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1.
Artigo em Inglês | MEDLINE | ID: mdl-35012972

RESUMO

Obesity and obesity-related metabolic disorders, such as obesity and chronic inflammation, have been positively associated both with postmenopausal breast cancer and with resting energy expenditure (REE). However, there is limited epidemiological evidence on the associations between REE and risk of postmenopausal breast cancer. We used multivariable Cox proportional hazards models to examine the association between predicted REE (calculated using the Ikeda, Livingston and Mifflin equations) and risk of postmenopausal breast cancer overall and by subtypes, and by level of body fat) among 137,305 postmenopausal women in the Women's Health Initiative (WHI). All predicted REEs were positively associated with risk of invasive breast cancer (HRq5 vs q1: 1.69; 95% CI: 1.57-1.81, HR: 1.69; 95% CI: 1.57-1.82 and HR: 1.68; 95% CI: 1.56-1.80 for Ikeda, Livingston and Mifflin, respectively). These positive associations were observed irrespective of the hormone receptor subtype, grade and stage of the tumors, but were most pronounced for estrogen receptor positive/progesterone receptor positive tumors. After additional adjustment for BMI, the associations were mostly attenuated and remained statistically significant for most of the outcomes. We also observed an interaction between the predicted REEs and BMI, with the associations being somewhat stronger among normal weight and overweight women than among obese women (pinteractions <0.05). Our findings indicate that relatively high REE is associated with increased risk of invasive breast cancer among postmenopausal women (particularly for the obesity-related tumor subtypes), irrespective of the equation used. Further studies using more objective measures of REE are, however, needed to confirm our findings.

2.
J Nutr ; 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-35015878

RESUMO

BACKGROUND: We recently developed protein and carbohydrate intake biomarkers using metabolomics profiles in serum and urine, and used them to correct self-reported dietary data for measurement error. Biomarker-calibrated carbohydrate density was inversely associated with chronic disease risk, while protein density associations were mixed. OBJECTIVE: To elucidate and extend this earlier work through biomarker development for protein and carbohydrate components, including animal protein and fiber. METHODS: Prospective disease association analyses in WHI cohorts of postmenopausal U.S. women, aged 50-79 when enrolled at 40 U.S. Clinical Centers. Biomarkers are developed using an embedded human feeding study (n = 153). Calibration equations for protein and carbohydrate components are developed using a WHI nutritional biomarker study (n = 436). Calibrated intakes are associated with chronic disease incidence in WHI cohorts (n = 81,954) over a 20-year (median) follow-up period, using hazard ratio regression methods. RESULTS: Previously reported elevations in cardiovascular disease (CVD) with higher protein diets tended to be explained by animal protein density. For example, for coronary heart disease a 20% increment in animal protein density had hazard ratio (HR) and 95% confidence interval (CI) of 1.20 (1.02, 1.42) relative to the HR for total protein density. In comparison, cancer and diabetes risk showed little association with animal protein density beyond that attributable to total protein density. Inverse carbohydrate density associations with total CVD were mostly attributable to fiber density, with 20% increment HR (95% CI) factor of 0.89 (0.83, 0.94). Cancer risk showed little association with fiber density, while diabetes risk has 20% increment HR (95% CI) of 0.93 (0.88, 0.98) relative to the HRs for total carbohydrate density. CONCLUSIONS: In a population of postmenopausal U.S. women, CVD risk is associated with high animal protein and low fiber diets, cancer risk is associated with low carbohydrate diets, and diabetes risk is associated with low fiber/low carbohydrate diets.This study is registered with clinicaltrials.gov identifier: NCT00000611.

3.
J Nutr ; 2021 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-34905061

RESUMO

BACKGROUND: Dietary biomarkers measured in biospecimens can play an important role in correcting for random and systematic measurement error in self-reported nutrient intake when assessing diet-disease associations. To date, high quality biomarkers for calibrating self-reported dietary intake have only been developed for a few nutrients. OBJECTIVE: To investigate new study designs and regression calibration approaches for calibrating self-reported nutrient intake for use in disease association analyses. METHODS: We studied three regression calibration approaches: (I) an existing approach built on a calibration cohort assuming the existence of an objective biomarker, i.e., biomarker with random independent measurement error, (II) a proposed approach utilizing a biomarker development cohort, and (III) a proposed two-stage approach utilizing both cohorts. We conducted simulation studies to compare performance of different study designs/methods for estimating diet-disease associations, and applied suitable methods to examine the association of sodium and potassium intake with cardiovascular disease (CVD) risk in Women's Health Initiative cohorts. RESULTS: Simulation studies showed that approach (I) can lead to biased association estimation when the objective biomarker assumption is violated; the proposed approaches (II) and (III) obviate the need for such an objective biomarker. Precision for estimating the association depends critically on sample size of the biomarker development cohort and the strength of the self-reported nutrient intake. Analyses based on approaches (II) and (III) support previously reported significant findings using approach (I) about associations of the ratio of sodium to potassium intake with CVD risk, while providing efficiency gain for some outcomes. CONCLUSIONS: Self-reported dietary intake needs to be calibrated for measurement error correction in diet-disease association analyses. When there are no existing objective biomarkers that can be used for calibration purpose, controlled feeding studies can be used to develop new biomarkers for use in calibration, or can be used to calibrate self-reported dietary intake directly.

4.
Curr Dev Nutr ; 5(11): nzab125, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34761160

RESUMO

Background: Assessing estimated sodium (Na) and potassium (K) intakes derived from 24-h urinary excretions compared with a spot urine sample, if comparable, could reduce participant burden in epidemiologic and clinical studies. Objectives: In a 2-week controlled-feeding study, Na and K excretions from a 24-h urine collection were compared with a first-void spot urine sample, applying established algorithms and enhanced models to estimate 24-h excretion. Actual and estimated 24-h excretions were evaluated relative to mean daily Na and K intakes in the feeding study. Methods: A total of 153 older postmenopausal women ages 75.4 ± 3.5 y participated in a 2-wk controlled-feeding study with a 4-d repeating menu cycle based on their usual intake (ClinicalTrials.gov Identifier: NCT00000611). Of the 150 participants who provided both a first-void spot urine sample and a 24-h urine collection on the penultimate study day, statistical methods included Pearson correlations for Na and K between intake, 24-h collections, and the 24-h estimated excretions using 4 established algorithms: enhanced biomarker models by regressing ln-transformed intakes on ln-transformed 24-h excretions or ln-transformed 24-h estimated excretions plus participant characteristics and sensitivity analyses for factors potentially influencing Na or K excretion (e.g., possible kidney disease estimated glomerular filtration rate <60 mL/min/1.73 m2 ). Results: Pearson correlation coefficients between Na and K intakes and actual 24-h excretions were 0.57 and 0.38-0.44 for estimated 24-h excretions, depending on electrolyte and algorithm used. Enhanced biomarker model cross-validated R 2 (CVR2) for 24-h excretions were 38.5% (Na), 40.2% (K), and 42.0% (Na/K). After excluding participants with possible kidney disease, the CVR2 values were 43.2% (Na), 40.2% (K), and 38.1% (Na/K). Conclusions: Twenty-four-hour urine excretion measurement performs better than estimated 24-h excretion from a spot urine as a biomarker for Na and K intake among a sample of primarily White postmenopausal women.

5.
J Am Stat Assoc ; 116(535): 1330-1345, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34629570

RESUMO

Semiparametric, multiplicative-form regression models are specified for marginal single and double failure hazard rates for the regression analysis of multivariate failure time data. Cox-type estimating functions are specified for single and double failure hazard ratio parameter estimation, and corresponding Aalen-Breslow estimators are specified for baseline hazard rates. Generalization to allow classification of failure times into a smaller set of failure types, with failures of the same type having common baseline hazard functions, is also included. Asymptotic distribution theory arises by generalization of the marginal single failure hazard rate estimation results of Danyu Lin, L.J. Wei and colleagues. The Péano series representation for the bivariate survival function in terms of corresponding marginal single and double failure hazard rates leads to novel estimators for pairwise bivariate survival functions and pairwise dependency functions, at specified covariate history. Related asymptotic distribution theory follows from that for the marginal single and double failure hazard rates and the continuity, compact differentiability of the Péano series transformation and bootstrap applicability. Simulation evaluation of the proposed estimation procedures are presented, and an application to multiple clinical outcomes in the Women's Health Initiative Dietary Modification Trial is provided. Higher dimensional marginal hazard rate regression modeling is briefly mentioned.

6.
Am J Epidemiol ; 190(11): 2461-2473, 2021 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-34142699

RESUMO

Dietary guidance emphasizes healthy dietary patterns, but supporting evidence comes from self-reported dietary data, which are prone to measurement error. We explored whether nutritional biomarkers from the Women's Health Initiative Nutrition and Physical Activity Assessment Study Feeding Study (NPAAS-FS) (n = 153; 2010-2014) and the Women's Health Initiative Nutrition and Physical Activity Assessment Study Observational Study (NPAAS-OS) (n = 450; 2006-2009) could identify biomarker signatures of dietary patterns for development of corresponding regression calibration equations to help mitigate measurement error. Fasting blood samples were assayed for a specific panel of vitamins, carotenoids, and phospholipid fatty acids; 24-hour urine samples were assayed for nitrogen, sodium, and potassium levels. Intake records from the NPAAS-FS were used to calculate Healthy Eating Index 2010 (HEI-2010), Alternative Healthy Eating Index 2010 (AHEI-2010), alternative Mediterranean diet (aMED), and Dietary Approaches to Stop Hypertension (DASH) scores. Scores were regressed on blood and urine nutritional measures for discovery of dietary pattern biomarkers using a cross-validated model R2 ≥ 36% criterion (stage 1). Next, stepwise models (P ≤ 0.10 for entry/removal) using NPAAS-OS data were used to regress stage 1 dietary pattern biomarkers on NPAAS-OS self-reported dietary pattern scores using a food frequency questionnaire, a 4-day food record, and a 24-hour recall (stage 2). HEI-2010 and aMED analyses met the cross-validated R2 ≥ 36% criterion in stage 1, while AHEI-2010 and DASH analyses did not. The R2 values for HEI-2010 stage 2 calibration equations were as follows: food frequency questionnaire, 63.5%; 4-day food record, 83.1%; and 24-hour recall, 77.8%. Stage 2 aMED R2 values were 34.9%-46.8%. Dietary pattern biomarkers have potential for calibrating self-reports to enhance studies of diet-disease associations.


Assuntos
Biomarcadores/sangue , Dieta Saudável , Estado Nutricional , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/urina , Dieta Mediterrânea , Abordagens Dietéticas para Conter a Hipertensão , Feminino , Humanos , Pessoa de Meia-Idade , Pós-Menopausa/sangue , Pós-Menopausa/urina
8.
Eur J Nutr ; 60(8): 4207-4218, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33991228

RESUMO

PURPOSE: Objective biomarkers of dietary exposure are needed to establish reliable diet-disease associations. Unfortunately, robust biomarkers of macronutrient intakes are scarce. We aimed to assess the utility of serum, 24-h urine and spot urine high-dimensional metabolites for the development of biomarkers of daily intake of total energy, protein, carbohydrate and fat, and the percent of energy from these macronutrients (%E). METHODS: A 2-week controlled feeding study mimicking the participants' habitual diets was conducted among 153 postmenopausal women from the Women's Health Initiative (WHI). Fasting serum metabolomic profiles were analyzed using a targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for aqueous metabolites and a direct-injection-based quantitative lipidomics platform. Urinary metabolites were analyzed using 1H nuclear magnetic resonance (NMR) spectroscopy at 800 MHz and by untargeted gas chromatography-mass spectrometry (GC-MS). Variable selection was performed to build prediction models for each dietary variable. RESULTS: The highest cross-validated multiple correlation coefficients (CV-R2) for protein intake (%E) and carbohydrate intake (%E) using metabolites only were 36.3 and 37.1%, respectively. With the addition of established dietary biomarkers (doubly labeled water for energy and urinary nitrogen for protein), the CV-R2 reached 55.5% for energy (kcal/d), 52.0 and 45.0% for protein (g/d, %E), 55.9 and 37.0% for carbohydrate (g/d, %E). CONCLUSION: Selected panels of serum and urine metabolites, without the inclusion of doubly labeled water and urinary nitrogen biomarkers, give a reliable and robust prediction of daily intake of energy from protein and carbohydrate.


Assuntos
Metabolômica , Espectrometria de Massas em Tandem , Biomarcadores , Carboidratos , Cromatografia Líquida , Dieta , Feminino , Humanos
9.
Am J Clin Nutr ; 113(5): 1083-1092, 2021 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-33876183

RESUMO

The dietary modification (DM) clinical trial, within the Women's Health Initiative (WHI), studied a low-fat dietary pattern intervention that included guidance to increase vegetables, fruit, and grains. This study was motivated in part from uncertainty about the reliability of observational studies examining the association between dietary fat and chronic disease risk by using self-reported dietary data. In addition to this large trial, which had breast and colorectal cancer as its primary outcomes, a substantial biomarker research effort was initiated midway in the WHI program to contribute to nutritional epidemiology research more broadly. Here we review and update findings from the DM trial and from the WHI nutritional biomarker studies and examine implications for future nutritional epidemiology research. The WHI included the randomized controlled DM trial (n = 48,835) and a prospective cohort observational (OS) study (n = 93,676), both among postmenopausal US women, aged 50-79 y when enrolled during 1993-1998. Also reviewed is a nutrition and physical activity assessment study in a subset of 450 OS participants (2007-2009) and a related controlled feeding study among 153 WHI participants (2010-2014). Long-term follow-up in the DM trial provides evidence for intervention-related reductions in breast cancer mortality, diabetes requiring insulin, and coronary artery disease in the subset of normotensive healthy women, without observed adverse effects or changes in all-cause mortality. Studies of intake biomarkers, and of biomarker-calibrated intake, suggest important associations of total energy intake and macronutrient dietary composition with the risk for major chronic diseases among postmenopausal women. Collectively these studies argue for a nutrition epidemiology research agenda that includes major efforts in nutritional biomarker development, and in the application of biomarkers combined with self-reported dietary data in disease association analyses. We expect such efforts to yield novel disease association findings and to inform disease prevention approaches for potential testing in dietary intervention trials. This trial was registered at clinicaltrials.gov as NCT00000611.


Assuntos
Dieta , Fenômenos Fisiológicos da Nutrição , Saúde da Mulher , Feminino , Humanos , Estado Nutricional
10.
J Nutr ; 151(8): 2330-2341, 2021 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-33880504

RESUMO

BACKGROUND: Knowledge about macronutrient intake and chronic disease risk has been limited by the absence of objective macronutrient measures. Recently, we proposed novel biomarkers for protein, protein density, carbohydrate, and carbohydrate density, using established biomarkers and serum and urine metabolomics profiles in a human feeding study. OBJECTIVES: We aimed to use these biomarkers to develop calibration equations for macronutrient variables using dietary self-reports and personal characteristics and to study the association between biomarker-calibrated intake estimates and cardiovascular disease, cancer, and diabetes risk in Women's Health Initiative (WHI) cohorts. METHODS: Prospective disease association analyses are based on WHI cohorts of postmenopausal US women aged 50-79 y when enrolled at 40 US clinical centers (n = 81,954). We used biomarker intake values in a WHI nutritional biomarker study (n = 436) to develop calibration equations for each macronutrient variable, leading to calibrated macronutrient intake estimates throughout WHI cohorts. We then examined the association of these intakes with chronic disease incidence over a 20-y (median) follow-up period using HR regression methods. RESULTS: In analyses that included doubly labeled water-calibrated total energy, HRs for cardiovascular diseases and cancers were mostly unrelated to calibrated protein density. However, many were inversely related to carbohydrate density, with HRs (95% CIs) for a 20% increment in carbohydrate density of 0.81 (0.69, 0.95) and 0.83 (0.74, 0.93), respectively, for primary outcomes of coronary heart disease and breast cancer, as well as 0.74 (0.60, 0.91) and 0.87 (0.81, 0.93) for secondary outcomes of heart failure and total invasive cancer. Corresponding HRs (95% CIs) for type 2 diabetes incidence in relation to protein density and carbohydrate density were 1.17 (1.09, 1.75) and 0.73 (0.66, 0.80), respectively. CONCLUSIONS: At specific energy intake, a diet high in carbohydrate density is associated with substantially reduced risk of major chronic diseases in a population of US postmenopausal women. This trial was registered at clinicaltrials.gov as NCT00000611.

12.
Am J Epidemiol ; 190(3): 365-375, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33025002

RESUMO

The health benefits and risks of menopausal hormone therapy among women aged 50-59 years are examined in the Women's Health Initiative randomized, placebo-controlled trials using long-term follow-up data and a parsimonious statistical model that leverages data from older participants to increase precision. These trials enrolled 27,347 healthy postmenopausal women aged 50-79 years at 40 US clinical centers during 1993-1998, including 10,739 post-hysterectomy participants in a trial of conjugated equine estrogens and 16,608 participants with a uterus in the trial of these estrogens plus medroxyprogesterone acetate. Over a (median) 18-year follow-up period (1993-2016), risk for a global index (defined as the earliest of coronary heart disease, invasive breast cancer, stroke, pulmonary embolism, colorectal cancer, endometrial cancer, hip fracture, and all-cause mortality) was reduced with conjugated equine estrogens with a hazard ratio of 0.82 (95% confidence interval: 0.71, 0.95), and with nominally significant reductions for coronary heart disease, breast cancer, hip fracture, and all-cause mortality. Corresponding global index hazard ratio estimates of 1.06 (95% confidence interval: 0.95, 1.19) were nonsignificant for combined estrogens plus progestin, but increased breast cancer risk and reduced endometrial cancer risk were observed. These results, among women 50-59 years of age, substantially agree with the worldwide observational literature, with the exception of breast cancer for estrogens alone.


Assuntos
Terapia de Reposição de Estrogênios/estatística & dados numéricos , Doença das Coronárias/epidemiologia , Estrogênios Conjugados (USP)/administração & dosagem , Feminino , Fraturas do Quadril/epidemiologia , Humanos , Acetato de Medroxiprogesterona/administração & dosagem , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Pós-Menopausa , Modelos de Riscos Proporcionais , Embolia Pulmonar/epidemiologia , Acidente Vascular Cerebral/epidemiologia
13.
Biometrics ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33021738

RESUMO

The identification of valid surrogate markers of disease or disease progression has the potential to decrease the length and costs of future studies. Most available methods that assess the value of a surrogate marker ignore the fact that surrogates are often measured with error. Failing to adjust for measurement error can erroneously identify a useful surrogate marker as not useful or vice versa. We investigate and propose robust methods to correct for the effect of measurement error when evaluating a surrogate marker using multiple estimators developed for parametric and nonparametric estimates of the proportion of treatment effect explained by the surrogate marker. In addition, we quantify the attenuation bias induced by measurement error and develop inference procedures to allow for variance and confidence interval estimation. Through a simulation study, we show that our proposed estimators correct for measurement error in the surrogate marker and that our inference procedures perform well in finite samples. We illustrate these methods by examining a potential surrogate marker that is measured with error, hemoglobin A1c, using data from the Diabetes Prevention Program clinical trial.

14.
J Nutr ; 150(10): 2764-2771, 2020 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-32712658

RESUMO

BACKGROUND: The carbon isotope ratio (CIR) is a proposed biomarker for added sugar (AS) intake in the United States; however, because the CIR is also associated with meat intake in most populations the need for specificity remains. The CIR of amino acids (AAs) has the potential to differentiate sugars from meat intakes, because essential AAs must derive from dietary protein whereas certain nonessential AAs can be synthesized from sugars. OBJECTIVES: We tested whether serum CIR-AAs in combination with participant characteristics could meet a prespecified biomarker criterion for AS intake in the Nutrition and Physical Activity Assessment Study Feeding Study (NPAAS-FS) of the Women's Health Initiative, a population in which the whole-serum CIR was not associated with AS intake. METHODS: Postmenopausal women (n = 145) from Seattle, WA, were provided with individualized diets that approximated their habitual food intakes for 2 wk. Dietary intakes from consumed foods were characterized over the feeding period using the Nutrition Data System for Research. The CIR of 7 AAs-Ala, Gly, Val, Leu, Ile, Pro, and Phe-were measured in fasting serum collected at the end of the 2-wk feeding period, using gas chromatography-combustion isotope ratio mass spectrometry. Biomarker models were evaluated using regression R2 ≥ 0.36 as a major biomarker criterion, based on the benchmark R2 values of well-established recovery biomarkers in the NPAAS-FS. RESULTS: AS intake was associated with CIR-Ala (ρ = 0.32; P < 0.0001). A model of AS intake based on CIR-Ala, CIR-Gly, CIR-Ile, smoking, leisure physical activity, and body weight met the biomarker criterion (R2 = 0.37). Biomarker-estimated AS intake was not associated with meat or animal protein intake. CONCLUSIONS: Results support serum CIR-AAs in combination with participant characteristics as potential biomarkers of AS intake in US populations, including those with low AS intake.The Women's Health Initiative is registered at clinicaltrials.gov (NCT00000611).


Assuntos
Aminoácidos/sangue , Isótopos de Carbono/sangue , Açúcares da Dieta/administração & dosagem , Pós-Menopausa , Idoso , Biomarcadores/sangue , Dieta , Açúcares da Dieta/metabolismo , Comportamento Alimentar , Feminino , Humanos , Fenômenos Fisiológicos da Nutrição , Estado Nutricional , Estados Unidos
15.
JAMA ; 324(4): 369-380, 2020 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-32721007

RESUMO

Importance: The influence of menopausal hormone therapy on breast cancer remains unsettled with discordant findings from observational studies and randomized clinical trials. Objective: To assess the association of prior randomized use of estrogen plus progestin or prior randomized use of estrogen alone with breast cancer incidence and mortality in the Women's Health Initiative clinical trials. Design, Setting, and Participants: Long-term follow-up of 2 placebo-controlled randomized clinical trials that involved 27 347 postmenopausal women aged 50 through 79 years with no prior breast cancer and negative baseline screening mammogram. Women were enrolled at 40 US centers from 1993 to 1998 with follow-up through December 31, 2017. Interventions: In the trial involving 16 608 women with a uterus, 8506 were randomized to receive 0.625 mg/d of conjugated equine estrogen (CEE) plus 2.5 mg/d of medroxyprogesterone acetate (MPA) and 8102, placebo. In the trial involving 10 739 women with prior hysterectomy, 5310 were randomized to receive 0.625 mg/d of CEE alone and 5429, placebo. The CEE-plus-MPA trial was stopped in 2002 after 5.6 years' median intervention duration, and the CEE-only trial was stopped in 2004 after 7.2 years' median intervention duration. Main Outcomes and Measures: The primary outcome was breast cancer incidence (protocol prespecified primary monitoring outcome for harm) and secondary outcomes were deaths from breast cancer and deaths after breast cancer. Results: Among 27 347 postmenopausal women who were randomized in both trials (baseline mean [SD] age, 63.4 years [7.2 years]), after more than 20 years of median cumulative follow-up, mortality information was available for more than 98%. CEE alone compared with placebo among 10 739 women with a prior hysterectomy was associated with statistically significantly lower breast cancer incidence with 238 cases (annualized rate, 0.30%) vs 296 cases (annualized rate, 0.37%; hazard ratio [HR], 0.78; 95% CI, 0.65-0.93; P = .005) and was associated with statistically significantly lower breast cancer mortality with 30 deaths (annualized mortality rate, 0.031%) vs 46 deaths (annualized mortality rate, 0.046%; HR, 0.60; 95% CI, 0.37-0.97; P = .04). In contrast, CEE plus MPA compared with placebo among 16 608 women with a uterus was associated with statistically significantly higher breast cancer incidence with 584 cases (annualized rate, 0.45%) vs 447 cases (annualized rate, 0.36%; HR, 1.28; 95% CI, 1.13-1.45; P < .001) and no significant difference in breast cancer mortality with 71 deaths (annualized mortality rate, 0.045%) vs 53 deaths (annualized mortality rate, 0.035%; HR, 1.35; 95% CI, 0.94-1.95; P= .11). Conclusions and Relevance: In this long-term follow-up study of 2 randomized trials, prior randomized use of CEE alone, compared with placebo, among women who had a previous hysterectomy, was significantly associated with lower breast cancer incidence and lower breast cancer mortality, whereas prior randomized use of CEE plus MPA, compared with placebo, among women who had an intact uterus, was significantly associated with a higher breast cancer incidence but no significant difference in breast cancer mortality.


Assuntos
Neoplasias da Mama/epidemiologia , Estrogênios Conjugados (USP)/efeitos adversos , Terapia de Reposição Hormonal/efeitos adversos , Histerectomia , Acetato de Medroxiprogesterona/efeitos adversos , Idoso , Neoplasias da Mama/induzido quimicamente , Neoplasias da Mama/mortalidade , Neoplasias da Mama/prevenção & controle , Estrogênios Conjugados (USP)/uso terapêutico , Feminino , Seguimentos , Humanos , Histerectomia/efeitos adversos , Incidência , Acetato de Medroxiprogesterona/uso terapêutico , Pessoa de Meia-Idade , Pós-Menopausa , Risco
17.
Am J Epidemiol ; 189(9): 972-981, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32314781

RESUMO

Dual-outcome intention-to-treat hazard rate analyses have potential to complement single-outcome analyses for the evaluation of treatments or exposures in relation to multivariate time-to-response outcomes. Here we consider pairs formed from important clinical outcomes to obtain further insight into influences of menopausal hormone therapy on chronic disease. As part of the Women's Health Initiative, randomized, placebo-controlled hormone therapy trials of conjugated equine estrogens (CEE) among posthysterectomy participants and of these same estrogens plus medroxyprogesterone acetate (MPA) among participants with an intact uterus were carried out at 40 US clinical centers (1993-2016). These data provide the context for analyses covering the trial intervention periods and a nearly 20-year (median) cumulative duration of follow-up. The rates of multiple outcome pairs were significantly influenced by hormone therapy, especially over cumulative follow-up, providing potential clinical and mechanistic insights. For example, among women randomized to either regimen, hazard ratios for pairs defined by fracture during intervention followed by death from any cause were reduced and hazard ratios for pairs defined by gallbladder disease followed by death were increased, though these findings may primarily reflect single-outcome associations. In comparison, hazard ratios for diabetes followed by death were reduced with CEE but not with CEE + MPA, and those for hypertension followed by death were increased with CEE + MPA but not with CEE.


Assuntos
Terapia de Reposição de Estrogênios , Ensaios Clínicos Controlados Aleatórios como Assunto , Idoso , Doenças Cardiovasculares/epidemiologia , Estrogênios Conjugados (USP)/administração & dosagem , Feminino , Fraturas Ósseas/epidemiologia , Doenças da Vesícula Biliar/epidemiologia , Humanos , Incidência , Análise de Intenção de Tratamento , Acetato de Medroxiprogesterona/administração & dosagem , Pessoa de Meia-Idade , Pós-Menopausa , Fatores de Risco , Estados Unidos/epidemiologia
19.
Cancer ; 126(13): 2956-2964, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32212335

RESUMO

After reports from the Women's Health Initiative randomized trial evaluating estrogen plus progestin, there was a sudden, substantial, and sustained decrease in all categories of menopausal hormone therapy, and the first reduction in age-adjusted breast cancer incidence in more than 20 years was seen in 2003-2004 among US women 50 years of age or older. Subsequent trends in breast cancer incidence have been described, but most reports have not focused on the postmenopausal age group or fully engaged the potential influence of reduced hormone therapy on breast cancer incidence trends by race/ethnicity. To address this gap, this commentary examines trends for annual age-adjusted breast cancer incidence over a 40-year period from 1975 to 2015 for white and black women on the basis of findings from the Surveillance, Epidemiology, and End Results 9 registries. Overall, the sharp decline in breast cancer incidence seen in 2003-2004 was followed in the subsequent decade by a continued low breast cancer incidence plateau in white women that has largely persisted. In contrast, a new discordance between breast cancer incidence trends in black and white women has emerged. In the 2005-2015 decade, a sustained increase in breast cancer incidence in black women has resulted in annual incidence rates comparable, for the first time, to those in white women. This commentary explores the hypothesis that the over-decade-long and discordant changes in breast cancer incidence rates in postmenopausal black and white women are, to a large extent, associated with changes in hormone therapy use in these 2 groups.


Assuntos
Afro-Americanos/estatística & dados numéricos , Neoplasias da Mama/epidemiologia , Terapia de Reposição de Estrogênios/tendências , Pós-Menopausa , /estatística & dados numéricos , Idoso , Neoplasias da Mama/induzido quimicamente , Neoplasias da Mama/etnologia , Terapia de Reposição de Estrogênios/efeitos adversos , Estrogênios/administração & dosagem , Estrogênios/efeitos adversos , Estrogênios Conjugados (USP)/administração & dosagem , Estrogênios Conjugados (USP)/efeitos adversos , Feminino , Terapia de Reposição Hormonal/efeitos adversos , Terapia de Reposição Hormonal/tendências , Humanos , Incidência , Acetato de Medroxiprogesterona/administração & dosagem , Acetato de Medroxiprogesterona/efeitos adversos , Pessoa de Meia-Idade , Pós-Menopausa/etnologia , Programa de SEER , Fatores de Tempo , Estados Unidos/epidemiologia , Saúde da Mulher
20.
Am J Clin Nutr ; 112(1): 168-179, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32133498

RESUMO

BACKGROUND: We recently presented associations between serum-based biomarkers of carotenoid and tocopherol intake and chronic disease risk in a Women's Health Initiative (WHI) Measurement Precision subcohort (n = 5488). Questions remain as to whether self-reported dietary data can usefully augment such biomarkers or can be calibrated using biomarkers for reliable disease association estimation in larger WHI cohorts. OBJECTIVES: The aims were to examine the potential of FFQ data to explain intake variation in a WHI Feeding Study and to compare association parameter estimates and their precision from studies based on biomarker-calibrated FFQ intake in larger WHI cohorts, with those previously presented. METHODS: Serum-based intake measures were augmented by using FFQ data in a WHI Feeding Study (n = 153). Corresponding calibration equations were generated, both in a companion Nutritional Biomarker Study (n = 436) and in the previously mentioned subcohort (n = 5488), by regressing these intake measures on dietary data and participant characteristics, for α- and ß-carotene, lutein plus zeaxanthin, and α-tocopherol. The supplemental value of FFQ data was considered by examining the fraction of feeding study intake variation explained by these regression models. Calibrated intake and disease association analyses were evaluated by comparisons with previously reported subcohort results. RESULTS: The inclusion of FFQ data led to some increases in feeding study intake variation explained (total R2 of ∼50%). Calibrated intake estimates explained 25-75% of serum-based intake variation, whether developed using either of the 2 cohort subsamples. Related disease associations for micronutrients were precisely estimated in larger WHI cohorts (n = 76,691) but were often closer to the null compared with previously reported associations. CONCLUSIONS: FFQ data may usefully augment blood concentrations in estimating the intake of carotenoids and tocopherols. Calibrated intake estimates using FFQ, dietary supplement, and participant characteristics only may require further justification to ensure reliable estimation of related disease associations.


Assuntos
Micronutrientes/sangue , Idoso , Biomarcadores/sangue , Carotenoides/sangue , Doença Crônica , Estudos de Coortes , Feminino , Humanos , Micronutrientes/metabolismo , Pessoa de Meia-Idade , Estado Nutricional , Saúde da Mulher , alfa-Tocoferol/sangue , beta Caroteno/sangue
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