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

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

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

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

Effect of Life Review on Quality of Life in Terminal Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Enhancing quality of life takes precedence in the terminal stage of a disease, when a cure is considered impossible and all alternative methods to prevent disease progression have been exhausted. Life review, involving appreciating accomplishments and resolving conflicts, is widely considered to be an effective approach to bringing peace to terminal patients. PURPOSE: This study was conducted to assess the effects of life review on quality of life in terminal patients. METHODS: The Cochrane Library, PubMed, MEDLINE, CINAHL, CEPS, and ProQuest databases were searched for original studies published between 2007 and July 2018. Studies that used experimental designs to assess the effects of life review on quality of life in terminal patients, involved patients aged >18 years, and were published in English or Chinese were considered eligible for inclusion. Studies that measured quality of life in individuals other than patients as well as unpublished papers or data were excluded. The search terms used included "life review," "end of life," "terminal or terminally ill," "advanced cancer," "palliative," "hospice," and "quality of life." The quality of each included study was assessed using the Downs and Black checklist. RESULTS: Six studies with 296 patients were included in the review. The participants in the included studies were from multiple countries. Life review was found to affect quality of life significantly (95% CI [0.147, 0.668], Z = 3.062, p < .05). The selected studies exhibited moderate heterogeneity (I = 42.407, p > .1). CONCLUSIONS: Life review was found to affect quality of life significantly in the participants in the included studies. The feasibility and safety of applying life review interventions should be considered for terminal patients, and implementers of these interventions should be trained and qualified. Only a few studies in the literature have evaluated the effects of life review therapy in terminal patients. Further studies that use stricter selection criteria are necessary to evaluate the efficacy of the life review intervention before its adoption in clinical practice.

Healthy Lifestyle During the Midlife Is Prospectively Associated With Less Subclinical Carotid Atherosclerosis: The Study of Women's Health Across the Nation.

Background Measures of subclinical atherosclerosis are predictors of future cardiovascular outcomes as well as of physical and cognitive functioning. The menopausal transition is associated with accelerated progression of atherosclerosis in women. The prospective association between a healthy lifestyle during the midlife and subclinical atherosclerosis is unclear. Methods and Results Self-reported data on smoking, diet, and physical activity from 1143 women in the Study of Women's Health Across the Nation were used to construct a 10-year average Healthy Lifestyle Score ( HLS ) during the midlife. Markers of subclinical atherosclerosis were measured 14 years after baseline and included common carotid artery intima-media thickness ( CCA - IMT ), adventitial diameter ( CCA - AD ), and carotid plaque. The associations of average HLS with CCA - IMT and CCA - AD were estimated using linear models; the association of average HLS with carotid plaque was estimated using cumulative logit models. Average HLS was associated with smaller CCA - IMT and CCA - AD in the fully adjusted models ( P=0.0031 and <0.001, respectively). Compared with participants in the lowest HLS level, those in the highest level had 0.024 mm smaller CCA - IMT (95% confidence interval: -0.048, 0.000), which equals 17% of the SD of CCA - IMT , and 0.16 mm smaller CCA - AD (95% confidence interval: -0.27, -0.04), which equals 24% of the SD of CCA - AD . Among the 3 components of the HLS , abstinence from smoking had the strongest association with subclinical atherosclerosis. Conclusions Healthy lifestyle during the menopausal transition is associated with less subclinical atherosclerosis, highlighting the growing recognition that the midlife is a critical window for cardiovascular prevention in women.

The Effect of a Healthy Lifestyle on Future Physical Functioning in Midlife Women.

PURPOSE: This study aimed to examine the prospective association between healthy lifestyle behaviors and objectively measured physical function in midlife women. METHODS: Participants included 1769 racially/ethnically diverse women, ages 56-68 yr, from the Study of Women's Health Across the Nation cohort. Physical function was assessed at the 13th follow-up visit with the Short Physical Performance Battery (4-m walk, repeated chair stands, and balance test) and grip strength. A healthy lifestyle score (HLS), which ranged from 0 to 6, was calculated by averaging as many as three repeated measures of self-reported smoking, physical activity, and diet, all assessed before the 13th follow-up. Multivariable linear and logistic regressions modeled each component of physical performance as a function of HLS and, in separate models, of each lifestyle behavior, adjusted for the other behaviors. RESULTS: In multivariable analyses, the time for the 4-m walk was 0.06 s faster (P = 0.001) for every 1 point increase in the HLS. The time for the repeated chair stands was significantly shorter by approximately 0.20 s. Neither grip strength nor balance problems were significantly associated with the HLS (P = 0.28 and P = 0.19, respectively). The model examining the individual health behaviors showed that only physical activity was significantly associated with physical performance. CONCLUSION: Regular physical activity in early midlife has the potential to reduce the likelihood of physical functional limitations later in midlife.

[Treatment of adenomyosis patients by bushen huoxue sanyu decoction: a clinical study].

OBJECTIVE: To observe the clinical efficacy of Bushen Huoxue Sanyu Decoction (BHSD) in treatment of adenomyosis (AM) patients. METHODS: Seventy AM patients of Shen deficiency blood stasis syndrome (SDBSS) were randomly assigned to two groups, the CM treatment group (50 cases) and the Mirena group (20 cases). Patients in the CM treatment group were treated with BHSD, one dose per day. Levonorgestrel intrauterine system (Mirena) was placed in the uterine cavity of those in the Mirena group. The therapeutic course for all was 3 months. Changes of dysmenorrhea, menstrual quantity, SDBSS, CM syndrome, uterine volume, and serum CA125 levels were observed before and after treatment. RESULTS: Compared with before treatment in the same group, scores for dysmenorrhea integral, scores for menstrual quantity, scores for SDBSS, and scores for CM syndrome all decreased in the two groups after treatment (P < 0.01). Compared with before treatment in the same group, the uterine volume was reduced after treatment in the two groups (P < 0.05) and serum carbohydrate antigen CA125 levels decreased between the two groups (P < 0.05, P < 0.01). Compared with the Mirena group, scores for dysmenorrhea integral increased and scores for SDBSS decreased in the CM treatment group (P < 0.01, P < 0.05). There was no statistical difference in the uterine volume or serum carbohydrate antigen CA125 levels (P > 0.05). CONCLUSIONS: BHSD could effectively alleviate main symptoms of AM patients of QSBSS such as dysmenorrhea, profuse menstrual blood volume, and increased uterine volume, and lower scores for QSBSS and the total score for CM syndrome.

Serum sex steroid levels and longitudinal changes in bone density in relation to the final menstrual period.

CONTEXT: The associations of serum sex steroid and FSH levels with change of bone mineral density (BMD) across the complete menopausal transition are incompletely understood. OBJECTIVE: The objective of the study was to examine the associations of annual serum levels of FSH, estradiol (E2), T, and SHBG with the rates of bone loss in 3 phases: pretransmenopausal [baseline to 1 year before the final menstrual period (FMP)], transmenopausal (1 year before to 2 years after the FMP), later postmenopausal (≥ 2 years after the FMP). DESIGN: The design of the study was a repeated-measures, mixed-effects regression. SETTING: This was a community-based observational study, with a 10-year follow-up. PARTICIPANTS: A total of 720 participants of the Study of Women's Health Across the Nation Bone Study participated in the study. OUTCOME MEASURES: Annualized lumbar spine (LS) and femoral neck (FN) BMD decline was measured. RESULTS: The mean annual change in BMD was slowest in pretransmenopause (0.27%/year in FN) and fastest in transmenopause (2.16%/year in LS). In the pretransmenopausal phase, for every doubling of FSH level, LS BMD change was faster by -0.32%/year (P < .0001). In the transmenopausal phase, for every doubling of FSH level, LS BMD change was -0.35%/year faster (P < .0001); for every doubling of SHBG level, LS BMD change was -0.36%/year faster (P < .0001). In the later postmenopausal phase, for each doubling of the E2 level, the LS BMD change was slower by +0.26%/year (P = .049); for each SHBG doubling, the LS BMD change was 0.21%/year slower (P = .048). The FN associations were weaker and inconsistent. CONCLUSIONS: Higher E2 levels and lower FSH levels were associated with lower rates of LS bone loss in some but not all menopausal transition phases.

Factors associated with kyphosis progression in older women: 15 years' experience in the study of osteoporotic fractures.

Age-related hyperkyphosis is thought to be a result of underlying vertebral fractures, but studies suggest that among the most hyperkyphotic women, only one in three have underlying radiographic vertebral fractures. Although commonly observed, there is no widely accepted definition of hyperkyphosis in older persons, and other than vertebral fracture, no major causes have been identified. To identify important correlates of kyphosis and risk factors for its progression over time, we conducted a 15-year retrospective cohort study of 1196 women, aged 65 years and older at baseline (1986 to 1988), from four communities across the United States: Baltimore County, MD; Minneapolis, MN; Portland, OR; and the Monongahela Valley, PA. Cobb angle kyphosis was measured from radiographs obtained at baseline and an average of 3.7 and 15 years later. Repeated measures, mixed effects analyses were performed. At baseline, the mean kyphosis angle was 44.7 degrees (SE = 0.4, SD = 11.9) and significant correlates included a family history of hyperkyphosis, prevalent vertebral fracture, low bone mineral density, greater body weight, degenerative disc disease, and smoking. Over an average of 15 years, the mean increase in kyphosis was 7.1 degrees (SE = 0.25). Independent determinants of greater kyphosis progression were prevalent and incident vertebral fractures, low bone mineral density and concurrent bone density loss, low body weight, and concurrent weight loss. Thus, age-related kyphosis progression may be best prevented by slowing bone density loss and avoiding weight loss.

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.

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%) vs. 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.

Progestogen levels, progesterone receptor gene polymorphisms, and mammographic density changes: results from the Postmenopausal Estrogen/Progestin Interventions Mammographic Density Study.

OBJECTIVE: Estrogen plus progestin therapy (EPT) in postmenopausal women increases breast cancer risk and mammographic density to a higher extent than does estrogen therapy alone. Data from the randomized placebo-controlled Postmenopausal Estrogen/Progestinv Interventions trial showed that EPT-induced increases in serum estrone and estrone sulfate levels were positively correlated with increases in mammographic density. Here, after adjusting for serum estrone and estrone sulfate levels, we investigated the roles of posttreatment serum progestogen increase and of progesterone receptor gene (PGR) genetic variations on changes in mammographic density. METHODS: We measured the percent mammographic density and serum progestogen levels in 280 Postmenopausal Estrogen/Progestin Interventions trial participants randomized to EPT treatment. Analyses of genetic variations in PGR were limited to 260 white women for whom we successfully obtained PGR genotypes. We used linear regression analyses to determine how an increase in progestogen levels and PGR genetic variation influenced mammographic density change after EPT. RESULTS: The increase in posttreatment serum progestogen level was positively associated with greater increases in mammographic density after adjustment for covariates (P trend = 0.044). Compared with women in the lowest quartile of serum progestogen level, women in the highest quartile experienced a 3.5% greater increase in mammographic density (P = 0.046). We did not find a strong indication that genetic variation in PGR was associated with mammographic density increase or modified the association with serum progestogen; however, confidence in these null findings is constrained by our small sample size. CONCLUSIONS: Our results suggest that higher serum progestogen levels resulting from EPT treatment lead to greater increases in mammographic density.

Diabetes and femoral neck strength: findings from the Hip Strength Across the Menopausal Transition Study.

CONTEXT: Diabetes mellitus is associated with increased hip fracture risk, despite being associated with higher bone mineral density in the femoral neck. OBJECTIVE: The objective of the study was to test the hypothesis that composite indices of femoral neck strength, which integrate dual-energy x-ray absorptiometry derived femoral neck size, femoral neck areal bone mineral density, and body size and are inversely associated with hip fracture risk, would be lower in diabetics than in nondiabetics and be inversely related to insulin resistance, the primary pathology in type 2 diabetes. DESIGN: This was a cross-sectional analysis. SETTING AND PARTICIPANTS: The study consisted of a multisite, multiethnic, community-dwelling sample of 1887 women in pre- or early perimenopause. OUTCOME MEASUREMENTS: Composite indices for femoral neck strength in different failure modes (axial compression, bending, and impact) were measured. RESULTS: Adjusted for age, race/ethnicity, menopausal stage, body mass index, smoking, physical activity, calcium and vitamin D supplementation, and study site, diabetic women had higher femoral neck areal bone mineral density [+0.25 sd, 95% confidence interval (CI) (+0.06, +0.44) sd] but lower composite strength indices [-0.20 sd, 95% CI (-0.38, -0.03) sd for compression, -0.19 sd, 95% CI (-0.38, -0.003) sd for bending, -0.19 sd, 95% CI (-0.37, -0.02) sd for impact] than nondiabetic women. There were graded inverse relationships between homeostasis model-assessed insulin resistance and all three strength indices, adjusted for the same covariates. CONCLUSIONS: Despite having higher bone density, diabetic women have lower indices of femoral neck strength relative to load, consistent with their documented higher fracture risk. Insulin resistance appears to play an important role in bone strength reduction in diabetes.

Predictors of breast discomfort among women initiating menopausal hormone therapy.

OBJECTIVE: The aim of this study was to analyze the determinants of breast discomfort among postmenopausal women initiating menopausal hormone therapy (HT). METHODS: We analyzed questionnaire, anthropometric, and serum estrone data from the Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial, a randomized trial comparing placebo, conjugated equine estrogens (CEE) alone, or CEE with a progestogen (continuous or cyclical medroxyprogesterone acetate or cyclical micronized progesterone) among postmenopausal women. HT users could join the PEPI Trial after stopping HT for 2 months. We modeled the relation between smoking, body weight, alcohol consumption, age, quitting HT for the PEPI Trial, physical activity, and alpha-tocopherol consumption and new-onset breast discomfort at the 12-month follow-up among 662 participants without baseline breast discomfort. RESULTS: The associations of new-onset breast discomfort with weight and with strenuous exercise varied by treatment assignment. Among women assigned to CEE + progestogen, strenuous exercise was associated with a 49% lower odds of new-onset breast discomfort (odds ratio, 0.51; 95% CI, 0.29-0.89; P = 0.02), whereas among women assigned to placebo or CEE alone, strenuous exercise was not significantly associated with new-onset breast discomfort. Surprisingly, among women taking CEE alone, each kilogram higher weight was associated with a 6% lower odds of new-onset breast discomfort (P = 0.04), whereas among women taking placebo, the association was in the opposite direction (P = 0.04). Adjustment for estrone level had negligible effects on odds ratios. alpha-Tocopherol intake, age, smoking, and alcohol intake were not significantly associated with new-onset breast discomfort in adjusted analyses. CONCLUSIONS: Strenuous exercise and higher body weight may decrease the odds of new-onset breast discomfort among postmenopausal women initiating HT.

Effects of alcohol and cigarette smoking on change in serum estrone levels in postmenopausal women randomly assigned to fixed doses of conjugated equine estrogens with or without a progestin.

OBJECTIVE: To determine the effects of alcohol and smoking on serum estrone levels among women assigned to hormone therapy. DESIGN: We analyzed the data from 676 participants in the Postmenopausal Estrogen/Progestin Interventions study. RESULTS: Those who consumed more than 5.5 g of alcohol daily demonstrated greater rises in serum estrone than those who drank less (>0 to < or =5.5 g/d) (P = 0.07) and those who were abstinent (P = 0.09). Current smokers had lesser gains in serum estrone compared with former smokers (P < 0.0001) and never smokers (P < 0.0001). CONCLUSIONS: Alcohol consumption augmented and smoking diminished serum estrone levels achieved while women were taking hormone therapy.

Menopause transition stage and endogenous estradiol and follicle-stimulating hormone levels are not related to cognitive performance: cross-sectional results from the study of women's health across the nation (SWAN).

BACKGROUND: By one estimate, 60% of women experiencing the menopause transition perceive that they have memory problems, but most studies that have used cognitive function tests have not substantiated a relation between menopause stage and cognitive performance. We sought to describe the cross-sectional relation between menopause status, estradiol (E(2)), follicle-stimulating hormone (FSH), and measured cognitive function. METHODS: Cross sectional analysis of a community-based cohort of midlife women was used. Cognitive tests were the East Boston Memory Test, Symbol Digit Modalities, and Digits Span Backward. Menopause categories (premenopausal, early perimenopausal, late perimenopausal, and postmenopausal) were defined based on menstrual patterns. One set of general linear models assessed the relations between each cognitive test and menopause transition category, initially adjusted for age, race/ethnicity, education, symptoms, self-rated general health, and body mass index (BMI); next, these were additionally adjusted for FSH and E(2). A second set of models, stratified by menopause status, examined the possible relations between each cognitive test and either E(2) or FSH, adjusted for age, race/ethnicity, education, symptoms, self-related general health, and BMI. RESULTS: The mean age of the analytical sample (n = 1657) was 49.7 years. Only 5% of the sample had less than a high school education, 16% graduated from high school, and the rest had at least some college. The percent of women in each menopause category was premenopausal (9.0%), early perimenopausal (57.0%), late perimenopausal (13.4%), postmenopausal (20.6%). Although clinical-site adjusted models showed moderate differences between menopause transition groups and cognitive performance, no association was found between each of the measured cognitive performance tests and menopause transition status when adjusting for covariates. Similarly, no association between each cognitive test and E(2) or FSH was found. CONCLUSIONS: This study does not support a cross-sectional relation between cognitive test performance and menopause stage, FSH, or E(2).

Serum prolactin levels are positively associated with mammographic density in postmenopausal women.

BACKGROUND: Prolactin is a polypeptide hormone that promotes normal breast proliferation and differentiation, but it is also implicated in the development and growth of mammary tumors. Mammographic density is a strong, independent predictor of breast cancer and, therefore, a potential surrogate indicator of breast cancer risk. METHODS: To test the hypothesis that serum prolactin is positively related to mammographic density, we conducted a cross-sectional analysis of baseline data from the Postmenopausal Estrogen/Progestin Interventions (PEPI) Mammographic Density Study. Based on prior work, we further hypothesized that this association would be apparent only in women who had not recently used postmenopausal hormone therapy (HT). RESULTS: In linear regression models adjusted for age, body mass index, race, smoking, alcohol use, parity and physical activity, among the 400 women who were not recent users of HT, prolactin was positively and statistically significantly associated with mammographic density (Beta log base 2 prolactin 0.0369 [95% CI: 0.0094-0.0645]. Thus, for each doubling of serum prolactin, there was an absolute increase in mammographic density of 3.69%. Additional adjustment for serum levels of estradiol, progesterone, sex hormone binding globulin and age at first pregnancy did not affect this result. There was no association between prolactin and mammographic density among the 169 participants who had recently used HT. CONCLUSION: The correspondence between higher prolactin and higher mammographic density is consistent with prolactin's mitogenic properties and the associations between prolactin and breast tumor promotion. These results support the thesis that prolactin deserves investigation as a target for breast cancer risk reduction.

Association of new-onset breast discomfort with an increase in mammographic density during hormone therapy.

BACKGROUND: Postmenopausal use of estrogen and progestin therapy increases breast density and breast discomfort. Whether this increase in breast density is heralded by new-onset breast discomfort is unknown. METHODS: We used data from the Postmenopausal Estrogen/Progestin Interventions Mammographic Density Study, which retrieved and examined baseline and 12-month mammograms for 594 (67.9%) of 875 women aged 45 to 64 years enrolled in the randomized controlled trial. Treatments included placebo, 0.625 mg/d of conjugated equine estrogens, 0.625 mg/d of conjugated equine estrogens and medroxyprogesterone acetate (10 mg/d for 12 d/mo or 2.5 mg/d continuously), or 0.625 mg/d of conjugated equine estrogens and 200 mg/d of micronized progestin for 12 d/mo. Breast density (the percent of the breast composed of dense tissue) was calculated from digitized mammograms obtained at baseline and at 12-month follow-up. Breast discomfort was ascertained at baseline and at follow-up using standardized self-report questionnaires. In bivariate analysis, and then in multivariable linear regression models, we assessed the association between change in percent breast density from baseline to 12-month follow-up and new-onset breast discomfort in participants who had no breast discomfort at baseline (N = 533). RESULTS: After adjustment for age, treatment assignment (placebo, conjugated equine estrogens, or progestin-containing regimen), and other potential confounders, women with new-onset breast discomfort had a 3.9% increase in percent breast density compared with a 0.6% increase in percent breast density among women without new-onset breast discomfort (beta = .033, P<.001). The association between incident breast discomfort and increased percent breast density was similar in all active treatment arms. CONCLUSION: In postmenopausal women randomly assigned to menopausal hormone therapy vs placebo, new-onset breast discomfort is associated with increased mammographic density.

The effects of serum beta-carotene concentration and burden of inflammation on all-cause mortality risk in high-functioning older persons: MacArthur studies of successful aging.

BACKGROUND: It remains unclear to what extent the associations between low serum beta-carotene concentration and increased risk for cardiovascular disease and cancers are attributable to inflammation. The objective of this study was to evaluate simultaneously the effects of serum beta-carotene concentration and inflammation on the subsequent all-cause mortality risk in high-functioning older persons. METHODS: The authors conducted a prospective cohort study using information from 672 participants from the MacArthur Studies of Successful Aging. Baseline information was obtained for serum concentrations of beta-carotene, C-reactive protein, interleukin-6, cholesterols, and albumin; body mass index; waist:hip ratio; prevalent medical conditions; health behaviors; and medications. Sex-specific univariate and multivariate logistic regression analyses were used to study the effects of low beta-carotene, high inflammation burden, or both on 7-year all-cause mortality rates while adjusting for other confounders. RESULTS: The serum beta-carotene concentration was inversely associated with C-reactive protein and interleukin-6 levels. After adjustment for inflammation markers and other covariates, the relative risks for low beta-carotene for the 7-year all-cause mortality risk were 2.30 (95% confidence interval [CI], 1.23 to 4.31) in men and 0.85 (95% CI, 0.42 to 1.75) in women. Compared with men with high beta-carotene levels and low inflammation, the multiply adjusted relative risk for low beta-carotene and high inflammation burden was 3.78 (95% CI, 1.69 to 8.47) in men. CONCLUSIONS: Low levels of serum beta-carotene are independently associated with an increased all-cause mortality risk in older men, even after adjustment for the effects of inflammation and other risk factors. In men, but not women, a synergistic effect occurs between low beta-carotene concentration and high inflammation burden in predicting higher mortality rates.

Sport and home physical activity are independently associated with bone density.

PURPOSE: To study the relations between four domains of physical activity-sport, home, work, and active living-and bone mineral density (BMD). METHODS: Baseline data from African-American (N = 544), Caucasian (N= 1044), Chinese (N= 230), and Japanese (N= 239) participants, aged 42-52 yr, from the study of Women's Health Across the Nation were analyzed. BMD was measured with Hologic 2000 or 4500A densitometers. Physical activity was assessed with the Kaiser Physical Activity Scale, which rates each domain of activity between 1 (low) and 5 (high). Multiply adjusted linear regression models were used to estimate the relations between each activity domain and BMD. RESULTS: The mean and median values of sport, home, work, and active living each approximated the midpoint of the scale and did not differ substantially among ethnic groups. Scores for each domain of activity were not highly correlated, with r values ranging between -0.03 and 0.33. Independent of age, body mass index, ethnic group, alcohol use, dietary calcium, smoking, menopause status, SWAN site, and other domains of physical activity, higher sport activity was statistically significantly associated with greater BMD at the lumbar spine (P= 0.008), femoral neck (P= 0.0002), and total hip (P< 0.0001). More home physical activity was associated with higher BMD at the spine (P= 0.049) and femoral neck (P= 0.008). Neither work physical activity nor active living was related to BMD at any bone site. CONCLUSIONS: These results highlight the need to consider domain-specific physical activity in relation to health outcomes in women.

Dietary soy isoflavones and bone mineral density: results from the study of women's health across the nation.

Isoflavones are naturally occurring selective estrogen receptor modulators, with potential bone protective effects. To study the relation between soy isoflavone intake and bone mineral density (BMD), the authors analyzed baseline data from the Study of Women's Health Across the Nation, a US community-based cohort study of women aged 42-52 years. Their 1996-1997 analysis included African-American (n = 497), Caucasian (n = 1,003), Chinese (n = 200), and Japanese (n = 227) participants. Genistein and daidzein intakes were highly correlated (r = 0.98); therefore, analyses were conducted by using genistein. Median intakes of genistein (measured in micrograms/day) by African Americans and Caucasians were too low to pursue relational analyses further. For Chinese and Japanese women, median genistein intakes were 3,511 and 7,151 microg/day, respectively. Ethnic-specific, linear models were used to predict BMD as a function of energy-adjusted tertile of intake, controlled for relevant covariates. For Chinese women, no association between genistein and BMD was found. Premenopausal, but not perimenopausal, Japanese women whose intakes were greater had higher spine and femoral neck BMD. Adjusted mean spinal BMD of those in the highest tertile of intake was 7.7% greater than that of women in the lowest tertile (p = 0.02); femoral neck BMD was 12% greater in the highest versus the lowest tertile (p < 0.0001).