMP. Higher educational level, prior oral contraceptive use, and higher weight at baseline, as well as being employed, not smoking, consuming alcohol, having less physical activity, and having better self-rated health over follow-up, were significantly associated with later age at the FMP. These results suggest that age at the natural FMP reflects a complex interrelation of health and socioeconomic factors, which could partially explain the relation of late age at FMP to reduced morbidity and mortality.

Change in Follicle-Stimulating Hormone and Estradiol Across the Menopausal Transition: Effect of Age at the Final Menstrual Period

BACKGROUND AND OBJECTIVE To determine whether patterns of change in serum estradiol (E2) and FSH across the menopausal transition were associated with age at the final menstrual period (FMP). DESIGN AND SETTING The Study of Womens Health Across the Nation (SWAN) is a seven-site, multiethnic, longitudinal study of the menopausal transition being conducted in 3302 menstruating women who were aged 42-52 yr at the 1996 study baseline. MEASUREMENTS Annually collected serum was assayed for E2 and FSH levels. Patterns of hormone change were evaluated in the 1215 women with a documented natural FMP by follow-up visit 9 (2006) using semiparametric stochastic and piecewise linear mixed modeling. RESULTS The FSH pattern across the menopausal transition began with an increase 6.10 yr before the FMP, an acceleration 2.05 yr before the FMP, deceleration beginning 0.20 yr before the FMP, and attainment of stable levels 2.00 yr after the FMP, independent of age at the FMP, race/ethnicity, or smoking status. Obesity attenuated the FSH rise and delayed the initial increase to 5.45 yr before the FMP. The mean E2 concentration did not change until 2.03 yr before the FMP when it began decreasing, achieving maximal rate of change at the FMP, then decelerating to achieve stability 2.17 yr after the FMP. Obesity, smoking behavior, and being Chinese or Japanese were associated with some variation in E2 levels but not the pattern of E2 change. CONCLUSIONS Time spans and overall patterns of change in serum FSH and E2 across the menopausal transition were not related to age at FMP or smoking, whereas time spans but not overall patterns were related to obesity and race/ethnicity.

Narrative Review: Hyperkyphosis in Older Persons

Key Summary Points Hyperkyphosis is a common geriatric condition that affects as many as 20% to 40% of older adults. Hyperkyphosis affects both men and womenthe lay term dowagers hump is a misnomer. Vertebral fractures are present in only about one third of the older adults with the worst degrees of thoracic curvature. Hyperkyphosis may be associated with multiple adverse health outcomes, including impaired pulmonary and physical function, fractures, and possibly increased risk for death. Research about the cause, consequences, and treatment for hyperkyphosis is urgently needed because available evidence is scant and the prevalence of the condition will probably increase as the population ages. With aging, the sagittal convexity of the normal thoracic spine, known as kyphosis, tends to progress (1). Hyperkyphosis, an excess of this process, is often called the dowagers hump. Although not precisely known, the prevalence and incidence of hyperkyphosis in older persons is probably between 20% and 40% (24). The causes and consequences of hyperkyphosis are not well understood. Most clinicians and laypersons assume that hyperkyphosis results from underlying vertebral fractures; however, vertebral fractures are present in only 36% to 37% of the most severe kyphosis cases (5, 6). Furthermore, hyperkyphosis is not simply an undesirable cosmetic consequence of aging. It may be associated with several adverse health outcomes, such as poor pulmonary and physical function. Our narrative review presents evidence that hyperkyphosis cannot be fully explained by osteoporosis and that it is a distinct geriatric syndrome deserving of more attention. With increased clinical awareness informed by continued research, physicians can begin to help prevent and treat hyperkyphosis and may avoid or lessen attendant adverse health consequences. Methods We searched MEDLINE and PubMed (OLDMEDLINE for pre-1966) for studies from 1950 through 28 November 2006 by using the following Medical Subject Heading terms and keywords: kyphosis, hyperkyphosis, and kyphotic posture. We reviewed all citations and available abstracts (4734 for kyphosis, 77 for hyperkyphosis, and 87 for kyphotic posture). We classified 618 abstracts as not relevant (n= 408) or warranting detailed consideration of the original article (n= 210). We also excluded reports that were not in English (n= 1365) and those that addressed the following: 1) primary surgical interventions in children or young adults (n= 1386); 2) trauma-induced hyperkyphosis, such as thoracolumbar burst fractures (n= 107); 3) hyperkyphosis caused by chronic diseases, such as Pott disease (n= 558); and 4) other conditions, such as scoliosis or kyphoscoliosis (n= 1108). As we reviewed the remaining publications, we paid attention to study design and sample size, characteristics of the participants, and whether studies addressed factors other than kyphosis that could have influenced outcomes. How Does One Measure Kyphosis? The normal spine has 3 curves in the sagittal plane: cervical lordosis (anteriorly convex), thoracic kyphosis (anteriorly concave), and lumbar lordosis. Kyphosis can be measured from radiographs or with such devices as the kyphometer (7), goniometer (8), inclinometer (9), and flexible ruler (1) (Figure 1). Developed first to assess scoliosis angles on spinal radiographs, the Cobb angle was modified to measure kyphosis. Considered the current gold standard measurement, it is calculated by drawing a line at the upper border of the vertebral body, marking the beginning of the thoracic curve (commonly T4), and at the inferior border of the vertebral body, representing the interface between the thoracic and lumbar curves (commonly T12). Perpendicular lines are drawn from these 2 lines, and the angle of their intersection is the Cobb angle (Figure 2). Other clinical assessments of kyphosis include qualitative visual measurements (3, 4) and measurement of either the distance from the occiput to wall (10) or the number of 1.7-cm blocks between the head and examination table while the patient is lying flat with the neck in a neutral position (2). Figure 1. The flexicurve: a noninvasive measurement of thoracic kyphosis. Spine Figure 2. The Cobb angle of thoracic kyphosis, calculated from a lateral radiograph. Spine Research has not fully disentangled the differences between clinical and radiologic kyphosis measures. In a study of 26 postmenopausal women (7), independent observers measured kyphosis similarly when they used Debrunner kyphometer, flexicurve-derived kyphosis angle, and radiographic Cobb angle measurements. Intraclass correlation estimates for the measures ranged from 0.87 to 0.92 (7). Traditionally, the Cobb angle is measured from standing lateral spine films. However, in elderly persons, spinal radiography is usually performed with the patient in the supine position for comfort. Because gravitys effect on posture is lost while supine, the kyphosis angle measured in the lying position may underestimate kyphosis. In a study that compared the standing Debrunner kyphometer angle with a supine radiographic Cobb angle measurement in 120 women age 55 to 80 years (11), the mean difference between the 2 measures was only 4. The Debrunner method overestimated the Cobb angle slightly, and the intraclass correlation coefficient for the measures was 0.68 (11). How Does One Define Hyperkyphosis? In younger populations, normal kyphosis angles range between 20 and 40 (12). In older adults, the mean kyphosis angle is about 48 to 50 in women (6, 1315) and about 44 in men (6). We know that the angle increases with age (1, 6, 12, 1626), but we do not have uniformly accepted thresholds for defining either hyperkyphosis or normal thoracic spine changes associated with aging. One longitudinal study of 100 healthy men and women age 50 years or older (mean age, 62 years) reported a mean thoracic angle increase of 3 per decade (27). In a longitudinal study of 10 women (mean age, 77 years) followed for 3 years after a vertebral fracture (24), the mean angle increase was 5.6. Cross-sectional studies reported that the oldest age groups had the most pronounced increases in kyphosis (12, 21, 23). For example, 1 study of men and women reported mean thoracic kyphosis angles of 26 in persons in their 20s, 53 in those 60 to 74 years of age, and 66 in those older than 75 years of age (23). An ongoing large prospective cohort study will soon provide important longitudinal data on rates of progression in older women (28). Potential Causes of Hyperkyphosis Vertebral fractures do not explain all cases of hyperkyphosis (29). Only 36% to 37% of older persons with the worst degrees of kyphosis have underlying vertebral fractures (5, 6). Other postulated causes of hyperkyphosis include postural changes, degenerative disk disease, muscular weakness, ligamentous degeneration, and genetic predisposition (Figure 3). Figure 3. Postulated causes and consequences of hyperkyphosis in older persons. Vertebral Fractures: The Most Cited Cause of Hyperkyphosis In 1963, 2 publications noted an association between vertebral body wedging and kyphosis (30, 31). In the 1970s, Milne and Lauder (1) developed the flexicurve measurement of kyphosis and quantified the vertebral wedging index from lateral chest radiographs. The wedge deformity index increased with age and explained 42% of the variation in kyphosis in men and 48% in women (29). Other studies reported correlations between wedge angles and kyphosis ranging from 0.45 to 0.78 (14, 18, 19). In studies that compared kyphosis between people with and without vertebral fractures, those with vertebral fractures had worse kyphosis (6, 15, 32). Postural Changes Postural changes affecting the cervical, lumbar, and sacral spinal areas and postural flexibility may influence thoracic curvature. For example, investigators have found weak but statistically significant correlations between Cobb angle thoracic kyphosis and cervical lordosis in men (r= 0.27; P < 0.03) and women (r= 0.33; P < 0.009) (23). In 300 volunteers age 20 to 70 years, researchers reported a correlation of 0.35 between radiographic measures of thoracic kyphosis and maximum lumbar lordosis (P= 0.001) (33). In a study involving 51 women (34), those age 66 to 88 years had greater flexicurve kyphosis than those age 21 to 51 years (mean kyphotic index, 11.1 [SD, 3.9] vs. 7.2 [SD, 2.2] during erect stance). The older women were less able to actively correct their posture from a relaxed to an erect position (34). Degenerative Disk Disease A few cross-sectional studies report an association between degenerative disk disease and kyphosis (6, 19, 35). In a study of 100 healthy women age 39 to 91 years (19), investigators found a statistically significant correlation between anterior disk height and kyphosis angle (r = 0.34; P < 0.001). Using measurements of lateral spine radiographs and mid-sagittal computed tomography films of 93 ex vivo spines from men and women age 18 to 94 years, researchers reported a correlation of 0.52 (P < 0.001) between anterior disk wedging and Cobb angle (35). In a third study of 1407 older men and women (6), with each 5-increase in Cobb angle, participants had a 36% (95% CI, 1.26 to 1.48) increased odds of having degenerative disk disease. These cross-sectional studies did not establish whether degenerative disk disease contributed to or was a consequence of hyperkyphosis. Muscle Weakness With 2 exceptions (36, 37), most studies report an inverse correlation between muscle strength and hyperkyphosis (8, 3842). Although not a direct measure of spinal muscle strength, grip strength measured in 151 men and women age 65 to 85 years correlated with worse kyphosis measured from a lateral photograph (r = 0.25; P < 0.005) (38). Similar findings of upper-extremity strength and flexicurve-measured kyphosis include a correlation of 0.32 in 47 women volunteers age 50 to 60 years (P < 0.05) (39). Three studies reported a s

Association of breast cancer and its therapy with menopause-related symptoms

Objective:To study the relationship between current menopause status, occurrence of menopause transition during cancer treatment, and prevalence and severity of possible menopause-related symptoms. Design:Data from the Cancer and Menopause Study (CAMS), a tumor-registry-based cohort of breast cancer survivors (BCS) diagnosed before age 50, were used. Using a standardized symptom checklist, women reported whether they were not at all, slightly, moderately, quite, or extremely bothered in the past 4 weeks by hot flashes, night sweats, vaginal dryness, pain with intercourse, breast sensitivity, joint pains, frequent mood changes, restless sleep, weight gain, forgetfulness, and difficulty concentrating. Current menopause status (by standard categories based on menstruation) and whether a persistent menopause transition occurred during cancer treatment were the main exposures. Linear (symptom severity as continuous outcome) and logistic (symptom present vs absent) regression models were adjusted for age, ethnicity, current smoking, alcohol use, chemotherapy, tamoxifen, body mass index, and depression scores. Results:Mean age of the participants was 50 years. The prevalence of symptoms was high. Hot flashes occurred in 17%, 51%, and 71% of pre-, peri-, and postmenopausal BCS, respectively. Hot flashes, vaginal dryness, and pain with intercourse were more severe in postmenopausal compared with perimenopausal BCS. Having had a transition during breast cancer treatment was associated with worse hot flash severity, independent of current menopause status. Conclusions:Menopause-related symptoms are common in BCS. Effective treatment options are needed. Having a treatment-related transition confers a persistent effect on hot flash severity. Clinicians should include this information when counseling women on potential outcomes of their cancer therapy.

Beyond frequency: who is most bothered by vasomotor symptoms?

Objective: Most menopausal women report vasomotor symptoms (hot flashes, night sweats). However, not all women with vasomotor symptoms, including frequent symptoms, are bothered by them. The primary aim was to identify correlates of vasomotor symptom bother beyond symptom frequency. Design: The Study of Womens Health Across the Nation participants reporting vasomotor symptoms at annual visit 7 comprised the sample (N = 1,042). Assessments included hot flash and night sweats frequency (number per week) and bother (1, not at all- 4, very much). Negative affect (index of depressive symptoms, anxiety, perceived stress, negative mood), symptom sensitivity, sleep problems, and vasomotor symptom duration (number of years) were examined cross-sectionally in relation to bother in ordinal logistic regression models with symptom frequency and covariates. Hot flashes and night sweats were considered separately. Results: In multivariable models controlling for hot flash frequency, negative affect (odds ratio [OR] = 1.27, 95% CI: 1.08-1.51), symptom sensitivity (OR = 1.18, 95% CI: 1.03-1.37), sleep problems (OR = 1.38, 95% CI: 1.04-1.85), poorer health (OR = 1.24, 95% CI: 1.03-1.48), duration of hot flashes (OR = 1.14, 95% CI: 1.06-1.23), younger age (OR = 0.94, 95% CI: 0.89-0.99), and African American race (vs white, OR = 1.59, 95% CI: 1.12-2.26) were associated with hot flash bother. After controlling for night sweats frequency and covariates, sleep problems (OR = 1.84, 95% CI:1.33-2.55) and night sweats duration (OR = 1.10, 95% CI: 1.02-1.20) were associated with night sweats bother. Conclusions: Beyond frequency, factors associated with bothersome hot flashes include mood, symptom sensitivity, symptom duration, sleep problems, age, and race. Correlates of bothersome night sweats include sleep problems and symptom duration. In addition to reducing frequency, interventions for vasomotor symptoms might consider addressing modifiable factors related to symptom bother.

Comparative Effectiveness of Pharmacologic Treatments to Prevent Fractures: An Updated Systematic Review

Osteoporosis is a skeletal disorder characterized by compromised bone strength, increasing the risk for fracture (1). Risk factors include, but are not limited to, increasing age, female sex, postmenopause for women, low body weight, parental history of a hip fracture, cigarette smoking, race, hypogonadism, certain medical conditions (particularly rheumatoid arthritis), and certain medications for chronic diseases (such as glucocorticoids). During ones expected remaining life, 1 in 2 postmenopausal women and 1 in 5 older men are at risk for an osteoporosis-related fracture (2). The increasing prevalence and cost of osteoporosis have heightened interest in the effectiveness and safety of the many interventions currently available to prevent osteoporotic fracture. In 2007, we conducted a systematic review of the comparative effectiveness of treatments to prevent fractures in men and women with low bone density or osteoporosis (3, 4). Since that time, new drugs have been approved for treatment, and new studies have been published about existing drugs. Additional issues about pharmacologic treatments for osteoporosis that have become particularly salient include the optimal duration of therapy; the safety of long-term therapy; and the role of bone mineral density (BMD) measurement, both for screening and for monitoring treatment. Therefore, we updated our original systematic review. Methods This article is a condensed and further updated version of an evidence review conducted for the Agency for Healthcare Research and Quality (AHRQ) Evidence-based Practice Centers program (5). This article focuses on the comparative benefits and risks of short- and long-term pharmacologic treatments for low bone density. In addition, we address issues regarding monitoring and duration of therapy. For this updated review, we followed the same methods as our 2007 review, with a few exceptions. A protocol for this review was developed and posted on the Effective Health Care Program Web site (6). Data Sources and Searches We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, the ACP Journal Club database, the National Institute for Clinical Excellence, the Food and Drug Administrations (FDA) MedWatch database, and relevant pharmacologic databases from 2 January 2005 to 3 June 2011. The search strategy followed that of the original report, with the addition of terms for new FDA-approved drugs (such as denosumab) and newly reported adverse events. The full search strategies are in our evidence report (5). We later updated this search to 21 January 2013 and used a machine learning method that a previous study showed had high sensitivity for detecting relevant evidence for updating a search of the literature on osteoporosis treatments (7) and then updated the searches to 4 March 2014 using the full search strategy. Study Selection Eligible studies were systematic reviews and randomized, controlled trials (RCTs) that studied FDA-approved pharmacotherapy (excluding calcitonin and etidronate) for women or men with osteoporosis that was not due to a secondary cause (such as glucocorticoid therapy and androgen-deprivation therapy) and also measured fractures as an outcome at a minimum follow-up of 6 months. In addition, we included observational studies with more than 1000 participants for adverse events and case reports for rare events. As in our original review, only English-language studies were included. Data Extraction and Quality Assessment Reviews were done in duplicate by pairs of reviewers. Study characteristics were extracted in duplicate, and outcomes data (both benefits and harms) were extracted by the study statistician. Study quality was assessed as it was in the 2007 report using the Jadad scale for clinical trials (with several questions added to assess allocation concealment and other factors) and the NewcastleOttawa Scale for observational studies (8, 9). Systematic reviews were assessed using a modified version of the 11 AMSTAR (A Measurement Tool to Assess Systematic Reviews) criteria (the modifications included eliminating the requirements to list all of the excluded studies and assess the conflicts of interest for all of the included studies) (10). The assessments of efficacy and effectiveness used reduction in fracture (all, vertebral, nonvertebral, spine, hip, wrist, or other) as the outcome (studies reporting changes in BMD but not fracture were excluded). Data Synthesis and Analysis Evidence on efficacy and effectiveness was synthesized narratively. For adverse events, we pooled data as in the 2007 report: We compared agent versus placebo and agent versus agent for agents within the same class and across classes. For groups of events that occurred in 3 or more trials, we estimated the pooled odds ratio (OR) and its associated 95% CI. Because many events were rare, we used exact conditional inference to perform the pooling rather than applying the usual asymptotic methods that assume normality. StatXact PROCs software was used for the analysis (11, 12). Large cohort and casecontrol studies were included to assess adverse events. Strength of evidence was assessed using the criteria of the Agency for Healthcare Research and Quality Evidence-based Practice Centers program, which are similar to those proposed by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group (13). Role of the Funding Source The update that included studies identified in the 3 June 2011 search was funded by AHRQ. Subsequent updating received no external funding. Although AHRQ formulated the initial study questions for the original report, it did not participate in the literature search, determination of study eligibility criteria, data analysis, or interpretation of the data. Staff from AHRQ reviewed and provided comments on the report. Results The first search yielded 26366 titles, 2440 of which were considered potentially relevant (Figure). Of these, 661 full-text articles were reviewed, resulting in 255 articles that were included in the update report. Of these, 174 articles were relevant to this article. The second update search plus hand searching initially yielded 16589 titles, and machine learning and full-text review identified 107 as relevant. The third update yielded 12131 titles. After title, abstract, and full-text screening, 34 were relevant. Thus, 55086 titles were screened and 315 articles met eligibility criteria for inclusion. Not every eligible study is cited in this article. A complete list of studies that met eligibility criteria is available at www.rand.org/health/centers/epc. Figure. Summary of evidence search and selection. FRAX = Fracture Risk Assessment Tool; HRT = hormone replacement therapy; LBD = low bone density. *Original LBD report (4). Fracture Prevention Our previous review (3) identified 76 randomized trials and 24 meta-analyses and concluded that there was good-quality evidence that alendronate, etidronate, ibandronate, risedronate, zoledronic acid, estrogen, parathyroid hormone, and raloxifene prevented osteoporotic fractures, although not all of these agents prevented hip fractures. The principal new efficacy findings since that time are additional data about zoledronic acid and data about a new agent, denosumab (Tables 1 and 2). The data for zoledronic acid came from 6 placebo-controlled studies of various doses in postmenopausal women (1419), the 2 largest of which enrolled 7230 women (15) and 2127 women (14). Both studies showed statistically significant reductions in nearly all types of fractures assessed, with relative risk reductions ranging from 0.23 to 0.73 at time points from 24 to 36 months after initiation of treatment. The data for denosumab came from 2 placebo-controlled trials in postmenopausal women, one small (332 enrolled women) (20) and one much larger that followed 7521 women for 36 months (21). This latter study found statistically significant reductions in each anatomical fracture type measured (hip, nonvertebral, vertebral, and new clinical vertebral), with hazard ratios of 0.31 to 0.80. Many secondary analyses and open-label extension results of this trial report the effectiveness of denosumab in various subpopulations and other circumstances (2228). Table 1. Principal Conclusions About Drug Efficacy/Effectiveness and Adverse Events Table 2. Principal Conclusions About Monitoring and Treatment Duration Despite some difficulties in comparing results across trials because of differences in the outcomes reported, high-strength evidence shows that bisphosphonates (alendronate, ibandronate, risedronate, and zoledronic acid), denosumab, and teriparatide (the 1,34 amino acid fragment of the parathyroid hormone) reduce fractures compared with placebo in postmenopausal women with osteoporosis, with relative risks for fractures generally in the range of 0.40 to 0.60 for vertebral fractures and 0.60 to 0.80 for nonvertebral fractures. This range translates into a number needed to treat of 60 to 89 to prevent 1 vertebral fracture and 50 to 67 to prevent 1 hip fracture over 1 to 3 years of treatment, using a pooled average of the incidence of these fractures in the placebo groups from included studies. The effect of ibandronate on hip fracture risk reduction is unclear because hip fracture was not a separately reported outcome in placebo-controlled trials of this agent. The selective estrogen receptor modulator raloxifene has been shown in placebo-controlled trials to reduce only vertebral fractures; reduction in the risk for hip or nonvertebral fractures was not statistically significant. There is only one randomized, controlled trial of men with osteoporosis that was designed with a primary fracture reduction outcome. Nearly 1200 men with osteoporosis were randomly assigned to placebo or zoledronic acid intravenously once per year for 2 years. At follow-up, 1.6% of treated men had new radio

Gains in Body Fat and Vasomotor Symptom Reporting Over the Menopausal Transition The Study of Women's Health Across the Nation

Although most women report vasomotor symptoms (hot flashes, night sweats) during midlife, their etiology and risk factors are incompletely understood. Body fat is positively associated with vasomotor symptoms cross-sectionally, but the longitudinal relation between changes in body fat and vasomotor symptoms is uncharacterized. The study aim was to examine whether gains in body fat were related to vasomotor symptom reporting over time. Measures of bioelectrical impedance for body fat, reproductive hormones, and reported vasomotor symptoms were assessed annually over 4 years from 2002 to 2006 among 1,659 women aged 47-59 years participating in the Study of Womens Health Across the Nation. Body fat change was examined in relation to vasomotor symptoms by using generalized estimating equations. Body fat gains were associated with greater odds of reporting hot flashes in models adjusted for age, site, race/ethnicity, education, smoking, parity, anxiety, and menopausal status (relative to stable body fat, gain: odds ratio = 1.23, 95% confidence interval: 1.02, 1.48; P = 0.03; loss: odds ratio = 1.07, 95% confidence interval: 0.89, 1.29; P = 0.45). Findings persisted controlling for estradiol, the free estradiol index, or follicle-stimulating hormone concentrations. The relations between body fat changes and night sweats were not statistically significant. Body fat gains are associated with greater hot flash reporting during the menopausal transition.

Bone mineral density loss in relation to the final menstrual period in a multiethnic cohort: Results from the Study of Women's Health Across the Nation (SWAN)

The objective of this study was to describe the time of onset and offset of bone mineral density (BMD) loss relative to the date of the final menstrual period (FMP); the rate and amount of BMD decline during the 5 years before and the 5 years after the FMP; and the independent associations between age at FMP, body mass index (BMI), and race/ethnicity with rates of BMD loss during this time interval. The sample included 242 African American, 384 white, 117 Chinese, and 119 Japanese women, pre‐ or early perimenopausal at baseline, who had experienced their FMP and for whom an FMP date could be determined. Loess‐smoothed curves showed that BMD loss began 1 year before the FMP and decelerated (but did not cease) 2 years after the FMP, at both the lumbar spine (LS) and femoral neck (FN) sites. Piecewise, linear, mixed‐effects regression models demonstrated that during the 10‐year observation period, at each bone site, the rates and cumulative amounts of bone loss were greatest from 1 year before through 2 years after the FMP, termed the transmenopause. Postmenopausal loss rates, those occurring between 2 and 5 years after the FMP, were less than those observed during transmenopause. Cumulative, 10‐year LS BMD loss was 10.6%; 7.38% was lost during the transmenopause. Cumulative FN loss was 9.1%; 5.8% was lost during the transmenopause. Greater BMI and African American heritage were related to slower loss rates, whereas the opposite was true of Japanese and Chinese ancestry.

Mammographic density in a multiethnic cohort

Objectives:To compare mammographic density among premenopausal and early perimenopausal women from four racial/ethnic groups and to examine density and acculturation among Japanese and Chinese women. Design:The study included 391 white, 60 African American, 171 Japanese, and 179 Chinese participants in the Study of Womens Health Across the Nation, a multisite study of US women transitioning through menopause. Mammograms done when women were premenopausal or early perimenopausal were assessed for area of dense breast tissue and the percent of the breast occupied by dense tissue (percent density). Information on race/ethnicity, acculturation, and other factors was obtained from standardized instruments. Multiple linear regression modeling was used to examine the association between race/ethnicity or acculturation and density measures. Results:Age-adjusted mean percent density was highest for Chinese (52%) and lowest for African American (34%) women. After additional adjustment for body mass index, menopause status, age at first birth, breast-feeding duration, waist circumference, and smoking, African Americans had the highest mean percent density (51%) and Japanese women had the lowest (39%). In contrast, the area of dense tissue was highest for African Americans and similar for white, Japanese, and Chinese women. Less acculturated Chinese and Japanese women tended to have a larger area of density and a higher percent density. Conclusions:Neither the age-adjusted nor fully adjusted results for percent density or area of dense tissue reflected current differences in breast cancer incidence rates among similarly aged African American, Japanese, Chinese, and white women. In addition, mammographic density was higher in less acculturated Asian women.