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ObjectiveWeight gain frequently occurs after smoking cessation. The objective of this study was to examine whether weight gain after smoking cessation was attenuated by physical activity (PA) in postmenopausal women.MethodsA total of 4,717 baseline smokers from the Women's Health Initiative were followed for 3 years. One thousand two hundred eighty-two women quit smoking, and 3,435 continued smoking. Weight was measured at baseline and at the year 3 visit. PA was assessed at both times by self-report, summarized as metabolic equivalent task-hours per week. Multiple linear regression models were used to assess the association between PA and postcessation weight gain, adjusting for potential confounding factors.ResultsCompared with continuing smokers, quitters gained an average of 3.5 kg (SD = 5.6) between the baseline and year 3 visit. Quitters with decreased PA had the highest amount of weight gain (3.88 kg, 95% CI: 3.22-4.54); quitters with increased PA (≥15 metabolic equivalent task-hours /week) had the lowest weight gain (2.55 kg, 95% CI: 1.59-3.52). Increased PA had a stronger beneficial association for postcessation weight gain for women with obesity compared to normal weight women. Quitters who had low PA at baseline and high PA at year 3 and were also enrolled in a dietary modification intervention had nonsignificant weight gain (1.88 kg, 95% CI: -0.21-3.96) compared with continuing smokers.ConclusionsOur data demonstrate that even a modest increase in PA (equivalent to current recommendations) can attenuate weight gain after quitting smoking among postmenopausal women, especially in combination with improved diet.

BACKGROUND Out-of-office blood pressure (BP) measurement is recommended when making a new hypertension diagnosis. In practice, however, hypertension is primarily diagnosed using clinic BP. The study objective was to understand patient attitudes about accuracy and patient-centeredness regarding hypertension diagnostic methods. METHODS Qualitative study within a randomized controlled diagnostic study conducted between May 2017 and March 2019 comparing the accuracy and acceptability of BP measurement methods among patients in an integrated healthcare delivery system. All participants completed 24-hour ambulatory blood pressure monitoring (ABPM), plus either clinic BP, home BP monitoring (HBPM), or kiosk BP diagnostic testing. Qualitative interviewees (aged 31–76 years, n  = 35) were recruited from the main study. RESULTS Participants who completed HBPM found it to be comfortable and low burden, and believed it produced accurate results. Participants in the clinic arm described clinic measurements as inconvenient. Participants in the kiosk arm overall did not favor kiosks due to concerns about accuracy and privacy. Participants described ABPM as the most accurate method due to repeated measurements over the 24-hour period in real-world contexts, but many found it uncomfortable and disruptive. Participants also noted methods that involved repeated measures such as HBPM and ABPM particularly influenced their understanding of whether or not they had hypertension. CONCLUSIONS Hypertension diagnostic methods that include more BP measurements help patients gain a deeper understanding of BP variability and the lower reliability of infrequent measurements in the clinic. These findings warrant implementing strategies to enhance out-of-office BP diagnostic testing in primary care. CLINICAL TRIALS REGISTRATION Trial number NCT03130257. [ABSTRACT FROM AUTHOR]

High‐quality randomized trial evidence is lacking on whether low‐dose aspirin exerts significant effects on blood pressure (BP) in older adults. The authors assessed longitudinal BP changes in participants enrolled in ASPirin in Reducing Events in the Elderly (ASPREE), a randomized, placebo‐controlled trial of 100 mg daily aspirin in 19 114 community‐dwelling Australian and U.S. adults without cardiovascular disease (CVD), dementia, or independence‐limiting physical disability. Participants' BP was recorded at baseline and annual study visits, and managed by their usual care provider. BP trajectories for aspirin versus placebo during 4.7 years of follow‐up were examined for systolic and diastolic BP separately, using linear mixed models to account for between and within‐individual variability in BP. Analyses by subgroups were also explored with inclusion of interaction terms in the models. The difference in mean change in systolic BP between aspirin and placebo during study follow‐up was −0.03 mm Hg (95% confidence interval [CI]: −0.13, 0.07; p =.541) (aspirin minus placebo), while the mean difference for change in diastolic BP was −0.05 mm Hg (95% CI: –0.11, 0.01; p =.094). These small, non‐significant differences in BP change between the aspirin and placebo groups were consistent across baseline levels of BP and antihypertensive treatment status (treated/untreated). Likewise, subgroups of age, sex, chronic kidney disease, diabetes, and frailty revealed no interaction effect between the subgroup, aspirin treatment, and time. Interval‐censored Cox proportional hazards regression showed no difference in rates of incident treated hypertension between aspirin and placebo‐treated participants. The authors conclude that daily low‐dose aspirin does not significantly affect BP in older adults when managed by usual care. [ABSTRACT FROM AUTHOR]

ImportanceHealth outcomes from the Women's Health Initiative Estrogen Plus Progestin and Estrogen-Alone Trials have been reported, but previous publications have generally not focused on all-cause and cause-specific mortality.ObjectiveTo examine total and cause-specific cumulative mortality, including during the intervention and extended postintervention follow-up, of the 2 Women's Health Initiative hormone therapy trials.Design, setting, and participantsObservational follow-up of US multiethnic postmenopausal women aged 50 to 79 years enrolled in 2 randomized clinical trials between 1993 and 1998 and followed up through December 31, 2014.InterventionsConjugated equine estrogens (CEE, 0.625 mg/d) plus medroxyprogesterone acetate (MPA, 2.5 mg/d) (n = 8506) vs placebo (n = 8102) for 5.6 years (median) or CEE alone (n = 5310) vs placebo (n = 5429) for 7.2 years (median).Main outcomes and measuresAll-cause mortality (primary outcome) and cause-specific mortality (cardiovascular disease mortality, cancer mortality, and other major causes of mortality) in the 2 trials pooled and in each trial individually, with prespecified analyses by 10-year age group based on age at time of randomization.ResultsAmong 27 347 women who were randomized (baseline mean [SD] age, 63.4 [7.2] years; 80.6% white), mortality follow-up was available for more than 98%. During the cumulative 18-year follow-up, 7489 deaths occurred (1088 deaths during the intervention phase and 6401 deaths during postintervention follow-up). All-cause mortality was 27.1% in the hormone therapy group vs 27.6% in the placebo group (hazard ratio [HR], 0.99 [95% CI, 0.94-1.03]) in the overall pooled cohort; with CEE plus MPA, the HR was 1.02 (95% CI, 0.96-1.08); and with CEE alone, the HR was 0.94 (95% CI, 0.88-1.01). In the pooled cohort for cardiovascular mortality, the HR was 1.00 (95% CI, 0.92-1.08 [8.9 % with hormone therapy vs 9.0% with placebo]); for total cancer mortality, the HR was 1.03 (95% CI, 0.95-1.12 [8.2 % with hormone therapy vs 8.0% with placebo]); and for other causes, the HR was 0.95 (95% CI, 0.88-1.02 [10.0% with hormone therapy vs 10.7% with placebo]), and results did not differ significantly between trials. When examined by 10-year age groups comparing younger women (aged 50-59 years) to older women (aged 70-79 years) in the pooled cohort, the ratio of nominal HRs for all-cause mortality was 0.61 (95% CI, 0.43-0.87) during the intervention phase and the ratio was 0.87 (95% CI, 0.76-1.00) during cumulative 18-year follow-up, without significant heterogeneity between trials.Conclusions and relevanceAmong postmenopausal women, hormone therapy with CEE plus MPA for a median of 5.6 years or with CEE alone for a median of 7.2 years was not associated with risk of all-cause, cardiovascular, or cancer mortality during a cumulative follow-up of 18 years.Trial registrationclinicaltrials.gov Identifier: NCT00000611.

BackgroundFew previous studies investigating depression before the diagnosis of breast cancer and breast cancer-specific mortality have examined depression measured at more than 1 time point. This study investigated the effect of depression (combining depressive symptoms alone with antidepressant use) measured at 2 time points before the diagnosis of breast cancer on all-cause mortality and breast cancer-specific mortality among older postmenopausal women.MethodsA large prospective cohort, the Women's Health Initiative, was used. The study included 3095 women with incident breast cancer who had measures of depressive symptoms and antidepressant use before their diagnosis at the baseline and at year 3. Multivariate Cox proportional hazards regression was used to estimate adjusted hazard ratios (HRs) between depression at the baseline, depression at year 3, and combinations of depression at these time points and all-cause mortality and breast cancer-specific mortality.ResultsDepression at year 3 before a breast cancer diagnosis was associated with higher all-cause mortality after adjustments for multiple covariates (HR, 1.35; 95% confidence interval [CI], 1.02-1.78). There was no statistically significant association of baseline depression and all-cause mortality or breast cancer-specific mortality whether or not depression was also present at year 3. In women with late-stage (regional- or distant-stage) breast cancer, newly developed depression at year 3 was significantly associated with both all-cause mortality (HR, 2.00; 95% CI, 1.13-3.56) and breast cancer-specific mortality (HR, 2.42; 95% CI, 1.24-4.70).ConclusionsWomen with newly developed depression before the diagnosis of breast cancer had a modestly but significantly increased risk for death from any cause and for death from breast cancer at a late stage. Cancer 2017;123:3107-15. © 2017 American Cancer Society.

Background: Use of calcium channel blockers (CCBs) has been associated with increased risk of breast cancer in some, but not all, studies. Differences in reported associations from prior studies may be due, in part, to inadequate control of confounding factors.Methods: Participants were 28,561 postmenopausal women from the Women's Health Initiative who reported use of either CCBs or other antihypertensive medications (AHMs) at baseline; 1,402 incident breast cancer cases were diagnosed during 12 years of follow-up. Adjusted Cox regression models were used to estimate HRs and 95% confidence intervals (CI) for the associations between CCB use relative to other AHM use and breast cancer risk.Results: Use of CCBs was not associated with breast cancer risk (HR, 1.06; 95% CI, 0.94-1.20) relative to use of other AHMs. Associations approximated the null value when CCBs were considered by duration of use, length of action, or drug class.Conclusions: We provide additional evidence that CCBs do not influence breast cancer risk in postmenopausal women.Impact: The results from this study, which includes strong control for potential confounding factors, cast doubt on increases in risk with CCBs. Cancer Epidemiol Biomarkers Prev; 26(8); 1345-8. ©2017 AACR.

BackgroundThis post hoc analysis determined if the Women's Health Initiative (WHI) Diet Modification intervention (DM-I) resulted in a significantly different rate of incident hypertension (HTN), as well as longitudinal changes in blood pressure.MethodsParticipants were 48,835 postmenopausal women aged 50-79 years who were randomly assigned to either the intervention or comparison group. HTN was defined as self-report of treated HTN collected semiannually or blood pressure ≥140/90mm Hg at one of the annual follow-up clinic visits.ResultsAfter a mean follow-up of 8.3 years, and among those who did not have HTN at baseline (n = 31,146), there were 16,174 (51.9%) HTN cases and those assigned to the intervention group had a 4% lower overall risk of developing incident HTN (hazard ratio (HR): 0.96, 95% confidence interval (CI): 0.93-0.99). Although the risk of HTN was lower in the DM-I group in the first few years, the HR became greater than 1 after year 5 (P-trend < 0.01). Similarly, randomization to the DM-I arm resulted in a small but significantly lower average systolic blood pressure (SBP) at 1 year of follow-up (-0.66mm Hg, 0.44-0.89) that increased over the following 8 years (0.16mm Hg/year, 0.11-0.21), such that any early benefit was eliminated by year 5 and a minimal deleterious effect emerged by year 7.ConclusionRandomization to an intensive behavioral dietary modification program aimed at a lower total fat intake is not associated with sustained reductions in blood pressure or risk of HTN in postmenopausal women.Clinical trial registrationurl http://www.clinicaltrials.gov, unique identifier nct00000611.

BackgroundThe aims of this study are to investigate the impact of pre-existing diabetes and diabetes treatments on lung cancer prognosis.MethodsA total of 2484 women with confirmed incident lung cancer from the Women's Health Initiative were followed for an average of 2.9 years through the date of death or 29 August 2014.ResultsCompared with women with lung cancer but without diabetes, women with lung cancer and diabetes had significantly increased risk of overall mortality (HR=1.27, 95% CI: 1.07-1.50). Women with diabetes receiving insulin or metformin or women who had long duration of diabetes also had increased risk of overall mortality.ConclusionsOur large prospective study provides evidence that pre-existing diabetes is associated with poor overall survival among women with lung cancer, but do not support the hypothesis that metformin use may have a protective effect in women with lung cancer and diabetes.

BackgroundExposure to interpersonal violence, namely verbal and physical abuse, is a highly prevalent threat to women's health and well-being. Among older, post-menopausal women, several researchers have characterized a possible bi-directional relationship of abuse exposure and diminished physical functioning. However, studies that prospectively examine the relationship between interpersonal abuse exposure and physical functioning across multiple years of observation are lacking. To address this literature gap, we prospectively evaluate the association between abuse exposure and physical functioning in a large, national cohort of post-menopausal women across 12 years of follow-up observation.MethodsMultivariable logistic regression was used to measure the adjusted association between experiencing abuse and physical function score at baseline in 154,902 Women's Health Initiative (WHI) participants. Multilevel modeling, where the trajectories of decline in physical function were modeled as a function of time-varying abuse exposure, was used to evaluate the contribution of abuse to trajectories of physical function scores over time.ResultAbuse was prevalent among WHI participants, with 11 % of our study population reporting baseline exposure. Verbal abuse was the most commonly reported abuse type (10 %), followed by combined physical and verbal abuse (1 %), followed by physical abuse in the absence of verbal abuse (0.2 %). Abuse exposure (all types) was associated with diminished physical functioning, with women exposed to combined physical and verbal abuse presenting baseline physical functioning scores consistent with non-abused women 20 years senior. Results did not reveal a differential rate of decline over time in physical functioning based on abuse exposure.ConclusionsTaken together, our findings suggest a need for increased awareness of the prevalence of abuse exposure among postmenopausal women; they also underscore the importance of clinician's vigilance in their efforts toward the prevention, early detection and effective intervention with abuse exposure, including verbal abuse exposure, in post-menopausal women. Given our findings related to abuse exposure and women's diminished physical functioning at WHI baseline, our work illuminates a need for further study, particularly the investigation of this association in younger, pre-menopausal women so that the temporal ordering if this relationship may be better understood.

Living near major roadways has been associated with increased risk of cardiovascular morbidity and mortality, presumably from exposure to elevated levels of traffic-related air and/or noise pollution. This association may potentially be mediated through increased risk of incident hypertension, but results from prior studies are equivocal. Using Cox proportional hazards models we examined residential proximity to major roadways and incident hypertension among 38,360 participants of the Women's Health Initiative (WHI) Clinical Trial cohorts free of hypertension at enrollment and followed for a median of 7.9 years. Adjusting for participant demographics and lifestyle, trial participation, and markers of individual and neighborhood socioeconomic status, the hazard ratios for incident hypertension were 1.13 (95% CI: 1.00, 1.28), 1.03 (0.95, 1.11), 1.05 (0.99, 1.11), and 1.05 (1.00, 1.10) for participants living ≤50, >50-200, >200-400, and >400-1000 m vs >1000 m from the nearest major roadway, respectively (ptrend=0.013). This association varied substantially by WHI study region with hazard ratios for women living ≤50 m from a major roadway of 1.61 (1.18, 2.20) in the West, 1.51 (1.22, 1.87) in the Northeast, 0.89 (0.70, 1.14) in the South, and 0.94 (0.75, 1.19) in the Midwest. In this large, national cohort of post-menopausal women, residential proximity to major roadways was associated with incident hypertension in selected regions of the U.S. If causal, these results suggest residential proximity to major roadways, as a marker for air, noise and other traffic-related pollution, may be a risk factor for hypertension.

BackgroundData collected as part of routine clinical practice could be used to detect cardiovascular outcomes in pragmatic clinical trials or clinical registry studies. The reliability of claims data for documenting outcomes is unknown.Methods and resultsWe linked records of Women's Health Initiative (WHI) participants aged ≥65 years to Medicare claims data and compared hospitalizations that had diagnosis codes for acute myocardial infarction or coronary revascularization with WHI outcomes adjudicated by study physicians. We then compared the hazard ratios for active versus placebo hormone therapy based solely on WHI-adjudicated events with corresponding hazard ratios based solely on claims data for the same hormone trial participants. Agreement between WHI-adjudicated outcomes and Medicare claims was good for the diagnosis of myocardial infarction (κ, 0.71-0.74) and excellent for coronary revascularization (κ, 0.88-0.91). The hormone:placebo hazard ratio for clinical myocardial infarction was 1.31 (95% confidence interval, 1.03-1.67) based on WHI outcomes and 1.29 (95% confidence interval, 1.00-1.68) based on Medicare data. The hazard ratio for coronary revascularization was 1.09 (95% confidence interval, 0.88-1.35) based on WHI outcomes and 1.10 (95% confidence interval, 0.89-1.35) based on Medicare data. The differences between hazard ratios derived from WHI and Medicare data were not significant in 1000 bootstrap replications.ConclusionsMedicare claims may provide useful data on coronary heart disease outcomes among patients aged ≥65 years in clinical research studies.Clinical trials registration informationURL: www.clinicaltrials.gov. Unique identifier: NCT00000611.

Steps per day were measured by accelerometer for 7 days among 5,545 women aged 63–97 years between 2012 and 2014. Incident falls were ascertained from daily fall calendars for 13 months. Median steps per day were 3,216. There were 5,473 falls recorded over 61,564 fall calendar-months. The adjusted incidence rate ratio comparing women in the highest versus lowest step quartiles was 0.71 (95% confidence interval [0.54, 0.95]; ptrend across quartiles =.01). After further adjustment for physical function using the Short Physical Performance Battery, the incidence rate ratio was 0.86 ([0.64, 1.16]; ptrend =.27). Mediation analysis estimated that 63.7% of the association may be mediated by physical function (p =.03). In conclusion, higher steps per day were related to lower incident falls primarily through their beneficial association with physical functioning. Interventions that improve physical function, including those that involve stepping, could reduce falls in older adults. [ABSTRACT FROM AUTHOR]

ImportanceMenopausal hormone therapy continues in clinical use but questions remain regarding its risks and benefits for chronic disease prevention.ObjectiveTo report a comprehensive, integrated overview of findings from the 2 Women's Health Initiative (WHI) hormone therapy trials with extended postintervention follow-up.Design, setting, and participantsA total of 27,347 postmenopausal women aged 50 to 79 years were enrolled at 40 US centers.InterventionsWomen with an intact uterus received conjugated equine estrogens (CEE; 0.625 mg/d) plus medroxyprogesterone acetate (MPA; 2.5 mg/d) (n = 8506) or placebo (n = 8102). Women with prior hysterectomy received CEE alone (0.625 mg/d) (n = 5310) or placebo (n = 5429). The intervention lasted a median of 5.6 years in CEE plus MPA trial and 7.2 years in CEE alone trial with 13 years of cumulative follow-up until September 30, 2010.Main outcomes and measuresPrimary efficacy and safety outcomes were coronary heart disease (CHD) and invasive breast cancer, respectively. A global index also included stroke, pulmonary embolism, colorectal cancer, endometrial cancer, hip fracture, and death.ResultsDuring the CEE plus MPA intervention phase, the numbers of CHD cases were 196 for CEE plus MPA vs 159 for placebo (hazard ratio [HR], 1.18; 95% CI, 0.95-1.45) and 206 vs 155, respectively, for invasive breast cancer (HR, 1.24; 95% CI, 1.01-1.53). Other risks included increased stroke, pulmonary embolism, dementia (in women aged ≥65 years), gallbladder disease, and urinary incontinence; benefits included decreased hip fractures, diabetes, and vasomotor symptoms. Most risks and benefits dissipated postintervention, although some elevation in breast cancer risk persisted during cumulative follow-up (434 cases for CEE plus MPA vs 323 for placebo; HR, 1.28 [95% CI, 1.11-1.48]). The risks and benefits were more balanced during the CEE alone intervention with 204 CHD cases for CEE alone vs 222 cases for placebo (HR, 0.94; 95% CI, 0.78-1.14) and 104 vs 135, respectively, for invasive breast cancer (HR, 0.79; 95% CI, 0.61-1.02); cumulatively, there were 168 vs 216, respectively, cases of breast cancer diagnosed (HR, 0.79; 95% CI, 0.65-0.97). Results for other outcomes were similar to CEE plus MPA. Neither regimen affected all-cause mortality. For CEE alone, younger women (aged 50-59 years) had more favorable results for all-cause mortality, myocardial infarction, and the global index (nominal P

Factors that contribute to bone fragility in type 2 diabetes are not well understood. We assessed the effects of intensive glycemic control, thiazolidinediones (TZDs), and A1C levels on bone geometry and strength at the radius and tibia. In a substudy of the Action to Control Cardiovascular Risk in Diabetes trial, peripheral quantitative computed tomographic (pQCT) scans of the radius and tibia were obtained 2 years after randomization on 73 participants (intensive n = 35, standard n = 38). TZD use and A1C levels were measured every 4 months during the trial. Effects of intervention assignment, TZD use, and A1C on pQCT parameters were assessed in linear regression models. Intensive, compared with standard, glycemic control was associated with 1.3 % lower cortical volumetric BMD at the tibia in men (p = 0.02) but not with other pQCT parameters. In women, but not men, each additional year of TZD use was associated with an 11 % lower polar strength strain index (SSIp) at the radius (p = 0.04) and tibia (p = 0.002) in models adjusted for A1C levels. In women, each additional 1 % increase in A1C was associated with an 18 % lower SSIp at the ultradistal radius (p = 0.04) in models adjusted for TZD use. There was no consistent evidence of an effect of intensive, compared with standard, glycemic control on bone strength at the radius or tibia. In women, TZD use may reduce bone strength at these sites. Higher A1C may also be associated with lower bone strength at the radius, but not tibia, in women.

BackgroundThe differences in the incidence of heart failure by race/ethnicity and the potential mechanisms for these differences are largely unexplored in women.Methods and resultsA total of 156 143 postmenopausal women free of self-reported heart failure enrolled from 1993 to 1998 at 40 clinical centers throughout the United States as part of the Women's Health Initiative and were followed up until 2005, for an average of 7.8 years, for incident hospitalized heart failure. Incident rates, hazard ratios (HRs), and 95% confidence intervals were determined by use of the Cox proportional hazard model comparing racial/ethnic groups, and population-attributable risk percentages were calculated for each racial/ethnic group. Blacks had the highest age-adjusted incidence of heart failure (380 in 100 000 person-years), followed by whites (274), Hispanics (193), and Asian/Pacific Islanders (103). The excess risk in blacks compared with whites (age-adjusted HR=1.45) was significantly attenuated by adjustment for household income (HR=0.97) and diabetes mellitus (HR=0.89), but the lower risk in Hispanics (age-adjusted HR=0.72) and Asian/Pacific Islanders (age-adjusted HR=0.44) remained despite adjustment for traditional risk factors, socioeconomic status, lifestyle, and access-to-care variables. The effect of adjustment for interim coronary heart disease on nonwhite versus white HRs for heart failure differed by race/ethnic group.ConclusionsAsian/Pacific Islander and Hispanic women have a lower incidence of heart failure and black women have higher rates of heart failure compared with white women. The excess risk of incident heart failure in black women is explained largely by adjustment for lower household incomes and diabetes mellitus in black women, whereas the lower rates of heart failure in Asian/Pacific Islanders and Hispanics are largely unexplained by the risk factors measured in this study.Clinical trial registrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT00000611.

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.

ContextThe Women's Health Initiative Estrogen-Alone Trial was stopped early after a mean of 7.1 years of follow-up because of an increased risk of stroke and little likelihood of altering the balance of risk to benefit by the planned trial termination date. Postintervention health outcomes have not been reported.ObjectiveTo examine health outcomes associated with randomization to treatment with conjugated equine estrogens (CEE) among women with prior hysterectomy after a mean of 10.7 years of follow-up through August 2009.Design, setting, and participantsThe intervention phase was a double-blind, placebo-controlled, randomized clinical trial of 0.625 mg/d of CEE compared with placebo in 10,739 US postmenopausal women aged 50 to 79 years with prior hysterectomy. Follow-up continued after the planned trial completion date among 7645 surviving participants (78%) who provided written consent.Main outcome measuresThe primary outcomes were coronary heart disease (CHD) and invasive breast cancer. A global index of risks and benefits included these primary outcomes plus stroke, pulmonary embolism, colorectal cancer, hip fracture, and death.ResultsThe postintervention risk (annualized rate) for CHD among women assigned to CEE was 0.64% compared with 0.67% in the placebo group (hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.75-1.25), 0.26% vs 0.34%, respectively, for breast cancer (HR, 0.75; 95% CI, 0.51-1.09), and 1.47% vs 1.48%, respectively, for total mortality (HR, 1.00; 95% CI, 0.84-1.18). The risk of stroke was no longer elevated during the postintervention follow-up period and was 0.36% among women receiving CEE compared with 0.41% in the placebo group (HR, 0.89; 95% CI, 0.64-1.24), the risk of deep vein thrombosis was lower at 0.17% vs 0.27%, respectively (HR, 0.63; 95% CI, 0.41-0.98), and the risk of hip fracture did not differ significantly and was 0.36% vs 0.28%, respectively (HR, 1.27; 95% CI, 0.88-1.82). Over the entire follow-up, lower breast cancer incidence in the CEE group persisted and was 0.27% compared with 0.35% in the placebo group (HR, 0.77; 95% CI, 0.62-0.95). Health outcomes were more favorable for younger compared with older women for CHD (P = .05 for interaction), total myocardial infarction (P = .007 for interaction), colorectal cancer (P = .04 for interaction), total mortality (P = .04 for interaction), and global index of chronic diseases (P = .009 for interaction).ConclusionsAmong postmenopausal women with prior hysterectomy followed up for 10.7 years, CEE use for a median of 5.9 years was not associated with an increased or decreased risk of CHD, deep vein thrombosis, stroke, hip fracture, colorectal cancer, or total mortality. A decreased risk of breast cancer persisted.Trial registrationclinicaltrials.gov Identifier: NCT00000611.

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 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