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Smoking, diet, and physical activity may impact chronic diseases in part by promoting or attenuating oxidative stress. We evaluated associations between lifestyle factors and urine F(2a)-isoprostanes, a marker of oxidative stress in 1610 participants of the Study of Women's Health Across the Nation (SWAN). Dietary intake and physical activity were assessed at baseline and the 5th year 05 (Y05). These data were related to Y05 urinary F(2a)-isoprostane concentration with regression analyses. Median urine F(2a)-isoprostane concentration was 433 ng/L overall, 917 ng/L in smokers [inter-quartile range (IQR): 467, 1832 ng/L], and 403 ng/L in nonsmokers (IQR: 228, 709 ng/L; P < 0.0001 for difference). Higher trans fat intake was associated with higher urine F(2a)-isoprostane concentration; partial Spearman correlations (rho(x|y)) between Y05 urine F(2a)-isoprostane concentration and trans fatty acids was 0.19 (P = 0.03) in smokers and 0.13 (P < 0.0001) in nonsmokers. Increased log trans fat intake from baseline to Y05 was associated with higher concentration of log urine F(2a)-isoprostanes in nonsmokers (beta = 0.131, SE = 0.04, P = 0.0003). In nonsmokers, the partial correlation (rho(x|y)) between lutein and urine F(2a)-isoprostane concentration was -0.13 (P < 0.0001). Increased intake of log lutein from baseline to Y05 was also associated with lower log urine F(2a)-isoprostane concentration (beta = -0.096, SE = 0.03, P = 0.0005) in nonsmokers. Increased zinc intake from baseline to Y05 was associated with lower log urine F(2a)-isoprostane concentration in smokers and nonsmokers (beta = -0.346, SE = 0.14, P = 0.01), and -0.117, 0.04 (P = 0.001), respectively]. In conclusion, diet (fat subtypes, zinc, and vegetable components) and smoking were associated with urine F(2a)-isoprostanes, a marker of oxidative stress.

Objectives To investigate the dependence of echocardiographic ratio indices (ERIs) on age, body weight (BW) and breed/study group using individually contributed and published summarized data in dogs. Background ERIs allow for narrow prediction intervals of M-mode echocardiographic measurements in generic adult dogs. Breed and age-specific differences have not been examined systematically using ERI methods. Animals, materials and methods Individual M-mode measurements were contributed by 15 published investigators from 661 dogs, allowing direct calculation of ERIs and summary statistics for each of these breed/study groups. M-mode ERI summary statistics were estimated from published summaries of 22 additional groups that included 527 adult and 36 growing dogs. Individual two-dimensional (2DE) left atrial (LA) and aortic root (Ao) measurements were contributed from 36 dogs. ERIs were analyzed for dependence on BW, breed/study group and age. Results The majority of variation among ERIs was due to differences in the breed or study technique with comparatively little dependence on BW. Age dependence of ERIs was seen in the early growth phases of young dogs, but expected values for each ERI became static long before maturity, roughly at 10–12 weeks of age. ERIs derived from individual 2DE LA and Ao measurements showed no significant dependence on BW. Conclusions ERIs are well normalized for body size and may be useful for clinical evaluation of individuals, prediction of expected M-mode and 2DE cardiac dimensions, and investigation of age or breed-specific cardiac shape changes.

Objective Criteria for staging the menopausal transition are not established. This article evaluates five bleeding criteria for defining early transition and provides empirically based guidance regarding optimal criteria. Design/Setting Prospective menstrual calendar data from four population-based cohorts: TREMIN, Melbourne Women's Midlife Health Project (MWMHP), Seattle Midlife Women's Health Study (SMWHS), and Study of Women's Health Across the Nation (SWAN) with annual serum FSH from MWMHP and SWAN. Participants 735 TREMIN, 279 SMWHS, 216 MWMHP, and 2270 SWAN women aged 35–57 at baseline who maintained menstrual calendars. Main Outcome Measure(s) Age at and time to menopause for: standard deviation >6 and >8 days, persistent difference in consecutive segments >6 days, irregularity, and ≥45 day segment. Serum FSH concentration. Result(s) Most women experienced each of the bleeding criteria. Except for a persistent >6 day difference that occurs earlier, the criteria occur at a similar age and at approximately the same age as late transition in a large proportion of women. FSH was associated with all proposed markers. Conclusion(s) The early transition may be best described by ovarian activity consistent with the persistent >6 day difference, but further study is needed, as other proposed criterion are consistent with later menstrual changes.

Hypothesis Sonographic hematoma-guided (SHG) lumpectomy achieves better margin clearance with a smaller volume of resection compared with wire-localized (WL) lumpectomy. Design Retrospective study. Setting University Comprehensive Breast Center. Patients Consecutive patients treated over 6 months at the breast center with stereotactic biopsy–proven cancers that were not visualized on ultrasonography. The SHG and WL techniques were compared. Main Outcome Measures The matching variables were age, mammographic abnormality, tumor size and type, and lymph node status. The outcome variables were the closest margin of resection, volume of resection, resection index (resection volume divided by tumor volume), and rate of margin revision. Results Twenty-nine patients had SHG lumpectomy and 34 had WL lumpectomy. The SHG and WL groups were similar in age, mammographic abnormality, tumor size and type, and lymph node status. The median (interquartile range) closest margin was 5.0 (5-8) mm in the SHG group vs 3.5 (1-7) mm in the WL group ( = .01). The median (interquartile range) resection volume was 85.0 (60-128) cm 3 in the SHG group vs 143.4 (54-229) cm 3 in the WL group ( = .048). The median (interquartile range) resection index was 77.1 (51-220) in the SHG group vs 315.9 (89-3025) in the WL group ( = .003). The margin was revised in 1 (3.4%) of the patients who underwent SHG lumpectomy vs 5 (14.7%) of the patients who underwent WL lumpectomy ( = .20). Conclusions Sonographic hematoma-guided lumpectomy is superior to WL lumpectomy in obtaining adequate margins while minimizing the volume of resection.

Children and youth with perinatally acquired HIV infection are living longer because of improved drug therapies, but they may be at risk for poor health-related quality of life (HRQOL) outcomes because of nondisease factors. Families affected by HIV disease are more likely to experience major negative life events (NLEs). The effects of NLEs, shown to impact HRQOL in children with other chronic illnesses, have not been evaluated in children with HIV infection. The primary objective of this study was to determine if NLEs occurring in the previous 12 months were associated with increased risk for poorer outcomes in three measures of HRQOL (health perception, behavior problems, and symptom distress) in a cohort of children and youth with HIV infection. The authors conducted a cross-sectional analysis of data determined in 1999 from 1,018 children and youth 5 to 21 years of age enrolled in a longitudinal follow-up study. Multivariate logistic regressions estimated the odds for worse HRQOL outcomes. Children and youth with one or more NLEs had significantly lower health perceptions, more behavior problems, and greater symptom distress than children with no reported NLEs. The occurrence of NLEs may present a significant nondisease risk for diminished HRQOL among children and youth challenged by HIV disease. Nursing efforts to support these younger patients and their families sustaining major family disruption caused by NLEs may improve overall health outcomes in this vulnerable population.

The goal of breast conservation in cancer treatment is to obtain adequate margins with minimum tissue loss to achieve acceptable oncologic and cosmetic outcome. The standard for resection of breast cancers visible only on mammogram is wire localization (WL), which has a high rate of positive margins. We hypothesized that sonographic hematoma guided (SHG) resection achieves better margin clearance while minimizing volume of resection by more accurate lesion localization.This retrospective study was conducted at the University Comprehensive Breast Center. Consecutive patients over the span of one year, undergoing breast conservation for stereotactic biopsy proven cancers that were not visualized on ultrasound were studied. SHG and WL technique were compared for age, mammographic abnormality, and tumor characteristics. Outcome variables included closest margin of resection, volume of resection, resection index (resection volume/tumor volume), and rate of margin revision.Forty-five patients had SHG, while 51 had WL lumpectomy. The SHG and WL groups were similar in age, mammographic abnormality, tumor type, and stage. Median (25th-75th centile) tumor size was larger in SHG group vs WL group [1.2 (1.1-1.3) vs 0.8 (0.4-1.4) cm; P = .009]. Median (25th-75th centile) closest margin in SHG vs WL group was 5.0 (5.0-8.0) vs 4.0 (1.0-10) mm [P = .0041]. Median (25th-75th centile) resection volume in SHG vs WL group was 85.0 (60.0-128.0) vs 142.2 (54.4-229.0) cm(3) [P = .0127]. Median (25th-75th centile) resection index in SHG vs WL group was 77.3 (59.3-285.7) vs 337.1 (88.9-3982.2) [P = .0004]. Margin was revised in 2 (4.4%) SHG vs 8 (15.7%) WL patients [P = .0978].Sonographic hematoma guided lumpectomy is superior to wire localization in obtaining adequate margins with minimal volume of resection.

Two previous retrospective studies reported a significantly decreased breast cancer risk among women who experienced menopausal vasomotor symptoms (VMS). It is possible that VMS are a marker of declining sex hormone levels during menopause. Elevated sex hormone levels have been associated with increased breast cancer risk, suggesting that VMS may be indicative of lower susceptibility to breast cancer. We evaluated this relationship in the prospective Study of Women's Health Across the Nation (SWAN), which includes annual data on VMS and endogenous hormone levels for 3,098 women who were pre- or early peri-menopausal at enrollment. We evaluated the effect of VMS on breast cancer risk using discrete survival analysis. Over an average 11.4 years of follow-up, 129 breast cancer cases were self-reported and approximately 50% of participants reported some VMS. Women reporting VMS at any current or previous visit had a reduced risk of breast cancer compared to those never experiencing VMS (OR 0.63, 95% CI 0.39, 1.02). Results were strengthened in the subgroup of women who fully transitioned to postmenopausal during follow-up (N=80 cases, OR 0.45, 95% CI 0.26, 0.77). Associations were unchanged upon adjustment for endogenous hormone levels. VMS appear to be a marker of reduced breast cancer risk. Future research is needed to fully understand this relationship, which does not appear to be mediated by endogenous hormone levels. Citation Format: Vicki Hart, Susan Sturgeon, Nicholas Reich, Lynnette Leidy Sievert, Sybil Crawford, Ellen Gold, Nancy Avis, Katherine W. Reeves. Menopausal vasomotor symptoms and incident breast cancer risk in the Study of Women's Health Across the Nation. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr A04.

In many health-related studies, investigators wish to assess the strength of an association between 2 measured (continuous) variables. For example, the relation between high-sensitivity C-reactive protein (hs-CRP) and body mass index (BMI) may be of interest. Although BMI is often treated as a categorical variable, eg, underweight, normal, overweight, and obese, a noncategorized version is more detailed and thus may be more informative in terms of detecting associations. Correlation and regression are 2 relevant (and related) widely used approaches for determining the strength of an association between 2 variables. Correlation provides a unitless measure of association (usually linear), whereas regression provides a means of predicting one variable (dependent variable) from the other (predictor variable). This report summarizes correlation coefficients and least-squares regression, including intercept and slope coefficients. Correlation provides a “unitless” measure of association between 2 variables, ranging from −1 (indicating perfect negative association) to 0 (no association) to +1 (perfect positive association). Both variables are treated equally in that neither is considered to be a predictor or an outcome. The most commonly used version is the Pearson product-moment coefficient of correlation, r . Suppose one wants to estimate the correlation between X=BMI, denoted for the ith subject as Xi, and Y=hs-CRP, denoted for the ith subject as Yi. This is estimated for a sample of size n (i=1,…, n) using the following formula1: equation ![Formula][1] where equation ![Formula][2] and equation ![Formula][3] Here, ![Graphic][4] indicates the sample mean of X (=BMI), and ![Graphic][5] the sample mean of Y (=hs-CRP). The numerator of r reflects how BMI and hs-CRP co-vary, and the denominator reflects the variability of both BMI and hs-CRP about their respective sample means. The Pearson correlation coefficient assumes that X and Y are jointly distributed as bivariate normal, ie, X and Y each are normally … [1]: /embed/graphic-1.gif [2]: /embed/graphic-2.gif [3]: /embed/graphic-3.gif [4]: /embed/inline-graphic-1.gif [5]: /embed/inline-graphic-2.gif

The relation of single nucleotide polymorphisms (SNPs) of genes involved in estrogen function to vasomotor symptoms (VMS) has been inadequately explored. We evaluated SNPs in sex steroid-metabolizing genes and estrogen receptors (ERs) for their association with VMS (hot flashes, night sweats, and/or cold sweats) reported by women who were premenopausal or in early perimenopause at baseline. The study population was drawn from participants in the Study of Women's Health Across the Nation (SWAN). African American, Caucasian, Chinese, and Japanese women, 42 to 52 years of age at baseline, who were enrolled in the longitudinal, community-based cohort of SWAN provided questionnaire, interview, weight and height measurements, and serum samples through the sixth annual visit. SNPs associated with the sex steroid hormone pathway were genotyped and available for 1,538 participants. These SNPs were associated with reporting VMS > or =6 days compared with

The Stages of Reproductive Aging Workshop proposed bleeding and hormonal criteria for the menopausal transition, but operational definitions of hormone parameters were not specified.This paper investigates the longitudinal relationship of annual serum FSH levels with four proposed bleeding criteria for the late menopausal transition in two cohort studies. The goal is to provide empirically based guidance regarding application of hormonal criteria that may be optimal for widespread application in clinical and research settings for assessing menopausal stage.Prospective menstrual calendar and annual serum FSH data were collected from two population-based cohort studies: the Melbourne Women's Midlife Health Project and the Study of Women's Health Across the Nation.Participants in the study were 193 Melbourne Women's Midlife Health Project and 2223 Study of Women's Health Across the Nation women aged 42-57 yr at baseline who contributed 10 or more menstrual cycles and at least one annual serum FSH value.Association between bleeding criteria for the late menopausal transition and FSH was a main outcome measure. Associations of bleeding criteria, FSH, and hot flashes with the final menstrual period were also measured.A single FSH measure is an independent marker of the late menopausal transition, but FSH concentrations are less predictive of menopausal stage than any of four proposed bleeding criteria. Criterion FSH values for the late transition are similar across both studies. Experience of hot flashes adds no information in the presence of hormonal and bleeding criteria.An annual serum FSH concentration of 40 IU/liter could be incorporated, in conjunction with bleeding markers, into the Stages of Reproductive Aging Workshop paradigm for markers of the late menopausal transition.

Menstrual cycle characteristics may be associated with cardiovascular disease (CVD) risk.The objective of this study was to describe the relationships between menstrual cycle characteristics and daily reproductive hormone measures with CVD risk factors in middle-aged women.Cross-sectional associations were examined between CVD risk factors and urinary LH, FSH, estrone conjugates, and pregnanediol glucuronide (Pdg) measured across one menstrual cycle or 50 d.Menstruating women (n = 500) who were free from diabetes or past stroke or heart attack enrolled in the Daily Hormone Study-Study of Women's Health across the Nation were studied.Body mass index (BMI), blood pressure, hemostatic, and metabolic factors were measured.Few differences existed in risk factors between women with evidence of luteal activity and those with no evidence of luteal activity. Associations between elevated CVD risk factors and long cycle length were reduced substantially by age and BMI adjustments. Those with lower estrone conjugate and PdG averaged across the follicular phase had higher waist circumference, triglycerides, insulin, plasminogen activator inhibitor type-1, tissue type plasminogen activator-antigen, and factor VIIc levels in age- and BMI-adjusted analyses (P0.05).In midlife menstruating women, a longer cycle length was related to CVD risk factors, in large part through their common association with BMI. More favorable levels of metabolic and hemostatic factors were associated with higher levels of follicular-phase estrogen, a pattern consistent with a more competent ovary, and higher levels of follicular-phase PdG, perhaps of adrenal origin. Metabolic and hemostatic factors may be sensitive to hormonal variation during the early perimenopausal transition.

Background We evaluated ethnic differences in the 10-year risk of myocardial infarction or coronary death derived from Framingham risk equation and in a composite measure of emerging cardiovascular disease risk factors in women and whether statistical adjustments for educational attainment, geographic location, and lifestyle attenuated the magnitude of the ethnic differences in risk. Methods Two thousand eight hundred thirty-four premenopausal women free of stroke, heart disease, or diabetes and aged of 42 to 52 years (1400 whites, 729 African American, 226 Hispanic, 231 Chinese, and 248 Japanese) had measurements of blood pressure, lipids and lipoproteins, waist circumference, glucose, insulin, lipoprotein(a), fibrinogen, factor VII, plasminogen activator inhibitor, tissue-type plasminogen activator antigen, and high-sensitivity C-reactive protein. Framingham risk score and number of risk factors in the top quartile of the distribution of risk factors not included in the Framingham score (called composite burden) were calculated. Results The unadjusted mean values for the two summary scores were higher among African Americans and Hispanics than other groups. Statistical adjustments for education and geographical site accounted for a majority of the ethnic differences, with an additional small effect of lifestyle for the composite burden score. Largest ethnic differences were apparent for waist circumference, lipoprotein(a), high-sensitivity C-reactive protein, and untreated blood pressure. Conclusions A substantial part of the risk associated with ethnicity can be attributed to socioeconomic status and geographical location. As the ethnic composition of the United States population becomes more diverse, it is important to appreciate the cardiovascular disease risk factor burden present in some minority groups.

Androgens influence sexual differentiation and behavior, body composition, and physical functioning in men, but their role in women is less well understood. Because circulating androgens decline with age, the use of androgen supplementation for women to improve health and well-being has been increasing.The aim of this study was to assess the association between androgens and a variety of end points thought to be affected by androgens.In a community-based baseline cohort of women aged 42-52 yr from the Study of Women's Health Across the Nation, we measured circulating testosterone (T), dehydroepiandrosterone sulfate, and SHBG, and calculated a free androgen index (FAI) in 2961 women.Correlations of androgen measures with each other and with body mass index, waist circumference, and waist-hip ratio were computed, and odds ratios (OR) were estimated for the categorical outcomes of functional limitations, functional status, self-reported health, scores indicative of depressed mood, quality of life, sexual desire and arousal, and the presence of the metabolic syndrome.Androgens, and particularly SHBG, were associated most strongly with body mass index, waist circumference, and waist-hip ratio. SHBG was associated prominently inversely with the metabolic syndrome (OR = 0.32; 95% confidence interval = 0.26-0.39), which was present in 17% of women at baseline. Dehydroepiandrosterone sulfate was associated modestly with functional status and self-reported health. T was associated minimally with increased sexual desire (OR = 1.09; 95% confidence interval = 1.00-1.18). The association of FAI with self-reported health and depressive symptomatology based on the Center for Epidemiologic Studies Depression Scale score was explained more by T than by SHBG, whereas the association of FAI with sexual arousal and metabolic syndrome was due more to SHBG than to T.Circulating SHBG and androgens are most strongly associated with physical characteristics and the metabolic syndrome in women in this community-based cohort. Androgens are related weakly to physical functioning and other symptoms to which they commonly are attributed, such as sexual desire, sexual arousal, and well-being.

Results of recent trials highlight the risks of hormone therapy, increasing the importance of identifying preventive lifestyle factors related to menopausal symptoms. The authors examined the relation of such factors to vasomotor symptoms in the multiethnic sample of 3,302 women, aged 42-52 years at baseline (1995-1997), in the Study of Women's Health Across the Nation (SWAN). All lifestyle factors and symptoms were self-reported. Serum hormone and gonadotropin concentrations were measured once in days 2-7 of the menstrual cycle. After adjustment for covariates using multiple logistic regression, significantly more African-American and Hispanic and fewer Chinese and Japanese than Caucasian women reported vasomotor symptoms. Fewer women with postgraduate education reported vasomotor symptoms. Passive exposure to smoke, but not active smoking, higher body mass index, premenstrual symptoms, perceived stress, and age were also significantly associated with vasomotor symptoms, although a dose-response relation with hours of smoke exposure was not observed. No dietary nutrients were significantly associated with vasomotor symptoms. These cross-sectional findings require further longitudinal exploration to identify lifestyle changes for women that may help prevent vasomotor symptoms.

There is substantial concern that incentives embedded in managed care (MC) will result in compromised quality of care (Druss et al. 2000). By shifting financial risk to the providers of care, the fear is that services may be withheld or delayed for economic reasons. The use of medications in the treatment of chronic medical conditions may be particularly susceptible to these forces because of the long-term need for costly therapy. If financial constraints cause key medications to be underused, then MC could result in reduced quality of care, especially for patients with chronic conditions. The growing elderly population and the promotion of MC for the Medicare population makes this a critical issue. Measurement of quality of care across the national spectrum of MC plans through the Health Plan Employer Data and Information Set (HEDIS, National Committee for Quality Assurance 1999) and other measures suggest that many indicators fall short of expectation and vary substantially among plans. Although those results show apparent deficits for MC patients compared to a norm, it is not clear whether they are disadvantaged compared to non-MC patients. Past studies have reported a range of findings, with some noting superior quality of care in MC and others noting inferior quality (Miller and Luft 1994; 1997; 2002; Hellinger 1998). No consistent differences have been observed, although a predominance of findings is consistent with equal or somewhat better quality in MC. Likewise, there are no consistent differences in patterns of medication use, although several studies suggest greater medication use among chronic disease patients in MC. The reason for the latter finding may reflect higher levels of benefits available to MC members or lower out-of-pocket expenses associated with seeking this service (Sullivan 1999; Miller and Luft 2002). To answer continuing questions about patterns of medication use in MC, we have acquired and analyzed claims data from multiple health plans in a single market for patients with a range of chronic conditions. Consistent with widely held perceptions of MC (Hilzenrath 1997), we specifically test whether medication therapy for diabetes mellitus (DM), congestive heart failure (CHF), and asthma were less likely for MC patients and whether their adoption of newer therapies by MC patients was less rapid.

To more completely understand the challenges African American families face when combining employment commitments and informal caregiving responsibilities, the authors used data from a community sample of 119 African American elder-caregiver dyads. This article examines the nature of caregiving relationships and extent to which caregivers' employment statuses affect the hours of care provided. The authors concluded that employed caregivers do not provide significantly less care than do unemployed caregivers, elderly people with employed caregivers are no more likely than those with unemployed caregivers to use formal services, and unemployed caregivers may remain unemployed partly because of caregiving responsibilities.

Because incentives for managed care organizations favor cost containment, concerns have been raised that quality of care has suffered, especially for chronically ill people. This study compares utilization rates of managed care and indemnity patients with three chronic conditions, using five years of claims records (1993–97) from private plans and Medicare in one market. Findings show that for all three conditions, managed care patients were more likely to see both primary care physicians and specialists within a year, but less likely to use a hospital emergency department or to be an inpatient. Assuming that patients with these illnesses should see a physician annually and that good primary care reduces the need for emergency and inpatient services, it appears that the patterns of care used by chronically ill managed care patients in this market do not reflect lower quality than that received by similar indemnity patients.

The association between blood lead level and dental caries was evaluated in cross-sectional analyses of baseline data for 543 children 6-10 years old screened for enrollment in the Children's Amalgam Trial, a study designed to assess potential health effects of mercury in silver fillings. Approximately half of the children were recruited from an urban setting (Boston/Cambridge, MA, USA) and approximately half from a rural setting (Farmington, ME, USA). Mean blood lead level was significantly greater among the urban subgroup, as was the mean number of carious tooth surfaces. Blood lead level was positively associated with number of caries among urban children, even with adjustment for demographic and maternal factors and child dental practices. This association was stronger in primary than in permanent dentition and stronger for occlusal, lingual, and buccal tooth surfaces than for mesial or distal surfaces. In general, blood lead was not associated with caries in the rural subgroup. The difference between the strength of the associations in the urban and rural settings might reflect the presence of residual confounding in the former setting, the presence of greater variability in the latter setting in terms of important caries risk factors (e.g., fluoride exposure), or greater exposure misclassification in the rural setting. These findings add to the evidence supporting a weak association between children's lead exposure and caries prevalence. A biologic mechanism for lead cariogenicity has not been identified, however. Our data are also consistent with residual confounding by factors associated with both elevated lead exposure and dental caries.

In recent years, research on menopausal symptomalogy has focused on identifying symptom groupings experienced by women as they progress from premenopausal to postmenopausal status. However, most of these studies have been conducted among Caucasian women from western cultures. This leaves open the question of whether the findings from these studies can be extended to women of other racial/ethnic groups or cultures. Furthermore, many of the previous studies have been conducted on relatively small samples. This paper addresses the diversity of the menopause experience by comparing symptom reporting in a large cross-sectional survey of women aged 40–55 years among racial/ethnic groups of women in the United States (Caucasian, African-American, Chinese, Japanese, and Hispanic). Evaluation of the extent to which symptoms group together and consistently relate to menopausal status across these five samples provides evidence for or against a universal menopausal syndrome. The specific research questions addressed in this paper are: (1) How does the factor structure of symptoms among mid-aged women compare across racial/ethnic groups? (2) Is symptom reporting related to race/ethnicity or menopausal status? and (3) Does the relation between menopausal status and symptoms vary across racial/ethnic groups? Analyses are based on 14,906 women who participated in the multi-ethnic, multi-race, multi-site study of mid-aged women called the Study of Women’s Health Across the Nation (SWAN). Study participants completed a 15-min telephone or in-person interview that contained questions on a variety of health-related topics. Items of interest for these analyses include symptoms, menstrual history (to assess menopausal status), health status, and sociodemographics. Factor analysis results showed that across all five racial/ethnic groups, two consistent factors emerged; one consisting of clearly menopausal symptoms — hot flashes and night sweats — and the other consisting of psychological and psychosomatic symptoms. Results of regression analyses showed racial/ethnic differences in symptom reporting, as well as differences by menopausal status. Controlling for age, education, health, and economic strain, Caucasian women reported significantly more psychosomatic symptoms than other racial/ethnic groups. African-American women reported significantly more vasomotor symptoms. Perimenopausal women, hormone users, and women who had a surgical menopause reported significantly more vasomotor symptoms. All of these groups, plus postmenopausal women, reported significantly more vasomotor symptoms than premenopausal women. The pattern of results argues against a universal menopausal syndrome consisting of a variety of vasomotor and psychological symptoms.

Objective The purpose of this study was to address whether: (1) there is an association between menopause status and various aspects of sexual functioning, and (2) the relative contributions of menopause status and other variables to various aspects of sexual functioning. Design Analyses are based on 200 women from the Massachusetts Women's Health Study II, a population-based sample of women transitioning through the menopause who were not HRT users, who had not had a surgical menopause, and who had partners. The women were classified as pre-, peri-, or postmenopausal according to menstrual cycle characteristics. Estradiol, estrone, and follicle-stimulating hormone were also measured. Sexual functioning was measured in terms of satisfaction, desire, frequency of sexual intercourse, belief that interest declines with age, arousal compared with a younger age, difficulty reaching orgasm, and pain. Predictor variables included sociodemographics, health, vasomotor symptoms, psychological variables, partner variables, and lifestyle behaviors. Results Menopause status was significantly related to lower sexual desire, a belief that interest in sexual activity declines with age, and women's reports of decreased arousal compared with when in their 40s. Menopause status was unrelated to other aspects of sexual functioning in either unadjusted or multiple regression analyses. In analyses in which log estradiol (E2) was included in addition to menopause status, log E2 was only related to pain. In multiple regression analyses, other factors such as health, marital status (or new partner), mental health, and smoking had a greater impact on women's sexual functioning than menopause status. Conclusions Menopause status, but not E2, is related to some, but not all, aspects of sexual functioning. This may be due to menopause per se or other factors associated with menopause and aging (e.g., increased sexual dysfunction among aging men). Menopause status has a smaller impact on sexual functioning than health or other factors.

Results of past studies of menopause and weight are inconsistent, in part because of problems in study design and analyses, such as retrospective assessment of age at menopause and failure to control for confounding factors. To address such shortcomings, we conducted multivariate analyses on longitudinal data from a large, community-based sample of initially pre- and perimenopausal women who were making the transition through menopause.Data were from the second phase of the Massachusetts Women's Health Study, a cohort of 418 women aged 50-60 years in 1986. We assessed the relationship between menopause transition and weight, after accounting for previous weight; age; and the behavioral factors of smoking, exercise, and annual ethanol consumption. Menopause status was defined in terms of months of amenorrhea. The association of hormone replacement therapy and weight also was examined.Menopause transition was not consistently associated with increased weight, and use of hormone replacement therapy was not significantly related to weight. Behavioral factors--particularly exercise and ethanol consumption--were more strongly related to weight than was menopause transition.These results are consistent with findings from other studies that suggest that the weight increases experienced by middle-aged women in the United States are not a result of the menopause transition.

OBJECTIVE: To assess the relative influence of menopausal status and hormone use on body mass index (BMI) among a multiethnic sample of mid-life women. DESIGN: Cross-sectional telephone survey conducted at seven sites where each site targeted an ethnic minority group and Caucasians as part of Study of Women's Health Across the Nation (SWAN). SUBJECTS: A total of 7181 Caucasians, 3949 African-Americans, 1660 Hispanics, 562 Chinese Americans, and 803 Japanese Americans between ages of 40 and 55 y residing in or near Boston, Chicago, Detroit, Los Angeles, Newark, NJ, Oakland, CA, and Pittsburgh, PA. MEASUREMENTS: Self-reported BMI based on weight in kg divided by height in m2 menopausal status, physical inactivity, postmenopausal hormone use, ethnicity, and age in years. RESULTS: Compared to premenopausal women (covariate adjusted M=27.3), women reporting a surgical menopause (M=28.2) or being in the perimenopausal transition (M=27.7 for early and 27.9 for late perimenopause) had higher BMI. Women reporting a natural menopause (M=27.4) did not have a higher BMI than premenopausal women, after adjusting for chronological age and other covariates. Hormone use was associated with lower BMI (M=26.5 vs 27.3). A comparison of effect sizes showed that menopausal status (F=13.1), followed by chronological age (F=24.0), were the least powerful predictors of BMI, whereas the more powerful predictors were physical activity level (F=1377.1) and ethnicity (F=400.5). CONCLUSIONS: The menopausal transition affects body mass index in mid-life, but the effect is small relative to other influences. Interventions to increase physical activity are highly recommended to prevent increases in adiposity common in mid-life.

Study of Women's Health Across the Nation (SWAN) is the first national study to describe women at midlife, an understudied age group. Its multidisciplinary approach provides the opportunity to consider the contributions of both culture and biology so that one may better understand health of women. The SWAN employs a prospective design that includes sufficient pre- and postmenopausal observations to ensure the separation of menopause-related and age-related physiological changes. Other attributes include the comprehensive standardized data collection related to biological, behavioral, physiological, social, environmental, and cultural factors; specialized data collection methodologies suitable to address the monthly and yearly variation in behavioral and biological patterns; general ability to community-dwelling populations recruited from major United States population centers; sufficiently large sample size and numbers of data points to ensure reliable estimates of associations and relevant effect sizes; and inclusion of sufficient numbers of racial/ethnic minorities to provide comparative information with the non-Hispanic Caucasian population. Because of these attributes, SWAN can contribute new and substantive knowledge about women's health in general and the menopause transition in particular.

This chapter discusses the methodological challenges in the study of menopause. The menopause is a complex and multifaceted phenomenon, one that is very challenging to study for a number of reasons. Study design can be logistically and scientifically demanding. Community-based samples are critical for an examination of menopause in the general population, as opposed to nonrepresentative clinic-based samples, but the former are much more costly to obtain. Moreover, choice of the length of follow up and eligibility criteria are complicated by variation within and across women in experiences of menopause transitions. In addition, the menopause involves multiple domains, including physiologic as well as psychological and lifestyle changes. This has implications for selection of data collection methods, in order to obtain a complete picture. A number of measurement issues also arise in a study of menopause, including how to define menopause status. Many measures, particularly those derived from self-report, are affected by physiologic changes as well as by sociodemographic characteristics, psychologic factors, culture, health-care patterns, and a subject's own perceptions of menopause. Statistical data analyses in both cross-sectional and longitudinal studies often require handling issues such as biases of recall and selection and censored and missing data, and complicated data structures such as daily symptoms or reproductive hormone levels.

Objective: To estimate how many patients who sustain a head injury might benefit from intervention and support each year and to consider whether relationships can be found between demographic data relating to patients' circumstances at the time of head injury, and their outcomes six months later. Design: Data collected on 625 patients through follow-up interviews and assessments by the Oxford Head Injury Service for a randomized controlled trial of intervention conducted in 1993–94. Setting: A mixed rural and urban Health District with a population of approximately 560 000. Patients: Patients were aged between 16 and 65 years and resident in Oxfordshire. They presented over 13 months to accident and emergency departments, or were admitted to hospital. All were diagnosed as having suffered a head injury. Outcome measures: The Rivermead Head Injury Follow Up Questionnaire and the Rivermead Post Concussion Symptoms Questionnaire. Results: Data are given on age, sex, social circumstances, employment, cause of injury, severity of associated injuries, post-traumatic amnesia (PTA), anticonvulsants, postconcussion symptoms and activities of everyday life. Outcome at six months was significantly worse for those who had been assaulted as against all other causes of injury combined ( p = 0.0001); and/or had been admitted to hospital ( p = 0.0001); and/or had sustained more severe additional injuries ( p = 0.04); and/or had experienced any PTA ( p = 0.00001). The minimum incidence of such injuries in those aged 16–65, calculated for Oxfordshire, is 292 per annum (74/100 000 aged 16–65 per year). Conclusions: In the general population 52/100 000 patients per annum will experience more serious head injuries as indicated by hospital admission and/or one or more fractures and/or any length of PTA and/or having been assaulted. This group may benefit from monitoring and support and their needs should be considered when planning services.

Among the consequences of downsizing and cost containment in hospitals are major changes in the work life of nurses. As hospitals become smaller, patient acuity rises, and the job of nursing becomes more technical and difficult. This article examines the effects of changes in the hospital environment on nurses' job satisfaction and voluntary turnover between 1993 and 1994.Data were collected in a longitudinal survey of 736 hospital nurses in one hospital to examine correlates of change in aspects of job satisfaction and predictors of leaving among nurses who terminated in that period.Unadjusted results showed decline in most aspects of satisfaction as measured by Hinshaw and Atwood's and Price and Mueller's scales. Multivariate analysis indicated that the most important determinants of low satisfaction were poor instrumental communication within the organization and too great a workload. Intent to leave was predicted by the perception of little promotional opportunity, high routinization, low decision latitude, and poor communication. Predictors of turnover were fewer years on the job, expressed intent to leave, and not enough time to do the job well.The authors conclude that although many aspects of job satisfaction are diminished, some factors predicting low satisfaction and turnover may be amenable to change by hospital administrators.

OBJECTIVE: To evaluate the Medical Disability Society's 1988 recommendation that "every patient attending hospital after a head injury should be registered and offered an outpatient follow up appointment" by determining whether offering a routine follow up service to patients presenting to hospital with a head injury of any severity affects outcome six months later. DESIGN: A randomised controlled trial design with masked assessment of outcome. SETTING: A mixed rural and urban health district with a population of about 560000. PATIENTS: 1156 consecutive patients resident in Oxfordshire aged between 16 and 65 years presenting over 13 months to accident and emergency departments or admitted to hospital and diagnosed as having a head injury of any severity, including those with other injuries. INTERVENTIONS: Patients were registered and randomised to one of two groups. Both groups continued to receive the standard service offered by the hospitals. The early follow up group were approached at 7-10 days after injury and offered additional information, advice, support, and further intervention as needed. All randomised patients were approached for follow up assessment six months after injury by independent clinicians blind to their group. MAIN OUTCOME MEASURES: Validated questionnaires were used to elicit ratings of post-concussion symptoms (the Rivermead postconcussion symptoms questionnaire), and changes in work, relationships, leisure, social, and domestic activities (the Rivermead head injury follow up questionnaire). RESULTS: The two groups were comparable at randomisation. Data was obtained at six months on 226 of 577 "control" patients and 252 of 579 "trial" patients (59% were lost to follow up). There were no significant differences overall between the trial and control groups at follow up, but subgroup analysis of the patients with moderate or severe head injuries (posttraumatic amnesia > or = one hour, or admitted to hospital), showed that those in the early intervention group had significantly fewer difficulties with everyday activities (P = 0.03). CONCLUSIONS: The results from the 41% of patients followed up do not support the recommendation of offering a routine follow up to all patients with head injury, but they do suggest that routine follow up is most likely to be beneficial to patients with moderate or severe head injuries. Some of those with less severe injuries do continue to experience difficulties and need access to services. A further trial is under way to test these conclusions.

Objective: To describe the interventions given by the Oxford Head Injury Service (OXHIS) to patients seen after head injury, predominantly mild or moderate, over the first six months after their injuries. Design: Descriptive data of the amounts of early intervention provided by OXHIS in relation to severity of head injury and the amount of service need identified at six month follow-up. Setting: OXHIS aimed to register all patients aged 16-65 with a head injury of any severity, resident in Oxfordshire. It contacted and provided interventions for a random half of those registered at 7-10 days post-injury as part of a randomized controlled trial to investigate the effectiveness of early follow-up. At six months post-injury, independent assessment of all those registered was undertaken to evaluate outcome and identify continuing service needs. Subjects: The data come from the 579 patients (of the 1156 registered), randomized to receive the new service at 7-10 days post-injury. All but eight of these received some form of service, and 252 of the randomized patients were available for interview at six months post-injury to assess their continuing service need. Results: In the first five months after head injury: 240 patients received postal information alone and were not otherwise in contact with the service; 127 had telephone contact, advice and information; 93 were seen in person, assessed and given advice and information; 78 needed more help and support from the OXHIS team over the telephone; and 33 required further face-to-face contact either from OXHIS or other services. Extensive use was made of standardized leaflets but only accompanied by individualized assessment and advice. At six months 252 of the 579 patients were interviewed: 101 had no problems; 136 needed further reassurance; and 15 required further intervention. Patients with longer periods of post-traumatic amnesia (PTA) were more likely to receive a higher level of service, but the majority of patients who received the more extensive services were those with 'mild' and 'moderate' head injuries. Conclusions: Although the amount of service provided at 7-10 days post injury increased with severity of head injury, most service was in fact given to patients with milder head injuries which were much more common. The majority of patients seen at six months post-injury needed reassurance, advice or other services, and monitoring of patients for some time after their head injuries does seem warranted. A population of 560 000 people could receive service from three whole-time equivalent (WTE) staff using these assessment and management protocols.

Objective Several conditions are associated with increased preeclampsia (PE) risk. Whether altered maternal angiogenic factor levels contribute to risk in these conditions is unknown. Our objective was to compare angiogenic biomarker patterns in high-risk pregnancies and low-risk controls. Study Design We conducted a planned secondary analysis of a 2-center observational study of angiogenic biomarkers in high-risk women. A total of 156 pregnant women with a PE risk factor and 59 low-risk controls were studied. Serial maternal serum samples were collected during 3 gestational windows: 23-27 weeks, 28-31 weeks, and 32-35 weeks. Soluble fms-like tyrosine kinase 1 (sFlt1), soluble endoglin (sEng), and placental growth factor (PlGF) were measured by enzyme-linked immunosorbent assay. Geometric mean angiogenic biomarker levels and angiogenic ratio (sFlt1 + sEng):PlGF were compared with low-risk controls for each risk group, at each gestational window. Results Gestational biomarker patterns differed in PE risk groups as compared with low-risk controls. Women with multiple gestations had markedly higher sFlt1 and sEng at all gestational windows. Women with prior PE had higher sFlt1 and angiogenic ratio, and lower PlGF, from 28 weeks onward. Women with chronic hypertension had significantly higher angiogenic ratio for all 3 gestational windows, but differences disappeared when women with PE were excluded. Obese and nulliparous women had significantly lower PlGF, but no differences in the angiogenic ratio. Conclusion High-risk groups have altered angiogenic biomarker patterns compared with controls, suggesting that altered production or metabolism of these factors may contribute to PE risk, particularly in women with multiple gestations and prior PE.

Longitudinal data from a representative sample of community-residing older persons were used to document changes in patterns and costs of care, both informal and formal. It was found that use of formal services was usually in conjunction with, and secondary to, informal care. Limited availability of informal care as well as increased disability raised the odds of using services. Substitution of formal services for informal care was limited and usually temporary. Total costs of community care, including living expenses, were generally less than the cost of nursing home care.

Longitudinal data were used to identify the relationship between different areas of negative impact and elder and caregiver characteristics. The extent and predictors of persistence and development of negative impact in different areas and the relationship between caregiving impact and subsequent caregiving patterns, including termination of care and institutionalization of the elder, were also examined. Caregiving exerted the greatest toll on a caregiver's personal life reported by 61%, in comparison to family life (18%), or employment (15%-20%). Those at particular risk of negative impact included offspring and other-relative caregivers who resided with the elder. All areas of negative impact persisted over time but did not result in any major disruption in care for the elder. However, those elders whose caregivers experienced personal impact were twice as likely to be institutionalized.

After head injuries, particularly mild or moderate ones, a range of post-concussion symptoms (PCS) are often reported by patients. Such symptoms may significantly affect patients' psychosocial functioning. To date, no measure of the severity of PCS has been developed. This study presents the Rivermead Post Concussion Symptoms Questionnaire (RPQ) as such a measure, derived from published material, and investigates its reliability. The RPQ's reliability was investigated under two experimental conditions. Study 1 examined its test-retest reliability when used as a self-report questionnaire at 7-10 days after injury. Forty-one head-injured patients completed an RPQ at 7-10 days following their head injury and again approximately 24 h later. Study 2 examined the questionnaire's inter-rater reliability when used as a measure administered by two separate investigators. Forty-six head-injured patients had an RPQ administered by an investigator at 6 months after injury. A second investigator readministered the questionnaire approximately 7 days later. Spearman rank correlation coefficients were calculated for ratings on the total symptom scores, and for individual items. High reliability was found for the total PCS scores under both experimental conditions (Rs = + 0.91 in study 1 and Rs = + 0.87 in study 2). Good reliability was also found for individual PCS items generally, although with some variation between different symptoms. The results are discussed in relation to the major difficulties involved when looking for appropriate experimental criteria against which measures of PCS can be validated.

Missing outcome values occur frequently in survey data and are rarely missing randomly. Depending on the pattern of missingness, the choice of analytic method has implications for accuracy of the estimated outcome distribution as well as multivariate models. Data from a study of patterns of care in disabled elders were used to evaluate several common methods when missingness of the outcome was nonrandom. Results from single and multiple model-based imputation were compared with results from complete-case analysis and mean imputation. By ignoring nonrespondents' covariate information, the latter two methods yielded biased estimates of population means. Mean imputation and single model-based imputation underestimated standard errors by treating imputed values as if they were observed. Mean imputation also distorted the relationship between the outcome and predictors. Multiple model-based imputation provided an easily implemented method of adjustment for non-random non-response in both univariate and multivariate analyses.

The growth in the number of dependent elderly and the concurrent decline in the availability of informal caregivers has led to increasing concern that use of publicly-funded long-term care services will rise, as community-residing elders substitute these formal services for informal care. To investigate the extent of service substitution and identify correlates, longitudinal data from a study of elders and their informal caregivers were analyzed. Over 50% of subjects were missing the outcome of interest, although only 8% had no partial outcome data. This paper compares results from three missing-data methods: complete-case analysis, single regression imputation, and multiple regression imputation. Prior assumptions regarding the distribution of the outcome among nonrespondents were varied in order to examine their effect on the estimates. Regardless of the prior assumptions, 22%–23% of elders were estimated to substitute formal services for informal care. Substitution was associated with greater demands on and lower availability of informal caregivers, occurring primarily in situations where the need for care exceeded the capacity of the informal care network. Imputation provided a straightforward means of estimating the probability of substitution among a subgroup of nonrespondents not represented among respondents. In addition, multiple imputation incorporated uncertainty about nonrespondent parameters.

OBJECTIVES. The purpose of this study was to identify the role of race in seeking and receipt of care for symptoms of coronary heart disease. METHODS. Data on medical care, sociodemographic characteristics, symptoms, risk factors, income, and insurance were collected in a telephone interview for a random sample of 2030 Black and White adults in inner-city Boston. Rates of care-seeking for symptoms, amounts of delay in seeking care, and rates of receipt of care were compared for Blacks and Whites after adjustment for other characteristics. RESULTS. Before and after adjustment for other factors, Blacks and Whites were equally likely to seek care. Average delay time was shorter for Blacks, particularly Black women. With the exception of a lower rate of referral to cardiologists among Blacks, receipt of care was similar for Blacks and Whites who sought medical attention for symptoms. CONCLUSIONS. In an urban population of Blacks and Whites who were similar in socioeconomic status and access to medical care, there were few racial differences in coronary heart disease-related care patterns.

OBJECTIVES. Latino adolescents in two urban New England areas were surveyed to assess risk of human immunodeficiency virus (HIV) transmission. METHODS. Probability of HIV infection during the previous 6 months was estimated from self-reported sexual contacts, condom usage rates, and number of partners. Teens were also asked to show condoms in their possession to the interviewer to validate self-reports of condom use. RESULTS. Overall, 8% of the 586 respondents were classified as high risk for HIV infection (estimated infection probability greater than .0001), 34% were at moderate risk, and the remaining 58% were classified as not at risk (no sexual activity or needle sharing). Teens who said they had purchased condoms or claimed to have used them recently were more likely than others to have condoms in their possession at the time of the interview. CONCLUSIONS. These estimates suggest that a small percentage of Latino adolescents may be at substantial risk for HIV infection over periods as short as 6 months, that self-reports of recent condom use are strongly related to condom possession, and that questionnaire items regarding condom use at last intercourse are poor surrogates for HIV risk.

Researchers have previously emphasized the importance of kinship tie to explaining the pattern of care received by a disabled elder. For example, it has been argued that spouses are a distinct group of caregivers, i.e., they provide more care with less help from others and experience more stress. However, based on the theory of primary group structures and functions, this study hypothesized that coresidence rather than the kinship tie is more important in determining the pattern of caregiving. When spouses are compared to other coresiding caregivers, patterns of informal care and use of formal services are similar. Variance in amounts of informal care is explained by elder gender and frailty level rather than by caregiver relationship. Similarly, level of frailty was the only important predictor of use of formal services.

The Harvard Medical Practice Study is a comprehensive study of the problems associated with medical malpractice costs and litigation in the state of New York. The medical records of roughly 31,000 hospital discharges in 1984 were reviewed for the occurrence of an adverse event (AE), an unintended outcome of medical treatment resulting in serious disability or death. A sample of patients with an AE were interviewed about costs attributable to the hospitalization; this analysis focuses on total medical care costs. Because many of the survey questions dealt with sensitive topics, nonignorable nonresponse was a significant problem. This paper discusses the implementation of Bayes modeling of medical costs subject to nonignorable nonresponse in a complex sample survey, using multiple imputation. In developing imputation models, we distinguish between non-located subjects, converted refusals, final refusals, and initial respondents. Missing response status is imputed for non-located cases. Because the outcome variable is highly skewed, we address the issues of appropriate transformations, outliers, and methods for drawing residuals for imputations.

Abstract #4140 Background: Isosulfan blue has proven invaluable for sentinel lymph node identification in breast cancer. However, an intermittent supply shortage of this agent over the last few years has led to alternative usage of methylene blue. Worldwide, methylene blue is traditionally viewed as a less expensive and safer equivalent to isosulfan, with few reports of significant side effects. Its increased usage has led to anecdotal reports of local skin reactions. This study serves to review the rate of local complications observed following subareolar infiltration of methylene blue for sentinel lymph node identification in breast cancer staging. Material Methods: This is a retrospective review of prospectively collected data in a university based surgical oncology practice. Records of all patients undergoing sentinel lymph node biopsy for breast cancer between August, 2007 and April, 2008 were reviewed (the switch from Isosulfan to Methylene blue was made in August of 2007). Local complication of fat necrosis was recorded. Tumor stage, neoadjuvant therapy, volume and dilution of dye used were analysed for association with fat necrosis. Results: One hundred and three patients underwent sentinel node biopsy for breast cancer during the study period. Seven (7%) patients developed fat necrosis at the site of injection. The rate of injection site fat necrosis is associated with the volume of methylene blue [0% for 3cc (p = 0.0071)]; there was no association with tumor stage [3.2% for stage Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4140.

Methods: This longitudinal, 9-year study of 949 participants in the Study of Women’s Health Across the Nation investigates the natural history of the menopausal transition. Participants of 5 ethnicities at 7 geographic sites were recruited when they were premenopausal or early perimenopausal and were eligible for this study if they (1) reached menopause during the study; (2) had never taken hormone therapy, and (3) did not have diabetes mellitus or the MetS at baseline. The primary outcome was the presence of MetS using National Cholesterol Education Program Adult Treatment Panel III criteria. Secondary outcomes were the components of the MetS. Results: By the final menstrual period, 13.7% of the women had new-onset MetS. Longitudinal analyses, centered at the final menstrual period, were adjusted for age at menopause, ethnicity, study site, marital status, education, body mass index, smoking, and aging. Odds of developing the MetS per year in perimenopause were 1.45 (95% confidence interval, 1.35-1.56); after menopause, 1.24 (95% confidence interval, 1.181.30). T hese o dds w ere s ignificantly d ifferent (P .001). An increase in bioavailable testosterone or a decrease in sex hormone–binding globulin levels increased the odds. Conclusions: As testosterone progressively dominates the hormonal milieu during the menopausal transition, the prevalence of MetS increases, independent of aging and other important covariates. This may be a pathway by which cardiovascular disease increases during menopause.

Objective Placental soluble fms-like tyrosine kinase-1 may contribute to the pathogenesis of preeclampsia. Here we describe alterations in serum angiogenic factor levels in women with multiple gestation pregnancies, a major preeclampsia risk factor. Study Design We collected serial serum specimens from 101 pregnant women at high preeclampsia risk between 22 and 36 weeks' gestation. Soluble fms-like tyrosine kinase-1 and placental growth factor were measured by enzyme-linked immunosorbent assay. Women who had preeclampsia or gestational hypertension develop were excluded. Results Maternal soluble fms-like tyrosine kinase-1 was higher in multiple gestation (n = 20) compared with high-risk singleton (n = 81) pregnancies for each gestational age range examined. Maternal placental growth factor was significantly higher in multiple vs high-risk singletons before 31 weeks' gestation, whereas the soluble fms-like tyrosine kinase-1/placental growth factor ratio was higher in multiple vs high-risk singletons after 27 weeks. Conclusion Alterations in circulating angiogenic factors are present in women with multiple gestations and may contribute to higher preeclampsia risk in this population.

Objective The objective of the study was to evaluate angiogenic factors for the prediction of preeclampsia in high-risk women. Study Design We collected serial serum specimens from 94 women at high preeclampsia risk between 22 and 36 weeks' gestation. Soluble fms-like tyrosine kinase-1 (sFlt1) and placental growth factor (PlGF) were measured by enzyme-linked immunosorbent assay. Results Mean serum sFlt1 and the sFlt1/PlGF ratio were higher in subjects who developed early-onset (less than 34 weeks) preeclampsia, as compared with subjects without preeclampsia, from 22 weeks gestation onward. In subjects who developed late-onset (34 weeks or later) preeclampsia, sFlt1 was significantly increased after 31 weeks' gestation. The sFlt1/PlGF ratio at 22-26 weeks was highly predictive of early-onset preeclampsia. The within-woman rate of change of the sFlt1/PlGF ratio was predictive of overall preeclampsia risk. Conclusions In high-risk women, serum sFlt1 and the sFlt1:PlGF ratio are altered prior to preeclampsia onset and may be predictive of preeclampsia. Larger studies are needed to confirm these findings.

Background In recent randomized trials, conjugated equine estrogens (CEE) with continuous medroxyprogesterone acetate provided no protection against coronary heart disease in postmenopausal women and may have increased cardiac risk. These trials did not address the role of unopposed estrogen for coronary protection. Methods A total of 10 739 women aged 50 to 79 years at baseline (mean age, 63.6 years) who had previously undergone hysterectomy were randomized to receive CEE, 0.625 mg/d, or placebo at 40 US clinical centers beginning in 1993. The trial was terminated early after 6.8 years of follow-up (planned duration, 8.5 years). This report includes final, centrally adjudicated results for the primary efficacy outcome (myocardial infarction or coronary death), secondary coronary outcomes, and subgroup analyses. Results During the active intervention period, 201 coronary events were confirmed among women assigned to receive CEE compared with 217 events among women assigned to receive placebo (hazard ratio, 0.95; nominal 95% confidence interval, 0.79-1.16). Among women aged 50 to 59 years at baseline, the hazard ratio for the primary outcome was 0.63 (nominal 95% confidence interval, 0.36-1.08). In that age group, coronary revascularization was less frequent among women assigned to receive CEE (hazard ratio, 0.55; nominal 95% confidence interval, 0.35-0.86), as were several composite outcomes, which included the primary outcome and coronary revascularization (hazard ratio, 0.66; nominal 95% confidence interval, 0.44-0.97). Conclusions Conjugated equine estrogens provided no overall protection against myocardial infarction or coronary death in generally healthy postmenopausal women during a 7-year period of use. There was a suggestion of lower coronary heart disease risk with CEE among women 50 to 59 years of age at baseline.