Psychological Traits, Heart Rate Variability, and Risk of Coronary Heart Disease in Healthy Aging Women-The Women's Health Initiative.

OBJECTIVE: Psychological traits such as optimism and hostility affect coronary heart disease (CHD) risk, but mechanisms for this association are unclear. We hypothesized that optimism and hostility may affect CHD risk via changes in heart rate variability (HRV). METHODS: We conducted a longitudinal analysis using data from the Women's Health Initiative Myocardial Ischemia and Migraine Study. Participants underwent 24-hour ambulatory electrocardiogram monitoring 3 years after enrollment. Optimism (Life Orientation Test-Revised), cynical hostility (Cook-Medley), demographics, and coronary risk factors were assessed at baseline. HRV measures included standard deviation of average N-N intervals (SDNN); standard deviation of average N-N intervals for 5 minutes (SDANN); and average heart rate (HR). CHD was defined as the first occurrence of myocardial infarction, angina, coronary angioplasty, and bypass grafting. Linear and Cox regression models adjusted for CHD risk factors were used to examine, respectively, associations between optimism, hostility, and HRV and between HRV and CHD risk. RESULTS: Final analyses included 2655 women. Although optimism was not associated with HRV, hostility was inversely associated with HRV 3 years later (SDANN: adjusted ß = -0.54; 95% CI = -0.97 to -0.11; SDNN: -0.49; 95% CI = -0.93 to -0.05). HRV was inversely associated with CHD risk; for each 10-millisecond increase in SDNN or SDANN, there was a decrease in CHD risk of 9% (p = .023) and 12% (p = .006), respectively. CONCLUSIONS: HRV did not play a major role in explaining why more optimistic women seem to be somewhat protected from CHD risk. Although hostility was inversely associated with HRV, its role in explaining the association between hostility and CHD risk remains to be established.

Parental longevity predicts healthy ageing among women.

Objective: to examine the association of parental longevity with healthy survival to age 90 years. Methods: this was a prospective study among a racially and ethnically diverse cohort of 22,735 postmenopausal women from the Women's Health Initiative recruited from 1993 to 1998 and followed through 2017. Women reported maternal and paternal ages at death and current age of alive parents. Parental survival categories were <70, 70-79 (reference), 80-89 and ≥90 years (longevity). Healthy ageing was defined as reaching age 90 without major chronic conditions (coronary heart disease, stroke, diabetes, cancer, or hip fracture) or physical limitations. Results: women whose mothers survived to ≥90 years were more likely to attain healthy ageing (OR, 1.25; 95% CI, 1.11-1.42) and less likely to die before age 90 (OR, 0.75; 95% CI, 0.68-0.83). Women whose fathers survived to ≥90 years did not have significantly increased odds of healthy ageing but showed 21% (OR, 0.79; 95% CI, 0.70-0.90) decreased odds of death before age 90. Women whose mother and father both lived to 90 had the strongest odds of healthy ageing (OR, 1.38; 95% CI, 1.09-1.75) and decreased odds of death (OR, 0.68; 95% CI, 0.54-0.85). The proportion of healthy survivors was highest among women whose mother and father lived to 90 (28.6%), followed by those whose mother only lived to 90 (23.2%). Conclusions: parental longevity predicted healthy ageing in a national cohort of postmenopausal women, supporting the view that genetic, environmental, and behavioral factors transmitted across generations may influence ageing outcomes among offspring.

Sleep duration, cognitive decline, and dementia risk in older women.

INTRODUCTION: Consistent evidence linking habitual sleep duration with risks of mild cognitive impairment (MCI) and dementia is lacking. METHODS: We conducted a prospective study on 7444 community-dwelling women (aged 65-80 y) with self-reported sleep duration, within the Women's Health Initiative Memory Study in 1995-2008. Incident MCI/dementia cases were ascertained by validated protocols. Cox models were used to adjust for multiple sociodemographic and lifestyle factors, depression, cardiovascular disease (CVD), and other clinical characteristics. RESULTS: We found a statistically significant (P = .03) V-shaped association with a higher MCI/dementia risk in women with either short (≤6 hours/night) or long (≥8 hours/night) sleep duration (vs. 7 hours/night). The multicovariate-adjusted hazard for MCI/dementia was increased by 36% in short sleepers irrespective of CVD, and by 35% in long sleepers without CVD. A similar V-shaped association was found with cognitive decline. DISCUSSION: In older women, habitual sleep duration predicts the future risk for cognitive impairments including dementia, independent of vascular risk factors.

Relationships of depression and antidepressant use with epigenetic age acceleration and all-cause mortality among postmenopausal women.

We investigated relations of depressive symptoms, antidepressant use, and epigenetic age acceleration with all-cause mortality risk among postmenopausal women. Data were analyzed from ≤1,900 participants in the Women's Health Initiative study testing four-way decomposition models. After a median 20.4y follow-up, 1,161 deaths occurred. Approximately 11% had elevated depressive symptoms (EDS+), 7% were taking antidepressant medication at baseline (ANTIDEP+), while 16.5% fell into either category (EDS_ANTIDEP+). Baseline ANTIDEP+, longitudinal transition into ANTIDEP+ and accelerated epigenetic aging directly predicted increased mortality risk. GrimAge DNA methylation age acceleration (AgeAccelGrim) partially mediated total effects of baseline ANTIDEP+ and EDS_ANTIDEP+ on all-cause mortality risk in socio-demographic factors-adjusted models (Pure Indirect Effect >0, P < 0.05; Total Effect >0, P < 0.05). Thus, higher AgeAccelGrim partially explained the relationship between antidepressant use and increased all-cause mortality risk, though only prior to controlling for lifestyle and health-related factors. Antidepressant use and epigenetic age acceleration independently predicted increased all-cause mortality risk. Further studies are needed in varying populations.

Vitamin D supplementation and depression in the women's health initiative calcium and vitamin D trial.

While observational studies have suggested that vitamin D deficiency increases risk of depression, few clinical trials have tested whether vitamin D supplementation affects the occurrence of depression symptoms. The authors evaluated the impact of daily supplementation with 400 IU of vitamin D(3) combined with 1,000 mg of elemental calcium on measures of depression in a randomized, double-blinded US trial comprising 36,282 postmenopausal women. The Burnam scale and current use of antidepressant medication were used to assess depressive symptoms at randomization (1995-2000). Two years later, women again reported on their antidepressant use, and 2,263 completed a second Burnam scale. After 2 years, women randomized to receive vitamin D and calcium had an odds ratio for experiencing depressive symptoms (Burnam score ≥0.06) of 1.16 (95% confidence interval: 0.86, 1.56) compared with women in the placebo group. Supplementation was not associated with antidepressant use (odds ratio = 1.01, 95% confidence interval: 0.92, 1.12) or continuous depressive symptom score. Results stratified by baseline vitamin D and calcium intake, solar irradiance, and other factors were similar. The findings do not support a relation between supplementation with 400 IU/day of vitamin D(3) along with calcium and depression in older women. Additional trials testing higher doses of vitamin D are needed to determine whether this nutrient may help prevent or treat depression.

Psychotropic medication use and Parkinson's disease risk amongst older women.

OBJECTIVE: To examine associations of antidepressant, anxiolytic and hypnotic use amongst older women (≥65 years) with incident Parkinson's Disease (PD), using data from Women's Health Initiative linked to Medicare claims. METHODS: PD was defined using self-report, first diagnosis, medications and/or death certificates and psychotropic medications were ascertained at baseline and 3-year follow-up. Cox regression models were constructed to calculate adjusted hazard ratios (aHR) with 95% confidence intervals (CI), controlling for socio-demographic, lifestyle and health characteristics, overall and amongst women diagnosed with depression, anxiety and/or sleep disorders (DASD). RESULTS: A total of 53,996 WHI participants (1,756 PD cases)-including 27,631 women diagnosed with DASD (1,137 PD cases)-were followed up for ~14 years. Use of hypnotics was not significantly associated with PD risk (aHR = 0.98, 95% CI: 0.82, 1.16), whereas PD risk was increased amongst users of antidepressants (aHR = 1.75, 95% CI: 1.56, 1.96) and anxiolytics (aHR = 1.48, 95% CI: 1.25, 1.73). Compared to non-users of psychotropic medications, those who used 1 type had ~50% higher PD risk, whereas those who used ≥2 types had ~150% higher PD risk. Women who experienced transitions in psychotropic medication use ('use to non-use' or 'non-use to use') between baseline and 3-year follow-up had higher PD risk than those who did not. We obtained similar results with propensity scoring and amongst DASD-diagnosed women. INTERPRETATION: The use of antidepressants, anxiolytics or multiple psychotropic medication types and transitions in psychotropic medication use was associated with increased PD risk, whereas the use of hypnotics was not associated with PD risk amongst older women.

Association of sleep disturbance with Parkinson disease: evidence from the Women's Health Initiative.

OBJECTIVE: To examine the association of sleep disturbance with Parkinson disease (PD) during 10+ years of follow-up among postmenopausal women, 50 to 79 years of age at baseline. METHODS: Longitudinal data on 130,502 study-eligible women (mean ± standard deviation baseline age = 63.16 ±â€Š7.20 y) from the Women's Health Initiative Clinical Trials and Women's Health Initiative Observational Study were analyzed. The cohort was followed for 15.88 ±â€Š6.50 years, yielding 2,829 (2.17%) PD cases. Sleep disturbance (habitual sleep duration, insomnia symptoms, obstructive sleep apnea risk factors, sleep aids among those with WHI Insomnia Rating Scale scores (WHIIRS) > 9) was measured at baseline and one follow-up time by September 12, 2005. Cox proportional hazards models evaluated relationships controlling for sociodemographic, lifestyle, and health characteristics. RESULTS: PD was significantly associated with long sleep duration (≥9 h) versus a benchmark of 7 to 8 hours (hazard ratio [HR] = 1.296, 95% confidence interval [CI]: 1.153-1.456), WHIIRS (>9 vs ≤9) (HR = 1.114, 95% CI:1.023-1.214), and use of sleep aids (yes vs no) (HR = 1.332, 95% CI:1.153-1.539) among those with WHIIRS > 9. Compared with 7 to 8 hours, short (<7 h) sleep duration was unrelated to PD. Finally, the presence of obstructive sleep apnea risk factors was not associated with PD. CONCLUSIONS: Among postmenopausal women, sleep disturbance was associated with approximately 10% to 30% increased PD risk after ∼16 years follow-up. Prospective cohort studies with objective exposures and adjudicated outcomes that include men and women of diverse backgrounds are required to confirm and extend these findings.

The effect of calcium plus vitamin D on risk for invasive cancer: results of the Women's Health Initiative (WHI) calcium plus vitamin D randomized clinical trial.

In the Women's Health Initiative (WHI) trial of calcium plus vitamin D (CaD), we examined the treatment effect on incidence and mortality for all invasive cancers. Postmenopausal women (N = 36,282) were randomized to 1,000 mg of elemental calcium with 400 IU vitamin D3 or placebo. Cox models estimated risk of cancer incidence and mortality. After 7.0 yr, 1,306 invasive cancers were diagnosed in the supplement and 1,333 in the placebo group [hazard ratio (HR) = 0.98; CI = 0.90, 1.05, unweighted P = 0.54]. Mortality did not differ between supplement (315, annualized% = .26) and placebo [(347, 0.28%; P = 0.17; HR = 0.90 (0.77, 1.05)]. Significant treatment interactions on incident cancer were found for family history of cancer, personal total intake of vitamin D, smoking, and WHI dietary trial randomized group. Calcium/vitamin D supplementation did not reduce invasive cancer incidence or mortality. Supplementation lowered cancer risk in the WHI healthy diet trial arm and in women without a first-degree relative with cancer. The interactions are only suggestive given multiple testing considerations. The low vitamin D dose provided, limited adherence, and lack of serum 25(OH)D values should be considered when interpreting these findings.

Subtypes of mild cognitive impairment in older postmenopausal women: the Women's Health Initiative Memory Study.

Mild cognitive impairment (MCI) is a transitional state between normal cognitive functioning and dementia. A proposed MCI typology classifies individuals by the type and extent of cognitive impairment, yet few studies have characterized or compared these subtypes. Four hundred forty-seven women 65 years of age and older from the Women's Health Initiative Memory Study were classified into the 4 MCI subgroups and a "no impairment" group and compared on clinical, sociodemographic, and health variables. A cognitive deficit in at least 1 domain was present in 82.1% of participants, with most (74.3%) having deficits in multiple cognitive domains. Only 4.3% had an isolated memory deficit, whereas 21.3% had an isolated nonmemory deficit. Of the 112 women who met all MCI criteria examined, the most common subtype was amnestic multidomain MCI (42.8%), followed by nonamnestic multiple domain MCI (26.7%), nonamnestic single domain (24.1%), and amnestic single domain MCI (6.3%). Subtypes were similar with respect to education, health status, smoking, depression, and prestudy and onstudy use of hormone therapy. Despite the attention it receives in the literature, amnestic MCI is the least common type highlighting the importance of identifying and characterizing other nonamnestic and multidomain subtypes. Further research is needed on the epidemiology of MCI subtypes, clinical and biologic differences between them, and rates for conversion to dementia.

Calcium plus vitamin D supplementation and the risk of fractures.

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.).

Calcium plus vitamin D supplementation and the risk of colorectal cancer.

BACKGROUND: Higher intake of calcium and vitamin D has been associated with a reduced risk of colorectal cancer in epidemiologic studies and polyp recurrence in polyp-prevention trials. However, randomized-trial evidence that calcium with vitamin D supplementation is beneficial in the primary prevention of colorectal cancer is lacking. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 36,282 postmenopausal women from 40 Women's Health Initiative centers: 18,176 women received 500 mg of elemental calcium as calcium carbonate with 200 IU of vitamin D3 [corrected] twice daily (1000 mg of elemental calcium and 400 IU of vitamin D3) and 18,106 received a matching placebo for an average of 7.0 years. The incidence of pathologically confirmed colorectal cancer was the designated secondary outcome. Baseline levels of serum 25-hydroxyvitamin D were assessed in a nested case-control study. RESULTS: The incidence of invasive colorectal cancer did not differ significantly between women assigned to calcium plus vitamin D supplementation and those assigned to placebo (168 and 154 cases; hazard ratio, 1.08; 95 percent confidence interval, 0.86 to 1.34; P=0.51), and the tumor characteristics were similar in the two groups. The frequency of colorectal-cancer screening and abdominal symptoms was similar in the two groups. There were no significant treatment interactions with baseline characteristics. CONCLUSIONS: Daily supplementation of calcium with vitamin D for seven years had no effect on the incidence of colorectal cancer among postmenopausal women. The long latency associated with the development of colorectal cancer, along with the seven-year duration of the trial, may have contributed to this null finding. Ongoing follow-up will assess the longer-term effect of this intervention. (ClinicalTrials.gov number, NCT00000611.).

Associations of parental ages at childbirth with healthy aging among women.

OBJECTIVE: To examine associations of parental ages at childbirth with healthy survival to age 90 years among older women. STUDY DESIGN: This study included a racially and ethnically diverse sub-cohort of 8,983 postmenopausal women from the larger Women's Health Initiative population, recruited during 1993-1998 and followed for up to 25 years through 2018. MAIN OUTCOME MEASURES: The outcome was categorized as: 1) healthy survival, defined as survival to age 90 without major morbidities (coronary heart disease, stroke, diabetes, cancer, or hip fracture) or mobility disability; 2) usual survival, defined as survival to age 90 without healthy aging (reference category); or 3) death before age 90. Women reported their own and their parents' birth years, and parental ages at childbirth were calculated and categorized as <25, 25-29, 30-34, or ≥35 years. RESULTS: Women were aged on average 71.3 (standard deviation 2.7; range 65-79) years at baseline. There was no significant association of maternal age at childbirth with healthy survival to age 90 or death before age 90. Women born to fathers aged ≥35 compared with 30-34 years at their births were more likely to achieve healthy than usual survival (OR, 1.15; 95% CI, 1.00-1.32). There was no association of paternal age at childbirth with death before age 90. CONCLUSIONS: Findings suggest that being born to older fathers was associated with healthy survival to age 90 among women who had survived to ages 65-79 years at study baseline. There was no association of maternal age at childbirth with healthy survival to age 90 among these older women.

Sleep duration and risk of ischemic stroke in postmenopausal women.

BACKGROUND AND PURPOSE: Many studies have shown a U-shape association between sleep duration and mortality, but epidemiological evidence linking cardiovascular diseases with habitual sleep patterns is limited and mixed. METHODS: We conducted a prospective study on 93 175 older women (aged 50 to 79 years) in the Women's Health Initiative Observational study cohort to examine the risk of ischemic stroke in relation to self-reported sleep duration. Cox models were used to investigate the putative associations, adjusting for multiple sociodemographic and lifestyle factors, depression, snoring, sleepiness symptoms, and other cardiovascular disease-related clinical characteristics. RESULTS: At baseline, 8.3% of subjects had reported their sleep duration as or=9 hours/night). After an average of 7.5 years of follow-up, 1166 cases of ischemic stroke had occurred. Multivariable-adjusted relative risk (RR) and 95% CI for ischemic stroke (using a sleep time of 7 hours/night as the reference) were 1.14 (0.97, 1.33), 1.24 (1.04, 1.47), and 1.70 (1.32, 2.21) for women reporting or=9 hours of sleep. A modestly stronger association with sleep duration or=9 hours/night) need further elucidation.

Depressive symptoms, bone loss, and fractures in postmenopausal women.

BACKGROUND: Osteoporosis and depression may be associated through common physiologic systems or risk factors. OBJECTIVE: To assess the associations between depressive symptoms (Burnam's scale) or antidepressant use and bone outcomes. DESIGN: Prospective cohort study. PARTICIPANTS: A total of 93,676 postmenopausal women (50 to 79 years old) enrolled in the Women's Health Initiative Observational Study. MEASUREMENTS: Self-reported fractures (n = 14,982) (hip [adjudicated], spine, wrist, and "other"). Analyses included 82,410 women with complete information followed on average for 7.4 years. Bone mineral density (BMD) of the hip (n = 4539), spine (n = 4417), and whole body (n = 4502) was measured at baseline and 3 years in women enrolled at 3 densitometry study sites. RESULTS: Overall, there were no statistically significant associations between depressive symptoms or antidepressant therapy and 3-year change in BMD. In a subset of women not using antidepressants, there was a significant difference in whole-body BMD change between women with and without depressive symptoms (P = .05). Depressive symptoms (hazard ratio [HR] 1.08; 95% CI = 1.02 to 1.14) and antidepressant therapy (HR = 1.22; CI = 1.15 to 1.30) independently increased risk of any fracture, the majority of which occurred at "other" anatomic sites. Antidepressant therapy increased the risk of spine fracture (HR = 1.36; CI = 1.14 to 1.63). No associations were observed between depressive symptoms or antidepressant therapy and hip or wrist fracture. CONCLUSION: In this study of postmenopausal women, average age 64, we observed minimal association between depressive symptoms and 3-year changes in either BMD or fracture risk. Antidepressant use was not associated with changes in BMD, but was associated with increased risk of fractures at the spine and "other " anatomic sites.

Calcium, vitamin D supplementation, and physical function in the Women's Health Initiative.

OBJECTIVES: The Women's Health Initiative (WHI) randomized trial of calcium/vitamin D supplementation found reduced bone loss with active treatment compared to placebo. Now we examine whether the treatment affected self-reported physical functioning and objective measures of physical functioning. DESIGN: A randomized, double-blind, placebo-controlled trial of 1,000 mg calcium carbonate plus 400 IU vitamin D(3) per day or matching placebo pills. SUBJECTS/SETTING: The study included 33,067 women (50 to 79 years old) at 40 US study centers. MAIN OUTCOME MEASURES: Physical functioning was assessed by questionnaire at enrollment in WHI, 1 year prior to calcium/vitamin D trial randomization and at study close-out (average follow-up 7.1 years). Objective physical performance and self-reported exercise measures were collected at WHI baseline (1 year prior to calcium/vitamin D enrollment) and 2 years and 4 years after calcium/vitamin D trial enrollment in a subsample (n=3,137). STATISTICAL ANALYSES PERFORMED: Calcium/vitamin D effects were tested in unadjusted and interaction linear models for each of the physical function measures. Covariates were baseline total calcium intake, fracture risk score, treatment arm in the hormone therapy and dietary modification trials (ie, active drug or placebo, low-fat diet intervention or usual diet, respectively) and age. RESULTS: Neither intention to treat nor high adherence analyses produced substantial effects of calcium/vitamin D compared to placebo on physical functioning or performance. The interaction analyses also did not result in differences because of calcium/vitamin D. CONCLUSIONS: As the first long-term randomized trial to examine the effectiveness of calcium and vitamin D in protecting against decline of physical functioning in older women, the results did not support benefit.

The association of sleep duration and quality with all-cause and cause-specific mortality in the Women's Health Initiative.

BACKGROUND/OBJECTIVE: Many studies have shown a U-shaped association of sleep duration with mortality; however, this association is difficult to interpret owing to possible reverse causation, residual confounding, and measurement issues. We used data from the Women's Health Initiative to examine the associations of sleep duration, insomnia, and use of sleep aids with death from cardiovascular disease (CVD), cancer, "other" causes, and all causes combined. METHODS: Cox proportional hazards models were used in the analysis of baseline data and in time-dependent analyses of repeated measures to estimate associations of sleep-related factors with mortality. Among 158,203 women with information regarding sleep, 30,400 total deaths, 8857 CVD deaths, 9284 cancer deaths, and 11,928 other deaths were ascertained over a median of 17.8 years. RESULTS: In both baseline and time-dependent analyses, both short (≤5 h) and long sleep (≥9 h) durations were associated with increased risk of total, CVD, and "other" deaths, but not with cancer deaths. Insomnia showed no association with mortality, whereas use of sleep medications was associated with an increased mortality risk. CONCLUSIONS: While our findings showed a small but robust association of sleep duration with mortality in postmenopausal women, studies including objective measurements of sleep quality and efficiency are needed to clarify these associations.

Effects of estrogen plus progestin on health-related quality of life.

BACKGROUND: The Women's Health Initiative (WHI) and other clinical trials indicate that significant health risks are associated with combination hormone use. Less is known about the effect of hormone therapy on health-related quality of life. METHODS: The WHI randomly assigned 16,608 postmenopausal women 50 to 79 years of age (mean, 63) with an intact uterus at base line to estrogen plus progestin (0.625 mg of conjugated equine estrogen plus 2.5 mg of medroxyprogesterone acetate, in 8506 women) or placebo (in 8102 women). Quality-of-life measures were collected at base line and at one year in all women and at three years in a subgroup of 1511 women. RESULTS: Randomization to estrogen plus progestin resulted in no significant effects on general health, vitality, mental health, depressive symptoms, or sexual satisfaction. The use of estrogen plus progestin was associated with a statistically significant but small and not clinically meaningful benefit in terms of sleep disturbance, physical functioning, and bodily pain after one year (the mean benefit in terms of sleep disturbance was 0.4 point on a 20-point scale, in terms of physical functioning 0.8 point on a 100-point scale, and in terms of pain 1.9 points on a 100-point scale). At three years, there were no significant benefits in terms of any quality-of-life outcomes. Among women 50 to 54 years of age with moderate-to-severe vasomotor symptoms at base line, estrogen and progestin improved vasomotor symptoms and resulted in a small benefit in terms of sleep disturbance but no benefit in terms of the other quality-of-life outcomes. CONCLUSIONS: In this trial in postmenopausal women, estrogen plus progestin did not have a clinically meaningful effect on health-related quality of life.

Comparison of the Simplified sWHI and the Standard CHS Frailty Phenotypes for Prediction of Mortality, Incident Falls, and Hip Fractures in Older Women.

BACKGROUND: We compared the simplified Women's Health Initiative (sWHI) and the standard Cardiovascular Health Study (CHS) frailty phenotypes in predicting falls, hip fracture, and death in older women. METHODS: Participants are from the WHI Clinical Trial. CHS frailty criteria included weight loss, exhaustion, weakness, slowness, and low physical activity. The sWHI frailty score used two items from the RAND-36 physical function and vitality subscales, one item from the WHI physical activity scale plus the CHS weight loss criteria. Specifically, level of physical function was the capacity to walk one block and scored as severe (2-points), moderate (1-point), or no limitation (0). Vitality was based on feeling tired most or all of the time (1-point) versus less often (0). Low physical activity was walking outside less than twice a week (1-point) versus more often (0). A total score of 3 resulted in a frailty classification, a score of 1 or 2 defined pre-frailty, and 0 indicated nonfrailty. Outcomes were modeled using Cox regression and Harrell C-statistics were used for comparisons. RESULTS: Approximately 5% of the participants were frail based on the CHS or sWHI phenotype. The sWHI frailty phenotype was associated with higher rates of mortality (hazard ratio [HR] = 2.36, p ≤ .001) and falls (HR = 1.45, p = .005). Comparable HRs in CHS-phenotype were 1.97 (p < .001) and 1.36 (p = .03), respectively. Neither phenotype predicted hip fracture. Harrell C-statistics revealed nonsignificant differences in HRs between the CHS and sWHI frailty phenotypes. CONCLUSION: The sWHI phenotype, which is self-reported and brief, might be practical in settings with limited resources.

Effects of conjugated equine estrogen on health-related quality of life in postmenopausal women with hysterectomy: results from the Women's Health Initiative Randomized Clinical Trial.

BACKGROUND: The Women's Health Initiative (WHI) clinical trial of conjugated equine estrogens (CEEs), involving 10,739 postmenopausal women with hysterectomy, aged 50 to 79 years, was stopped early owing to lack of overall health benefit and increased risk of stroke. Because CEE is still prescribed for treatment of menopausal symptoms and prevention of osteoporosis, it is important to understand the overall impact of this therapy on health-related quality of life (HRQOL). METHODS: All participants completed 6 specific measures of quality of life at baseline and 1 year, and a subsample (n = 1189) also completed the questions 3 years after randomization. Changes in scores were analyzed for treatment effect. RESULTS: Randomization to CEE was associated with a statistically significant but small reduction in sleep disturbance at year 1 compared with baseline (mean benefit, 0.4 points on a 20-point scale) and a statistically significant but small negative effect on social functioning (mean effect, -1.3 points on a 100-point scale). There were no significant improvements due to CEE in the areas of general health, physical functioning, pain, vitality, role functioning, mental health, depressive symptoms, cognitive function, or sexual satisfaction at year 1. A subgroup examined 3 years after baseline had no significant benefits for any HRQOL outcomes. Among women aged 50 to 54 years with moderate to severe vasomotor symptoms at baseline, CEE did not improve any of the HRQOL variables at year 1. CONCLUSION: In this trial of postmenopausal women with prior hysterectomy, oral CEE did not have a clinically meaningful effect on HRQOL.

Low-fat dietary pattern and risk of invasive breast cancer: the Women's Health Initiative Randomized Controlled Dietary Modification Trial.

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.