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INTRODUCTION: During adolescence the breasts undergo rapid growth and development under the influence of sex hormones. Although the hormonal etiology of breast cancer is hypothesized, it remains unknown whether adolescent sex hormones are associated with adult breast density, which is a strong risk factor for breast cancer. METHODS: Percentage of dense breast volume (%DBV) was measured in 2006 by magnetic resonance imaging in 177 women aged 25-29 years who had participated in the Dietary Intervention Study in Children from 1988 to 1997. They had sex hormones and sex hormone-binding globulin (SHBG) measured in serum collected on one to five occasions between 8 and 17 years of age. Multivariable linear mixed-effect regression models were used to evaluate the associations of adolescent sex hormones and SHBG with %DBV. RESULTS: Dehydroepiandrosterone sulfate (DHEAS) and SHBG measured in premenarche serum samples were significantly positively associated with %DBV (all P trend ≤0.03) but not when measured in postmenarche samples (all P trend ≥0.42). The multivariable geometric mean of %DBV across quartiles of premenarcheal DHEAS and SHBG increased from 16.7 to 22.1 % and from 14.1 to 24.3 %, respectively. Estrogens, progesterone, androstenedione, and testosterone in pre- or postmenarche serum samples were not associated with %DBV (all P trend ≥0.16). CONCLUSIONS: Our results suggest that higher premenarcheal DHEAS and SHBG levels are associated with higher %DBV in young women. Whether this association translates into an increased risk of breast cancer later in life is currently unknown. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov Identifier, NCT00458588 April 9, 2007; NCT00000459 October 27, 1999.
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Mama/metabolismo , Hormonas Esteroides Gonadales/metabolismo , Imagen por Resonancia Magnética , Adolescente , Adulto , Mama/patología , Neoplasias de la Mama/sangre , Niño , Sulfato de Deshidroepiandrosterona/sangre , Sulfato de Deshidroepiandrosterona/metabolismo , Femenino , Hormonas Esteroides Gonadales/sangre , Humanos , Factores de Riesgo , Globulina de Unión a Hormona Sexual/metabolismoRESUMEN
PURPOSE: Breast density is strongly related to breast cancer risk, but determinants of breast density in young women remain largely unknown. METHODS: Associations of reproductive and menstrual characteristics with breast density measured by magnetic resonance imaging were evaluated in a cross-sectional study of 176 healthy women, 25-29 years old, using linear mixed effects models. RESULTS: Parity was significantly inversely associated with breast density. In multivariable adjusted models that included non-reproductive variables, mean percent dense breast volume (%DBV) decreased from 20.5 % in nulliparous women to 16.0 % in parous women, while mean absolute dense breast volume (ADBV) decreased from 85.3 to 62.5 cm(3). Breast density also was significantly inversely associated with the age women started using hormonal contraceptives, whereas it was significantly positively associated with duration of hormonal contraceptive use. In adjusted models, mean %DBV decreased from 21.7 % in women who started using hormones at 12-17 years of age to 14.7 % in those who started using hormones at 22-28 years of age, while mean ADBV decreased from 86.2 to 53.7 cm(3). The age at which women started using hormonal contraceptives and duration of hormone use were inversely correlated, and mean %DBV increased from 15.8 % in women who used hormones for not more than 2.0 years to 22.0 % in women who used hormones for more than 8 years, while mean ADBV increased from 61.9 to 90.4 cm(3) over this interval. CONCLUSIONS: Breast density in young women is inversely associated with parity and the age women started using hormonal contraceptives but positively associated with duration of hormone use.
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Mama/anatomía & histología , Menarquia/fisiología , Menstruación/fisiología , Reproducción/fisiología , Adulto , Factores de Edad , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/prevención & control , Anticoncepción/estadística & datos numéricos , Anticonceptivos Hormonales Orales/administración & dosificación , Estudios Transversales , Femenino , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética/métodos , Análisis Multivariante , Encuestas y Cuestionarios , Factores de TiempoRESUMEN
INTRODUCTION: Breast density is one of the strongest risk factors for breast cancer, but determinants of breast density in young women remain largely unknown. METHODS: Associations of height, adiposity and body fat distribution with percentage dense breast volume (%DBV) and absolute dense breast volume (ADBV) were evaluated in a cross-sectional study of 174 healthy women, 25 to 29 years old. Adiposity and body fat distribution were measured by anthropometry and dual-energy X-ray absorptiometry (DXA), while %DBV and ADBV were measured by magnetic resonance imaging. Associations were evaluated using linear mixed-effects models. All tests of statistical significance are two-sided. RESULTS: Height was significantly positively associated with %DBV but not ADBV; for each standard deviation (SD) increase in height, %DBV increased by 18.7% in adjusted models. In contrast, all measures of adiposity and body fat distribution were significantly inversely associated with %DBV; a SD increase in body mass index (BMI), percentage fat mass, waist circumference and the android:gynoid fat mass ratio (A:G ratio) was each associated significantly with a 44.4 to 47.0% decrease in %DBV after adjustment for childhood BMI and other covariates. Although associations were weaker than for %DBV, all measures of adiposity and body fat distribution also were significantly inversely associated with ADBV before adjustment for childhood BMI. After adjustment for childhood BMI, however, only the DXA measures of percentage fat mass and A:G ratio remained significant; a SD increase in each was associated with a 13.8 to 19.6% decrease in ADBV. In mutually adjusted analysis, the percentage fat mass and the A:G ratio remained significantly inversely associated with %DBV, but only the A:G ratio was significantly associated with ADBV; a SD increase in the A:G ratio was associated with an 18.5% decrease in ADBV. CONCLUSION: Total adiposity and body fat distribution are independently inversely associated with %DBV, whereas in mutually adjusted analysis only body fat distribution (A:G ratio) remained significantly inversely associated with ADBV in young women. Research is needed to identify biological mechanisms underlying these associations.
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Absorciometría de Fotón , Adiposidad , Distribución de la Grasa Corporal , Estatura , Glándulas Mamarias Humanas , Adulto , Factores de Edad , Pesos y Medidas Corporales , Neoplasias de la Mama/patología , Estudios Transversales , Femenino , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética , Factores de RiesgoRESUMEN
BACKGROUND: To evaluate the U.K. Prospective Diabetes Study (UKPDS) and Framingham risk equations for predicting short-term risk of coronary heart disease (CHD) events among adults with long-standing type 2 diabetes, including those with and without preexisting CHD. METHODS: Prospective cohort of U.S. managed care enrollees aged ≥ 18 years and mean diabetes duration of more than 10 years, participating in the Translating Research into Action for Diabetes (TRIAD) study, was followed for the first occurrence of CHD events from 2000 to 2003. The UKPDS and Framingham risk equations were evaluated for discriminating power and calibration. RESULTS: A total of 8303 TRIAD participants, were identified to evaluate the UKPDS (n = 5914, 120 events), Framingham-initial (n = 5914, 218 events) and Framingham-secondary (n = 2389, 374 events) risk equations, according to their prior CHD history. All of these equations exhibited low discriminating power with Harrell's c-index <0.65. All except the Framingham-initial equation for women and the Framingham-secondary equation for men had low levels of calibration. After adjsusting for the average values of predictors and event rates in the TRIAD population, the calibration of these equations greatly improved. CONCLUSIONS: The UKPDS and Framingham risk equations may be inappropriate for predicting the short-term risk of CHD events in patients with long-standing type 2 diabetes, partly due to changes in medications used by patients with diabetes and other improvements in clinical care since the Frmaingham and UKPDS studies were conducted. Refinement of these equations to reflect contemporary CHD profiles, diagnostics and therapies are needed to provide reliable risk estimates to inform effective treatment.
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CONTEXT: Childhood diet is hypothesized to influence development of chronic disease in adulthood. OBJECTIVE: Our objective was to evaluate the long-term effects of a dietary intervention to reduce fat and increase fiber intake during childhood and adolescence on the prevalence of metabolic syndrome in young adult women. DESIGN: A follow-up study was conducted in 2006-2008, 9 yr after termination of the Dietary Intervention Study in Children (DISC). SETTING: The study took place at six DISC clinical centers in the United States. PARTICIPANTS: A total of 230 (76%) DISC female participants who were 25-29 yr old and had not been pregnant or breastfeeding in the previous 3 months participated in the follow-up study. INTERVENTION: There was no intervention between the end of the DISC trial and the follow-up visit. MAIN OUTCOME MEASURE: Metabolic syndrome was the primary study endpoint planned before data collection and was hypothesized to be less common in the intervention group participants. RESULTS: Metabolic syndrome was uncommon, and its prevalence did not differ by treatment group. However, after adjustment for nondietary variables, mean systolic blood pressures of intervention and control group participants were 107.7 and 110.0 mm Hg, respectively (P = 0.03), whereas mean fasting plasma glucose levels were 87.0 and 89.1 mg/dl, respectively (P = 0.01). Intervention group participants also had lower concentrations of large very-low-density lipoprotein particles, a marker of hepatic insulin resistance, compared with control group participants. Adjustment for current diet did not materially alter results. CONCLUSION: Consumption of a diet lower in fat and higher in fiber during childhood and adolescence may benefit glycemic control and blood pressure long term.
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Dieta , Conducta Alimentaria , Síndrome Metabólico/metabolismo , Adolescente , Adulto , Presión Sanguínea/fisiología , Niño , Grasas de la Dieta , Fibras de la Dieta , Femenino , Estudios de Seguimiento , Humanos , Resistencia a la Insulina/fisiología , Estudios Longitudinales , Síndrome Metabólico/etiología , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
OBJECTIVE: To determine the effectiveness of the 12-week workplace intervention (WIP) on energy intake, weight, physical activity (PA) and cardiovascular disease (CVD) risk and the effect of delivery method on outcomes. METHODS: A prospective clinical trial of a 12-week WIP comparing In-person and Internet-based delivery. All subjects received identical intervention with dietitian visits at baseline and weeks 6, 12 and 26. Subjects included overweight/obese academic health science center employees. Changes in weight, PA and CVD-risk were primary outcomes. RESULTS: There was no significant treatment effect repeated-measure-ANOVA. Within subjects, significant main effects indicating improvement were noted at week-12 in weight, WC, body-fat, HRQOL and energy intake and at week-26 in weight, WC, body-fat, HRQOL, energy intake and systolic and diastolic BP. CONCLUSIONS: Improvements in some outcomes following a 12-week WIP were independent of delivery method.
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Promoción de la Salud/métodos , Sobrepeso/terapia , Pérdida de Peso , Lugar de Trabajo , Adulto , Análisis de Varianza , Peso Corporal , Enfermedades Cardiovasculares/prevención & control , Consejo/métodos , Dieta , Ejercicio Físico , Femenino , Humanos , Internet , Masculino , Persona de Mediana Edad , Actividad Motora , New Jersey/epidemiología , Sobrepeso/epidemiología , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Studies have associated thiazolidinedione (TZD) treatment with cardiovascular disease (CVD) and questioned whether the two available TZDs, rosiglitazone and pioglitazone, have different CVD risks. We compared CVD incidence, cardiovascular (CV), and all-cause mortality in type 2 diabetic patients treated with rosiglitazone or pioglitazone as their only TZD. METHODS: We analyzed survey, medical record, administrative, and National Death Index (NDI) data from 1999 through 2003 from Translating Research Into Action for Diabetes (TRIAD), a prospective observational study of diabetes care in managed care. Medications, CV procedures, and CVD were determined from health plan (HP) administrative data, and mortality was from NDI. Adjusted hazard rates (AHR) were derived from Cox proportional hazard models adjusted for age, sex, race/ethnicity, income, history of diabetic nephropathy, history of CVD, insulin use, and HP. RESULTS: Across TRIAD's 10 HPs, 1,815 patients (24%) filled prescriptions for a TZD, 773 (10%) for only rosiglitazone, 711 (10%) for only pioglitazone, and 331 (4%) for multiple TZDs. In the seven HPs using both TZDs, 1,159 patients (33%) filled a prescription for a TZD, 564 (16%) for only rosiglitazone, 334 (10%) for only pioglitazone, and 261 (7%) for multiple TZDs. For all CV events, CV, and all-cause mortality, we found no significant difference between rosiglitazone and pioglitazone. CONCLUSIONS: In this relatively small, prospective, observational study, we found no statistically significant differences in CV outcomes for rosiglitazone- compared to pioglitazone-treated patients. There does not appear to be a pattern of clinically meaningful differences in CV outcomes for rosiglitazone- versus pioglitazone-treated patients.
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Enfermedades Cardiovasculares/inducido químicamente , Hipoglucemiantes/efectos adversos , Tiazolidinedionas/efectos adversos , Anciano , Enfermedades Cardiovasculares/mortalidad , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Femenino , Humanos , Hipoglucemiantes/uso terapéutico , Masculino , Programas Controlados de Atención en Salud , Persona de Mediana Edad , Pioglitazona , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Factores de Riesgo , Rosiglitazona , Tiazolidinedionas/uso terapéuticoRESUMEN
BACKGROUND: Adolescent diet is hypothesized to influence breast cancer risk. We evaluated the long-term effects of an intervention to lower fat intake among adolescent girls on biomarkers that are related to breast cancer risk in adults. METHODS: A follow-up study was conducted on 230 girls who participated in the Dietary Intervention Study in Children (DISC), in which healthy, prepubertal, 8 to 10 year olds were randomly assigned to usual care or to a behavioral intervention that promoted a reduced fat diet. Participants were 25 to 29 years old at follow-up visits. All tests of statistical significance are two-sided. RESULTS: In analyses that did not take account of diet at the time of the follow-up visit, the only statistically significant treatment group difference was higher bone mineral content in intervention group participants compared with usual care group participants; their mean bone mineral contents were 2,444 and 2,377 g, respectively. After adjustment for current diet, the intervention group also had statistically significantly higher bone mineral density and luteal phase serum estradiol concentrations. Serum progesterone concentrations and breast density did not differ by treatment group in unadjusted or adjusted analyses. CONCLUSIONS: Results do not support the hypothesis that consumption of a lower fat diet during adolescence reduces breast cancer risk via effects on subsequent serum estradiol and progesterone levels, breast density, or bone mineral density. It remains unclear, however, if the results are specific to the DISC intervention or are more broadly applicable. IMPACT: Modest reductions in fat intake during adolescence are unlikely to lower later breast cancer risk via long-term effects on the biomarkers measured.
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Densidad Ósea , Neoplasias de la Mama/prevención & control , Mama/anatomía & histología , Dieta con Restricción de Grasas , Hormonas Gonadales/sangre , Adolescente , Adulto , Niño , LDL-Colesterol/sangre , Dieta , Estradiol/sangre , Femenino , Estudios de Seguimiento , Humanos , Mamografía , Progesterona/sangre , Globulina de Unión a Hormona Sexual/metabolismo , Adulto JovenRESUMEN
OBJECTIVES: The aim of this study was to investigate whether multiple biomarkers contribute to improved coronary heart disease (CHD) risk prediction in post-menopausal women compared with assessment using traditional risk factors (TRFs) only. BACKGROUND: The utility of newer biomarkers remains uncertain when added to predictive models using only TRFs for CHD risk assessment. METHODS: The Women's Health Initiative Hormone Trials enrolled 27,347 post-menopausal women ages 50 to 79 years. Associations of TRFs and 18 biomarkers were assessed in a nested case-control study including 321 patients with CHD and 743 controls. Four prediction equations for 5-year CHD risk were compared: 2 Framingham risk score covariate models; a TRF model including statin treatment, hormone treatment, and cardiovascular disease history as well as the Framingham risk score covariates; and an additional biomarker model that additionally included the 5 significantly associated markers of the 18 tested (interleukin-6, d-dimer, coagulation factor VIII, von Willebrand factor, and homocysteine). RESULTS: The TRF model showed an improved C-statistic (0.729 vs. 0.699, p = 0.001) and net reclassification improvement (6.42%) compared with the Framingham risk score model. The additional biomarker model showed additional improvement in the C-statistic (0.751 vs. 0.729, p = 0.001) and net reclassification improvement (6.45%) compared with the TRF model. Predicted CHD risks on a continuous scale showed high agreement between the TRF and additional biomarker models (Spearman's coefficient = 0.918). Among the 18 biomarkers measured, C-reactive protein level did not significantly improve CHD prediction either alone or in combination with other biomarkers. CONCLUSIONS: Moderate improvement in CHD risk prediction was found when an 18-biomarker panel was added to predictive models using TRFs in post-menopausal women.
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Enfermedad Coronaria/sangre , Enfermedad Coronaria/etiología , Factores de Edad , Anciano , Biomarcadores/sangre , Estudios de Casos y Controles , Estudios de Cohortes , Enfermedad Coronaria/diagnóstico , Femenino , Humanos , Modelos Logísticos , Persona de Mediana Edad , Posmenopausia/sangre , Valor Predictivo de las Pruebas , Pronóstico , Factores de Riesgo , Factores SexualesRESUMEN
INTRODUCTION: Many patients with diabetes have poorly controlled blood glucose, lipid, or blood pressure levels, increasing their risk for cardiovascular disease (CVD) and other complications. Relatively little is known about what physicians perceive to be barriers to good CVD risk factor control or their own role in helping patients achieve good control. METHODS: We interviewed 34 primary care physicians in 4 states to assess their perceptions of patients' barriers to CVD risk factor control. Interviews were coded and analyzed for emergent themes. RESULTS: Physicians attributed barriers primarily to patients (socioeconomic issues, competing medical conditions, and lack of motivation) or to health system barriers (cost of care or lack of a multidisciplinary team). Physicians also expressed high levels of frustration with their efforts to address barriers. CONCLUSIONS: Physicians felt that barriers to CVD risk factor control often were beyond their abilities to address. Training physicians or other members of the primary health care team to address patients' personal barriers and health system barriers to good control could help alleviate high frustration levels, improve relationships with patients, and improve the treatment of diabetes. Supporting such efforts with adequate reimbursement should be a focus of health care reform.
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Actitud del Personal de Salud , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/psicología , Angiopatías Diabéticas/prevención & control , Angiopatías Diabéticas/psicología , Accesibilidad a los Servicios de Salud , Cooperación del Paciente/psicología , Rol del Médico/psicología , Conducta Cooperativa , Frustación , Conductas Relacionadas con la Salud , Investigación sobre Servicios de Salud , Humanos , Estilo de Vida , Programas Controlados de Atención en Salud , Grupo de Atención al Paciente , Relaciones Médico-Paciente , Atención Primaria de Salud , Garantía de la Calidad de Atención de Salud , Factores de Riesgo , Estados UnidosRESUMEN
Women with benign proliferative breast disease are at increased risk of subsequent breast cancer. Estrogens and progesterone exert proliferative effects on mammary epithelium, and combined hormone replacement therapy has been associated with increased breast cancer risk. We tested the effect of conjugated equine estrogen plus progestin on the risk of benign proliferative breast disease in the Women's Health Initiative (WHI) randomized controlled trial. In the WHI trial of estrogen plus progestin, 16,608 postmenopausal women were randomly assigned either to 0.625 mg/day of conjugated equine estrogen plus 2.5 mg/day of medroxyprogesterone acetate or to placebo. Baseline and annual breast exams and mammograms were required. The trial was terminated early (average follow-up, 5.5 years). We identified women who had had a biopsy for benign breast disease, and subjected histologic sections from the biopsies to standardized review. Overall, 178 incident cases of benign proliferative breast disease were ascertained in the estrogen plus progestin group and 99 in the placebo group. The use of estrogen plus progestin was associated with a 74% increase in the risk of benign proliferative breast disease [hazard ratio, 1.74; 95% confidence interval (CI), 1.35-2.25]. For benign proliferative breast disease without atypia the hazard ratio was 2.00 (95% CI, 1.50-2.66), while for atypical hyperplasia it was 0.76 (95% CI, 0.38-1.52). The risk varied little by levels of baseline characteristics. The results of this study suggest that the use of estrogen plus progestin may increase the risk of benign proliferative breast disease.
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Enfermedades de la Mama/inducido químicamente , Terapia de Reemplazo de Estrógeno/efectos adversos , Estrógenos/efectos adversos , Progestinas/efectos adversos , Anciano , Biopsia , Enfermedades de la Mama/diagnóstico , Enfermedades de la Mama/epidemiología , Estrógenos/administración & dosificación , Femenino , Humanos , Hiperplasia/inducido químicamente , Hiperplasia/diagnóstico , Hiperplasia/epidemiología , Incidencia , Mamografía , Persona de Mediana Edad , Posmenopausia , Lesiones Precancerosas/inducido químicamente , Lesiones Precancerosas/diagnóstico , Lesiones Precancerosas/epidemiología , Progestinas/administración & dosificación , Modelos de Riesgos Proporcionales , Riesgo , Estados Unidos/epidemiologíaRESUMEN
Blood lipids and high-sensitivity C-reactive protein (hs-CRP) are altered by hormone therapy. The goal of the present study was to determine whether lipids and hs-CRP have predictive value for hormone therapy benefit or risk for coronary heart disease events in postmenopausal women without previous cardiovascular disease. A nested case-control study was performed in the Women's Health Initiative hormone trials. Baseline lipids and hs-CRP were obtained from 271 incident patients with coronary heart disease (cases) and 707 controls. In a combined trial analysis, favorable lipid status at baseline tended to predict better coronary heart disease outcomes when using conjugated equine estrogen (CEE) with or without medroxyprogesterone acetate (MPA). Women with a low-density lipoprotein (LDL)/high-density lipoprotein (HDL) cholesterol ratio <2.5 had no increase in risk of coronary heart disease when using CEE with or without MPA (odds ratio 0.60, 95% confidence interval 0.34 to 1.06), whereas women with an LDL/HDL cholesterol ratio > or =2.5 had increased risk of coronary heart disease (odds ratio 1.73, 95% confidence interval 1.18 to 2.53, p for interaction = 0.02). Low hs-CRP added marginally to the value of LDL/HDL ratio <2.5 when predicting coronary heart disease benefit on hormone therapy. In conclusion, postmenopausal women with undesirable lipid levels had excess coronary heart disease risk when using CEE with or without MPA. However, women with favorable lipid levels, especially LDL/HDL cholesterol ratio <2.5, did not have increased risk of coronary heart disease with CEE with or without MPA irrespective of hs-CRP.
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Proteína C-Reactiva/metabolismo , Enfermedad Coronaria/inducido químicamente , Estrógenos Conjugados (USP)/efectos adversos , Estrógenos/efectos adversos , Lípidos/sangre , Menopausia/sangre , Anciano , Biomarcadores/sangre , Enfermedad Coronaria/sangre , Enfermedad Coronaria/epidemiología , Estrógenos/uso terapéutico , Estrógenos Conjugados (USP)/uso terapéutico , Femenino , Estudios de Seguimiento , Humanos , Menopausia/efectos de los fármacos , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Factores de RiesgoRESUMEN
CONTEXT: Diet reportedly alters serum sex hormone concentrations in adults, but little is known about the influence of diet during puberty on these hormones. OBJECTIVE: We aimed to determine whether an intervention to lower fat intake during adolescence alters serum sex hormone concentrations and progression through puberty. DESIGN: In 1990-1997, we conducted an ancillary study to the Dietary Intervention Study in Children, a multicenter, randomized, controlled clinical trial to test the safety and efficacy of a cholesterol-lowering dietary intervention in children. PARTICIPANTS: Healthy, prepubertal, 8 to 10 yr olds with elevated low-density lipoprotein cholesterol were randomized to usual care or a behavioral intervention. Of 362 randomized Dietary Intervention Study in Children boys, 354 participated in the ancillary study. Eighty-four percent of boys attended last visits when their median time on trial was 7.1 yr. INTERVENTION: The behavioral intervention continued throughout the duration of the trial and promoted a diet with 28% energy from total fat, less than 8% from saturated fat, 9% or less from polyunsaturated fat, and less than 75 mg cholesterol per 1000 kcal. OUTCOME MEASURES: The main outcome measure for boys formulated before study initiation was non-SHBG bound testosterone concentration. Secondary outcomes included serum total testosterone, dihydrotestosterone, androstenedione, estradiol, estrone, SHBG, and Tanner stage. RESULTS: There were no significant treatment group differences in boys' serum hormone levels, SHBG, or Tanner stages at any individual visit or over the course of the trial when evaluated by longitudinal models. CONCLUSION: Modest reductions in total fat, saturated fat, and possibly energy intake do not alter progression through puberty or serum sex hormone concentrations in adolescent boys.
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Dieta , Hormonas Esteroides Gonadales/sangre , Pubertad/sangre , Androstenodiona/sangre , Niño , LDL-Colesterol/sangre , Dihidrotestosterona/sangre , Estradiol/sangre , Humanos , Masculino , Globulina de Unión a Hormona Sexual/análisis , Testosterona/sangreRESUMEN
OBJECTIVES: To assess the extent to which prior hormone therapy modifies the breast cancer risk found with estrogen plus progestin (E+P) in the Women's Health Initiative (WHI) randomized trial. METHODS: Subgroup analyses of prior hormone use on invasive breast cancer incidence in 16,608 postmenopausal women in the WHI randomized trial of E+P over an average 5.6 years of follow-up. RESULTS: Small but statistically significant differences were found between prior HT users and non-users for most breast cancer risk factors but Gail risk scores were similar. Duration of E+P use within the trial (mean 4.4 years, S.D. 2.0) did not vary by prior use. Among 4311 prior users, the adjusted hazard ratio (HR) for E+P versus placebo was 1.96 (95% confidence interval [CI]: 1.17-3.27), significantly different (p=0.03) from that among 12,297 never users (HR 1.02; 95% CI: 0.77-1.36). The interaction between study arm and follow-up time was significant overall (p=0.01) and among never users (p=0.02) but not among prior users (p=0.10). The cumulative incidence over time for the E+P and placebo groups appeared to cross after about 3 years in prior users, and after about 5 years in women with no prior use. No interaction was found with duration (p=0.08) or recency of prior use (p=0.17). Prior hormone use significantly increased the E+P hazard ratio for larger, more advanced tumors. CONCLUSION: A safe interval for combined hormone use could not be reliably defined with these data. However, the significant increase in breast cancer risk in the trial overall after only 5.6 years of follow-up, initially concentrated in women with prior hormone exposure, but with increasing risk over time in women without prior exposure, suggests that durations only slightly longer than those in the WHI trial are associated with increased risk of breast cancer. Longer-term exposure and follow-up data are needed.
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Neoplasias de la Mama/etiología , Terapia de Reemplazo de Estrógeno/efectos adversos , Anciano , Neoplasias de la Mama/epidemiología , Distribución de Chi-Cuadrado , Método Doble Ciego , Estrógenos Conjugados (USP)/efectos adversos , Femenino , Estudios de Seguimiento , Humanos , Acetato de Medroxiprogesterona/efectos adversos , Persona de Mediana Edad , Factores de Riesgo , Salud de la MujerRESUMEN
National screening guidelines for hypertension and cholesterol were applied to the multiethnic sample of perimenopausal women (N = 1349) in the Study of Women's Health Across the Nation (SWAN). To reduce low-density lipoprotein, lifestyle modification was indicated in 9.5% of patients and drug therapy in 5%. Chinese and Japanese women were least likely and African Americans were most likely to require interventions. Among all women, 27% were prehypertensive, 23% were hypertensive (blood pressure >140/90 mm Hg or treated), and 9.1% were untreated hypertensive. Untreated hypertension was lowest among Japanese and Chinese and highest among Hispanic and African-American women. Among all hypertensives, 60.5% were treated and only 58.5% of those treated were controlled. Control rates were lowest among African Americans and Hispanics. In this relatively low-risk population, a significant proportion of women with hypertension or hypercholesterolemia were either not treated, not treated adequately, or had borderline risk factors that would benefit from lifestyle interventions to prevent the need for future drug treatment.
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Presión Sanguínea , Enfermedades Cardiovasculares/prevención & control , Colesterol/sangre , Hipercolesterolemia/epidemiología , Hipertensión/epidemiología , Tamizaje Masivo/normas , Perimenopausia , Salud de la Mujer , Asiático , Población Negra , Enfermedades Cardiovasculares/etnología , Femenino , Hispánicos o Latinos , Humanos , Persona de Mediana Edad , Conducta de Reducción del Riesgo , Estados Unidos/epidemiología , Población BlancaRESUMEN
CONTEXT: The hypothesis that a low-fat dietary pattern can reduce breast cancer risk has existed for decades but has never been tested in a controlled intervention trial. OBJECTIVE: To assess the effects of undertaking a low-fat dietary pattern on breast cancer incidence. DESIGN AND SETTING: A randomized, controlled, primary prevention trial conducted at 40 US clinical centers from 1993 to 2005. PARTICIPANTS: A total of 48,835 postmenopausal women, aged 50 to 79 years, without prior breast cancer, including 18.6% of minority race/ethnicity, were enrolled. INTERVENTIONS: Women were randomly assigned to the dietary modification intervention group (40% [n = 19,541]) or the comparison group (60% [n = 29,294]). The intervention was designed to promote dietary change with the goals of reducing intake of total fat to 20% of energy and increasing consumption of vegetables and fruit to at least 5 servings daily and grains to at least 6 servings daily. Comparison group participants were not asked to make dietary changes. MAIN OUTCOME MEASURE: Invasive breast cancer incidence. RESULTS: Dietary fat intake was significantly lower in the dietary modification intervention group compared with the comparison group. The difference between groups in change from baseline for percentage of energy from fat varied from 10.7% at year 1 to 8.1% at year 6. Vegetable and fruit consumption was higher in the intervention group by at least 1 serving per day and a smaller, more transient difference was found for grain consumption. The number of women who developed invasive breast cancer (annualized incidence rate) over the 8.1-year average follow-up period was 655 (0.42%) in the intervention group and 1072 (0.45%) in the comparison group (hazard ratio, 0.91; 95% confidence interval, 0.83-1.01 for the comparison between the 2 groups). Secondary analyses suggest a lower hazard ratio among adherent women, provide greater evidence of risk reduction among women having a high-fat diet at baseline, and suggest a dietary effect that varies by hormone receptor characteristics of the tumor. CONCLUSIONS: Among postmenopausal women, a low-fat dietary pattern did not result in a statistically significant reduction in invasive breast cancer risk over an 8.1-year average follow-up period. However, the nonsignificant trends observed suggesting reduced risk associated with a low-fat dietary pattern indicate that longer, planned, nonintervention follow-up may yield a more definitive comparison. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov Identifier: NCT00000611.
Asunto(s)
Neoplasias de la Mama/prevención & control , Dieta con Restricción de Grasas , Anciano , Biomarcadores/sangre , Peso Corporal , Neoplasias de la Mama/epidemiología , LDL-Colesterol/sangre , Registros de Dieta , Femenino , Estudios de Seguimiento , Hormonas Esteroides Gonadales/sangre , Humanos , Incidencia , Persona de Mediana Edad , Posmenopausia , Prevención Primaria , Modelos de Riesgos Proporcionales , Riesgo , Globulina de Unión a Hormona Sexual/análisisRESUMEN
CONTEXT: Observational studies and polyp recurrence trials are not conclusive regarding the effects of a low-fat dietary pattern on risk of colorectal cancer, necessitating a primary prevention trial. OBJECTIVE: To evaluate the effects of a low-fat eating pattern on risk of colorectal cancer in postmenopausal women. DESIGN, SETTING, AND PARTICIPANTS: The Women's Health Initiative Dietary Modification Trial, a randomized controlled trial conducted in 48,835 postmenopausal women aged 50 to 79 years recruited between 1993 and 1998 from 40 clinical centers throughout the United States. INTERVENTIONS: Participants were randomly assigned to the dietary modification intervention (n = 19,541; 40%) or the comparison group (n = 29,294; 60%). The intensive behavioral modification program aimed to motivate and support reductions in dietary fat, to increase consumption of vegetables and fruits, and to increase grain servings by using group sessions, self-monitoring techniques, and other tailored and targeted strategies. Women in the comparison group continued their usual eating pattern. MAIN OUTCOME MEASURE: Invasive colorectal cancer incidence. RESULTS: A total of 480 incident cases of invasive colorectal cancer occurred during a mean follow-up of 8.1 (SD, 1.7) years. Intervention group participants significantly reduced their percentage of energy from fat by 10.7% more than did the comparison group at 1 year, and this difference between groups was mostly maintained (8.1% at year 6). Statistically significant increases in vegetable, fruit, and grain servings were also made. Despite these dietary changes, there was no evidence that the intervention reduced the risk of invasive colorectal cancer during the follow-up period. There were 201 women with invasive colorectal cancer (0.13% per year) in the intervention group and 279 (0.12% per year) in the comparison group (hazard ratio, 1.08; 95% confidence interval, 0.90-1.29). Secondary analyses suggested potential interactions with baseline aspirin use and combined estrogen-progestin use status (P = .01 for each). Colorectal examination rates, although not protocol defined, were comparable between the intervention and comparison groups. Similar results were seen in analyses adjusting for adherence to the intervention. CONCLUSION: In this study, a low-fat dietary pattern intervention did not reduce the risk of colorectal cancer in postmenopausal women during 8.1 years of follow-up. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov Identifier: NCT00000611.
Asunto(s)
Neoplasias Colorrectales/prevención & control , Dieta con Restricción de Grasas , Adenoma/epidemiología , Adenoma/prevención & control , Anciano , Aspirina/uso terapéutico , Pólipos del Colon/epidemiología , Pólipos del Colon/prevención & control , Neoplasias Colorrectales/epidemiología , Terapia de Reemplazo de Estrógeno , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Funciones de Verosimilitud , Persona de Mediana Edad , Posmenopausia , Prevención Primaria , Modelos de Riesgos Proporcionales , Riesgo , Factores de RiesgoRESUMEN
CONTEXT: Multiple epidemiologic studies and some trials have linked diet with cardiovascular disease (CVD) prevention, but long-term intervention data are needed. OBJECTIVE: To test the hypothesis that a dietary intervention, intended to be low in fat and high in vegetables, fruits, and grains to reduce cancer, would reduce CVD risk. DESIGN, SETTING, AND PARTICIPANTS: Randomized controlled trial of 48,835 postmenopausal women aged 50 to 79 years, of diverse backgrounds and ethnicities, who participated in the Women's Health Initiative Dietary Modification Trial. Women were randomly assigned to an intervention (19,541 [40%]) or comparison group (29,294 [60%]) in a free-living setting. Study enrollment occurred between 1993 and 1998 in 40 US clinical centers; mean follow-up in this analysis was 8.1 years. INTERVENTION: Intensive behavior modification in group and individual sessions designed to reduce total fat intake to 20% of calories and increase intakes of vegetables/fruits to 5 servings/d and grains to at least 6 servings/d. The comparison group received diet-related education materials. MAIN OUTCOME MEASURES: Fatal and nonfatal coronary heart disease (CHD), fatal and nonfatal stroke, and CVD (composite of CHD and stroke). RESULTS: By year 6, mean fat intake decreased by 8.2% of energy intake in the intervention vs the comparison group, with small decreases in saturated (2.9%), monounsaturated (3.3%), and polyunsaturated (1.5%) fat; increases occurred in intakes of vegetables/fruits (1.1 servings/d) and grains (0.5 serving/d). Low-density lipoprotein cholesterol levels, diastolic blood pressure, and factor VIIc levels were significantly reduced by 3.55 mg/dL, 0.31 mm Hg, and 4.29%, respectively; levels of high-density lipoprotein cholesterol, triglycerides, glucose, and insulin did not significantly differ in the intervention vs comparison groups. The numbers who developed CHD, stroke, and CVD (annualized incidence rates) were 1000 (0.63%), 434 (0.28%), and 1357 (0.86%) in the intervention and 1549 (0.65%), 642 (0.27%), and 2088 (0.88%) in the comparison group. The diet had no significant effects on incidence of CHD (hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.90-1.06), stroke (HR, 1.02; 95% CI, 0.90-1.15), or CVD (HR, 0.98; 95% CI, 0.92-1.05). Excluding participants with baseline CVD (3.4%), the HRs (95% CIs) for CHD and stroke were 0.94 (0.86-1.02) and 1.02 (0.90-1.17), respectively. Trends toward greater reductions in CHD risk were observed in those with lower intakes of saturated fat or trans fat or higher intakes of vegetables/fruits. CONCLUSIONS: Over a mean of 8.1 years, a dietary intervention that reduced total fat intake and increased intakes of vegetables, fruits, and grains did not significantly reduce the risk of CHD, stroke, or CVD in postmenopausal women and achieved only modest effects on CVD risk factors, suggesting that more focused diet and lifestyle interventions may be needed to improve risk factors and reduce CVD risk. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov Identifier: NCT00000611.
Asunto(s)
Enfermedad Coronaria/prevención & control , Dieta con Restricción de Grasas , Accidente Cerebrovascular/prevención & control , Anciano , Enfermedades Cardiovasculares/prevención & control , Enfermedad Coronaria/epidemiología , Enfermedad Coronaria/mortalidad , Ingestión de Energía , Ácidos Grasos/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Posmenopausia , Prevención Primaria , Modelos de Riesgos Proporcionales , Riesgo , Factores de Riesgo , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/mortalidadRESUMEN
Our objectives were to determine the prevalence and factors related to left ventricular hypertrophy (LVH) among older women for commonly used electrocardiographic criteria. LVH is a potent risk factor for cardiovascular disease, especially among women. However, its value has been limited, in part, by the use of different electrocardiographic criteria and the lack of a clearly defined standard for the general population. A total of 3,613 eligible women, aged 50 to 79 years, underwent medical history, physical measurements, and biochemical determinations and had behavioral factors recorded at baseline. Three LVH indexes were derived from computer measurement of the electrocardiogram: hypertrophied left ventricular mass > or =171.04 g (HLVM); Cornell voltage > or =2,200 microV; and Minnesota Code items. The prevalence of LVH ranged from <1% to 13% when stratified by age, ethnicity, and scoring technique. Baseline traits differed significantly for those meeting the LVH criteria. Predictors (p <0.01) of HLVM were age (odds ratio 0.66), height (odds ratio 1.47), waist/hip ratio (odds ratio 1.30), systolic blood pressure (odds ratio 1.18); low-density lipoprotein cholesterol (odds ratio 0.97), log insulin (odds ratio 2.10), dietary kilocalories (odds ratio 1.16), weekly energy expenditure (odds ratio 0.53), hypertension (odds ratio 1.61), current estrogen use (odds ratio 0.60), and current smoker (odds ratio 0.47). The presence of the metabolic syndrome was related to all LVH indexes, with odds ratios of 4.95, 2.24, and 2.35, respectively, for HLVM, Cornell voltage, and Minnesota Code. In conclusion, the prevalence of LVH varied by ethnicity and the electrocardiographic index used. However, the baseline traits, especially the factors associated with the metabolic syndrome, were consistently and strongly related to all LVH indexes, particularly HLVM. Intervention on these factors may provide strategies for reducing LVH, a strong independent risk factor for cardiovascular morbidity and mortality among women.
Asunto(s)
Hipertrofia Ventricular Izquierda/diagnóstico , Hipertrofia Ventricular Izquierda/epidemiología , Posmenopausia , Factores de Edad , Anciano , Electrocardiografía , Etnicidad , Femenino , Humanos , Síndrome Metabólico/diagnóstico , Persona de Mediana EdadRESUMEN
BACKGROUND: The efficacy of calcium with vitamin D supplementation for preventing hip and other fractures in healthy postmenopausal women remains equivocal. METHODS: We recruited 36,282 postmenopausal women, 50 to 79 years of age, who were already enrolled in a Women's Health Initiative (WHI) clinical trial. We randomly assigned participants to receive 1000 mg of elemental [corrected] calcium as calcium carbonate with 400 IU of vitamin D3 daily or placebo. Fractures were ascertained for an average follow-up period of 7.0 years. Bone density was measured at three WHI centers. RESULTS: Hip bone density was 1.06 percent higher in the calcium plus vitamin D group than in the placebo group (P<0.01). Intention-to-treat analysis indicated that participants receiving calcium plus vitamin D supplementation had a hazard ratio of 0.88 for hip fracture (95 percent confidence interval, 0.72 to 1.08), 0.90 for clinical spine fracture (0.74 to 1.10), and 0.96 for total fractures (0.91 to 1.02). The risk of renal calculi increased with calcium plus vitamin D (hazard ratio, 1.17; 95 percent confidence interval, 1.02 to 1.34). Censoring data from women when they ceased to adhere to the study medication reduced the hazard ratio for hip fracture to 0.71 (95 percent confidence interval, 0.52 to 0.97). Effects did not vary significantly according to prerandomization serum vitamin D levels. CONCLUSIONS: Among healthy postmenopausal women, calcium with vitamin D supplementation resulted in a small but significant improvement in hip bone density, did not significantly reduce hip fracture, and increased the risk of kidney stones. (ClinicalTrials.gov number, NCT00000611.).