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Background: Although the timing of menarche and menopause may be associated with cardiovascular disease (CVD), the entire reproductive life span has not been considered comprehensively as risk for CVD. We investigate the associations of reproductive life span duration and ages at menarche and menopause, induced by natural means or surgical bilateral oophorectomy, with incident CVD in women., Methods and Results: Prospective cohort study of 73 814 Nurses' Health Study following participants without CVD, defined as incident coronary heart disease or stroke, from 1980 through 2012. Duration of reproductive life span was generated by subtracting age at menarche from age at menopause. A shorter reproductive life span was associated with a higher risk of incident CVD after multivariable adjustment (relative risk, 1.32 [95% confidence interval, 1.16-1.49] comparing duration <30 with ≥42 years; P trend<0.0001). Early age at menopause was associated with higher multivariable-adjusted CVD risk (1.32 [1.16-1.51] comparing age <40 with 50 to <55 years; P trend<0.0001), with excess risk for both natural and surgical menopause. Compared with women with menarche at 13 years, the multivariable-adjusted CVD risk for early menarche at ≤10 years was 1.22 (1.09-1.36). The association between reproductive life span and CVD remained significant in sensitivity analyses excluding women who experienced extreme early age at menarche or who used hormone therapy., Conclusions: A shorter duration of reproductive life span is associated with a higher risk of CVD, which is likely driven by the timing of menopause induced either naturally or surgically. Extremely early age at menarche is also associated with a higher risk of CVD., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

To examine the association between urinary excretion of isoflavonoids and risk of type 2 diabetes (T2D), we conducted a nested case-control study among 1111 T2D pairs identified during 1995-2008 in the Nurses' Health Study (NHS) and NHSII, who were free of diabetes, CVD and cancer at urine sample collection. Urinary excretion of daidzein and genistein, as well as their metabolites O-desmethylangolensin (O-DMA), dihydrogenistein (DHGE) and dihydrodaidzein (DHDE) was assayed using liquid chromatography MS. Self-reported T2D incident cases were confirmed using a validated questionnaire. Higher urinary excretion of daidzein and genistein was associated with a lower risk of T2D in the combined cohorts. Comparing extreme tertiles of the urinary markers, the OR of T2D were 0·71 (95 % CI 0·55, 0·93) for daidzein and 0·74 (95 % CI 0·56, 0·97) for genistein, although the test for linear trend was not significant for genistein (P trend=0·03 and 0·15, respectively). DMA, DHDE and DHGE were non-significantly associated with a lower T2D risk. The inverse association of daidzein with T2D risk was stronger among post-menopausal women who did not use hormone replacement therapy (P interaction=0·001): the OR was 0·58 (95 % CI 0·34, 0·97) comparing extreme tertiles among these women. In conclusion, urinary excretion of isoflavones was associated with a lower T2D risk in US women, especially among post-menopausal women who did not use hormone. Further research is warranted to replicate these observations among western populations with similarly low overall isoflavone intake.

Purpose: To study the relation between type 2 diabetes mellitus (T2DM) and incident primary open-angle glaucoma (POAG) in women., Design: Prospective cohort analysis., Participants: Seventy-six thousand three hundred eighteen women enrolled in the Nurses' Health Study (NHS)., Methods: Women enrolled in the NHS from 1980 to 2000 were observed. Eligible participants were at least 40 years old, did not have POAG at baseline, and reported receiving eye examinations during follow-up. Potential confounders were assessed on biennial questionnaires, and a diagnosis of T2DM was confirmed on a validated supplemental questionnaire. During follow-up, 429 self-reported POAG cases confirmed by medical chart review were identified., Main Outcome Measures: Multivariable rate ratios (RRs) of POAG and associated 95% confidence intervals (CIs) obtained from proportional hazards models., Results: After controlling for age, race, hypertension, body mass index, physical activity, alcohol intake, smoking, and family history of glaucoma, T2DM was positively associated with POAG (RR = 1.82 [95% CI = 1.23-2.70]). Nonetheless, the association did not strengthen with longer duration of diabetes: RR = 2.24 (95% CI = 1.31-3.84) for duration < 5 years versus RR = 1.54 (95% CI = 0.90-2.62) for duration > or = 5 years). In secondary analyses, to evaluate the potential for detection bias we controlled for additional factors such as the number of eye examinations, but T2DM remained positively associated with POAG., Conclusion: Type 2 diabetes mellitus is associated with an increased risk of POAG in women.

The relationship between various diet quality indices and risk of type 2 diabetes (T2D) remains unsettled. We compared associations of 4 diet quality indices--the Alternate Mediterranean Diet Index, Healthy Eating Index 2010, Alternate Healthy Eating Index 2010, and the Dietary Approaches to Stop Hypertension (DASH) Index--with reported T2D in the Women's Health Initiative, overall, by race/ethnicity, and with/without adjustment for overweight/obesity at enrollment (a potential mediator). This cohort (n = 101,504) included postmenopausal women without T2D who completed a baseline food frequency questionnaire from which the 4 diet quality index scores were derived. Higher scores on the indices indicated a better diet. Cox regression was used to estimate multivariate hazard ratios for T2D. Pearson coefficients for correlation among the indices ranged from 0.55 to 0.74. Follow-up took place from 1993 to 2013. During a median 15 years of follow-up, 10,815 incident cases of T2D occurred. For each diet quality index, a 1-standard-deviation higher score was associated with 10%-14% lower T2D risk (P < 0.001). Adjusting for overweight/obesity at enrollment attenuated but did not eliminate associations to 5%-10% lower risk per 1-standard-deviation higher score (P < 0.001). For all 4 dietary indices examined, higher scores were inversely associated with T2D overall and across racial/ethnic groups. Multiple forms of a healthful diet were inversely associated with T2D in these postmenopausal women.

BackgroundThe Breast Cancer Risk Assessment Tool (BCRAT, "Gail model") is commonly used for breast cancer prediction; however, it has not been validated for women age 75 years and older.MethodsWe used Nurses' Health Study (NHS) data beginning in 2004 and Women's Health Initiative (WHI) data beginning in 2005 to compare BCRAT's performance among women age 75 years and older with that in women age 55 to 74 years in predicting five-year breast cancer incidence. BCRAT risk factors include: age, race/ethnicity, age at menarche, age at first birth, family history, history of benign breast biopsy, and atypia. We examined BCRAT's calibration by age by comparing expected/observed (E/O) ratios of breast cancer incidence. We examined discrimination by computing c-statistics for the model by age. All statistical tests were two-sided.ResultsSeventy-three thousand seventy-two NHS and 97 081 WHI women participated. NHS participants were more likely to be non-Hispanic white (96.2% vs 84.7% in WHI, P < .001) and were less likely to develop breast cancer (1.8% vs 2.0%, P = .02). E/O ratios by age in NHS were 1.16 (95% confidence interval [CI] = 1.09 to 1.23, age 57-74 years) and 1.31 (95% CI = 1.18 to 1.45, age ≥ 75 years, P = .02), and in WHI 1.03 (95% CI = 0.97 to 1.09, age 55-74 years) and 1.10 (95% CI = 1.00 to 1.21, age ≥ 75 years, P = .21). E/O ratio 95% confidence intervals crossed one among women age 75 years and older when samples were limited to women who underwent mammography and were without significant illness. C-statistics ranged between 0.56 and 0.58 in both cohorts regardless of age.ConclusionsBCRAT accurately predicted breast cancer for women age 75 years and older who underwent mammography and were without significant illness but had modest discrimination. Models that consider individual competing risks of non-breast cancer death may improve breast cancer risk prediction for older women.

Background To support mammography screening decision making, we developed a competing-risk model to estimate 5-year breast cancer risk and 10-year nonbreast cancer death for women aged 55 years and older using Nurses' Health Study data and examined model performance in the Black Women's Health Study (BWHS). Here, we examine model performance in predicting 10-year outcomes in the BWHS, Women's Health Initiative-Extension Study (WHI-ES), and Multiethnic Cohort (MEC) and compare model performance to existing breast cancer prediction models. Methods We used competing-risk regression and Royston and Altman methods for validating survival models to calculate our model's calibration and discrimination (C index) in BWHS (n = 17 380), WHI-ES (n = 106 894), and MEC (n = 49 668). The Nurses' Health Study development cohort (n = 48 102) regression coefficients were applied to the validation cohorts. We compared our model's performance with breast cancer risk assessment tool (Gail) and International Breast Cancer Intervention Study (IBIS) models by computing breast cancer risk estimates and C statistics. Results When predicting 10-year breast cancer risk, our model's C index was 0.569 in BWHS, 0.572 in WHI-ES, and 0.576 in MEC. The Gail model's C statistic was 0.554 in BWHS, 0.564 in WHI-ES, and 0.551 in MEC; IBIS's C statistic was 0.547 in BWHS, 0.552 in WHI-ES, and 0.562 in MEC. The Gail model underpredicted breast cancer risk in WHI-ES; IBIS underpredicted breast cancer risk in WHI-ES and in MEC but overpredicted breast cancer risk in BWHS. Our model calibrated well. Our model's C index for predicting 10-year nonbreast cancer death was 0.760 in WHI-ES and 0.763 in MEC. Conclusions Our competing-risk model performs as well as existing breast cancer prediction models in diverse cohorts and predicts nonbreast cancer death. We are developing a website to disseminate our model. [ABSTRACT FROM AUTHOR]

Objective: This study was undertaken to examine the relationship between alcohol consumption and hip osteoarthritis in women. Alcohol has been associated with both adverse and beneficial health effects generally; however, the relationship between alcohol consumption and hip osteoarthritis has been minimally studied. Methods: Among women in the Nurses' Health Study cohort in the US, alcohol consumption was assessed every 4 years, starting in 1980. Intake was computed as cumulative averages and simple updates with latency periods of 0–4 through 20–24 years. We followed 83,383 women without diagnosed osteoarthritis in 1988 to June 2012. We identified 1,796 cases of total hip replacement due to hip osteoarthritis defined by self‐report of osteoarthritis with hip replacement. Results: Alcohol consumption was positively associated with hip osteoarthritis risk. Compared with nondrinkers, multivariable hazard ratios (HRs) and 95% confidence intervals (95% CIs) were HR 1.04 (95% CI 0.90, 1.19) for drinkers of >0 to <5 grams/day, HR 1.12 (95% CI 0.94, 1.33) for 5 to <10 grams/day, HR 1.31 (95% CI 1.10, 1.56) for 10 to <20 grams/day, and HR 1.34 (95% CI 1.09, 1.64) for ≥20 grams/day (P for trend < 0.0001). This association held in latency analyses of up to 16–20 years, and for alcohol consumption between 35–40 years of age. Independent of other alcoholic beverages, the multivariable HRs (per 10 grams of alcohol) were similar for individual types of alcohol intake (wine, liquor, and beer; P = 0.57 for heterogeneity among alcohol types). Conclusion: Higher alcohol consumption was associated with greater incidence of total hip replacement due to hip osteoarthritis in a dose‐dependent manner in women. [ABSTRACT FROM AUTHOR]

Adiposity has been associated with several health conditions as well as timing of menopause. Prior epidemiologic studies on the association of adiposity and anti-Müllerian hormone (AMH) have been inconsistent. We evaluated the relations of anthropometric measures with AMH at two time periods in a subset of premenopausal participants in the Nurses' Health Study II. This prospective study included 795 women who provided a premenopausal sample in 1996–1999 and in 2010–2012. Current weight and height, and weight at age 18 were assessed in 1989 and weight again in 1996–1999. Waist and hip circumference were measured and reported in 1993. In linear regression models adjusted for smoking, reproductive events, and other factors, AMH was inversely related to BMI at age 18 (P =.03) and in 1996–1999 (P <.0001). Higher waist circumference was related to lower AMH levels in 1996–1999 (p =.0009). BMI in 1996–1999 was inversely associated with AMH levels in 2010–2012 (P =.005). Weight gain between age 18 and 1996–1999 was strongly inversely associated with AMH levels in 1996–1999 (P <.0001) and in 2010–2012 (P <.0001). Our results indicate that adiposity and weight gain are associated with lower AMH levels, suggesting an adverse impact on ovarian function. [ABSTRACT FROM AUTHOR]

Background Diet is one of the modifiable risk factors for cognitive decline. However, studies on dietary protein intake and cognitive decline have remained limited and inconclusive. Objectives In this study, we aimed to investigate the associations between long-term dietary protein intake and subsequent subjective cognitive decline (SCD). Methods We included 49,493 women from the Nurses' Health Study (NHS) (1984–2006) and 27,842 men from the Health Professionals Follow-up Study (HPFS) (1986–2002). For the NHS, average dietary intake was calculated from 7 repeated semi-quantitative FFQs (SFFQs), and SCD was assessed in 2012 and 2014. For the HPFS, average dietary intake was calculated from 5 repeated SFFQs, and SCD was assessed in 2008 and 2012. Poisson regression was used to examine the associations between dietary protein, amino acids, and various protein food sources with subsequent SCD. Results Higher protein intake compared with total carbohydrates was associated with lower odds of SCD. When substituting 5% energy from protein for the equivalent percentage of energy from total carbohydrates, the pooled multivariable-adjusted ORs (95% CIs) were 0.89 (0.85, 0.94) for total protein, 0.89 (0.84, 0.94) for animal protein, and 0.74 (0.62, 0.88) for plant protein. When substituting 5% of energy from animal protein with plant protein, the OR was 0.84 (95% CI: 0.72, 0.97). For protein food sources, higher intakes of beans/legumes, fish, and lean poultry were significantly associated with lower odds of SCD, but higher intake of hotdogs was associated with higher odds of SCD. Conclusions Higher protein intake was associated with lower odds of SCD when compared isocalorically with carbohydrate. Plant protein sources were also associated with lower odds when compared with animal protein sources. Our findings suggest that adequate protein intake, and choices of protein sources could play a role in the maintenance of cognition and should be studied further. [ABSTRACT FROM AUTHOR]

Background Carotenoids represent 1 of few modifiable factors to reduce breast cancer risk. Elucidation of interactions between circulating carotenoids and genetic predispositions or mammographic density (MD) may help inform more effective primary preventive strategies in high-risk populations. Objectives We tested whether women at high risk for breast cancer due to genetic predispositions or high MD would experience meaningful and greater risk reduction from higher circulating levels of carotenoids in a nested case-control study in the Nurses' Health Studies (NHS and NHSII). Methods This study included 1919 cases and 1695 controls in a nested case-control study in the NHS and NHSII. We assessed both multiplicative and additive interactions. RR reductions and 95% CIs were calculated using unconditional logistic regressions, adjusting for matching factors and breast cancer risk factors. Absolute risk reductions (ARR) were calculated based on Surveillance, Epidemiology, and End Results incidence rates. Results We showed that compared with women at low genetic risk or low MD, those with higher genetic risk scores or high MD had greater ARRs for breast cancer as circulating carotenoid levels increase (additive P -interaction = 0.05). Among women with a high polygenic risk score, those in the highest quartile of circulating carotenoids had a significant ARR (28.6%; 95% CI, 14.8–42.1%) compared to those in the lowest quartile of carotenoids. For women with a high percentage MD (≥50%), circulating carotenoids were associated with a 37.1% ARR (95% CI, 21.7–52.1%) when comparing the highest to the lowest quartiles of circulating carotenoids. Conclusions The inverse associations between circulating carotenoids and breast cancer risk appeared to be more pronounced in high-risk women, as defined by germline genetic makeup or MD. [ABSTRACT FROM AUTHOR]

Purpose: Previous studies suggest that coffee and caffeine intake may be associated with reduced breast cancer risk. To date, there is limited and inconsistent epidemiologic evidence for associations of adolescent diet with mammographic breast density, a strong and consistent predictor of breast cancer. We investigated the association of adolescent caffeine intake with mammographic density in premenopausal women. Methods: This study included 751 cancer-free women within the Nurses' Health Study II cohort. Percent breast density (PD), absolute dense (DA) and non-dense areas (NDA) were measured from digitized film mammograms using a computer-assisted thresholding technique; all measures were square root-transformed. Energy-adjusted adolescent caffeine intake was estimated using the data from a food frequency questionnaire. Information regarding breast cancer risk factors was obtained from questionnaires closest to the mammogram date. We used generalized linear regression to quantify associations of caffeine intake with breast density measures. Results: In multivariable analyses, adolescent caffeine intake was not associated with any of the density phenotypes (caffeine 4th vs. 1st quartile: β = − 1.27, 95% CI − 4.62; 2.09, p-trend = 0.55 for percent density; β = − 0.21, 95% CI − 0.76, 0.34, p-trend = 0.65 for absolute dense area, and β = 0.23, 95% CI − 0.28, 0.74, p-trend = 0.50 for non-dense area). Additional adjustment of the models for body mass index at age 18 resulted in attenuation of the risk estimates. Conclusions: Our findings do not support the hypothesis that adolescent caffeine intake is associated with premenopausal mammographic breast density. [ABSTRACT FROM AUTHOR]

Background Previous studies have examined dairy products with various fat contents in relation to type 2 diabetes (T2D) risk, although data regarding dairy fat intake per se are sparse. Objectives We aimed to evaluate the association between dairy fat intake and risk of T2D in 3 prospective cohorts. We also examined associations for isocalorically replacing dairy fat with other macronutrients. Methods We prospectively followed 41,808 men in the Health Professionals Follow-Up Study (HPFS; 1986–2012), 65,929 women in the Nurses' Health Study (NHS; 1984–2012), and 89,565 women in the NHS II (1991–2013). Diet was assessed quadrennially using validated FFQs. Fat intake from dairy products and other relevant sources was expressed as percentage of total energy. Self-reported incident T2D cases were confirmed using validated supplementary questionnaires. Time-dependent Cox proportional hazards regression was used to estimate the HR for dairy fat intake and T2D risk. Results During 4,219,457 person-years of follow-up, we documented 16,511 incident T2D cases. Dairy fat was not associated with risk of T2D when compared with calories from carbohydrates (HR for extreme quintiles: 0.98; 95% CI: 0.95, 1.02). Replacing 5% of calories from dairy fat with other sources of animal fat or carbohydrate from refined grains was associated with a 17% (HR: 1.17; 95% CI: 1.13, 1.21) and a 4% (HR: 1.04; 95% CI: 1.00, 1.08) higher risk of T2D, respectively. Conversely, a 5% calorie replacement with carbohydrate from whole grains was associated with a 7% lower risk of T2D (HR: 0.93; 95% CI: 0.88, 0.98). Conclusions Dairy fat intake was not associated with T2D risk in these cohort studies of US men and women when compared with calories from carbohydrate. Replacing dairy fat with carbohydrates from whole grains was associated with lower risk of T2D. Replacement with other animal fats or refined carbohydrates was associated with higher risk. [ABSTRACT FROM AUTHOR]

Background: Early natural menopause, the cessation of ovarian function before age 45 y, is positively associated with cardiovascular disease and other conditions. Dietary vitamin D intake has been inversely associated with early menopause; however, no previous studies have evaluated risk with regard to plasma 25-hydroxyvitamin D [25(OH)D] concentrations.Objective: We prospectively evaluated associations of total and free 25(OH)D and vitamin D-binding protein (VDBP) concentrations and the risk of early menopause in a case-control study nested within the Nurses' Health Study II (NHS2). We also considered associations of 25(OH)D and VDBP with anti-Müllerian hormone (AMH) concentrations.Methods: The NHS2 is a prospective study in 116,430 nurses, aged 25-42 y at baseline (1989). Premenopausal plasma blood samples were collected between 1996 and 1999, from which total 25(OH)D and VDBP concentrations were measured and free 25(OH)D concentrations were calculated. Cases experienced menopause between blood collection and age 45 y (n = 328) and were matched 1:1 by age and other factors to controls who experienced menopause after age 48 y (n = 328). Conditional logistic regression models were used to estimate ORs and 95% CIs for early menopause according to each biomarker. Generalized linear models were used to estimate AMH geometric means according to each biomarker.Results: After adjusting for smoking and other factors, total and free 25(OH)D were not associated with early menopause. Quartile 4 compared with quartile 1 ORs were 1.04 (95% CI: 0.60, 1.81) for total 25(OH)D and 0.70 (95% CI: 0.41, 1.20) for free 25(OH)D. 25(OH)D was unrelated to AMH concentrations. VDBP was positively associated with early menopause; the OR comparing the highest with the lowest quartile of VDBP was 1.80 (95% CI: 1.09, 2.98).Conclusions: Our findings suggest that total and free 25(OH)D are not importantly related to the risk of early menopause. VDBP may be associated with increased risk, but replication is warranted. [ABSTRACT FROM AUTHOR]

Study Question: Are anti-Müllerian hormone (AMH) levels assessed in women aged 32-44 associated with risk of incident early natural menopause?Summary Answer: We observed strong, significant associations between lower AMH levels and higher risk of early menopause.What Is Known Already: The ability to predict risk early menopause, defined as menopause before age 45, prior to fertility decline would improve options for family planning and cardiovascular disease prevention. Though AMH is an established marker of menopause timing in older reproductive-aged women, whether AMH is associated with risk of early menopause has not been evaluated.Study Design, Size, Duration: We assessed these relations in a nested case-control study within the prospective Nurses' Health Study II cohort. Premenopausal blood samples were collected in 1996-1999. Participants were followed until 2011 for early natural menopause, with follow-up rates >94%.Participants/materials, Setting, Methods: Early menopause cases (n = 327) were women reporting natural menopause between blood collection and age 45. Controls (n = 491) experienced menopause after age 45 and included 327 cases matched to controls on the basis of age at blood draw (±4 months) and other factors. AMH levels up to 12 years before early menopause were assayed in 2016.Main Results and the Role Of Chance: In multivariable conditional logistic regression models adjusting for matching factors, body mass index, smoking, parity, oral contraceptive use, and other factors, each 0.10 ng/ml decrease in AMH was associated with a 14% higher risk of early menopause (95% confidence interval (CI) 1.10 to 1.18; P < 0.001). In polynomial regression models including linear and quadratic terms for AMH, odds ratios for early menopause for women with AMH levels of 1.5, 1.0 and 0.5 ng/ml compared to 2.0 ng/ml were 2.6, 7.5 and 23 (all P < 0.001). Significant associations were observed irrespective of smoking status, adiposity, infertility history and menstrual cycle characteristics. Furthermore, models assessing the predictive ability of AMH showed high concordance, and C-statistics were high, ranging from 0.68 (age ≤35) to 0.93 (age 42).Limitations, Reasons For Caution: Our population was relatively homogenous with respect to race/ethnicity. Further work in more ethnically diverse populations is needed.Wide Implication Of the Findings: To our knowledge, this is the first prospective study to evaluate whether AMH levels are associated with early menopause. These findings support the utility of AMH as a clinical marker of early menopause in otherwise healthy women.Study Funding/competing Interest(s): This project was supported by UM1CA176726, R01CA67262, and R01HD078517 from the U.S. Department of Health and Human Services, National Institutes of Health. No competing interests declared. [ABSTRACT FROM AUTHOR]

Background: Dietary diversity scores (DDS) are considered as metrics for monitoring the implementation of the UN’s Sustainable Development Goals, but they need to be rigorously evaluated. Objective: To examine two DDS, the Food Groups Index (FGI), and the Minimum Dietary Diversity-Women (MDD-W), alongside two dietary quality scores, the Alternate Healthy Eating Index (AHEI-2010) and the Prime Diet Quality Score (PDQS), with risks of gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDPs). Design: The analysis included 21,312 (GDM) and 19,917 (HDPs) singleton births reported in the Nurses’ Health Study II cohort (1991–2001), among women without major chronic disease or GDM/HDPs. Scores were derived using prepregnancy diet collected by a comprehensive food frequency questionnaire. Multivariable models were utilized to calculate relative risks (RR) and confidence intervals (95%CIs). Results: Incident GDM (n = 916) and HDPs (n = 1,421) were reported. The MDD-W and FGI were not associated with risk of GDM or HDPs, but the AHEI-2010 and PDQS were associated with a lower risk of GDM and marginally lower risk of HDP. The RR’s of GDM comparing the highest vs. lowest quintiles were 1.00 (95%CI: 0.79, 1.27; p-trend = 0.82) for MDD-W, 0.96 (95%CI: 0.76, 1.22; p-trend = 0.88) for FGI, 0.63 (95%CI: 0.50, 0.81; p-trend <0.0001) for the AHEI-2010 and 0.68 (95%CI: 0.54, 0.86; p-trend = 0.003) for the PDQS. Similarly, the RR’s of HDPs were 0.92 (95%CI: 0.75, 1.12, p-trend = 0.94) for MDD-W, 0.97 (95%CI: 0.79, 1.17; p-trend = 0.83) for FGI, 0.84 (95%CI: 0.70, 1.02; p-trend = 0.07) for AHEI-2010 and 0.89 (95%CI: 0.74, 1.09; p-trend = 0.07) for PDQS. Conclusions: MDD-W and FGI did not predict the risk of GDM and HDPs. These DDS should not be widely used as metrics for achieving dietary goals in their present form. The Prime Diet Quality Score warrants further testing as a promising measure of a sustainable and healthy diet on a global scale. [ABSTRACT FROM AUTHOR]

Observational studies and randomized controlled trials of menopausal hormone therapy (HT) and chronic disease risk appear to have divergent results for cardiovascular disease. However, differences may be related to a modifying effect of age, time since menopause, and HT formulation. In the Nurses' Health Study (NHS) (enrolling during 1980-1994 and following participants until 2002), we investigated associations between the use of oral conjugated equine estrogens (CEE) (0.625 mg/day) plus medroxyprogesterone acetate (MPA) (<10 mg/day) or oral CEE alone and cardiovascular disease, cancer, all-cause mortality, and other major endpoints among postmenopausal women, aged 50-79 years at HT initiation. Among women aged 50-59 years at HT initiation, associations of CEE alone or CEE+MPA with most clinical outcomes were highly concordant between NHS and Women's Health Initiative (WHI). However, for myocardial infarction, results for CEE+MPA were in the direction of risk elevation in WHI and in the direction of risk reduction in NHS. When examined according to years since menopause onset (<10 years) rather than age group, results were nonsignificant and concordant for both studies. Because few women in the NHS initiated HT after age 60 years, we did not examine associations in this group. Discrepancies between NHS and WHI could largely be attributed to differences in the age structure of the populations and age at HT initiation. [ABSTRACT FROM AUTHOR]

Background: Early menopause, defined as the cessation of ovarian function before the age of 45 y, affects ~10% of women and is associated with higher risk of cardiovascular disease, osteoporosis, and other conditions. Few modifiable risk factors for early menopause have been identified, but emerging data suggest that high vitamin D intake may reduce risk. Objective: We evaluated how intakes of vitamin D and calcium are associated with the incidence of early menopause in the prospective Nurses' Health Study II (NHS2). Design: Intakes of vitamin D and calcium from foods and supplements were measured every 4 y with the use of a food-frequency questionnaire. Cases of incident early menopause were identified from all participants who were premenopausal at baseline in 1991; over 1.13 million person-years, 2041 women reported having natural menopause before the age of 45 y. We used Cox proportional hazards regression to evaluate relations between intakes of vitamin D and calcium and incident early menopause while accounting for potential confounding factors. Results: After adjustment for age, smoking, and other factors, women with the highest intake of dietary vitamin D (quintile median: 528 IU/d) had a significant 17% lower risk of early menopause than women with the lowest intake [quintile median: 148 IU/d; HR: 0.83 (95% CI: 0.72, 0.95); P-trend = 0.03]. Dietary calcium intake in the highest quintile (median: 1246 mg/d) compared with the lowest (median: 556 mg/d) was associated with a borderline significantly lower risk of early menopause (HR: 0.87; 95% CI: 0.76, 1.00; P-trend = 0.03). Associations were stronger for vitamin D and calcium from dairy sources than from nondairy dietary sources, whereas high supplement use was not associated with lower risk. Conclusions: Findings suggest that high intakes of dietary vitamin D and calcium may be modestly associated with a lower risk of early menopause. Further studies evaluating 25-hydroxyvitamin D concentrations, other dairy constituents, and early menopause are warranted. [ABSTRACT FROM AUTHOR]

Background: The role of body fatness in the aetiology of breast cancer is complex. We evaluated the independent and synergistic effects of body fatness, at different stages throughout a woman's life course, on premenopausal breast cancer risk. Methods: Premenopausal participants of the Nurses' Health Study II (NHSII) were followed from 1991 up to 2009. Body fatness factors including birthweight, somatotype (a 9-level pictogram with level 1 being the leanest) at ages 5 and 10 years and body mass index (BMI) at age 18 were collected at baseline. Current BMI was updated biennially. Multivariate Cox regression models were used to evaluate the association between each body fatness factor as well as cross-classification of all factors and the incidence of breast cancer. Results: Based on 1574 incident premenopausal breast cancer cases and 1 133 893 personyears of follow-up, a lower incidence was associated with lower birthweight: hazard ratio (HR) [95% confidence interval (CI)]=0.74 (0.58-0.95) for <2.5kg vs 3.9þkg, P for trend<0.001; higher somatotype at age 5: HR=0.57 (95% CI 0.44-0.73) for 5-9 vs 1, P fortrend<0.0001]; and at age 10: HR=0.61 (95% CI 0.49-0.75) for 5-9 vs 1, P for trend<0.0001]; and BMI at age 18: HR=0.67 (95% 0.47-0.95) for ≥ 27.5 kg/m² vs < 18.5 kg/m², P for trend=0.009], after adjusting for age and body fatness measures earlier in life and other risk factors, respectively. No significant interaction between body fatness measures was found. Women with the lowest birthweight, the highest somatotype at ages 5 and 10 and the highest BMI at age 18 and currently had a 72% (95% CI 54%-83%) lower incidence of invasive premenopausal breast cancer than women with the opposite extreme of each body fatness indicator. Conclusion: The lowest incidence of premenopausal breast cancer was associated with the lowest birthweight and the highest childhood, adolescent and early adult body fatness. [ABSTRACT FROM AUTHOR]

Background: Carbohydrate quality may be an important determinant of type 2 diabetes (T2D); however, relations between various carbohydrate quality metrics and T2D risk have not been systematically investigated. Objective: The purpose of this study was to prospectively examine the association between carbohydrates, starch, fibers, and different combinations of these nutrients and risk of T2D in women. Design: We prospectively followed 70,025 women free of cardiovascular disease, cancer, and diabetes at baseline from the Nurses' Health Study (1984-2008). Diet information was collected with the use of a validated questionnaire every 4 y. Cox regression was used to evaluate associations with incident T2D. Results: During 1,484,213 person-years of follow-up, we ascertained 6934 incident T2D cases. In multivariable analyses, when extreme quintiles were compared, higher carbohydrate intake was not associated with T2D (RR = 0.98; 95% CI: 0.89, 1.08; P-trend = 0.84), whereas starch was associated with a higher risk (RR = 1.23; 95% CI: 1.12, 1.35; P-trend,0.0001). Total fiber (RR = 0.80; 95% CI: 0.72, 0.89; P-trend < 0.0001), cereal fiber (RR = 0.71, 95% CI: 0.65, 0.78; P-trend < 0.0001), and fruit fiber (RR = 0.79; 95% CI: 0.72, 0.85; P-trend < 0.0001) were associated with a lower T2D risk. The ratio of carbohydrate to total fiber intake was marginally associated with a higher risk of T2D (RR = 1.09; 95% CI: 1.00, 1.20; P-trend = 0.04). On the other hand, we found positive associations between the ratios of carbohydrate to cereal fiber (RR = 1.28; 95% CI: 1.17, 1.39; P-trend < 0.0001), starch to total fiber (RR = 1.12; 95% CI: 1.02, 1.23; P-trend = 0.03), and starch to cereal fiber (RR = 1.39; 95% CI: 1.27, 1.53; P-trend < 0.0001) and T2D. Conclusions: Diets with high starch, low fiber, and a high starch-to-cereal fiber ratio were associated with a higher risk of T2D. The starch-to-cereal fiber ratio of the diet may be a novel metric for assessing carbohydrate quality in relation to T2D. [ABSTRACT FROM AUTHOR]

Background: Seafood consumption may prevent age-related cognitive decline. However, benefits may vary by nutrient contents in different seafood types. We examined associations between total seafood consumption and cognitive decline and whether these associations differ by seafood types.Methods: We conducted a prospective cohort study of 5,988 women (mean age, 72 years) from the Women's Health Study who self-reported seafood intake at Women's Health Study baseline and also participated in telephone assessments of general cognition, verbal memory, and category fluency administered 5.6 years after Women's Health Study baseline and 2 and 4 years thereafter. Primary outcomes were standardized composite scores of global cognition and verbal memory.Results: After adjusting for potential confounders, different amounts of total seafood consumption were not associated with changes in global cognition (p = .56) or verbal memory (p = .29). Considering seafood types, however, compared with women consuming less than once-weekly tuna or dark-meat finfish, those with once-weekly or higher consumption had significantly better verbal memory (0.079 standard units; p < .01) after 4 years-a difference comparable to that for women 2.1 years apart in age. There was also a statistically nonsignificant suggestion of better global cognition (p = .13) with once-weekly or higher tuna or dark-meat fish consumption. No significant associations were observed for light-meat finfish or shellfish.Conclusions: The relation of seafood to cognition may depend on the types consumed. Total consumption levels of seafood were unrelated to cognitive change. However, consumption of tuna and dark-meat fish once weekly or higher was associated with lower decline in verbal memory for a period of 4 years. [ABSTRACT FROM AUTHOR]

Ruth Pfeiffer and colleagues describe models to calculate absolute risks for breast, endometrial, and ovarian cancers for white, non-Hispanic women over 50 years old using easily obtainable risk factors. Please see later in the article for the Editors' Summary [ABSTRACT FROM AUTHOR]

Background: Abnormal one-carbon metabolism may lead to general genomic (global) hypomethylation, which may predispose an individual to the development of colorectal neoplasia. Methods: We evaluated the association between pre-diagnostic leukocyte genomic DNA methylation level and the risk of colorectal cancer in a nested case-control study of 358 colorectal cancer cases and 661 matched controls within the all-female cohort of the Nurses’ Health Study (NHS). Among control subjects, we further examined major plasma components in the one-carbon metabolism pathway in relation to genomic DNA methylation level. Liquid chromatography/tandem mass spectrometry was used to examine leukocyte genomic DNA methylation level. We calculated odds ratios (ORs) and 95% confidence intervals (95% CIs) using logistic regression. Results: Overall genomic DNA methylation level was not associated with the risk of colorectal cancer (p for trend, 0.45). Compared with women in the lowest quintile of methylation, the multivariate OR of colorectal cancer risk was 1.32 (95% CI, 0.82–2.13) for those in the highest quintile. We did not find significant associations between major plasma components of one-carbon metabolism or risk factors for colorectal cancer and genomic DNA methylation level (all p for trend >0.05). Also, neither one-carbon metabolism-related plasma components nor well-known risk factors for colorectal cancer modified the association between genomic DNA methylation level and the risk of colorectal cancer (all p for interaction >0.05). Conclusions: We found no evidence that hypomethylation of leukocyte genomic DNA increases risk of colorectal cancer among women. Additional studies are needed to investigate the association between pre-diagnostic genomic DNA methylation level and colorectal cancer risk among diverse populations. [ABSTRACT FROM AUTHOR]

The article discusses research on the development of benign breast disease (BBD) in older girls and the risk of breast cancer in women during childhood and adolescent stage. The Growing Up Today Study in 1996 surveyed female participants aged 9 to 15 years old and monitored their menarche, height, and weight through 2007. Results of the study revealed that BBD risks are most visible to girls with rapid growth, thinner girls, and taller women.

The article presents a study assessing the relationship between cigarette smoking and cessation on mortality in women. The outcomes measured by a prospective observational study included hazard ratios for total mortality categorized into vascular and respiratory diseases, lung cancer, and other causes. Researchers concluded the risk of vascular mortality due to smoking in women may be rapidly eliminated upon cessation and significantly reduced within 20 years for lung diseases. Delaying the age at which a women starts smoking also reduced the risk for respiratory disease, lung cancer and other smoking-related cancer deaths.

Dietary fat in midlife has not been associated with breast cancer risk in most studies, but few have followed women beyond one decade. The authors examined the relation of dietary fat, assessed by repeated questionnaires, to incidence of postmenopausal breast cancer in a cohort of 80,375 US women (3,537 new cases) prospectively followed for 20 years between 1980 and 2000. The multivariable relative risk for an increment of 5% of energy from total dietary fat intake was 0.98 (95% confidence interval: 0.95, 1.00). Additionally, specific types of fat were not associated with an increased risk of breast cancer. Furthermore, secondary analyses indicated no differences in breast cancer risk by estrogen receptor or progesterone receptor status. However, stratification by waist circumference indicated a significant decrease in breast cancer risk for participants with a waist circumference of 35 inches (88.9 cm) or greater (p-trend = 0.04). None of the latency intervals investigated were associated with an increased risk of breast cancer. In addition, fat intake before menopause was not related to risk of postmenopausal breast cancer. These results suggest a reduction in breast cancer risk for women with insulin resistance syndrome who consume high-fat diets and no association between specific sources of fat during midlife and risk of postmenopausal breast cancer. [ABSTRACT FROM PUBLISHER]

The article reports on a study which looked at whether adult weight change affected the risk of postmenopausal breast cancer. Researchers found that women who gained weight later in life, especially after menopause, had an increased risk of breast cancer. Weight loss after menopause was found to be associated with a decreased risk.

Background Experimental evidence suggests that statins protect against breast carcinogenesis by interrupting cell cycle progression and promoting apoptosis. Evidence in humans is limited and inconsistent. The relation between serum cholesterol levels and breast cancer risk is itself unclear; because cholesterol is the precursor to sex steroid hormones, higher levels could plausibly increase risk. Methods The associations of statins, general lipid-lowering drugs, and reported cholesterol levels with breast cancer risk were assessed in the Nurses’ Health Study, with 6 to 12 years of follow-up. A total of 79 994 women aged 42 to 69 years and free of cancer were followed prospectively for up to 12 years. Current statin use, including duration, was assessed retrospectively in 2000 in 75 828 women. Self-reported serum cholesterol level was assessed prospectively between 1990 and 2000 in 71 921 women. Results Overall, we documented 3177 incident cases of invasive breast cancer. Compared with nonusers, current lipid-lowering drug users experienced similar breast cancer risk (multivariate relative risk [RR], 0.99; 95% confidence interval [CI], 0.86-1.13). Current use of statins also was not significantly associated with breast cancer risk (RR, 0.91; 95% CI, 0.76-1.08). Associations by duration of current use were similarly null. Self-reported serum cholesterol levels were not associated with breast cancer risk in postmenopausal women with levels of 240 mg/dL or higher (≥6.22 mmol/L) compared with less than 180 mg/dL (<4.66 mmol/L) (RR, 1.04; 95% CI, 0.91-1.17). Conclusion Overall, these data suggest that serum cholesterol levels and the use of lipid-lowering drugs in general and of statins in particular are not substantially associated with breast cancer risk. [ABSTRACT FROM AUTHOR]

Background Analgesics are commonly used and may impair kidney function. However, limited prospective information is available on the long-term effects of aspirin, other nonsteroidal anti-inflammatory drugs (NSAIDs), and acetaminophen on renal function. Methods A total of 1697 women participating in the Nurses' Health Study provided information on a mailed questionnaire in 1999 about lifetime use of acetaminophen, aspirin, and NSAIDs and provided blood samples in 1989 and 2000. The main outcome was change in estimated glomerular filtration rate (GFR) in 11 years. Multivariate logistic regression was used to determine the odds of developing the outcome according to lifetime analgesic intake. Results The mean ± SD estimated GFR decreased from 88 ± 17 to 79 ± 17 mL/min per 1.73 m2. There were no substantial differences in the unadjusted or estimated GFR levels among the categories of lifetime intake for the 3 analgesic groups at baseline or after 11 years. Acetaminophen use was associated with an increased risk of a GFR decline of at least 30 mL/min per 1.73 m2 (P trend = .01) and a GFR decline of 30% or greater (P trend<.001), but aspirin and NSAID use were not. Compared with women consuming less than 100 g of acetaminophen, multivariate-adjusted odds ratio (95% confidence intervals) for a decline in GFR of at least 30 mL/min per 1.73 m2 for women consuming more than 3000 g was 2.04 (1.28-3.24). Conclusions Higher lifetime use of aspirin and NSAIDs is not associated with renal function decline, but high acetaminophen use may increase the risk of loss of renal function. The absolute risk of renal function decline due to even high lifetime analgesic intake seems to be modest. [ABSTRACT FROM AUTHOR]

Background: Evaluations of epidemiologic risk factors in relation to breast cancer classified jointly by estrogen receptor (ER) and progesterone receptor (PR) status have been inconsistent. To address this issue, we conducted a prospective evaluation of risk factors for breast cancer classified according to receptor status. Methods: During 1 029 414 person-years of follow-up of 66 145 women participating in the Nurses' Health Study from 1980 through 2000, we identified 2096 incident cases of breast cancer for which information on ER/PR status was available: 1281 were ER+/ PR+, 318 were ER+/PR-, 80 were ER-/PR+, and 417 were ER-/PR-. We fit a log-incidence model of breast cancer and used polychotomous logistic regression to compare coefficients for breast cancer risk factors in patients with different ER/PR status. To test for differences in risk factor odds ratios based on marginal ER/PR categories, we evaluated ER status controlling for PR status and vice versa. The predictive ability of our log-incidence model to discriminate between women who would develop ER+/PR+ breast cancer and those who would not (and similarly for ER-/ PR-breast cancer) was evaluated by using receiver operator characteristic curve analysis. All statistical tests were two-sided. Results: We observed statistically significant heterogeneity among the four ER/PR categories for some risk factors (age, menopausal status, body mass index [BMI] after menopause, the one-time adverse effect of first pregnancy, and past use of postmenopausal hormones) but not for others (benign breast disease, family history of breast cancer, alcohol use, and height). The one-time adverse association of first pregnancy with incidence was present for PR- but not for PR+ tumors after controlling for ER status (P = .007). However, the association of BMI after menopause with incidence was present for PR+ but not PR-tumors (P = .005). Statistically significant differences in the incidence of ER+ and ER-tumors were seen with age, both before and after menopause (P = .003), and with past use of postmenopausal hormones (P = .01). Area under the receiver operator characteristic curve, adjusted for age, was 0.64 (95% confidence interval [CI] = 0.63 to 0.66) for ER+/PR+ tumors and 0.61 (95% CI = 0.58 to 0.64) for ER-/PR-tumors. Conclusions: Incidence rates and risk factors for breast cancer differ according to ER and PR status. Thus, to accurately estimate breast cancer risk, breast cancer cases should be divided according to the ER and PR status of the tumor. [ABSTRACT FROM AUTHOR]

Background: In addition to their antipyretic, antiinflammatory, and pain-relieving effects, analgesics may interfere with blood pressure regulation. However, little prospective information is available on the association between analgesic use and the risk of hypertension. Methods: We performed a prospective study of 80020 women aged 31 to 50 years who participated in the Nurses' Health Study II and had no previous history of hypertension. Frequency of use (in days per month) of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), and acetaminophen was collected by mailed questionnaire in 1995. Incident cases of physician-diagnosed hypertension were identified by self-report on the 1997 biennial questionnaire. Results: During 164090 person-years of follow-up, 1650 incident cases of hypertension were identified. At least 1 d/mo, 51.2% of the cohort used aspirin, 76.7% used NSAIDs, and 72.5% used acetaminophen. After adjusting for age, all 3 classes of analgesics were associated with an increased risk of incident hypertension (P<.001 for trend). After further adjustment for all 3 analgesics and other potential risk factors, only NSAIDs and acetaminophen (P<.001 for trend for both) were significantly associated with risk of hypertension. Compared with nonusers, the relative risk of hypertension for women taking NSAIDs 22 d/mo or more was 1.86 (95% confidence interval, 1.51-2.28) and for those taking acetaminophen 22 d/mo or more was 2.00 (95% confidence interval, 1.52-2.62). Conclusions: Use of NSAIDs and use of acetaminophen were significantly associated with increased risk of hypertension, but aspirin use was not. A substantial proportion of hypertension in the United States, and the associated morbidity and mortality, may be due to the use of these medications. [ABSTRACT FROM AUTHOR]

In 1993–1995, the authors evaluated risk factors for elevated blood and bone lead levels in 264 Boston, Massachusetts, area women previously selected for a case-control study of lead and hypertension. Bone lead was measured at the tibia and patella with K x-ray fluorescence. Blood lead was analyzed by graphite furnace atomic absorption. Participants were aged 46–74 years and had mean lead levels of 3 (standard deviation, 2) µg/dl (blood), 13 (standard deviation, 9) µg/g (tibia), and 17 (standard deviation, 11) µg/g (patella). In multivariate linear regression models, use of postmenopausal estrogen (inverse) and alcohol intake (positive) were significantly associated with blood lead levels. Both bone lead measures were significantly and positively associated with blood lead but only among postmenopausal women not using estrogen; for example, an increase from the first to the fifth quintile of tibia lead level (19 µg/g) was associated with a 1.7-µg/dl increase in blood lead (p = 0.0001) in this group. Older age and lower parity were associated with higher tibia lead; only age was associated with patella lead. The observed interaction of bone lead with estrogen status in determining blood lead supports the hypothesis that increased bone resorption, as occurs postmenopausally because of decreased estrogen production, results in heightened release of bone lead stores into blood. [ABSTRACT FROM PUBLISHER]

Events during perinatal and early life may influence the incidence of breast cancer in adult life, and some case-control studies suggest that having been breastfed may reduce breast cancer risk. The authors studied this association among premenopausal and postmenopausal women by using data from the two Nurses' Health Studies, the Nurses' Health Study (using data from 1992 to 1996) and the Nurses' Health Study II (using data from 1991 to 1997). A history of being breastfed was self-reported by the study participants. During a total of 695,655 person-years, 1,073 cases of invasive breast cancer were diagnosed. The authors did not observe any important overall association between having been breastfed and the development of breast cancer later in life among premenopausal women (covariate-adjusted relative risk = 0.97, 95% confidence interval (CI): 0.78, 1.20) or postmenopausal women (covariate-adjusted relative risk = 1.12, 95% CI: 0.92, 1.37). No significant trend was observed with increasing duration of breastfeeding. The authors also used data on breastfeeding retrospectively collected from 2,103 mothers of participants of the two Nurses' Health Studies. With the mothers' reports, the covariate-adjusted odds ratio of breast cancer was 1.11 (95% CI: 0.88, 1.39) for women who were breastfed compared with those who were not. Data from these two large cohorts do not support the hypothesis that being breastfed confers protection against subsequent breast cancer. [ABSTRACT FROM PUBLISHER]

Previous cohort studies of fat intake and risk of coronary heart disease (CHD) have been inconsistent, probably due in part to methodological differences and various limitations, including inadequate dietary assessment and incomplete adjustment for total energy intake. The authors analyzed repeated assessment of diet from the Nurses' Health Study to examine the associations between intakes of four major types of fat (saturated, monounsaturated, polyunsaturated, and trans fats) and risk of CHD during 14 years of follow-up (1980–1994) by using alternative methods for energy adjustment. In particular, the authors compared four risk models for energy adjustment: the standard multivariate model, the energy-partition model, the nutrient residual model, and the multivariate nutrient density model. Within each model, the authors compared four different approaches for analyzing repeated dietary measurements: baseline diet only, the most recent diet, and two different algorithms for calculating cumulative average diets. The substantive results were consistent across all models; that is, higher intakes of saturated and trans fats were associated with increased risk of CHD, while higher intakes of monounsaturated and polyunsaturated fats were associated with reduced risk. When nutrients were considered as continuous variables, the four energy-adjustment methods yielded similar associationˇs. However, the interpretation of the relative risks differed across models. In addition, within each model, the methods using the cumulative averages in general yielded stronger associations than did those using either only baseline diet or the most recent diet. When the nutrients were categorized according to quintiles, the residual and the nutrient density models, which gave similar results, yielded statistically more significant tests for linear trend than did the standard and the partition models. Am J Epidemiol 1999;149:531–40. [ABSTRACT FROM AUTHOR]

Obesity is an established risk factor for non-insulin-dependent diabetes mellitus (NIDDM). Anthropometric measures of overall and central obesity as predictors of NIDDM risk have not been as well studied, especially in women. Among 43,581 women enrolled in the Nurses' Health Study who in 1986 provided waist, hip, and weight information and who were initially free from diabetes and other major chronic diseases, NIDDM incidence was followed from 1986 to 1994. After adjustment for age, family history of diabetes, smoking, exercise, and several dietary factors, the relative risk of NIDDM for the 90th percentile of body mass index (BMI) (weight (kg)/height (m)2) (BMI = 29.9) versus the 10th percentile (BMI = 20.1) was 11.2 (95% confidence interval (CI) 7.9–15.9). Controlling for BMI and other potentially confounding factors, the relative risk for the 90th percentile of waist: hip ratio (WHR) (WHR = 0.86) versus the 10th percentile (WHR = 0.70) was 3 1 (95% CI 2.3–4.1), and the relative risk for the 90th percentile of waist circumference (36.2 inches or 92 cm) versus the 10th percentile (26.2 inches or 67 cm) was 5.1 (95% CI 2.9–8.9). BMI, WHR, and waist circumference are powerful independent predictors of NIDDM in US women. Measurement of BMI and waist circumference (with or without hip circumference) are potentially useful tools for clinicians in counseling patients regarding NIDDM risk and risk reduction. [ABSTRACT FROM AUTHOR]

Examines the association between the dietary intake of supplements and cataract extraction in women in the United States. Participation of female registered nurses in the study; Incidence of extraction of senile cataracts; Support of the findings to the antioxidant hypothesis of cataract prevention.

Objective: Adverse pregnancy outcomes (APOs) and early menopause are each associated with increased risk of cardiovascular disease (CVD); whether APOs are associated with age at menopause is unclear. We examined the association of gestational diabetes (GDM), hypertensive disorders of pregnancy (HDP), preterm birth, and multiple gestation with age at natural menopause.Study Design: Observational, prospective study within the Nurses' Health Study II cohort (1989-2019).Main Outcomes Measures: Risk of early natural menopause, defined as occurring before the age of 45 years, and age at onset of natural menopause (hazard ratio (HR) >1 indicates younger age at menopause).Results: The mean [SD] baseline age of 69,880 parous participants was 34.5 [4.7] years. Compared with participants who had a term singleton first birth, those with a term multiple-gestation first birth had higher risk of early menopause (HR: 1.65, 95% CI: 1.05, 2.60) and younger age at natural menopause (HR: 1.46, 95% CI: 1.31, 1.63). Estimates for preterm multiple gestation were of similar magnitude. Menopause occurred at a younger age for those with a preterm birth with spontaneous labor (HR: 1.08, 95% CI: 1.03, 1.14) compared to those with a term birth with spontaneous labor. Conversely, estimates for GDM (HR: 0.95, 95% CI: 0.89, 1.02) and HDP (preeclampsia, HR: 0.93, 95% CI: 0.89, 0.97) suggested an association with older age at menopause.Conclusions: In this large cohort study, several statistically significant associations between APOs and age at natural menopause were observed. A deeper understanding of the relationships among APOs, menopause, and CVD is needed to help identify people at higher risk for early menopause and later CVD. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the association between parity and breastfeeding and anti-Müllerian hormone levels (AMH) and change in AMH levels over time. Furthermore, we examined whether AMH levels mediate the relation of parity and breastfeeding with age at menopause.Study Design: Observational, prospective cohort study.Main Outcome Measures: AMH levels were assessed in a subset of premenopausal participants in the Nurses' Health Study II, including 1619 women who provided a blood sample in 1996-1999 and an additional 800 women who provided a second premenopausal sample in 2010-2012.Results: In multivariable linear regression models adjusted for parity, body mass index, smoking, and other factors, mean log AMH levels in 1996-1999 were 39% higher in women reporting ≥25 months of total breastfeeding vs. <1 month (P for trend = 0.009). Parity was not associated with AMH levels after adjustment for breastfeeding. Neither parity nor breastfeeding was associated with decline in AMH levels over 11 to 15 years. Breastfeeding duration was positively associated with age at menopause (P for trend = 0.01), with evidence that the association was mediated via AMH.Conclusions: Our results suggest that breastfeeding is associated with higher AMH levels and later onset of menopause, and support the hypothesis that observed relations of parity with AMH levels and menopause timing may be largely attributable to breastfeeding. [ABSTRACT FROM AUTHOR]

Background: Genomewide association studies have identified multiple genetic variants associated with breast cancer. The extent to which these variants add to existing risk-assessment models is unknown. Methods: We used information on traditional risk factors and 10 common genetic variants associated with breast cancer in 5590 case subjects and 5998 control subjects, 50 to 79 years of age, from four U.S. cohort studies and one case–control study from Poland to fit models of the absolute risk of breast cancer. With the use of receiver-operating-characteristic curve analysis, we calculated the area under the curve (AUC) as a measure of discrimination. By definition, random classification of case and control subjects provides an AUC of 50%; perfect classification provides an AUC of 100%. We calculated the fraction of case subjects in quintiles of estimated absolute risk after the addition of genetic variants to the traditional risk model. Results: The AUC for a risk model with age, study and entry year, and four traditional risk factors was 58.0%; with the addition of 10 genetic variants, the AUC was 61.8%. About half the case subjects (47.2%) were in the same quintile of risk as in a model without genetic variants; 32.5% were in a higher quintile, and 20.4% were in a lower quintile. Conclusions: The inclusion of newly discovered genetic factors modestly improved the performance of risk models for breast cancer. The level of predicted breast-cancer risk among most women changed little after the addition of currently available genetic information. N Engl J Med 2010;362:986-93. [ABSTRACT FROM AUTHOR]

A response from the author of the article "Association of fecundity with changes in adult female weight," by A. Gaskins in the 2015 issue is presented.

Background: Postmenopausal hormone therapy has both benefits and hazards, including decreased risks of osteoporosis and cardiovascular disease and an increased risk of breast cancer. Methods: We examined the relation between the use of postmenopausal hormones and mortality among participants in the Nurses' Health Study, who were 30 to 55 years of age at base line in 1976. Data were collected by biennial questionnaires beginning in 1976 and continuing through 1992. We documented 3637 deaths from 1976 to 1994. Each participant who died was matched with 10 controls alive at the time of her death. For each death, we defined the subject's hormone status according to the last biennial questionnaire before her death or before the diagnosis of the fatal disease; this reduced bias caused by the discontinuation of hormone use between the time of diagnosis of a potentially fatal disease and death. Results: After adjustment for confounding variables, current hormone users had a lower risk of death (relative risk, 0.63; 95 percent confidence interval, 0.56 to 0.70) than subjects who had never taken hormones; however, the apparent benefit decreased with long-term use (relative risk, 0.80; 0.67 to 0.96, after 10 or more years) because of an increase in mortality from breast cancer among long-term hormone users. Current hormone users with coronary risk factors (69 percent of the women) had the largest reduction in mortality (relative risk, 0.51; 95 percent confidence interval, 0.45 to 0.57), with substantially less benefit for those at low risk (13 percent of the women; relative risk, 0.89; 95 percent confidence interval, 0.62 to 1.28). Conclusions: On average, mortality among women who use postmenopausal hormones is lower than among nonusers; however, the survival benefit diminishes with longer duration of use and is lower for women at low risk for coronary disease. (N Engl J Med 1997;336:1769-75.) [ABSTRACT FROM AUTHOR]

Background: Although it has been hypothesized that large intakes of the antioxidant vitamins C, E, and A reduce the risk of breast cancer, few prospective data are available. Methods: We prospectively studied 89,494 women who were 34 to 59 years old in 1980 and who did not have diagnosed cancer. Their intakes of vitamins C, E, and A from foods and supplements were assessed at base line and in 1984 with the use of a validated semiquantitative food-frequency questionnaire. Results: Breast cancer was diagnosed in 1439 women during eight years of follow-up. After multivariate adjustment for known risk factors, the relative risk among women in the highest quintile group for intake of vitamin C as compared with the risk among those in the lowest quintile group was 1.03 (95 percent confidence interval, 0.87 to 1.21); for vitamin E, after vitamin A intake had been controlled for, the relative risk was 0.99 (95 percent confidence interval, 0.83 to 1.19). In contrast, among women in the highest quintile group for intake of total vitamin A the relative risk was 0.84 (95 percent confidence interval, 0.71 to 0.98; P for trend = 0.001). Among women in the lowest quintile group for intake of vitamin A from food, consumption of vitamin A from supplements was associated with a reduced risk (P = 0.03). The significant inverse association of vitamin A intake with the risk of breast cancer was also found on study of data based on the 1984 questionnaire and four years of follow-up. Conclusions: Large intakes of vitamin C or E did not protect women in our study from breast cancer. A low intake of vitamin A may increase the risk of this disease; any benefit of vitamin A supplements may be limited to women with diets low in vitamin A. (N Engl J Med 1993;329:234-40.) [ABSTRACT FROM AUTHOR]