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author:("Vuga, marine")
1.  Factors Related to Age at Natural Menopause: Longitudinal Analyses From SWAN 
American Journal of Epidemiology  2013;178(1):70-83.
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 Women's 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.
PMCID: PMC3698989  PMID: 23788671
age; education; ethnicity; menopause; oral contraceptives; race; smoking; weight
2.  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
3.  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
4.  Elevated gastrin-releasing peptide receptor mRNA expression in buccal mucosa: association with head and neck squamous cell carcinoma 
Head & neck  2012;35(2):270-279.
Expression of gastrin-releasing peptide receptor (GRPR) is elevated in mucosa adjacent to head and neck squamous cell carcinoma (HNSCC) compared with mucosa from cancer-free controls, suggesting elevated GRPR expression may indicate presence of HNSCC.
We measured GRPR mRNA levels in histologically normal buccal mucosa from 65 surgical patients with HNSCC and 75 cancer-free control subjects using quantitative polymerase chain reaction (PCR). We tested for association between GRPR expression and HNSCC and evaluated differences in patient progression-free survival (PFS).
Buccal GRPR expression was higher in cases but not controls who were active smokers (p = .04). High GRPR expression was associated with HNSCC (odds ratio [OR] = 3.55; 95% confidence interval [CI] = 1.15–10.93), even after adjustment for age, sex, tobacco use, and sample storage time. PFS did not differ between patients with HNSCC with high versus low GRPR expression (p = .22).
Elevated buccal GRPR expression was significantly associated with HNSCC independent of known risk factors but was not an indicator of disease prognosis.
PMCID: PMC3553276  PMID: 22431275
gastrin-releasing peptide receptor; head and neck cancer; case-control study; surrogate tissue biomarker; risk factor
5.  Circulating Dehydroepiandrosterone Sulfate Levels in Women with Bilateral Salpingo-Oophorectomy during the Menopausal Transition 
Menopause (New York, N.Y.)  2011;18(5):494-498.
A rise in circulating dehydroepiandrosterone sulfate (DHEAS) concentration occurs during the menopausal transition (MT) that is ovarian-stage but not age-related. The objective of this study was to determine the source of the rise in circulating DHEAS.
Circulating DS concentrations in women that had undergone bilateral salpingo-oophorectomy (BSO) were compared to the pattern of circulating DHEAS in women that progressed through the MT naturally. Annual serum samples from the Study of Women's Health Across the Nation (SWAN) over a ten year study period were used. From1272 women in the SWAN cohort that were eligible for longitudinal evaluation of DHEAS annual samples, eighty one underwent BSO during the pre- or early-perimenopause stage of the menopausal transition and were potentially available for study. Of these eighty one BSO participants, twenty had sufficient annual samples for evaluation of the post-BSO trajectory of circulating DHEAS. SWAN women not having previous hormone replacement therapy those with intact ovaries were compared to women that underwent a BSO immediately after a pre- or early perimenopausal annual visit. There were no intervention and circulating concentrations of DHEAS was the main outcome.
A detectable rise in DHEAS was observed in fourteen (70%) of the twenty BSO women which is similar to the proportion (85%) of women with intact ovaries that had a detectable DHEAS rise. The mean rise in DHEAS (5-8%) was similar in both BSO and non-BSO women.
The MT rise in DHEAS (5-8%) occurring in the absence of ovaries is largely of adrenal origin.
PMCID: PMC3123411  PMID: 21178790
Dehydroepiandrosterone sulfate; menopause; adrenal; ovary
6.  A Method to Estimate Off-Schedule Observations in a Longitudinal Study 
Annals of epidemiology  2011;21(4):297-303.
Data in epidemiological studies sometimes are collected off-schedule from planned study visits. In an ancillary study to the Study of Women's Health Across the Nation (SWAN), longitudinal breast density data were collected retrospectively from mammograms that were not acquired at the study visits. We propose a method to estimate the off-schedule breast density measurements at the time of study visits.
This method uses local linear interpolation, withmultiply imputed error terms drawn from assumed subject-specific normal distributions based on the within-subject standard deviations of mammographic density measurements. We evaluate the validity and implications of this approach.
Coefficients of random intercept models assessing the association between annual changes in body mass index and dense breast area estimated with this approach (β=-0.17, P=0.46) differed from those obtained when each mammogram was matched to the nearest study visit (β=-0.30, P=0.04). The proposed estimation approach had a small average prediction error (0.11 cm2).
Because matching does not incorporatebreast density changes over time, ourlocal linear interpolation with multiple imputation approach may provide more accurate results. The proposed approach is applicable to other epidemiologic studies with off-schedule data where the missing variable changes linearly over relatively short periods of time.
PMCID: PMC3073647  PMID: 21376277
Epidemiologic Methods; Missing Data; Multiple Imputation; Linear Interpolation; Mammography
7.  Long-Term Stability of Electroencephalographic Asymmetry and Power in 3 to 9 Year Old Children 
We investigated test-retest stability of resting EEG asymmetry and power in the alpha frequency range across a 0.6 - to 3-year interval in 125 children (57 girls and 68 boys) for two age groups, 87 preschool children (3 to 5 year-olds) and 38 school-age children (6 to 9 year-olds). Children were from families with a parent’s history of unipolar or bipolar depression (36 girls and 43 boys) or control families with no parent history of depression nor any other psychiatric disorder (21 girls and 25 boys). Frontal EEG asymmetry stability was low to moderate; intraclass correlations ranged from zero to 0.48 in the eyes-open condition, and from 0.19 to 0.45 in the eyes-closed condition. Also, parietal EEG asymmetry was low to moderate; intraclass correlations ranged from 0.21 to 0.52 in the eyes-open condition and from 0.27 to 0.72 in the eyes-closed condition. Stability of EEG asymmetry was not related to age, sex of the child, or parent’s history of mood disorder. Frontal and parietal EEG power appeared moderately to highly stable. Intraclass correlations were between 0.65 and 0.86 in the eyes-open condition and between 0.52 and 0.90 in the eyes-closed condition. Although stability of EEG power was not statistical significantly different between preschool and school-age children, it consistently showed higher stability values in school-age children than in preschool children. Stability in school-aged children approached values as has been reported for adults. The findings provide partial support to the concept of frontal EEG asymmetry as a trait marker in childhood.
PMCID: PMC2704384  PMID: 18045715
Stability; longitudinal study; EEG asymmetry; EEG power; development; sex; depression

Results 1-7 (7)