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1.  Childhood Socioeconomic Status and Adult Femoral Neck Bone Strength: Findings from The Midlife in the United States Study 
Bone  2013;56(2):320-326.
Bone acquisition in childhood impacts adult bone mass, and can be influenced by childhood socioeconomic conditions. Socioeconomic status is also associated with body weight which affects the load that bone is exposed to in a fall. We hypothesized that socioeconomic advantage in childhood is associated with greater bone strength relative to load in adulthood.
Hip dual x-ray absorptiometry scans from 722 participants in the Midlife in the United States Study were used to measure femoral neck size and bone mineral density, and combined with body weight and height to create composite indices of femoral neck strength relative to load in different failure modes: compression, bending, and impact. A childhood socioeconomic advantage score was created for the same participants from parental education, self-rated financial status relative to others, and not being on welfare. Multiple linear regression was used to determine the association of childhood socioeconomic advantage score with femoral neck composite strength indices, stratified by gender and race (white/non-white), and adjusted for study site, age, menopause status in women, education, and current financial advantage.
Childhood socioeconomic advantage was independently associated with higher indices of all three composite strength indices in white men (adjusted standardized effect sizes, 0.19 to 0.27, all p values <0.01), but not in the other three race/gender groups. Additional adjustment for adult obesity, physical activity in different life stages, smoking, and heavy drinking over the life-course significantly attenuated the associations in white men.
Socioeconomic disadvantage in childhood is associated with lower hip strength relative to load in white men, and these influences are dampened by healthy lifestyle choices.
PMCID: PMC3784306  PMID: 23810840
bone strength; femoral neck; childhood socioeconomic advantage; health behaviors
2.  Simultaneous determination of eleven phytoestrogens in human serum using a two minute liquid chromatography/tandem mass spectrometry method 
A rapid two minute liquid chromatography tandem mass spectrometry (LC-MS/MS) method operating in multiple reaction ion monitoring mode was developed and validated that allows for the characterization and simultaneous quantification of eleven phytoestrogen metabolites with mass transitions m/z 241/119 (equol), 253/132(daidzein), 255/149 (dihydrodaidzein), 257/108 (O-desmethylangolesin), 269/133 (genistein), 283/184 (glycitein), 267/191 (formononetin), 289/109 (biochanin A), 267/91 (coumestrol), enterodiol (301/253), and enterolactone (297/253). The method was demonstrated to be specific and sensitive, and a linear response for each phytoestrogen was observed over a range of 1–5,000 ng/mL in human serum with the exception of dihydrodaidzein, whose lower limit of quantification was 2 ng/mL. The separation was carried out on a Synergi Polar-RP 2.5 micron (50 × 2.0 mm, i.d.) column at 50°C with water and acetonitrile (both containing 10 mM ammonium acetate) as the mobile phase under gradient conditions at a flow rate of 0.75 mL/min. This LC-MS/MS method is very useful for high throughput analysis of phytoestrogens and proved to be simple, sensitive, reproducible, and reliable.
PMCID: PMC4037236  PMID: 20346741
LC-MS/MS; phytoestrogens; serum; analysis
3.  The Relationship Between Dietary Phytoestrogens and Development of Urinary Incontinence in Midlife Women 
Menopause (New York, N.Y.)  2013;20(4):428-436.
Because exogenous estrogen treatment has been associated with a higher risk of urinary incontinence, our objective was to evaluate the longitudinal relationships of dietary phytoestrogen intakes (isoflavones, coumestans and lignans) and the development of incontinence in midlife women transitioning through menopause.
The Study of Women’s health Across the Nation (SWAN) Phytoestrogen Study was developed within SWAN, a community-based, multisite, multi-racial/ethnic, prospective cohort study. SWAN interviewers administered a food consumption assessment at baseline and at follow-up visits 5 and 9. The SWAN Phytoestrogen study created a phytonutrient data base that allowed estimation of usual daily intakes of four isoflavones, four lignans and coumestrol. On an annual self-administered questionnaire, participants reported on frequency and type of incontinence. We used discrete proportional hazards models to evaluate whether estimated daily intake of each phytoestrogen class at the visit previous to the first report of incontinence was associated with the development of monthly or more incontinence compared to remaining continent.
We found no association or patterns of association between developing any, stress or urge incontinence and the reported daily dietary intake of isoflavones, coumestrol, and lignans in the visit previous to the onset of incontinence.
The results of this longitudinal study provide important information to better understand estrogen-like substances on the continence mechanism in midlife women. Our study shows that neither high nor low dietary intakes of isoflavones, coumestrol and lignans prevent stress or urge incontinence. Future studies should evaluate whether serum levels of phytoestrogens or their metabolites impact incontinence symptoms.
PMCID: PMC3568456  PMID: 23096248
Phytoestrogen; isoflavone; coumestrol; lignan; urinary incontinence
4.  Ethnic variability in bone geometry as assessed by hip structure analysis: Findings from the Hip Strength Across the Menopausal Transition study 
Racial/ethnic origin plays an important role in fracture risk. Racial/ethnic differences in fracture rates cannot be fully explained by bone mineral density (BMD). Studies examining the influence of bone geometry and strength on fracture risk have focused primarily on older adults and have not included people from diverse racial/ethnic backgrounds. Our goal was to explore racial/ethnic differences in hip geometry and strength in a large sample of midlife women. We performed Hip Structure Analysis (HSA) on hip DXA scans from 1942 pre- and early peri-menopausal women. The sample included Caucasian (50%), African American (27%), Chinese (11%) and Japanese (12%) women, age 42–52 years. HSA was performed using software developed at John’s Hopkins University. African American women had higher conventional (8.4–9.7%) and HSA BMD (5.4–19.8%) than other groups with the exception being Japanese women who had the highest HSA BMD (9.7–31.4%). HSA indices associated with more favorable geometry and greater strength and resistance to fracture were more prevalent in African American and Japanese women. Femurs of African American women had a smaller outer diameter, a larger cross-sectional area and section modulus, and a lower buckling ratio. Japanese women presented a different pattern with a higher section modulus and lower buckling ratio, similar to African American women, but a wider outer diameter; this was offset by a greater cross-sectional area and a more centrally located centroid. Chinese women had similar conventional BMD as Caucasian women but a smaller neck region area and HSA BMD at both regions. They also had a smaller cross-sectional area and section modulus, a more medially located centroid, and a higher buckling ratio than Caucasian women. The observed biomechanical differences may help explain racial/ethnic variability in fracture rates. Future research should explore the contribution of hip geometry to fracture risk across all race/ethnicities.
PMCID: PMC3586935  PMID: 23044816
Hip Structure Analysis; Bone Geometry; Bone Mineral Density; Ethnicity; Women
5.  A comparison of DXA and CT based methods for estimating the strength of the femoral neck in post-menopausal women 
Simple 2-dimensional (2D) analyses of bone strength can be done with dual energy x-ray absorptiometry (DXA) data and applied to large data sets. We compared 2D analyses to 3-dimensional (3D) finite element analyses (FEA) based on quantitative computed tomography (QCT) data.
213 women participating in the Study of Women’s Health across the Nation (SWAN) received hip DXA and QCT scans. DXA BMD and femoral neck diameter and axis length were used to estimate geometry for composite bending (BSI) and compressive strength (CSI) indices. These and comparable indices computed by Hip Structure Analysis (HSA) on the same DXA data were compared to indices using QCT geometry. Simple 2D engineering simulations of a fall impacting on the greater trochanter were generated using HSA and QCT femoral neck geometry; these estimates were benchmarked to a 3D FEA of fall impact.
DXA-derived CSI and BSI computed from BMD and by HSA correlated well with each other (R= 0.92 and 0.70) and with QCT-derived indices (R= 0.83–0.85 and 0.65–0.72). The 2D strength estimate using HSA geometry correlated well with that from QCT (R=0.76) and with the 3D FEA estimate (R=0.56).
Femoral neck geometry computed by HSA from DXA data corresponds well enough to that from QCT for an analysis of load stress in the larger SWAN data set. Geometry derived from BMD data performed nearly as well. Proximal femur breaking strength estimated from 2D DXA data is not as well correlated with that derived by a 3D FEA using QCT data.
PMCID: PMC3606278  PMID: 22810918
Hip Structure Analysis; DXA; QCT; Bone Mineral Density; Fracture; Women
6.  Yoga Improves Upper-Extremity Function and Scapular Posturing in Persons with Hyperkyphosis 
Hyperkyphosis (excess thoracic spine curvature) is associated with upper-extremity functional limitations and altered scapular posturing. The purpose of this study was to quantify the changes in upper-extremity function and scapular posturing following a 6-month yogaintervention in persons with hyperkyphosis.
Twenty-one older adults with hyperkyphosis (75.5+7.4 yrs) enrolled in the UCLA Yoga for Kyphosis randomized controlled trial, elected to participate in this uncontrolled, prepost substudy of upper-extremity function. They were measured at baseline and after a 24-week yoga intervention. Maximum vertical reach and timed book tests were used to evaluate upper-extremity function. Scapular posturing was quantified using a motion analysis system and data was obtained under 4 conditions: 1) quiet-standing, 2) normal walking, 3) fast walking, and 4) seated. Paired t-tests were used to test for changes between baseline and 6-month follow-up measures and Cohen’s d was calculated to examine effect sizes.
Following the 6-month yoga intervention, participants improved their book test performance by 26.4% (p < 0.001; d = 1.5). Scapular protraction decreased by 2.9% during the static-sitting condition (p < 0.001; d = 0.5) and the overall excursion of the scapulae decreased for both fast (25.0%, p < 0.05; d = 0.6) and self-selected walking (29.4%, p < 0.01; d = 0.9). There were no changes in maximum vertical reach.
Subjects demonstrated significant improvements with small to large effect sizes in the timed book test and scapular posturing to a less protracted position during both static and dynamic conditions after the intervention. These adaptations are likely to reduce the risk of scapular impingement and help preserve functional independence in older adults.
PMCID: PMC3965199  PMID: 24678442
Hyperkyphosis; Upper-extremity function; Scapular posture; Yoga
7.  Phytoestrogen and Fiber Intakes in Relation to Incident Vasomotor Symptoms: Results From the Study of Women’s Health Across the Nation 
Menopause (New York, N.Y.)  2013;20(3):305-314.
While reduction of vasomotor symptoms (VMS, hot flashes/night sweats) has been reported in postmenopausal women who used isoflavones, a clear dose-response has not been shown, has largely not been reported for perimenopausal women and has largely only been for reducing prevalent VMS, not preventing newly developing VMS. We analyzed longitudinal data from the Study of Women’s Health Across the Nation (SWAN) for the relation of dietary phytoestrogens and fiber intake to incident VMS in this multi-racial/ethnic cohort.
SWAN included 3302 pre- and early perimenopausal women, 1651 of whom reported no VMS at baseline, who were followed with annual visits for 10 years. Dietary intakes of isoflavones, coumestrol, lignans and fiber were assessed by a food frequency questionnaire at baseline and annual visits 5 and 9 and interpolated for intervening years. Number of days of having VMS in the past two weeks was self-reported annually. Using generalized estimating equations multinomial logistic regressions, we modeled incident VMS in relation to isoflavones, lignans, fiber, coumestrol, or total phytoestrogens intake and covariates.
No consistent monotonic relations were observed for any dietary phytoestrogens or fiber to incident VMS, although adjusted odds ratios for some individual quartiles were statistically significant.
To be certain of any effect of dietary phytoestrogens or fiber in preventing incident VMS, a randomized, placebo-controlled, double-masked trial with sufficient numbers of women in different racial/ethnic, menopausal status and metabolic groups with years of follow-up is required, but our results suggest that a clinically significant or large effect is unlikely.
PMCID: PMC3566363  PMID: 23435028
diet; phytoestrogens; vasomotor symptoms; menopause; race/ethnicity
8.  C-Reactive Protein, Bone Strength, and Nine-Year Fracture Risk: Data From the Study of Women’s Health Across the Nation (SWAN) 
Higher levels of C-reactive protein (CRP), an inflammatory marker, are associated with increased fracture risk, although previous studies on CRP and bone mineral density (BMD) have yielded conflicting results. We aimed to test the hypotheses that composite indices of femoral neck strength relative to load, which are inversely associated with fracture risk, would also be inversely associated with CRP, and would explain part of the association between CRP and fracture risk. We analyzed data from a multisite, multiethnic prospective cohort of 1872 community-dwelling women, premenopausal or early perimenopausal at baseline. Femoral neck composite strength indices in three failure modes were calculated using dual-energy X-ray absorptiometry (DXA)-derived femoral neck width (FNW), femoral neck axis length (FNAL), femoral neck BMD and body size at baseline, as BMD*FNW/weight for compression strength, BMD*(FNW)2/(FNAL*weight) for bending strength, and BMD*FNW*FNAL/(height*weight) for impact strength. Incident nondigital, noncraniofacial fractures were ascertained annually over a median follow-up of 9 years. In analyses adjusted for age, race/ethnicity, diabetes, menopause transition stage, body mass index, smoking, alcohol use, physical activity, medications, prior fracture, and study site, CRP was associated inversely with each composite strength index (0.035–0.041 SD decrement per doubling of CRP, all p< 0.001), but not associated with femoral neck or lumbar spine BMD. During the follow-up, 194 women (10.4%) had fractures. In Cox proportional hazards analyses, fracture hazard increased linearly with loge(CRP), only for CRP levels ≥ 3 mg/L. Addition of femoral neck or lumbar spine BMD to the model did not attenuate the CRP-fracture association. However, addition of any of the composite strength indices attenuated the CRP-fracture association and made it statistically nonsignificant. We conclude that fracture risk increases with increasing CRP, only above the threshold of 3 mg/L. Unlike BMD, composite strength indices are inversely related to CRP levels, and partially explain the increased fracture risk associated with inflammation.
PMCID: PMC3880424  PMID: 23456822
9.  Physical Activity as Determinant of Femoral Neck Strength Relative to Load in Adult Women: Findings from the Hip Strength Across the Menopause Transition Study 
Our objective was to examine the associations of physical activity in different life domains with peak femoral neck strength relative to load in adult women. Composite indices of femoral neck strength integrate body size with femoral neck size and bone mineral density to gauge bone strength relative to load during a fall, and are inversely associated with incident fracture risk.
Participants were 1919 pre- and early perimenopausal women from the Study of Women’s Health Across the Nation. Composite indices of femoral neck strength relative to load in three failure modes (compression, bending, and impact) were created from hip DXA scans and body size. Usual physical activity within the past year was assessed with the Kaiser Physical Activity Survey in four domains: sport, home, active living, and work. We used multiple linear regression to examine the associations.
Greater physical activity in each of the four domains was independently associated with higher composite indices, adjusted for age, menopausal transition stage, race/ethnicity, SWAN study site, smoking status, smoking pack-years, alcohol consumption level, current use of supplementary calcium, current use of supplementary vitamin D, current use of bone-adverse medications, prior use of any sex steroid hormone pills or patch, prior use of depo-provera injections, history of hyperthyroidism, history of previous adult fracture, and employment status: standardized effect sizes ranged from 0.04 (p<0.05) to 0.20 (p<0.0001).
Physical activity in each domain examined was associated with higher peak femoral neck strength relative to load in pre- and early perimenopausal women.
PMCID: PMC3877714  PMID: 23812598
Physical Activity; Peak Bone Strength; Composite Strength Indices; Femoral Neck Strength Relative to Load; Active Living
10.  Bone resorption and fracture across the menopausal transition: the Study of Women’s Health Across the Nation 
Menopause (New York, N.Y.)  2012;19(11):1200-1207.
Bone turnover markers (BTMs) predict fracture in older women, whereas data on younger women are lacking. To test the hypothesis that BTMs measured before and after menopause predict fracture risk, we performed a cohort study of 2,305 women.
Women attended up to nine clinic visits for an average of 7.6 ± 1.6 years; all were aged 42 to 52 years and were premenopausal or early perimenopausal at baseline. Incident fractures were self-reported. Serum osteocalcin and urinary cross-linked N-telopeptide of type I collagen (NTX) were measured at baseline. NTX was measured at each annual follow-up. Interval-censored survival models or generalized estimating equations were used to test whether baseline BTMs and changes in NTX, respectively, were associated with fracture risk. Hazard ratios (HRs) or odds ratios were calculated with 95% CIs.
Women who fractured (n = 184) had about a 10% higher baseline median NTX (34.4 vs 31.5 nanomoles of bone collagen equivalents per liter per nanomole of creatinine per liter; P = 0.001), but there was no difference in osteocalcin. A 1-SD decrease in lumbar spine bone mineral density (BMD) measured premenopausally was associated with a higher fracture risk during menopause (HR, 1.55; 95% CI, 1.32–1.73). Women with a baseline NTX greater than the median had a 45% higher risk of fracture, multivariable-adjusted (HR, 1.45; 95% CI, 1.04–2.23). The HR of fracture among women with both the lowest spine BMD (quartile 1) and the highest NTX (quartile 4) at baseline was 2.87 (95% CI, 1.61–6.01), compared with women with lower NTX and higher BMD. Women whose NTX increased more than the median had a higher risk of fracture (odds ratio, 1.51; 95% CI, 1.08–2.10). Women who had baseline NTX greater than the median experienced greater loss of spine and hip BMD.
A higher urinary NTX excretion measured before menopause and across menopause is associated with a higher risk of fracture. Our results are consistent with the pathophysiology of transmenopausal changes in bone strength.
PMCID: PMC3483443  PMID: 22850443
Bone resorption; Fracture; Menopause; Osteoporosis; Bone mineral density
11.  Physical Demand Profiles of Hatha Yoga Postures Performed by Older Adults 
Understanding the physical demands placed upon the musculoskeletal system by individual postures may allow experienced instructors and therapists to develop safe and effective yoga programs which reduce undesirable side effects. Thus, we used biomechanical methods to quantify the lower extremity joint angles, joint moments of force, and muscle activities of 21 Hatha yoga postures, commonly used in senior yoga programs. Twenty older adults, 70.7 years ± 3.8 years, participated in a 32-wk yoga class (2 d/wk) where they learned introductory and intermediate postures (asanas). They then performed the asanas in a motion analysis laboratory. Kinematic, kinetic, and electromyographic data was collected over three seconds while the participants held the poses statically. Profiles illustrating the postures and including the biomechanical data were then generated for each asana. Our findings demonstrated that Hatha yoga postures engendered a range of appreciable joint angles, JMOFs, and muscle activities about the ankle, knee, and hip, and that demands associated with some postures and posture modifications were not always intuitive. They also demonstrated that all of the postures elicited appreciable rectus abdominis activity, which was up to 70% of that induced during walking.
PMCID: PMC3814077  PMID: 24282431
12.  Dietary Phytoestrogen Intakes and Cognitive Function During the Menopause Transition: Results from the SWAN Phytoestrogen Study 
Menopause (New York, N.y.)  2012;19(8):894-903.
Phytoestrogens, which consist mainly of isoflavones, lignans and coumestans have estrogenic and anti-inflammatory properties. Prior research suggests that higher dietary or supplemental intakes of isoflavones and lignans are related to better cognitive performance in middle aged and older women.
We conducted longitudinal analysis of dietary phytoestrogens and cognitive performance in a cohort of African-American, white, Chinese and Japanese women undergoing the menopause transition (MT). Tests were: Symbol Digit Modalities, East Boston Memory and Digits Span Backward. Phytoestrogens were assessed by Food Frequency Questionnaire. We modeled each cognitive score as a function of concurrent value of the primary predictors (highest tertile of isoflavones, lignans or coumestrol) and covariates including MT stage.
Coumestrol and isoflavone intakes were 10 and 25 times greater, respectively, in Asian versus non-Asian participants. During late perimenopause and postmenopause, Asian women with high isoflavone intakes did better on processing speed, but during early perimenopause and postmenopause, high isoflavone Asian consumers performed worse on verbal memory. The highest isoflavone consumers among non-Asians likewise posted lower verbal memory scores during early perimenopause. A verbal memory benefit of higher dietary lignan consumption was apparent only during late perimenopause, when women from all ethnic/racial groups who were in the highest tertile of intake demonstrated a small advantage. Coumestrol was unrelated to cognitive performance.
Cognitive effects of dietary phytoestrogens are small, appear to be class-specific, vary by menopause stage and cognitive domain and differ among ethic/racial groups (but whether this is related to dose or to host factors cannot be discerned).
PMCID: PMC3376653  PMID: 22415567
menopause transition; cognitive function; phytoestrogen; isoflavone; lignan; coumestrol
13.  Yoga for persistent fatigue in breast cancer survivors: A randomized controlled trial 
Cancer  2011;118(15):3766-3775.
Cancer-related fatigue afflicts up to one-third of breast cancer survivors, yet there are no empirically-validated treatments for this symptom.
We performed a two-group RCT to determine the feasibility and efficacy of an Iyengar yoga intervention for breast cancer survivors with persistent post-treatment fatigue. Participants were breast cancer patients who had completed cancer treatments (other than endocrine therapy) at least 6 months prior to enrollment, reported significant cancer-related fatigue, and had no other medical conditions that would account for fatigue symptoms or interfere with yoga practice. Block randomization was used to assign participants to a 12-week Iyengar-based yoga intervention or to 12 weeks of health education (control). The primary outcome was change in fatigue measured at baseline, immediately post-treatment, and 3 months after treatment completion. Additional outcomes included changes in vigor, depressive symptoms, sleep, perceived stress, and physical performance. Intent to treat analyses were conducted with all randomized participants using linear mixed models.
Thirty-one women were randomly assigned to yoga (n = 16) or health education (n = 15). Fatigue severity declined significantly from baseline to post-treatment and over a 3 month follow-up in the yoga group relative to controls (P = .032). In addition, the yoga group showed significant increases in vigor relative to controls (P = .011). Both groups showed positive changes in depressive symptoms and perceived stress (P < .05). No significant changes in sleep or physical performance were observed.
A targeted yoga intervention led to significant improvements in fatigue and vigor among breast cancer survivors with persistent fatigue symptoms.
PMCID: PMC3601551  PMID: 22180393
14.  Yoga decreases kyphosis in senior women and men with adult onset hyperkyphosis: results of a randomized controlled trial 
To assess whether a specifically designed Yoga intervention can reduce hyperkyphosis.
A 6-month, 2 group, randomized, controlled, single masked trial.
Community research unit.
118 women and men aged >60 years with kyphosis angle >40 degrees. Major exclusions were: serious medical comorbidity; use of assistive device; unable to hear or see adequately for participation; or unable to pass a physical safety screen.
The active treatment group attended hour-long Yoga classes, 3 days per week, for 24 weeks. The control group attended a monthly luncheon/seminar and received mailings.
Primary outcomes were change (baseline to 6 months) in Debrunner kyphometer-assessed kyphosis angle, standing height, timed chair stands, functional reach and walking speed. Secondary outcomes were change in: kyphosis index, flexicurve kyphosis angle, the Rancho Bernardo Blocks posture assessment and health-related quality of life (HRQOL).
Compared to control participants, those randomized to Yoga experienced a 4.4% improvement in flexicurve kyphosis angle (p=0.006) and a 5% improvement in kyphosis index (p=0.004). The intervention did not result in statistically significant improvement in Debrunner kyphometer angle, measured physical performance or in self-assessed HRQOL (each p>0.1).
The decrease in flexicurve kyphosis angle in the Yoga treatment group shows that hyperkyphosis is remediable, a critical first step in the pathway to treating or preventing this condition. Larger, more definitive studies of Yoga or other interventions for hyperkyphosis should be considered. Targeting individuals with more malleable spines and using longitudinally precise measures of kyphosis could strengthen the treatment effect.
PMCID: PMC3700806  PMID: 19682114
kyphosis; hyperkyphosis; yoga; randomized controlled clinical trial
15.  Socioeconomic status over the life-course and adult bone mineral density: The Midlife in the U.S. Study 
Bone  2012;51(1):107-113.
Adult bone mass depends on acquisition in childhood and decline in adulthood, and may be influenced by socioeconomic conditions over the entire life course.
We examined associations of bone mineral density (BMD) in adulthood with life course socioeconomic status in 729 participants in the Midlife in the United States Biomarker Project, adjusting for age, menopausal transition stage, race, gender, body weight, smoking, physical activity in several life stages, and research site. Primary predictors were a) childhood socioeconomic advantage score (including parental education, self-rated financial status relative to others, not being on welfare), b) adult education level (no college vs. some college vs. college graduate), and c) adult current financial advantage score (including family-adjusted poverty to income ratio, self-assessed current financial situation, having enough money to meet needs, ease in paying bills).
Mean age was 56.9 (range 34–85) years. After adjustment for covariates, childhood socioeconomic advantage and adult education level were positively associated with lumbar spine BMD: 0.27 standard deviations (SD) higher at 90th compared to 10th percentile of childhood advantage score (P = 0.009), and 0.24 SD higher in college graduates compared to participants without college education (P = 0.01). Adult current financial advantage was not associated with lumbar spine BMD. None of the three socioeconomic indicators was significantly associated with femoral neck BMD.
Childhood socioeconomic advantage and adult education level were associated with higher adult lumbar spine BMD. Current financial advantage was not associated with BMD. Childhood socioeconomic factors may influence acquisition of lumbar BMD.
PMCID: PMC3371160  PMID: 22543227
bone mineral density; socioeconomic status; poverty; education; income
16.  Development of an updated phytoestrogen database for use with the SWAN Food Frequency Questionnaire: intakes and food sources in a community-based, multiethnic cohort study 
Nutrition and cancer  2012;64(2):228-244.
Phytoestrogens, heterocyclic phenols found in plants, may benefit several health outcomes. However, epidemiologic studies of the health effects of dietary phytoestrogens have yielded mixed results, in part due to challenges inherent in estimating dietary intakes. The goal of this study was to improve the estimates of dietary phytoestrogen consumption using a modified Block Food Frequency Questionnaire (FFQ), a 137-item FFQ created for the Study of Women’s Health Across the Nation (SWAN) in 1994. To expand the database of sources from which phytonutrient intakes were computed, we conducted a comprehensive PubMed/Medline search covering January, 1994 through September, 2008. The expanded database included 4 isoflavones, coumestrol and 4 lignans. The new database estimated isoflavone content of 105 food items (76.6%) versus 14 (10.2%) in the 1994 version and computed coumestrol content of 52 food items (38.0%), compared to 1 (0.7%) in the original version. Newly added were lignans; values for 104 FFQ food items (75.9%) were calculated. In addition, we report here the phytonutrient intakes for each racial and language group in the SWAN sample and present major food sources from which the phytonutrients came. This enhanced ascertainment of phytoestrogens will permit improved studies of their health effects.
PMCID: PMC3674882  PMID: 22211850
17.  Socioeconomic Status, Race, and Bone Turnover in the Midlife in the U.S. Study 
Osteoporosis International  2011;23(5):1503-1512.
To determine socioeconomic status (SES) and race differences in levels of bone turnover.
Using data from the Biomarker Substudy of the Midlife in the U.S. (MIDUS) study (491 men, 449 women), we examined cross-sectional associations of SES and race with serum levels of bone turnover markers (bone-specific alkaline phosphatase [BSAP], procollagen type I N-terminal propeptide [PINP], and N-telopeptide [Ntx]) separately in men and women. Linear multivariable regression was used to control for body weight, menopausal transition stage, and age.
Among men, low family poverty-to-income ratio (FPIR) was associated with higher turnover, but neither education nor race was associated with turnover. Men with FPIR <3 had 1.808 nM BCE higher Ntx (P = 0.05), 3.366 U/L higher BSAP (P = 0.02), and 7.066 higher PINP (P = 0.02). Among women, neither education nor FPIR was associated with bone turnover, but Black women had 3.688 nM BCE higher Ntx (P = 0.001), 5.267 U/L higher BSAP (P=0.005), and 11.906 μg/L higher PINP (P=0.008) compared to non-Black women.
Economic adversity was associated with higher bone turnover in men, and minority race status was associated with higher bone turnover in women, consistent with the hypothesis that higher levels of social stresses cause increased bone turnover. The magnitude of these associations was comparable to the effects of some osteoporosis medications on levels of turnover.
PMCID: PMC3257365  PMID: 21811862
bone turnover; bone resorption; socioeconomic status; SES; N-telopeptide; bone-specific alkaline phosphatase; procollagen type I N-terminal propeptide; poverty; income; Ntx; PINP; BSAP
18.  Metabolic syndrome and mammographic density: The Study of Women’s Health Across the Nation (SWAN) 
The metabolic syndrome (MetS) is associated with an increase in breast cancer risk. In this study, we evaluated whether the MetS was associated with an increase in percent mammographic density (MD), a breast cancer risk factor. We used linear regression and mixed models to examine the cross-sectional and longitudinal associations of the MetS and components of the MetS to percent MD in 790 pre- and early perimenopausal women enrolled in the Study of Women’s Health Across the Nation (SWAN). In cross-sectional analyses adjusted for body mass index (BMI), modest inverse associations were observed between percent MD and the MetS (β = −2.5, SE = 1.9, p = 0.19), abdominal adiposity (β = −4.8, SE = 1.9, p = 0.01) and raised glucose (β = −3.7, SE = 2.4, p = 0.12). In longitudinal models adjusted for covariates including age and BMI, abdominal adiposity (β = 0.34, SE = 0.17, p = 0.05) was significantly positively associated with slower annual decline in percent MD with time. In conclusion, our results do not support the hypothesis that the MetS increases breast cancer risk via a mechanism reflected by an increase in percent MD.
PMCID: PMC3610563  PMID: 21105041
adiposity; body mass index; breast cancer risk factor; mammographic density; metabolic syndrome
19.  Factors Associated with Worsening and Improving Urinary Incontinence Across the Menopausal Transition 
Obstetrics and gynecology  2008;111(3):667-677.
To evaluate whether the menopausal transition is associated with worsening of urinary incontinence symptoms over 6 years in mid-life women.
We analyzed data from 2415 women who reported monthly or more incontinence in self-administered questionnaires at baseline and during the first 6 annual follow-up visits (1995–2002) of the prospective cohort Study of Women’s Health Across the Nation. We defined worsening as a reported increase and improving as a reported decrease in frequency of incontinence between annual visits. We classified the menopausal status of women not taking hormone therapy annually from reported menstrual bleeding patterns and hormone therapy use by interviewer questionnaire. We used Generalized Estimating Equations (GEE) methodology to evaluate factors associated with improving and worsening incontinence from year to year.
Over 6 years, 14.7% of incontinent women reported worsening, 32.4% reported improvement, and 52.9% reported no change in the frequency of incontinence symptoms. Compared with pre-menopause, peri- and post menopause were not associated with worsening incontinence; for example, early peri-menopause was associated with improvement (OR 1.19; 95% CI 1.06, 1.35) and post-menopause reduced odds of worsening (OR 0.80; 95% CI 0.66, 0.95). Meanwhile, each pound of weight gain increased odds of worsening (OR 1.04; 95% CI 1.03, 1.05) and reduced odds of improving (OR 0.97; 95% CI 0.96, 0.98) incontinence.
In mid-life incontinent women, worsening of incontinence symptoms was not attributable to the menopausal transition. Modifiable factors such as weight gain account for worsening of incontinence during this life stage.
PMCID: PMC3598598  PMID: 18310370
20.  Bone Mineral Density Loss in Relation to the Final Menstrual Period in a Multi-ethic 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 final menstrual period (FMP), body mass index (BMI) and race/ethnicity with rates of BMD loss during this time interval. The sample included 242 African-American, 384 Caucasian, 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. Piece-wise, 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, while the opposite was true of Japanese and Chinese ancestry.
PMCID: PMC3378821  PMID: 21976317
Menopause; perimenopause; bone mineral density; ethnic differences; longitudinal cohort
21.  The biomechanical demands of standing yoga poses in seniors: The Yoga empowers seniors study (YESS) 
The number of older adults participating in yoga has increased dramatically in recent years; yet, the physical demands associated with yoga performance have not been reported. The primary aim of the Yoga Empowers Seniors Study (YESS) was to use biomechanical methods to quantify the physical demands associated with the performance of 7 commonly-practiced standing yoga poses in older adults.
20 ambulatory older adults (70.7 + − 3.8 yrs) attended 2 weekly 60-minute Hatha yoga classes for 32 weeks. The lower-extremity net joint moments of force (JMOFs), were obtained during the performance of the following poses: Chair, Wall Plank, Tree, Warrior II, Side Stretch, Crescent, and One-Legged Balance. Repeated-measure ANOVA and Tukey’s post-hoc tests were used to identify differences in JMOFs among the poses. Electromyographic analysis was used to support the JMOF findings.
There was a significant main effect for pose, at the ankle, knee and hip, in the frontal and sagittal planes (p = 0.00 – 0.03). The Crescent, Chair, Warrior II, and One-legged Balance poses generated the greatest average support moments. Side Stretch generated the greatest average hip extensor and knee flexor JMOFs. Crescent placed the highest demands on the hip flexors and knee extensors. All of the poses produced ankle plantar-flexor JMOFs. In the frontal plane, the Tree generated the greatest average hip and knee abductor JMOFs; whereas Warrior II generated the greatest average hip and knee adductor JMOFs. Warrior II and One-legged Balance induced the largest average ankle evertor and invertor JMOFs, respectively. The electromyographic findings were consistent with the JMOF results.
Musculoskeletal demand varied significantly across the different poses. These findings may be used to guide the design of evidence-based yoga interventions that address individual-specific training and rehabilitation goals in seniors.
Clinical trial registration
This study is registered with NIH #NCT 01411059
PMCID: PMC3557154  PMID: 23302513
Intervention; Lower-extremity; Biomechanics; Moment; EMG; Older adult
22.  Serum Estradiol Levels Are Not Associated with Urinary Incontinence in Mid-life Women Transitioning through Menopause 
Menopause (New York, N.y.)  2011;18(12):1283-1290.
We evaluated the relationship between annually measured serum endogenous estradiol and the development or worsening of stress and urge incontinence symptoms over 8 years in women transitioning through menopause.
This is a longitudinal analysis of women with incontinence in the Study of Women’s Health Across the Nation (SWAN), a multi-center, multi-racial/ethnic prospective cohort study of community-dwelling women transitioning through menopause. At baseline and each of 8 annual visits, SWAN elicited frequency and type of incontinence in a self-administered questionnaire and drew a blood sample on days 2-5 of the menstrual cycle. All endocrine assays were performed using a double-antibody chemiluminescent immunoassay. We analyzed data using discrete Cox survival models and generalized estimating equations with time dependent covariates.
Estradiol levels drawn at either the annual visit concurrent with or previous to the first report of incontinence were not associated with the development of any (hazard ratio (HR) = 0.99, 95% CI 0.99, 1.01), stress, or urge incontinence in previously continent women. Similarly, estradiol levels were not associated with worsening of any (odds ratio (OR) = 1.00, 95% CI 0.99, 1.01), stress, or urge incontinence in incontinent women. Change in estradiol levels from one year to the next was also not associated with the development (HR = 0.98, 95% confidence interval 0.97, 1.00) or worsening (OR = 1.03, 95% CI 0.99, 1.05) of incontinence.
We found that annually measured values and year-to-year changes in endogenous estradiol levels had no effect on the development or worsening of incontinence in women transitioning through menopause.
PMCID: PMC3308014  PMID: 21785372
Urinary incontinence; Estradiol; Reproductive hormones; Menopause transition; Epidemiology; Prospective cohort study
23.  Relationships among body weight, joint moments generated during functional activities, and hip bone mass in older adults 
To investigate the relationships among hip joint moments produced during functional activities and hip bone mass in sedentary older adults.
Eight male and eight female older adults (70–85 yr) performed functional activities including walking, chair sit–stand–sit, and stair stepping at a self-selected pace while instrumented for biomechanical analysis. Bone mass at proximal femur, femoral neck, and greater trochanter were measured by dual-energy X-ray absorptiometry. Three-dimensional hip moments were obtained using a six-camera motion analysis system, force platforms, and inverse dynamics techniques. Pearson’s correlation coefficients were employed to assess the relationships among hip bone mass, height, weight, age, and joint moments. Stepwise regression analyses were performed to determine the factors that significantly predicted bone mass using all significant variables identified in the correlation analysis.
Hip bone mass was not significantly correlated with moments during activities in men. Conversely, in women bone mass at all sites were significantly correlated with weight, moments generated with stepping, and moments generated with walking (p < 0.05 to p < 0.001). Regression analysis results further indicated that the overall moments during stepping independently predicted up to 93% of the variability in bone mass at femoral neck and proximal femur; whereas weight independently predicted up to 92% of the variability in bone mass at greater trochanter.
Submaximal loading events produced during functional activities were highly correlated with hip bone mass in sedentary older women, but not men. The findings may ultimately be used to modify exercise prescription for the preservation of bone mass.
PMCID: PMC3474346  PMID: 16631283
Bone mineral density; Functional activity; Hip; Joint moment; Submaximal loads
24.  Squatting Exercises in Older Adults: Kinematic and Kinetic Comparisons 
Squatting activities may be used, within exercise programs, to preserve physical function in older adults. This study characterized the lower-extremity peak joint angles, peak moments, powers, work, impulse, and muscle recruitment patterns (electromyographic; EMG) associated with two types of squatting activities in elders.
Twenty-two healthy, older adults (ages 70–85) performed three trials each of: 1) a squat to a self-selected depth (normal squat; SQ) and 2) a squat onto a chair with a standardized height of 43.8 cm (chair squat; CSQ). Descending and ascending phase joint kinematics and kinetics were obtained using a motion analysis system and inverse dynamics techniques. Results were averaged across the three trials. A 2 × 2 (activity × phase) ANOVA with repeated measures was used to examine the biomechanical differences among the two activities and phases. EMG temporal characteristics were qualitatively examined.
CSQ generated greater hip flexion angles, peak moments, power, and work, whereas SQ generated greater knee and ankle flexion angles, peak moments, power, and work. SQ generated a greater knee extensor impulse, a greater plantar flexor impulse and a greater total support impulse. The EMG temporal patterns were consistent with the kinetic data.
The results suggest that, with older adults, CSQ places greater demand on the hip extensors, whereas SQ places greater demand on the knee extensors and ankle plantar flexors. Clinicians may use these discriminate findings to more effectively target specific lower-extremity muscle groups when prescribing exercise for older adults.
PMCID: PMC3474357  PMID: 12673148
25.  Biomechanical Attributes of Lunging Activities for Older Adults 
The purpose of this study was to characterize the mechanical demands of the lower-extremity musculature during the standing forward lunge (FL) and the standing lateral lunge (LL) exercises performed by older adults. Twenty healthy older adults (9 men, 11 women, mean age 75.0 ± 4.4 years) performed FL and LL while instrumented for biomechanical analysis. Low-er-extremity net joint moments, powers, impulse, and mechanical energy expenditure were determined using standard inverse dynamics techniques. The FL preferentially targeted the hip extensors, producing a greater flexion angle (12.8%), peak joint moment (13.6%), joint power (56.5%), and mechanical energy expenditure (25.1%). Conversely, LL targeted the ankle plantar flexors, producing greater dorsiflexion angles (19.3%), joint moments (40.9%), impulse (87.0%), and mechanical energy expenditure (61.1%). Kinetic differences at the knee were less consistent. Fitness professionals may use this information to better match the biomechanical attributes of FL and LL activities with the needs of the trainee.
PMCID: PMC3463242  PMID: 15320687
strength training; functional exercise; mechanical energy expenditure; impulse

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