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Dual-energy X-ray absorptiometry (DXA) is more available than gold-standard magnetic resonance imaging (MRI), but DXA ability to estimate abdominal skeletal muscle mass (SMM) is unknown. DXA-derived abdominal fat-free mass (FFM; Hologic QDR2000 or QDR4500w) was correlated with single-slice MRI SMM at L4 (N = 69; r QDR2000 = 0.71, QDR4500w = 0.69; p < 0.0001). Linear regression to predict SMM, including DXA FFM, BMI, and age, resulted in an R-squared of 0.72 and 0.65 for QDR2000 and QDR4500. Bland-Altman limits of agreement were ±21 and ±31 g for 2–3 standard deviations from the mean difference. DXA predicted abdominal SSM is a moderate proxy for MRI abdominal SMM. [ABSTRACT FROM AUTHOR]

Objective: To assess weight change and attempted weight loss during the 12-18 months before spontaneous conception in relation to the risk of pregnancy loss.Design: Prospective cohort study.Setting: United States, 2007-2011.Methods: Women (n = 629) who were attempting pregnancy reported at baseline any weight loss attempts over the past 12 months, and their minimum and maximum weights during that time. Follow up lasted one to six menstrual cycles and throughout pregnancy. Using bodyweight measured at 4 weeks' gestation, participants were categorised as having weight loss ≥5%, weight gain ≥5%, both, or neither, over the previous 12-18 months. Log-binomial models adjusted for potential confounders.Main Outcome Measures: Risk ratio (RR) and 95% confidence interval (CI) of pregnancy loss.Results: Attempted weight loss was reported by 44% of women and actual weight loss by 11%, but neither was consistently associated with pregnancy loss. The RR for recent weight gain ≥5% was 1.65 (CI 1.09, 2.49).Conclusions: Weight gain over the period spanning 12-18 months pre-conception to 4 weeks' gestation may increase the risk of pregnancy loss among fertile women with prior pregnancy losses. Attempted and actual weight loss were not associated with pregnancy loss; however, replication is needed from larger studies with data on particular weight-loss methods.Tweetable Abstract: Recent weight gain before and around the time of conception may increase the risk of pregnancy loss. [ABSTRACT FROM AUTHOR]

Understanding of the oral microbiome in relation to periodontal disease in older adults is limited. The composition and diversity of the subgingival microflora and their oligotypes in health and levels of periodontal disease were investigated in this study on older postmenopausal women. The 16S rRNA gene was sequenced using the Illumina MiSeq platform in 1,206 women aged 53 to 81 y. Presence and severity of periodontal disease were defined by Centers for Disease Control and Prevention/American Academy of Periodontology criteria. Composition of the microbiome was determined by 16S rRNA amplicon sequencing and the abundance of taxa described by the centered log2-ratio (CLR) transformed operational taxonomic unit (OTU) values. Differences according to periodontal disease status were determined by analysis of variance with Bonferroni correction. Bacteria oligotypes associated with periodontal disease and health were determined by minimum entropy decomposition and their functions estimated in silico using PICRUSt. Prevalence of none/mild, moderate, and severe periodontal disease was 25.1%, 58.3%, and 16.6%, respectively. Alpha diversity of the microbiome differed significantly across the 3 periodontal disease categories. β-Diversity differed between no/mild and severe periodontal disease, although considerable overlap was noted. Of the 267 bacterial species identified at ≥0.02% abundance, 56 (20.9%) differed significantly in abundance according to periodontal disease status. Significant linear correlations for pocket depth and clinical attachment level with bacterial amounts were observed for several taxa. Of the taxa differing in abundance according to periodontal disease status, 53% had multiple oligotypes appearing to differ between none/mild and severe periodontal disease. Among older women, taxonomic differences in subgingival microbiome composition and diversity were observed in relation to clinical periodontal disease measures. Potential differences in bacterial subspecies (oligotypes) and their function were also identified in periodontal disease compared with health. [ABSTRACT FROM AUTHOR]

Background: While progestin addition to estrogen mitigates endometrial cancer risk, the magnitude of the effect on incidence, specific endometrial cancer histologies, and endometrial cancer mortality remains unsettled. These issues were assessed by analyses after extended follow-up of the Women's Health Initiative (WHI) randomized clinical trial evaluating continuous combined estrogen plus progestin use.Methods: The WHI enrolled 16 608 postmenopausal women into a randomly assigned, double-blind, placebo-controlled trial. Women age 50 to 79 years with intact uteri with normal endometrial biopsy at entry were randomly assigned to once-daily 0.625 mg conjugated equine estrogen plus 2.5mg medroxyprogesterone acetate (n = 8506) as a single pill or matching placebo (n = 8102). Follow-up beyond the original trial completion date required reconsent, obtained from 12 788 (83%) of surviving participants. Analyses were by intent-to-treat. All statistical tests were two-sided.Results: After 5.6 years' median intervention and 13 years' median cumulative follow-up, there were fewer endometrial cancers in the combined hormone therapy compared with the placebo group (66 vs 95 case patients, yearly incidence, 0.06% vs 0.10%; hazard ratio [HR] = 0.65, 95% confidence interval [CI] = 0.48 to 0.89, P = .007). While there were somewhat fewer endometrial cancers during intervention (25 vs 30, respectively; HR = 0.77, 95% CI = 0.45 to 1.31), the difference became statistically significant postintervention (41 vs 65, respectively; HR = 0.59, 95% CI = 0.40 to 0.88, P = .008), but hazard ratios did not differ between phases (P difference = .46). There was a statistically nonsignificant reduction in deaths from endometrial cancer in the estrogen plus progestin group (5 vs 11 deaths, HR = 0.42, 95% CI = 0.15 to 1.22).Conclusion: In postmenopausal women, continuous combined estrogen plus progestin decreases endometrial cancer incidence. [ABSTRACT FROM AUTHOR]

In early adjuvant breast cancer trial reports, aromatase inhibitors more effectively reduced breast recurrence with lower risk of thromboembolic events and endometrial cancer than tamoxifen, while aromatase inhibitors had higher fracture and cardiovascular disease risk. We used data from updated patient-level meta-analyses of adjuvant trials in analyses to summarize the benefits and risks of these agents in various clinical circumstances. Baseline incidence rates for health outcomes by age and race/ethnicity, absent aromatase inhibitor, or tamoxifen use were estimated from the Women's Health Initiative. Aromatase inhibitor and tamoxifen effects on distant recurrence were obtained from a meta-analysis of the Arimidex, Tamoxifen, Alone or in Combination (ATAC) and Breast International Group (Big-1-98) clinical trials. Impact on other health outcomes were obtained from meta-analyses of randomized trials comparing aromatase inhibitor to tamoxifen use and from placebo-controlled chemoprevention trials. All health outcomes were given equal weight when modeling net benefit/risk for aromatase inhibitor compared to tamoxifen use by breast cancer recurrence risk, age (decade), race/ethnicity, hysterectomy (yes/no), and by prior myocardial infarction. Over a 10-year period, the benefit/risk index was more favorable for aromatase inhibitor than for tamoxifen as adjuvant breast cancer therapy in almost all circumstances regardless of patient age, race/ethnicity, breast cancer recurrence risk, or presence or absence of a uterus. Only in older women with prior myocardial infarction and low recurrence risk was an advantage for tamoxifen seen. Using a benefit/risk index for endocrine adjuvant breast cancer therapy in postmenopausal women, benefit was higher for aromatase inhibitor use in almost all circumstances. [ABSTRACT FROM AUTHOR]

Background:The objective of this study was to assess the impact of pre-existing diabetes on breast cancer prognosis.Methods:Women (n=2833) with centrally confirmed invasive breast cancer in the Women's Health Initiative, who were linked to Medicare claims data (CMS) were followed from the date of breast cancer diagnosis to date of death or 20 September 2013. Information on diabetes was identified through the CMS Chronic Condition Warehouse algorithm. Cox proportional hazard regression was used to estimate adjusted hazard ratios for overall mortality. A competing risks model (proportional subdistribution) model was used to estimate hazard ratios for breast cancer-specific mortality.Results:Women with diabetes were more likely to have factors related to delayed diagnosis (less recent mammograms, and more advanced cancer stage) and were less likely to receive radiation therapy. Compared with women without diabetes, women with diabetes had significantly increased risk of overall mortality (HR=1.57, 95% CI: 1.23-2.01) and had nonsignificantly increased risk for breast cancer-specific mortality (HR=1.36, 95% CI: 0.86-2.15) before adjustment for factors related to delayed diagnosis and treatment. Adjustment for these factors resulted in a little change in the association of diabetes with overall mortality risk, but further attenuated the point estimate for breast cancer-specific mortality.Conclusions:Our study provides additional evidence that pre-existing diabetes increases the risk of total mortality among women with breast cancer. Very large studies with data on breast cancer risk factors, screening and diagnostic delays, treatment choices, and the biological influence of diabetes on breast cancer will be needed to determine whether diabetes also increases the risk for breast cancer-specific mortality. [ABSTRACT FROM AUTHOR]

STUDY QUESTION: Does use of commonly used over-the-counter (OTC) pain medication affect reproductive hormones and ovulatory function in premenopausal women? SUMMARY ANSWER: Few associations were found between analgesic medication use and reproductive hormones, but use during the follicular phase was associated with decreased odds of sporadic anovulation after adjusting for potential confounders. WHAT IS KNOWN ALREADY: Analgesic medications are the most commonly used OTC drugs among women, but their potential effects on reproductive function are unclear. STUDY DESIGN, SIZE, DURATION: The BioCycle Study was a prospective, observational cohort study (2005-2007) which followed 259 women for one (n = 9) or two (n = 250) menstrual cycles. participants, setting, methods: Two hundred and fifty-nine healthy, premenopausal women not using hormonal contraception and living in western New York state. Study visits took place at the University at Buffalo. MAIN RESULTS AND THE ROLE OF CHANCE: During study participation, 68% (n = 175) of women indicated OTC analgesic use. Among users, 45% used ibuprofen, 33% acetaminophen, 10% aspirin and 10% naproxen. Analgesic use during the follicular phase was associated with decreased odds of sporadic anovulation after adjusting for age, race, body mass index, perceived stress level and alcohol consumption (OR 0.36 [0.17, 0.75]). Results remained unchanged after controlling for potential confounding by indication by adjusting for 'healthy' cycle indicators such as amount of blood loss and menstrual pain during the preceding menstruation. Moreover, luteal progesterone was higher (% difference = 14.0, 2 1.6-32.1, P = 0.08 adjusted) in cycles with follicular phase analgesic use, but no associations were observed with estradiol, LH or FSH. limitations, reasons for caution: Self-report daily diaries are not validated measures of medication usage, which could lead to some classification error of medication use. We were also limited in our evaluation of aspirin and naproxen which were used by few women. WIDER IMPLICATIONS OF THE FINDINGS: The observed associations between follicular phase analgesic use and higher progesterone and a lower probability of sporadic anovulation indicate that OTC pain medication use is likely not harmful to reproduction function, and certain medications possibly improve ovulatory function. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (contract # HHSN275200403394C). The authors have no conflicts of interest to disclose. [ABSTRACT FROM AUTHOR]

STUDY QUESTION: Does use of commonly used over-the-counter (OTC) pain medication affect reproductive hormones and ovulatory function in premenopausal women? SUMMARY ANSWER: Few associations were found between analgesic medication use and reproductive hormones, but use during the follicular phase was associated with decreased odds of sporadic anovulation after adjusting for potential confounders. WHAT IS KNOWN ALREADY: Analgesic medications are the most commonly used OTC drugs among women, but their potential effects on reproductive function are unclear. STUDY DESIGN, SIZE, DURATION: The BioCycle Study was a prospective, observational cohort study (2005-2007) which followed 259 women for one (n = 9) or two (n = 250) menstrual cycles. PARTICIPANTS, SETTING, METHODS: Two hundred and fifty-nine healthy, premenopausal women not using hormonal contraception and living in western New York state. Study visits took place at the University at Buffalo. MAIN RESULTS AND THE ROLE OF CHANCE: During study participation, 68% (n = 175) of women indicated OTC analgesic use. Among users, 45% used ibuprofen, 33% acetaminophen, 10% aspirin and 10% naproxen. Analgesic use during the follicular phase was associated with decreased odds of sporadic anovulation after adjusting for age, race, body mass index, perceived stress level and alcohol consumption (OR 0.36 [0.17, 0.75]). Results remained unchanged after controlling for potential confounding by indication by adjusting for 'healthy' cycle indicators such as amount of blood loss and menstrual pain during the preceding menstruation. Moreover, luteal progesterone was higher (% difference = 14.0, 21.6-32.1, P = 0.08 adjusted) in cycles with follicular phase analgesic use, but no associations were observed with estradiol, LH or FSH. LIMITATIONS, REASONS FOR CAUTION: Self-report daily diaries are not validated measures of medication usage, which could lead to some classification error of medication use. We were also limited in our evaluation of aspirin and naproxen which were used by few women. wider implications of the findings: The observed associations between follicular phase analgesic use and higher progesterone and a lower probability of sporadic anovulation indicate that OTC pain medication use is likely not harmful to reproduction function, and certain medications possibly improve ovulatory function. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (contract # HHSN275200403394C). The authors have no conflicts of interest to disclose. [ABSTRACT FROM AUTHOR]

Background:A growing body of evidence suggests that diabetes is a risk factor for endometrial cancer incidence. However, most of these studies used case-control study designs and did not adjust for obesity, an established risk factor for endometrial cancer. In addition, few epidemiological studies have examined the association between diabetes treatment and endometrial cancer risk. The objective of this study was to assess the relationships among diabetes, diabetes treatment and endometrial cancer risk in postmenopausal women participating in the Women's Health Initiative (WHI).Methods:A total of 88 107 postmenopausal women aged 50-79 years who were free of cancer and had no hysterectomy at baseline were followed until date of endometrial cancer diagnosis, death, hysterectomy or loss to follow-up, whichever came first. Endometrial cancers were confirmed by central medical record and pathology report review. Multivariate Cox proportional hazards regression models were used to estimate hazard ratios (HRs) (95% confidence interval (CI)) for diagnosis of diabetes and metformin treatment as risk factors for endometrial cancer.Results:Over a mean of 11 years of follow-up, 1241 endometrial cancers developed. In the primary analysis that focused on prevalent diabetes at enrolment, compared with women without diabetes, women with self-reported diabetes, and the subset of women with treated diabetes, had significantly higher risk of endometrial cancer without adjusting for BMI (HR=1.44, 95% CI: 1.13-1.85 for diabetes, HR=1.57, 95% CI: 1.19-2.07 for treated diabetes). However after adjusting for BMI, the associations between diabetes, diabetes treatment, diabetes duration and the risk of endometrial cancer became non-significant. Elevated risk was noted when considering combining diabetes diagnosed at baseline and during follow-up as time-dependent exposure (HR=1.31, 95% CI: 1.08-1.59) even after adjusting for BMI. No significant association was observed between metformin use and endometrial cancer risk.Conclusions:Our results suggest that the relationship observed in previous research between diabetes and endometrial cancer incidence may be largely confounded by body weight, although some modest independent elevated risk remains. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Does serum anti-Müllerian hormone (AMH) vary significantly throughout both ovulatory and sporadic anovulatory menstrual cycles in healthy premenopausal women? SUMMARY ANSWER Serum AMH levels vary statistically significantly across the menstrual cycle in both ovulatory and sporadic anovulatory cycles of healthy eumenorrheic women. WHAT IS KNOWN ALREADY Studies to date evaluating serum AMH levels throughout the menstrual cycle have conflicting results regarding intra-woman cyclicity. No previous studies have evaluated an association between AMH and sporadic anovulation. STUDY DESIGN, SIZE, DURATION We conducted a prospective cohort study of 259 regularly menstruating women recruited between 2005 and 2007. PARTICIPANTS/MATERIALS, SETTING, METHODS Women aged 18–44 years were followed for one (n = 9) or two (n = 250) menstrual cycles. Anovulatory cycles were defined as any cycle with peak progesterone concentration ≤5 ng/ml and no serum LH peak on the mid or late luteal visits. Serum AMH was measured at up to eight-time points throughout each cycle. MAIN RESULTS AND THE ROLE OF CHANCE Geometric mean AMH levels were observed to vary across the menstrual cycle (P < 0.01) with the highest levels observed during the mid-follicular phase at 2.06 ng/ml, decreasing around the time of ovulation to 1.79 ng/ml and increasing thereafter to 1.93 (mid-follicular versus ovulation, P < 0.01; ovulation versus late luteal, P = 0.01; mid-follicular versus late luteal, P = 0.05). Patterns were similar across all age groups and during ovulatory and anovulatory cycles, with higher levels of AMH observed among women with one or more anovulatory cycles (P = 0.03). LIMITATIONS, REASONS FOR CAUTION Ovulatory status was not verified by direct visualization. AMH was analyzed using the original Generation II enzymatically amplified two-site immunoassay, which has been shown to be susceptible to assay interference. Thus, absolute levels should be interpreted with caution, however, patterns and associations remain consistent and any potential bias would be non-differential. WIDER IMPLICATIONS OF THE FINDINGS This study demonstrates a significant variation in serum AMH levels across the menstrual cycle regardless of ovulatory status. This variability, although statistically significant, is not large enough to warrant a change in current clinical practice to time AMH measurements to cycle day/phase. STUDY FUNDING/COMPETING INTEREST(S) This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Bethesda, MD (Contracts # HHSN275200403394C, HHSN275201100002I Task 1 HHSN27500001). The authors have no conflicts of interest to declare. [ABSTRACT FROM PUBLISHER]

STUDY QUESTION Do ovulatory hormone profiles among healthy premenopausal women differ between women with and without sporadic anovulation? SUMMARY ANSWER Women with one anovulatory cycle tended to have lower estradiol, progesterone and LH peak levels during their ovulatory cycle. WHAT IS KNOWN ALREADY Anovulation occurs sporadically in healthy premenopausal women, but the influence of hormones in a preceding cycle and the impact on a subsequent cycle's hormone levels is unknown. STUDY DESIGN, SIZE, DURATION The BioCycle Study was a prospective cohort including 250 healthy regularly menstruating women, 18–44 years of age, from Western New York with no history of menstrual or ovulation disorders. The women were followed with up to eight study visits per cycle for two cycles, most of which were consecutive. PARTICIPANTS/MATERIALS, SETTING AND METHODS All study visits were timed to menstrual cycle phase using fertility monitors and located at the University at Buffalo women's health research center from 2005 to 2007. The main outcomes measured were estradiol, progesterone, LH and follicle-stimulating hormone levels in serum at up to 16 visits over two cycles. Anovulation was defined as peak serum progesterone concentrations ≤5 ng/ml and no serum LH peak detected during the mid- or late-luteal phase visit. MAIN RESULTS AND THE ROLE OF CHANCE Reproductive hormone concentrations were lower during anovulatory cycles, but significant reductions were also observed in estradiol (−25%, P = 0.003) and progesterone (−22%, P = 0.001) during the ovulatory cycles of women with one anovulatory cycle compared with women with two ovulatory cycles. LH peak concentrations were decreased in the ovulatory cycle of women with an anovulatory cycle (significant amplitude effect, P = 0.004; geometric mean levels 38% lower, P < 0.05). LIMITATIONS, REASONS FOR CAUTION Follow-up was limited to two menstrual cycles, and no ultrasound assessment of ovulation was available. Data were missing for a total of 168 of a possible 4072 cycle visits (4.1%), though all women had at least five visits per cycle (94% had seven or more per cycle). WIDER IMPLICATIONS OF THE FINDINGS These results suggest a possible underlying cause of anovulation, such as a longer-term subclinical follicular, ovarian or hypothalamic/pituitary dysfunction, even among healthy, regularly menstruating women. STUDY FUNDING/COMPETING INTERESTS This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD (Contract no. HHSN275200403394C). The authors have no potential competing interests. [ABSTRACT FROM PUBLISHER]

STUDY QUESTION Do genetic associations identified in genome-wide association studies (GWAS) of age at menarche (AM) and age at natural menopause (ANM) replicate in women of diverse race/ancestry from the Population Architecture using Genomics and Epidemiology (PAGE) Study? SUMMARY ANSWER We replicated GWAS reproductive trait single nucleotide polymorphisms (SNPs) in our European descent population and found that many SNPs were also associated with AM and ANM in populations of diverse ancestry. WHAT IS KNOWN ALREADY Menarche and menopause mark the reproductive lifespan in women and are important risk factors for chronic diseases including obesity, cardiovascular disease and cancer. Both events are believed to be influenced by environmental and genetic factors, and vary in populations differing by genetic ancestry and geography. Most genetic variants associated with these traits have been identified in GWAS of European-descent populations. STUDY DESIGN, SIZE, DURATION A total of 42 251 women of diverse ancestry from PAGE were included in cross-sectional analyses of AM and ANM. MATERIALS, SETTING, METHODS SNPs previously associated with ANM (n = 5 SNPs) and AM (n = 3 SNPs) in GWAS were genotyped in American Indians, African Americans, Asians, European Americans, Hispanics and Native Hawaiians. To test SNP associations with ANM or AM, we used linear regression models stratified by race/ethnicity and PAGE sub-study. Results were then combined in race-specific fixed effect meta-analyses for each outcome. For replication and generalization analyses, significance was defined at P < 0.01 for ANM analyses and P < 0.017 for AM analyses. MAIN RESULTS AND THE ROLE OF CHANCE We replicated findings for AM SNPs in the LIN28B locus and an intergenic region on 9q31 in European Americans. The LIN28B SNPs (rs314277 and rs314280) were also significantly associated with AM in Asians, but not in other race/ethnicity groups. Linkage disequilibrium (LD) patterns at this locus varied widely among the ancestral groups. With the exception of an intergenic SNP at 13q34, all ANM SNPs replicated in European Americans. Three were significantly associated with ANM in other race/ethnicity populations: rs2153157 (6p24.2/SYCP2L), rs365132 (5q35/UIMC1) and rs16991615 (20p12.3/MCM8). While rs1172822 (19q13/BRSK1) was not significant in the populations of non-European descent, effect sizes showed similar trends. LIMITATIONS, REASONS FOR CAUTION Lack of association for the GWAS SNPs in the non-European American groups may be due to differences in locus LD patterns between these groups and the European-descent populations included in the GWAS discovery studies; and in some cases, lower power may also contribute to non-significant findings. WIDER IMPLICATIONS OF THE FINDINGS The discovery of genetic variants associated with the reproductive traits provides an important opportunity to elucidate the biological mechanisms involved with normal variation and disorders of menarche and menopause. In this study we replicated most, but not all reported SNPs in European descent populations and examined the epidemiologic architecture of these early reported variants, describing their generalizability and effect size across differing ancestral populations. Such data will be increasingly important for prioritizing GWAS SNPs for follow-up in fine-mapping and resequencing studies, as well as in translational research. STUDY FUNDING/COMPETING INTEREST(S) The Population Architecture Using Genomics and Epidemiology (PAGE) program is funded by the National Human Genome Research Institute (NHGRI), supported by U01HG004803 (CALiCo), U01HG004798 (EAGLE), U01HG004802 (MEC), U01HG004790 (WHI) and U01HG004801 (Coordinating Center), and their respective NHGRI ARRA supplements. The authors report ... [ABSTRACT FROM PUBLISHER]

Background/objectives:Adherence to the Mediterranean diet (MD), high in fruits, vegetables and monounsaturated fats, has been associated with lower body mass index. Associations with measured body fat, including regional adiposity, have not been previously investigated. We examined the associations between the alternate Mediterranean diet score (aMED), anthropometry and measured adiposity by dual-energy x-ray absorptiometry (DXA).Subjects/methods:This study included 248 healthy females, aged 18-44 years from the BioCycle Study. Each woman's aMED (range 0-9) was calculated from up to eight 24-h dietary recalls over 1-2 menstrual cycles (>97% had 7 recalls). Multiple linear regression was used to determine whether aMED and its specific components were associated with total and regional adiposity after adjusting for age, race, education, physical activity and energy intake.Results:Participants had an average (s.d.) aMED of 4.2 (1.7) and percent body fat of 29.5 (6.0)%. Significant inverse associations were found between aMED and all the examined adiposity measures except waist-to-hip ratio. Among the DXA measures, a 1-unit increment in aMED was associated with a 0.06 (95% confidence interval (CI): −0.09, −0.02) lower trunk-to-leg fat ratio (T/L), a measure of upper to lower body fat. In an analysis examining T/L as an outcome with the separate components of the aMED, T/L was lower with increased legume consumption (β=−0.280, 95% CI: −0.550, −0.010) but was higher with increased consumption of red and processed meat (β=0.060, 95% CI: 0.002, 0.117).Conclusions:Adherence to the aMED was associated with lower total and regional adiposity, adding to the mounting evidence of the health benefits of the MD. [ABSTRACT FROM AUTHOR]

Summary: The Women's Health Initiative (WHI) double-blind, placebo-controlled clinical trial randomly assigned 36,282 postmenopausal women in the U.S. to 1,000 mg elemental calcium carbonate plus 400 IU of vitamin D daily or placebo, with average intervention period of 7.0 years. The trial was designed to test whether calcium plus vitamin D supplementation in a population in which the use of these supplements was widespread would reduce hip fracture, and secondarily, total fracture and colorectal cancer. Introduction: This study further examines the health benefits and risks of calcium and vitamin D supplementation using WHI data, with emphasis on fractures, cardiovascular disease, cancer, and total mortality. Methods: WHI calcium and vitamin D randomized clinical trial (CT) data through the end of the intervention period were further analyzed with emphasis on treatment effects in relation to duration of supplementation, and these data were contrasted and combined with corresponding data from the WHI prospective observational study (OS). Results: Among women not taking personal calcium or vitamin D supplements at baseline, the hazard ratio [HR] for hip fracture occurrence in the CT following 5 or more years of calcium and vitamin D supplementation versus placebo was 0.62 (95 % confidence interval (CI), 0.38-1.00). In combined analyses of CT and OS data, the corresponding HR was 0.65 (95 % CI, 0.44-0.98). Supplementation effects were not apparent on the risks of myocardial infarction, coronary heart disease, total heart disease, stroke, overall cardiovascular disease, colorectal cancer, or total mortality, while evidence for a reduction in breast cancer risk and total invasive cancer risk among calcium plus vitamin D users was only suggestive. Conclusion: Though based primarily on a subset analysis, long-term use of calcium and vitamin D appears to confer a reduction that may be substantial in the risk of hip fracture among postmenopausal women. Other health benefits and risks of supplementation at doses considered, including an elevation in urinary tract stone formation, appear to be modest and approximately balanced. [ABSTRACT FROM AUTHOR]

Objective:To investigate the influence of adiposity on patterns of sex hormones across the menstrual cycle among regularly menstruating women.Subjects:The BioCycle Study followed 239 healthy women for 1-2 menstrual cycles, with up to eight visits per cycle timed using fertility monitors.Methods:Serum estradiol (E2), progesterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and sex hormone-binding globulin (SHBG) were measured at each visit. Adiposity was measured by anthropometry and by dual energy X-ray absorptiometry (DXA). Differences in hormonal patterns by adiposity measures were estimated using nonlinear mixed models, which allow for comparisons in overall mean levels, amplitude (i.e., lowest to highest level within each cycle) and shifts in timing of peaks while adjusting for age, race, energy intake and physical activity.Results:Compared with normal weight women (n=154), obese women (body mass index (BMI) 30 kg m−2, n=25) averaged lower levels of progesterone (−15%, P=0.003), LH (−17%, P=0.01), FSH (−23%, P=0.001) and higher free E2 (+22%, P=0.0001) across the cycle. To lesser magnitudes, overweight women (BMI: 25-30, n=60) also exhibited differences in the same directions for mean levels of free E2, FSH and LH. Obese women experienced greater changes in amplitude of LH (9%, P=0.002) and FSH (8%, P=0.004), but no differences were observed among overweight women. Higher central adiposity by top compared to bottom tertile of trunk-to-leg fat ratio by DXA was associated with lower total E2 (−14%, P=0.005), and FSH (−15%, P=0.001). Peaks in FSH and LH occurred later (∼0.5 day) in the cycle among women with greater central adiposity.Conclusion:Greater total and central adiposity were associated with changes in mean hormone levels. The greater amplitudes observed among obese women suggest compensatory mechanisms at work to maintain hormonal homeostasis. Central adiposity may be more important in influencing timing of hormonal peaks than total adiposity. [ABSTRACT FROM AUTHOR]

Background and Purpose: Previous studies have shown that physical inactivity and obesity are risk factors for the development of colorectal cancer. However, controversy exists regarding the influence of these factors on survival in colorectal cancer patients. We evaluated the impact of recreational physical activity and body mass index (BMI) before and after colorectal cancer diagnosis on disease-specific mortality and all-cause mortality.Patients and Methods: This prospective cohort study included 1,339 women enrolled in the Women's Health Initiative study who were diagnosed with colorectal cancer subsequent to study enrollment. BMI and recreational physical activity were measured before cancer diagnosis at study entry (pre-diagnostic) and after diagnosis at study follow-up interviews (post-diagnostic). We used Cox regression to estimate the association between pre- and post-diagnostic exposures and survival after colorectal cancer diagnosis.Results: Among women diagnosed with colorectal cancer, 265 (13 %) deaths occurred during a median study follow-up of 11.9 years, of which 171 (65 %) were attributed to colorectal cancer. Compared with women reporting no pre-diagnostic recreational physical activity, those reporting activity levels of ≥18 MET-h/week had significantly lower colorectal cancer-specific mortality (hazard ratio (HR) = 0.68; 95 % confidence interval (CI): 0.41-1.13) and all-cause mortality (HR = 0.63; 95 % CI: 0.42-0.96). Similar inverse associations were seen for post-diagnostic recreational physical activity. Neither pre- nor post-diagnostic BMI were associated with mortality after colorectal cancer diagnosis.Conclusion: Recreational physical activity before and after colorectal cancer diagnosis, but not BMI, is associated with more favorable survival. [ABSTRACT FROM AUTHOR]

Objective: To examine determinants of racial/ethnic differences in diabetes incidence among postmenopausal women participating in the Women's Health Initiative.Research Design and Methods: Data on race/ethnicity, baseline diabetes prevalence, and incident diabetes were obtained from 158,833 women recruited from 1993-1998 and followed through August 2009. The relationship between race/ethnicity, other potential risk factors, and the risk of incident diabetes was estimated using Cox proportional hazards models from which hazard ratios (HRs) and 95% CIs were computed.Results: Participants were aged 63 years on average at baseline. The racial/ethnic distribution was 84.1% non-Hispanic white, 9.2% non-Hispanic black, 4.1% Hispanic, and 2.6% Asian. After an average of 10.4 years of follow-up, compared with whites and adjusting for potential confounders, the HRs for incident diabetes were 1.55 for blacks (95% CI 1.47-1.63), 1.67 for Hispanics (1.54-1.81), and 1.86 for Asians (1.68-2.06). Whites, blacks, and Hispanics with all factors (i.e., weight, physical activity, dietary quality, and smoking) in the low-risk category had 60, 69, and 63% lower risk for incident diabetes. Although contributions of different risk factors varied slightly by race/ethnicity, most findings were similar across groups, and women who had both a healthy weight and were in the highest tertile of physical activity had less than one-third the risk of diabetes compared with obese and inactive women.Conclusions: Despite large racial/ethnic differences in diabetes incidence, most variability could be attributed to lifestyle factors. Our findings show that the majority of diabetes cases are preventable, and risk reduction strategies can be effectively applied to all racial/ethnic groups. [ABSTRACT FROM AUTHOR]

Few studies have prospectively examined predictors of change in plasma concentrations of 25-hydroxyvitamin D [25(OH)D]. We sought to determine the predictors of 5-y change in 25(OH)D. Plasma 25(OH)D concentrations were assessed at baseline (1997-2000) and 5 y later (2002-2005) in 668 postmenopausal women enrolled in the Osteoporosis and Periodontal Disease Study. Baseline and changes in demographic, dietary, lifestyle, and health-related factors were tested as predictors of change in 25(OH)D concentrations by using multivariable linear regression. The mean 5-y change in 25(OH)D (mean ± SD) was 7.7 ± 0.7 nmol/L (P < 0.001). In our predictive model (n = 643), predictors explained 31% of the variance in change in 25(OH)D concentrations and included baseline 25(OH)D, baseline and change in vitamin D supplementation and physical activity, change in season of blood draw, BMI, whole-body T score, and baseline hormone therapy use. Baseline 25(OH)D and change in vitamin D supplementation explained the most variation (25%) in 25(OH)D. Exploratory analyses showed a borderline significant interaction between tertiles of baseline 25(OH)D and change in vitamin D supplementation over time (P = 0.06). The greatest mean increase in 25(OH)D (22.9 ± 16.8 nmol/L), with adjustment for other statistically significant predictors, occurred in women whose baseline 25(OH)D concentration was ≤51.0 nmol/L (tertile 1) and who increased supplementation use over time. These results confirm the importance of supplementation in increasing 25(OH)D concentrations in aging women, even after other statistically significant predictors are controlled for. These data also suggest that this is especially true among aging women with inadequate 25(OH)D (e.g., <50 nmol/L). [ABSTRACT FROM AUTHOR]

Background: Case-control studies have reported that exogenous estrogen use is associated with increased risk of skin cancer. The effects of menopausal hormone therapy on incidence of nonmelanoma skin cancer and melanoma were evaluated in post hoc analyses of the Women's Health Initiative randomized placebo-controlled hormone therapy trials of combined estrogen plus progestin (E + P) and estrogen only (E-alone).Methods: Postmenopausal women aged 50-79 years were randomly assigned to conjugated equine estrogen (0.625 mg/d) plus medroxyprogesterone acetate (2.5 mg/d) or placebo in the E + P trial if they had an intact uterus (N = 16,608) or to conjugated equine estrogen alone or placebo in the E-alone trial if they had a hysterectomy (N = 10,739); the mean follow-up was 5.6 and 7.1 years, respectively. Incident nonmelanoma skin cancers (n = 980 [E + P trial]; n = 820 [E-alone trial]) and melanomas (n = 57 [E + P trial]; n =38 [E-alone trial]) were ascertained by self-report. Incident cases of cutaneous malignant melanoma were confirmed by physician review of medical records. Incidences of nonmelanoma skin cancer and melanoma were compared between the two randomization groups within each trial using hazard ratios (HRs), with corresponding 95% confidence intervals (CIs) and Wald statistic P values from Cox proportional hazards models. All statistical tests were two-sided.Results: Rates of incident nonmelanoma skin cancer and melanoma were similar between the active hormone (combined analysis of E + P and E-alone) and placebo groups (nonmelanoma skin cancer: HR = 0.98, 95% CI = 0.89 to 1.07; melanoma: HR = 0.92, 95% CI = 0.61 to 1.37). Results were similar for the E + P and E-alone trials when analyzed individually.Conclusions: Menopausal hormone therapy did not affect overall incidence of nonmelanoma skin cancer or melanoma. These findings do not support a role of menopausal estrogen, with or without progestin, in the development of skin cancer in postmenopausal women. [ABSTRACT FROM AUTHOR]

Background: Cadmium, lead and mercury have been identified in human follicular fluid and ovarian tissue, and have been associated with adverse reproductive outcomes in epidemiologic studies; however, few studies have examined the relationship between blood metal levels and reproductive hormones.Methods: Among 252 premenopausal women aged 18-44 years, we examined the association between blood metal levels (cadmium, lead and mercury), cycle length, and reproductive hormones [FSH, LH, estradiol (E(2)) and progesterone] measured at clinically relevant time points in the menstrual cycle. The association between metal levels (continuous) and hormone levels was assessed using linear regression with hormone levels (natural) log transformed and the results interpreted as the percentage difference in hormone level per unit increase in metal level.Results: Median (interquartile range) cadmium, lead and mercury levels were 0.30 µg/l (0.19, 0.43), 0.87 µg/dl (0.68, 1.20) and 1.10 µg/l (0.58, 2.10), respectively. Each 1 µg/l increase in cadmium levels was associated with a 21% [95% confidence interval (CI): -2.9, 49.9] increase in early follicular phase E(2) levels after adjusting for age, race/ethnicity, lead and mercury. This association decreased when restricted to never smokers (10%; 95% CI: -19.5, 51.3). Cadmium was also associated with a non-significant 9% (95% CI: -0.2, 19.9), or 2.7 day, increase in cycle length among never smokers. No associations were observed between lead or mercury and the outcomes in adjusted analyses.Conclusions: Further evaluation of the association between cadmium, E(2) and cycle length is warranted, taking into consideration cigarette smoke and its multiple components. [ABSTRACT FROM AUTHOR]

The purpose of the study was to test the hypothesis that the reduction in fractures with hormone therapy (HT) is greater in women with lower estradiol levels. We conducted a nested case–control study within the Women's Health Initiative HT Trials. The sample included 231 hip fracture case–control pairs and a random sample of 519 all fracture case–control pairs. Cases and controls were matched for age, ethnicity, randomization date, fracture history, and hysterectomy status. Hormones were measured prior to randomization. Incident cases of fracture were identified over an average follow-up of 6.53 years. There was no evidence that the effect of HT on fracture differed by baseline estradiol (E2) or sex hormone binding globulin (SHBG). Across all quartiles of E2 and SHBG, women randomized to HT had about a 50% lower risk of fracture, including hip fracture, compared to placebo. The effect of HT on fracture reduction is independent of estradiol and SHBG levels. [ABSTRACT FROM AUTHOR]

Background: Calcium and vitamin D (CaD) supplementation trials including the Women's Health Initiative (WHI) trial of CaD have shown nonsignificant reductions in total mortality. This report examines intervention effects on total and cause-specific mortality by age and adherence.Methods: The WHI CaD trial was a randomized, double-blind, placebo-controlled trial that enrolled 36,282 postmenopausal women aged 51-82 years from 40 U.S. clinical centers. Women were assigned to 1,000 mg of elemental calcium carbonate and 400 IU of vitamin D(3) daily or placebo with average follow-up of 7.0 years.Results: The hazard ratio (HR) for total mortality was 0.91 (95% confidence interval [CI], 0.83-1.01) with 744 deaths in women randomized to CaD versus 807 deaths in the placebo group. HRs were in the direction of reduced risk but nonsignificant for stroke and cancer mortality, but near unity for coronary heart disease and other causes of death. HRs for total mortality were 0.89 in the 29,942 women younger than 70 years (95% CI, 0.79-1.01) and 0.95 in the 6,340 women aged 70 and older (95% CI, 0.80-1.12; p value for age interaction = .10). No statistically significant interactions were observed for any baseline characteristics. Treatment effects did not vary significantly by season.Conclusions: In the WHI CaD trial, supplementation did not have a statistically significant effect on mortality rates but the findings support the possibility that these supplements may reduce mortality rates in postmenopausal women. These data can neither support nor refute recommendations for higher dose vitamin D supplementation to reduce cancer or total mortality. [ABSTRACT FROM AUTHOR]

The authors analyzed data from the Women's Health Initiative (WHI) Calcium and Vitamin D Supplementation Trial (CaD) to learn more about factors affecting adherence to clinical trial study pills (both active and placebo). Most participants (36,282 postmenopausal women aged 50-79 years) enrolled in CaD 1 year after joining either a hormone trial or the dietary modification trial of WHI. The WHI researchers measured adherence to study pills by weighing the amount of remaining pills at an annual study visit; adherence was primarily defined as taking &nvge; 80% of the pills. The authors in this study examined a number of behavioral, demographic, procedural, and treatment variables for association with study pill adherence. They found that relatively simple procedures (ie, phone contact early in the study [4 weeks post randomization] and direct social contact) later in the trial may improve adherence. Also, at baseline, past pill-use experiences, personal supplement use, and relevant symptoms may be predictive of adherence in a supplement trial. [ABSTRACT FROM AUTHOR]

Planning study visits during specific menstrual cycle phases is important if the exposure or outcome is influenced by hormonal variation. However, hormone profiles differ across cycles and across women. The value of using fertility monitors to time clinic visits was evaluated in the BioCycle Study (2005-2007). Women aged 18-44 years (mean, 27.4) with self-reported menstrual cycle lengths of 21-35 days were recruited in Buffalo, New York, for 2 cycles (n = 250). Participants were provided with home fertility monitors that measured urinary estrone-3-glucuronide and luteinizing hormone (LH). The women were instructed to visit the clinic for a blood draw when the monitor indicated an LH surge. The monitor recorded a surge during 76% of the first cycles and 78% of the second cycles. Scheduling visits by using set cycle days or algorithms based on cycle length, such as a midcycle window or a window determined by assuming a fixed luteal phase length, would be simpler. However, even with perfect attendance in a 3-day window, these methods would have performed poorly, capturing the monitor-detected LH surge only 37%-57% of the time. Fertility monitors appear to be useful in timing clinic visits in a compliant population with flexible schedules. [ABSTRACT FROM AUTHOR]

Studies have suggested that oral bone loss is independently influenced by local and systemic factors, including osteoporosis. This cross-sectional study of 1256 post-menopausal women, recruited from the Buffalo center of the Women's Health Initiative Observational Study, evaluated the influence of oral infection and age on the associations between osteoporosis and oral bone loss. Systemic bone density was measured by dual-energy x-ray absorptiometry. Alveolar crestal height was measured from standardized dental radiographs. Oral infection was assessed from subgingival plaque samples. Total forearm density [β (SE) = -0.931 (0.447), p = 0.038] and presence of Tannerella forsythensis [β (SE) = 0.125 (0.051), p = 0.015] were independently associated with mean alveolar height among women aged < 70 years after confounder adjustment. Women aged 70+ years had worse oral bone loss, in general, but neither bone density nor oral infection was significantly associated with mean alveolar height in this age group. Systemic bone density and oral infection independently influenced oral bone loss in post-menopausal women aged < 70 years. [ABSTRACT FROM AUTHOR]

Observational research on postmenopausal hormone therapy suggests a 40-50% reduction in coronary heart disease incidence among women using these preparations. In contrast, the Women's Health Initiative clinical trial of estrogen plus progestin found an elevated incidence over a 5.6-year intervention period through July 7, 2002. Toward explaining this discrepancy, the authors analyzed data from this trial, which included 16,608 postmenopausal women aged 50-79 years, and corresponding data from 53,054 women in the Women's Health Initiative observational study, 33% of whom were estrogen-plus-progestin users at baseline. Estrogen-plus-progestin hazard ratio estimates for coronary heart disease, stroke, and venous thromboembolism in the observational study were 39-48% lower than those in the clinical trial following age adjustment. However, hazard ratios tended to decrease with increasing time from initiation of estrogen-plus-progestin use, and observational study hazard ratio estimates are heavily weighted by longer-term use while clinical trial hazard ratio estimates reflect shorter-term use. Following control for time from estrogen-plus-progestin initiation and confounding, hazard ratio estimates were rather similar for the two cohorts, although there was evidence of some remaining difference for stroke. These analyses have implications for both the design and the analysis of observational studies. [ABSTRACT FROM AUTHOR]

BACKGROUND: Antioxidant defenses are one possible mechanism for decreasing oxidative damage and its potentially negative effects on age-related bone mass. OBJECTIVE: This study cross-sectionally examined whether higher dietary intakes, total intakes, and serum concentrations of antioxidants may be associated with higher bone mineral density (BMD). DESIGN: Total hip (and subregions), spine, and total-body BMDs were measured in 11 068 women aged 50-79 y enrolled in the Women's Health Initiative Observational Study and Clinical Trial at 3 clinics. Antioxidant intakes from diet (vitamin A, retinol, beta-carotene, vitamin C, vitamin E, and selenium) were estimated by using a self-reported food-frequency questionnaire. Antioxidants from supplements were estimated with an interviewer-administered questionnaire. A random subset (n = 379) had serum concentrations of retinol, carotenoids, and tocopherols measured. RESULTS: After adjustment for important BMD-related covariates, increasing intakes of antioxidants were not independently associated with BMD. A significant interaction effect was observed between intake of total vitamin C (lower three-fourths compared with highest one-fourth) and use of hormone therapy (HT) (P < 0.01). The beneficial effect of current HT use on femoral neck BMD appeared to be greater in women with higher concentrations of total vitamin C. This interaction was also significant for total-body (P < 0.045), spine (P = 0.03), and total-hip BMDs (P = 0.029). CONCLUSIONS: Our results do not support independent associations between dietary intake, total intake, or serum concentrations of antioxidants and BMD in women participating in the Women's Health Initiative. The extent to which HT use may interact with vitamin C intake and BMD warrants further exploration. Copyright © 2005 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

Background: Systemic bone loss has been proposed as a risk factor for periodontal disease; however, the relationship between these two diseases is still not clear. The objective of this study was to assess the relationship between systemic bone mineral density and periodontal disease, controlling for known confounders. Methods: The study population included 70 postmenopausal Caucasian women aged 51 to 78 (mean +/- SD: 62.10 +/- 7.1 years). Skeletal bone mineral density (BMD) was assessed by dual energy x-ray absorptiometry (DXA) at the neck, trochanter, intertrochanter, Ward's triangle, and total regions of the femur, and from the anterior-posterior view of the lumbar spine. Periodontal disease severity was represented by clinical attachment loss (CAL) and interproximal alveolar bone loss (ABL). Other measures of periodontal status included probing depth (PD), supragingival plaque, gingival bleeding on probing, and calculus. DXA and oral examinations were performed by calibrated examiners. Partial correlation coefficients (r) were obtained from multiple linear regression analysis adjusting for age, age at menopause, estrogen supplementation, cigarette smoking, body mass index, and supragingival plaque. Results: Mean ABL was significantly correlated with BMD of the trochanter (r =- 0.27), Ward's triangle (r = -0.26), and total regions of the femur (r = -0.25). Mean CAL appeared to be related to BMD consistently at all regions of the skeleton, although the association did not reach statistical significance. Conclusions: We can conclude that skeletal BMD is related to interproximal alveolar bone loss and, to a lesser extent, to clinical attachment loss, implicating postmenopausal osteopenia as a risk indicator for periodontal disease in postmenopausal Caucasian women. [ABSTRACT FROM AUTHOR]

The impact of the findings from the Women's Health Initiative trial of estrogen plus progestin cannot be attributed to any real or imagined conflicts of interest between government, researchers, and journals. Rather, the findings overturned decades of dogma in part promoted by the pharmaceutical industry, and the reaction to these unexpected findings was in direct proportion to their importance in reversing a misguided practice of prescribing the drug for chronic disease prevention. The findings have been widely accepted, as shown by the sustained subsequent reduction in prescriptions. However, conflicts of interest may influence a minority unwilling to accept the findings. The decrease in the use of a drug with an adverse risk profile for prevention of chronic disease is a public good. [ABSTRACT FROM AUTHOR]

Objective: To assess the associations between measures of adiposity and sex hormone- binding globulin (SHBG) and to evaluate whether such associations differ by race.Research Design and Methods: Adiposity was measured by anthropometry and dual-energy X-ray absorptiometry among women (146 white, 50 black, and 25 Asian) aged 18-44 years in the BioCycle study. SHBG was repeatedly measured over one to two menstrual cycles. The ratio of trunkal to leg fat (T/L) was used to assess upper to lower body adiposity.Results: Among whites, all adiposity measures were significantly and inversely associated with SHBG. Among blacks, BMI (β = -0.032), waist circumference (β = -0.016), and T/L (β = -0.033) were significantly associated with SHBG, whereas total and trunkal fat were not (P interaction with race <0.04). Among Asians, measures of central and upper body fat were significantly associated with SHBG (e.g., T/L, β = -0.84) but not BMI.Conclusions: Associations between SHBG and adiposity differ by race among premenopausal women. [ABSTRACT FROM AUTHOR]

A longitudinal case–control study was performed to measure the association of salivary biomarkers with alveolar bone loss from a sub-sample of 1,256 post-menopausal women enrolled in the Buffalo Women's Health Initiative. From this cohort, 40 subjects with significant alveolar bone loss over a 5-year period were compared to 40 age-matched control subjects having no alveolar bone loss. Several biomarkers were quantitated in saliva collected at baseline by immunoassay. A positive association was noted between alveolar bone loss and salivary concentrations of hepatocyte growth factor, and interleukin-1 beta, while a negative association was noted for alveolar bone loss and salivary osteonectin. This study provides preliminary evidence that several salivary biomarkers measured at baseline may serve to predict future alveolar bone loss. [ABSTRACT FROM AUTHOR]