Colorectal cancer in relation to postmenopausal estrogen and estrogen plus progestin in the Women’s Health Initiative clinical trial and observational study

Background: Colorectal cancer incidence was reduced among women assigned to active treatment in the Women’s Health Initiative (WHI) estrogen plus progestin randomized trial, but the interpretation was obscured by an associated later stage of diagnosis. In contrast the estrogen-alone trial showed no incidence reduction or differential stage at diagnosis. Here, data from the WHI observational study are considered, in conjunction with colorectal cancer mortality data from the hormone therapy trials, in an attempt to clarify postmenopausal hormone therapy effects. Participants and Methods: Postmenopausal women aged 50-79 at WHI enrollment. Estrogen-alone analyses include 21,552 and 10,739 women who were post-hysterectomy from the observational study and clinical trial respectively. Estrogen plus progestin analyses include 32,084 and 16,608 observational study and clinical trial women with uterus. Colorectal cancers were verified by central medical and pathology report review. Results: Hazard ratios (95% confidence intervals) from the WHI observational study were 0.80 (0.53 to 1.20) for estrogen and 1.15 (0.74 to 1.79) for estrogen plus progestin, with respectively 168 and 175 women diagnosed with colorectal cancer. Delayed diagnosis with estrogen plus progestin is not evident in the observational study. No protective effect on colorectal cancer mortality in the estrogen plus progestin trial is seen over an 8-year intervention and follow-up period. Conclusion: Hazard ratio patterns in the WHI clinical trial and observational study do not provide strong evidence of a clinically important colorectal cancer benefit with either estrogen-alone or estrogen plus progestin over 7-8 years of treatment and follow-up

Individual and joint trajectories of change in bone, lean mass and physical performance in older men.

BackgroundDeclines in bone, muscle and physical performance are associated with adverse health outcomes in older adults. However, few studies have described concurrent age-related patterns of change in these factors. The purpose of this study was to characterize change in four properties of muscle, physical performance, and bone in a prospective cohort study of older men.MethodsUsing repeated longitudinal data from up to four visits across 6.9 years from up to 4681 men (mean age at baseline 72.7 yrs. ±5.3) participating in the Osteoporotic Fractures in Men (MrOS) Study, we used group-based trajectory models (PROC TRAJ in SAS) to identify age-related patterns of change in four properties of muscle, physical performance, and bone: total hip bone mineral (BMD) density (g/m2) and appendicular lean mass/ht2 (kg/m2), by DXA; grip strength (kg), by hand dynamometry; and walking speed (m/s), by usual walking pace over 6 m. We also described joint trajectories in all pair-wise combinations of these measures. Mean posterior probabilities of placement in each trajectory (or joint membership in latent groups) were used to assess internal reliability of the model. The number of trajectories for each individual factor was limited to three, to ensure that the pair-wise determination of joint trajectories would yield a tractable number of groups as well as model fit considerations.ResultsThe patterns of change identified were generally similar for all measures, with three district groups declining over time at roughly similar rates; joint trajectories revealed similar patterns with no cross-over or convergence between groups. Mean posterior probabilities for all trajectories were similar and consistently above 0.8 indicating reasonable model fit to the data.ConclusionsOur description of trajectories of change with age in bone mineral density, grip strength, walking speed and appendicular lean mass found that groups identified by these methods appeared to have little crossover or convergence of change with age, even when considering joint trajectories of change in these factors

Self-perceived physical health predicts cardiovascular disease incidence and death among postmenopausal women

BACKGROUND: Physical and Mental Component Summary (PCS, MCS, respectively) scales of SF- 36 health-related-quality-of-life have been associated with all-cause and cardiovascular disease (CVD) mortality. Their relationships with CVD incidence are unclear. This study purpose was to test whether PCS and/or MCS were associated with CVD incidence and death. METHODS: Postmenopausal women (aged 50–79 years) in control groups of the Women’s Health Initiative clinical trials (n = 20,308) completed the SF-36 and standardized questionnaires at trial entry. Health outcomes, assessed semi-annually, were verified with medical records. Cox regressions assessed time to selected outcomes during the trial phase (1993–2005). RESULTS: A total of 1075 incident CVD events, 204 CVD-specific deaths, and 1043 total deaths occurred during the trial phase. Women with low versus high baseline PCS scores had less favorable health profiles at baseline. In multivariable models adjusting for baseline confounders, participants in the lowest PCS quintile (reference = highest quintile) exhibited 1.8 (95%CI: 1.4, 2.3), 4.7 (95%CI: 2.3, 9.4), and 2.1 (95%CI: 1.7, 2.7) times greater risk of CVD incidence, CVD-specific death, and total mortality, respectively, by trial end; whereas, MCS was not significantly associated with CVD incidence or death. CONCLUSION: Physical health, assessed by self-report of physical functioning, is a strong predictor of CVD incidence and death in postmenopausal women; similar self-assessment of mental health is not. PCS should be evaluated as a screening tool to identify older women at high risk for CVD development and death

Low Birth Weight and Risk of Later-Life Physical Disability in Women

Background: There is strong evidence that low and high birth weight due to in-utero programming results in elevated risk for adult diseases, though less research has been performed examining the influence of birth weight and physical disability later in life. Methods: Baseline data from 76,055 postmenopausal women in the Women's Health Initiative, a large multi-ethnic cohort, were used to examine the association between self-reported birth weight category (<6 lbs, 6-7 lbs 15 oz, 8-9 lbs 15 oz, and ≥10 lbs) and the self-reported physical functioning score on the RAND 36-item Health Survey. Linear regression models were adjusted for age, education, race/ethnicity, body mass index, and a comorbidity score. Results: Unadjusted models indicate that women born in the lowest and highest birth weight categories have significantly lower physical functioning scores as compared to women born in the normal weight category (β = -2.22, p < .0001 and β = -3.56, p < .0001, respectively). After adjustments, the relationship between the lowest birth weight category and physical functioning score remained significant (β = -1.52, p < .0001); however, the association with the highest birth weight category dissipated. Conclusions: Preconception and prenatal interventions aimed at reducing the incidence of low birth weight infants may subsequently reduce the burden of later-life physical disability

Association of active and passive smoking with risk of breast cancer among postmenopausal women: a prospective cohort study

Objective To examine the association between smoking and risk of invasive breast cancer using quantitative measures of lifetime passive and active smoking exposure among postmenopausal women

Race and Ethnicity, Obesity, Metabolic Health, and Risk of Cardiovascular Disease in Postmenopausal Women

Background It is unclear whether obesity unaccompanied by metabolic abnormalities is associated with increased cardiovascular disease risk across racial and ethnic subgroups. Methods and Results We identified 14 364 postmenopausal women from the Women\u27s Health Initiative who had data on fasting serum lipids and serum glucose and no history of cardiovascular disease or diabetes at baseline. We categorized women by body mass index (in kg/m2) as normal weight (body mass index 18.5 to P=0.05). Obese black women without metabolic syndrome had higher adjusted risk (HR 1.95) than obese white women (HR 1.07; interaction P=0.02). Among women with only 2 metabolic abnormalities, cardiovascular risk was increased in black women who were overweight (HR 1.77) or obese (HR 2.17) but not in white women who were overweight (HR 0.98) or obese (HR 1.06). Overweight and obese women with ≤1 metabolic abnormality did not have increased cardiovascular risk, regardless of race or ethnicity. Conclusions Metabolic abnormalities appeared to convey more cardiovascular risk among black women

Modifying effect of obesity on the association between sitting time and incident diabetes in post-menopausal women

Objective: To evaluate the association between self-reported daily sitting time and the incidence of type II diabetes in a cohort of postmenopausal women. Design and Methods Women (N = 88,829) without diagnosed diabetes reported the number of hours spent sitting over a typical day. Incident cases of diabetes were identified annually by self-reported initiation of using oral medications or insulin for diabetes over 14.4 years follow-up. Results: Each hour of sitting time was positively associated with increased risk of diabetes (Risk ratio (RR): 1.05; 95% confidence interval (CI): 1.02–1.08]. However, sitting time was only positively associated with incident diabetes in obese women. Obese women reporting sitting 8–11 (RR: 1.08; 95% CI 1.0–1.1), 12–15 (OR: 1.13; 95% CI 1.0–1.2), and ≥16 hours (OR: 1.25; 95% CI 1.0–1.5) hours per day had an increased risk of diabetes compared to women sitting ≤ 7 hours per day. These associations were adjusted for demographics, health conditions, behaviors (smoking, diet and alcohol intake) and family history of diabetes. Time performing moderate to vigorous intensity physical activity did not modify these associations. Conclusion: Time spent sitting was independently associated with increased risk of diabetes diagnosis among obese women— a population already at high risk of the disease

Usefulness of baseline lipids and C-reactive protein in women receiving menopausal hormone therapy as predictors of treatment-related coronary events.

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\u27s 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 ratioor =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 rati