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Although minerals are linked to several reproductive outcomes, it is unknown whether dietary minerals are associated with ovulatory function. We hypothesised that low intakes of minerals would be associated with an increased risk of anovulation. We investigated associations between dietary mineral intake and both reproductive hormones and anovulation in healthy women in the BioCycle Study, which prospectively followed up 259 regularly menstruating women aged 18-44 years who were not taking mineral supplements for two menstrual cycles. Intakes of ten selected minerals were assessed through 24-h dietary recalls at up to four times per cycle in each participant. Oestradiol, progesterone, luteinising hormone (LH), follicle-stimulating hormone (FSH), sex-hormone-binding globulin and testosterone were measured in serum up to eight times per cycle. We used weighted linear mixed models to evaluate associations between minerals and hormones and generalised linear models for risk of anovulation. Compared with Na intake ≥1500 mg, Na intake <1500 mg was associated with higher levels of FSH (21·3 %; 95 % CI 7·5, 36·9) and LH (36·8 %; 95 % CI 16·5, 60·5) and lower levels of progesterone (-36·9 %; 95 % CI -56·5, -8·5). Na intake <1500 mg (risk ratio (RR) 2·70; 95 % CI 1·00, 7·31) and Mn intake <1·8 mg (RR 2·00; 95 % CI 1·02, 3·94) were associated with an increased risk of anovulation, compared with higher intakes, respectively. Other measured dietary minerals were not associated with ovulatory function. As essential minerals are mostly obtained via diet, our results comparing insufficient levels with sufficient levels highlight the need for future research on dietary nutrients and their associations with ovulatory cycles.

Study Objectives: Night shift work is associated with increased breast cancer risk, possibly from altered sleep. Epidemiologic evidence is sparse regarding sleep disturbances and breast cancer tumor markers. We examined sleep disturbance in association with breast tumor aggressiveness and mortality following diagnosis., Methods: We analyzed associations of measures of sleep disturbance in a sample of 1,122 incident breast cancer cases from the Western New York Exposures and Breast Cancer (WEB) Study. Sleep disturbance was assessed using self-administered questionnaires; responses about difficulty falling asleep, waking up frequently, having trouble staying asleep, and waking up feeling tired and worn out were used to create a summary sleep disturbance score. We used general linear models to examine associations of sleep disturbance with markers of tumor aggressiveness among cases: estrogen receptor (ER) status, progesterone receptor (PR) status, and human epidermal growth factor receptor-2 (HER2) status; tumor size, stage, grade, lymph node involvement, and presence of metastasis. In addition, we examined the association between sleep disturbance and survival using Cox regression., Results: Among breast cancer cases, sleep disturbance was higher for women with ER- / PR- tumors compared to women with ER+ / PR+ tumors, even after adjusting for potential covariates ( P for trend = .02). Results suggest that the association of sleep quality differs by menopausal status, where mild sleep disturbance is associated with higher breast cancer mortality in premenopausal women; however, we had a relatively small sample size., Conclusions: Sleep disturbance may be associated with aggressive subtypes of breast cancer; however, further studies are needed., (© 2018 American Academy of Sleep Medicine)

Background: Although habitual low-to-moderate alcohol intake has been linked with reduced all-cause mortality and morbidity, the effect of recent alcohol intake on female reproductive function has not been clearly established., Objective: We assessed the relation between acute alcohol consumption, reproductive hormones, and markers of menstrual cycle dysfunction including sporadic anovulation, irregular cycle length, luteal phase deficiency, long menses, and heavy blood loss., Design: A total of 259 healthy, premenopausal women from Western New York were followed for ≤2 menstrual cycles (2005-2007) and provided fasting blood specimens during ≤8 visits/cycle and four 24-h dietary recalls/cycle. Linear mixed models were used to estimate associations between previous day's alcohol intake and hormone concentrations, whereas Poisson regression was used to assess RR of cycle-average alcohol intake and menstrual cycle function., Results: For every alcoholic drink consumed, the geometric mean total and free estradiol, total and free testosterone, and luteinizing hormone were higher by 5.26% (95% CI: 1.27%, 9.41%), 5.82% (95% CI: 1.81%, 9.99%), 1.56% (95% CI: 0.23%, 2.90%), 1.42% (95% CI: 0.02%, 2.84%), and 6.18% (95% CI: 2.02%, 10.52%), respectively, after adjustment for age, race, percentage of body fat, perceived stress, pain-medication use, sexual activity, caffeine, and sleep. Binge compared with nonbinge drinking (defined as reporting ≥4 compared with <4 drinks/d, respectively) was associated with 64.35% (95% CI: 18.09%, 128.71%) and 63.53% (95% CI: 17.41%, 127.73%) higher total and free estradiol. No statistically significant associations were shown between cycle-average alcohol intake and menstrual cycle function., Conclusion: Although recent moderate alcohol intake does not appear to have adverse short-term effects on menstrual cycle function, including sporadic anovulation, potential protective and deleterious long-term effects of alterations in reproductive hormones on other chronic diseases warrant additional investigation., (© 2015 American Society for Nutrition.)

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, -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., (Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Objective: To compare previously used algorithms to identify anovulatory menstrual cycles in women self-reporting regular menses., Design: Prospective cohort study., Setting: Western New York., Patient(s): Two hundred fifty-nine healthy, regularly menstruating women followed for one (n=9) or two (n=250) menstrual cycles (2005-2007)., Intervention(s): None., Main Outcome Measure(s): Prevalence of sporadic anovulatory cycles identified using 11 previously defined algorithms that use E2, P, and LH concentrations., Result(s): Algorithms based on serum LH, E2, and P levels detected a prevalence of anovulation across the study period of 5.5%-12.8% (concordant classification for 91.7%-97.4% of cycles). The prevalence of anovulatory cycles varied from 3.4% to 18.6% using algorithms based on urinary LH alone or with the primary E2 metabolite, estrone-3-glucuronide, levels., Conclusion(s): The prevalence of anovulatory cycles among healthy women varied by algorithm. Mid-cycle LH surge urine-based algorithms used in over-the-counter fertility monitors tended to classify a higher proportion of anovulatory cycles compared with luteal-phase P serum-based algorithms. Our study demonstrates that algorithms based on the LH surge, or in conjunction with estrone-3-glucuronide, potentially estimate a higher percentage of anovulatory episodes. Addition of measurements of postovulatory serum P or urine pregnanediol may aid in detecting ovulation., (Published by Elsevier Inc.)

Background: This study examines the accuracy of self-reported periodontal disease in a cohort of older females., Methods: The study comprised 972 postmenopausal females aged 53 to 83 years who completed baseline (1997 to 2001) and follow-up (2002 to 2006) whole-mouth oral examinations. Examinations included: 1) probing depth, 2) clinical attachment level, and 3) oral radiographs for alveolar crestal height in a study ancillary to the Women's Health Initiative Observational Study (WHI-OS) conducted in Buffalo, New York, called the OsteoPerio study. Participants also self-reported any history of diagnosis of periodontal/gum disease on a WHI-OS study-wide questionnaire administered during the time interval between the two OsteoPerio examinations., Results: Participants reporting diagnosis of periodontal/gum disease on the WHI-OS questionnaire (n = 259; 26.6%) had worse oral hygiene habits, periodontal disease risk factors, and clinical periodontal measures compared with those not reporting periodontal/gum disease. Frequency of reported periodontal/gum disease was 13.5%, 24.7%, and 56.2% across OsteoPerio baseline examination categories of none/mild, moderate, and severe periodontal disease, respectively (trend: P <0.001), defined by criteria of the Centers for Disease Control and Prevention/American Academy of Periodontology (CDC/AAP). Sensitivity, specificity, and positive and negative predictive values for reported periodontal disease status were 56.2%, 78.8%, 32.8%, and 90.7%, respectively, when CDC/AAP-defined severe periodontal disease at baseline was the criterion measure (prevalence of 15%) and were 76.0%, 77.4%, 22.0%, and 97.4%, respectively, when tooth loss to periodontitis (prevalence of 7%) was the criterion., Conclusion: A simple question for self-reported periodontal disease characterizes periodontal disease prevalence with moderate accuracy in postmenopausal females who regularly visit their dentist, particularly in those with more severe disease.

Background: The activity of paraoxonase 1 (PON1), an antioxidant enzyme whose polymorphisms have been associated with cancer risk, may be associated with metals exposure., Objective: To evaluate PON1 activity in relation to cadmium, lead, and mercury levels in healthy, premenopausal women., Methods: Women from upstate New York were followed for ≥ two menstrual cycles. Repeated measures linear mixed models estimated the association between cadmium, lead, and mercury levels (by tertile: T1, T2, T3) and PON1 arylesterase (PON1A) and PON1 paraoxonase (PON1P) activity, separately. Analyses were stratified by PON1 Q192R phenotype and un-stratified., Results: Median blood cadmium, lead, and mercury concentrations were 0.30 µg/L, 0.87 µg/dL, and 1.15 µg/L. In un-stratified analyses cadmium and mercury were associated with decreased PON1A activity (T2 vs. T1; not T3 vs. T1) but metals were not associated with PON1P. Phenotypes were distributed between QQ (n = 99), QR (n = 117), and RR (n = 34). Cadmium was associated with decreased PON1A activity for QR and RR phenotypes comparing T2 vs. T1 (-14.4% 95% confidence interval [CI] [-20.1, -8.4] and -27.9% [-39.5, -14.0],). Lead was associated with decreased PON1A (RR phenotype, T3 vs. T1 -18.9% [-32.5, -2.5]; T2 vs. T1 -19.6% [-32.4, -4.4]). Cadmium was associated with lower PON1P comparing T2 vs. T1 for the RR (-34.9% [-51.5, -12.5]) and QR phenotypes (-9.5% [-18.1, 0.0]) but not comparing T3 vs. T1. Cadmium was associated with increases in PON1P levels (QQ phenotype, T3 vs. T1 24.5% [7.0, 44.9]) and mercury was associated with increased PON1A levels (QQ phenotype, T3 vs. T1 6.2% [0.2, 12.6]). Mercury was associated with decreased PON1P (RR phenotype, T2 vs. T1 -22.8 [-37.8, -4.1])., Conclusion: Blood metals were associated with PON1 activity and these effects varied by phenotype. However, there was not a linear dose-response and these findings await replication.

Purpose: To evaluate the association between physical activity (PA) across the menstrual cycle and reproductive function., Methods: The BioCycle Study (2005-2007) followed 259 healthy premenopausal women not using hormonal contraceptives for up to two menstrual cycles (N = 509 cycles). Serum leptin, estradiol, progesterone, luteinizing hormone, follicle-stimulating hormone, and testosterone were measured five to eight times per cycle. Linear mixed models were used to estimate the effect of past-week PA (measured four times during each cycle) on hormone levels. Past-week PA was categorized into tertiles based on metabolic equivalent of task hours per week (cut-points were 15.3 and 35.7). Risk ratios for sporadic anovulation were estimated using generalized linear models. Analyses adjusted for habitual PA (assessed at baseline), body mass index, race, age, and perceived stress. Linear mixed models used inverse probability weights to control for concurrent reproductive hormones and caloric intake., Results: High past-week PA was inversely associated with leptin (-6.6%; 95% confidence interval, -10.6 to -2.5) and luteal phase progesterone (-22.1%; -36.2 to -4.7) as compared with low past-week PA. High past-week PA was not significantly associated with sporadic anovulation (adjusted risk ratio, 1.5; 0.6 to 3.4)., Conclusions: High levels of PA were modestly associated with changes in select hormones but not sporadic anovulation among moderate to highly active premenopausal women., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: To assess the association of total isoflavone intake with ovulatory function, including sporadic anovulation in healthy premenopausal women., Design: Prospective cohort study., Setting: University., Patient(s): Participants included 259 healthy regularly menstruating women aged 18-44 years., Intervention(s): None., Main Outcome Measure(s): Serum concentrations of E2, free E2, P, LH, FSH, and SHBG and sporadic anovulation in healthy premenopausal women., Result(s): Isoflavone intake was not associated with E2, free E2, P, LH, and FSH concentrations. Consumption in the highest quartile (Q4: 1.6-78.8 mg/d) was significantly associated with greater SHBG concentrations (β = 0.09; 95% confidence interval [CI] 0.02-0.16), compared with the first quartile (Q1: 0.0-0.3 mg/d)., Conclusion(s): Isoflavone intake was not associated with sporadic anovulation (Q4 vs. Q1: odds ratio 0.87, 95% CI 0.32-1.66). Dietary isoflavone intake among young premenopausal women was not related to sex hormone concentrations or anovulation, but was associated with minimally increased SHBG concentrations. These results suggest potential endocrine effects with no subsequent effects on ovulation, easing concerns regarding their impacts on fertility., (Published by Elsevier Inc.)

Background: Understanding of longitudinal characteristics of periodontal disease in older females is limited. This study examined 5-year changes in periodontal disease measures among postmenopausal females., Methods: Participants were 1,025 postmenopausal, 53- to 83-year-old females who completed baseline (1997 to 2001) and 5-year follow-up (2002 to 2006) whole-mouth oral examinations in a study ancillary to the Women's Health Initiative. Periodontal disease was characterized using probing depth (PD), clinical attachment level (CAL), alveolar crest height (ACH), and tooth loss. Differences in measures between examinations were used to characterize patterns of change., Results: Baseline prevalence of none/mild, moderate, and severe periodontal disease defined using criteria of the Centers for Disease Control and Prevention was 27%, 58%, and 15%, respectively. Tooth loss attributable to periodontitis occurred in 13% of females. Mean ± SD changes in whole-mouth mean measures showed progression when based on ACH (-0.19 ± 0.49 mm) yet relatively stable disease when based on PD (0.11 ± 0.42 mm) and CAL (0.06 ± 0.58 mm). Mean change in worst-site ACH was greater (P <0.001) in females with severe periodontitis and osteoporosis at baseline and with tooth loss during follow-up. Periodontal changes did not differ according to baseline age, hormone therapy use, smoking status, or age at menopause., Conclusions: Five-year changes in periodontal measures among generally healthy postmenopausal females were, on average, small and did not suggest a consistent pattern of disease progression. Females with history of severe periodontitis or osteoporosis may experience accelerated oral bone loss despite stability or small improvement in routine probing measures.

Reproductive hormone levels are highly variable among premenopausal women during the menstrual cycle. Accurate timing of hormone measurement is essential, especially when investigating day- or phase-specific effects. The BioCycle Study used daily urine home fertility monitors to help detect the luteinising hormone (LH) surge in order to schedule visits with biologically relevant windows of hormonal variability. However, as the LH surge is brief and cycles vary in length, relevant hormonal changes may not align with scheduled visits even when fertility monitors are used. Using monitor data, measurements were reclassified according to biological phase of the menstrual cycle to more accurate cycle phase categories. Longitudinal multiple imputation methods were applied after reclassification if no visit occurred during a given menstrual cycle phase. Reclassified cycles had more clearly defined hormonal profiles, with higher mean peak hormones (up to 141%) and reduced variability (up to 71%). We demonstrate the importance of realigning visits to biologically relevant windows when assessing phase- or day-specific effects and the feasibility of applying longitudinal multiple imputation methods. Our method has applications in settings where missing data may occur over time, where daily blood sampling for hormonal measurements is not feasible, and in other areas where timing is essential., (Published 2011. This article is a US Government work and is in the public domain in the USA.)

Introduction: Habitual energy expenditure seems to favorably alter oxidant/antioxidant balance. Sparse evidence suggests that hormones that fluctuate during the menstrual cycle, particularly estrogens, may influence concentrations of oxidative biomarkers and their relation to energy expenditure., Methods: We investigated the relation between energy expenditure and plasma free F2-isoprostane concentrations in 259 healthy, regularly menstruating 18- to 44-yr-old participants of the BioCycle Study. Habitual energy expenditure was measured using a baseline International Physical Activity Questionnaire and categorized as low, moderate, or high. Women were followed for one or two subsequent menstrual cycles. Past-week and past-day physical activity were measured during follow-up using questionnaires and diaries, respectively. F2-isoprostane concentrations were measured in blood samples collected at both menses (approximate cycle day 2; low serum estradiol concentration) and the late follicular phase (approximate cycle day 12; peak estradiol concentration). Generalized estimating equations were used to model the energy expenditure/isoprostane association, adjusting for confounders., Results: Habitual energy expenditure was positively associated with F2-isoprostane concentration (adjusted difference in median F2-isoprostane, high versus low energy expenditure: 17.4%; 95% confidence interval (CI)=3.3%-31.4%). This association was not modified by cycle phase (interaction, P=0.61) or differences in peak estradiol concentration across women (interaction, P=0.20). Past-week and past-day physical activity measures were not associated with F2-isoprostane concentration (category trend, P=0.50 and P=0.18, respectively)., Conclusions: These results suggest that higher habitual energy expenditure may be associated with higher concentration of F2-isoprostanes in healthy, reproductive-aged women. Estradiol concentration changes during the menstrual cycle do not seem to influence this relationship., (© 2011 by the American College of Sports Medicine)

Unlabelled:  , Objective: While risk factors for tooth loss in adults have been identified, limited studies describing factors associated with incident tooth loss in postmenopausal women exist. This study assessed both clinical and non-clinical risk factors for incident tooth loss., Methods: Postmenopausal women (N = 1341) were recruited between 1997 and 2000 from 1847 eligible Observational Study participants of the Buffalo, NY center of the Women's Health Initiative who had complete dental examinations to assess alveolar bone height, soft tissue attachment and general oral health, and completed questionnaires concerning demographics, general health, lifestyle and oral health (72.6% participation rate). Five years later (2002-2005), 1021 women (76.1%) repeated these examinations and questionnaires. Incident tooth loss was determined by oral examination., Results: After an average 5.1 years of follow-up (SD, 0.38), a total of 323 teeth were lost in 293 women, resulting in 28.7% of women with incident loss of at least one tooth. In multivariable models, diabetes history, gum disease history, smoking, previous tooth loss, BMI and plaque index, baseline clinical measures including alveolar crestal height (ACH) (OR = 1.22 per mm loss, 95% CI 1.11, 1.35), clinical attachment loss (CAL) (OR = 1.13 per mm loss, 95% CI 1.05, 1.23), and pocket depth (PD) (OR = 1.26 per mm loss, 95% CI 1.13, 1.41) were significant risk factors of incident tooth loss. In a community model that included no clinical measures, diabetes history (OR = 2.45, 95% CI 1.26, 4.77), prior gum disease (OR = 1.97, 95% CI 1.43, 2.70), ever smoking (OR = 1.42, 95% CI 1.06, 1.89), number of teeth lost at baseline (OR = 1.05 per tooth, 95% CI 1.02, 1.08), and BMI (OR = 1.15 per 5 km/m(2) increase, 95% CI 1.01, 1.33) were associated with an increased risk of incident tooth loss., Conclusions: Clinical and questionnaire-based models were found to provide similar risk estimates for incident tooth loss in postmenopausal women. These models identified high-risk postmenopausal women where preventive strategies may be targeted., (© 2010 John Wiley & Sons A/S.)

The prevalence of osteoporosis and factors associated with treatment initiation after detection of osteoporosis were determined for previously unscreened, postmenopausal women. Dual-energy x-ray absorptiometry screening was conducted in 1997-2000 as part of an ancillary study of the Buffalo, New York, center of the Women's Health Initiative Observational Study. A total of 945 women were previously unaware of their bone density, although, for 344 (36.4%), osteoporosis was newly detected through screening (T-score /=$50,000 (OR = 2.06, 95% CI: 1.03, 4.14), and discussing screening results with a gynecologist (OR = 3.20, 95% CI: 1.33, 7.67). These findings suggest that many postmenopausal women are unaware of their bone density and could benefit from screening. In this study, approximately half of the women with osteoporosis initiated treatment after screening. Disease severity, medical care frequency, education, income, and physician type predicted treatment initiation.

Uterine leiomyomas are reported to be the most common benign gynecologic tumors affecting premenopausal women, and they are often associated with considerable morbidity. The purpose of this study was to identify risk factors for uterine fibroids among women undergoing tubal sterilization. Cases comprised women aged 17-44 years whose uterine fibroids were first visualized at the time of tubal sterilization (1978-1979 or 1985-1987) or who reported a history of uterine fibroids (n = 317). Controls were randomly selected from women with no laparoscopic evidence of or history of fibroids (n = 1,268). Adjusted odds ratios were estimated using unconditional logistic regression separately for White (n = 1,235) and African-American (n = 350) women. Risk factors for White women included: age 40-44 years (odds ratio (OR) = 6.3; 95% confidence interval (CI): 3.5, 11.6), > or =5 years since last delivery (OR = 1.9; 95% CI: 1.1, 3.1), lifetime cigarette smoking of > or =1 pack/day (OR = 1.6; 95% CI: 1.1, 2.3), menstrual cycle length of >30 days (OR = 1.6; 95% CI: 1.1, 3.3), and menstrual bleeding for > or =6 days (OR = 1.4; 95% CI: 1.0, 2.0). Parous women were at reduced risk compared with nulliparous women (OR = 0.2; 95% CI: 0.1, 0.3). Advancing age was the only significant risk factor for African-American women (ages 40-44 years, OR = 27.5; 95% CI: 5.6, 83.6). Current oral contraceptive use and elective abortion were not associated with fibroids.