Alcohol Consumption and the Diversity of the Oral Microbiome in Postmenopausal Women.

BACKGROUND: Alcohol reduces neutrophil function and decreases salivary flow, which could affect the composition of the oral microbiome. OBJECTIVE: We hypothesized that the α- and ß-diversity of the oral microbiome and the relative abundance of bacterial taxa would differ by frequency and type of alcohol consumption. METHODS: We used a food frequency questionnaire to assess the frequency of consumption of beer, wine, and liquor (drinks/week) in a sample of 1179 postmenopausal women in the Osteoporosis and Periodontal Disease Study. Women were categorized as nondrinkers, drinking <1 drink/wk, ≥1 to <7 drinks/wk, or ≥7 drinks/wk for total alcohol consumption and for beer, wine, and liquor consumption. The composition and diversity of the oral microbiome was assessed from subgingival plaque samples using 16S ribosomal RNA amplicon sequencing. Permutational multivariate analysis of variance (PERMANOVA) was used to examine ß-diversity (between-sample diversity) in the microbiome between alcohol consumption categories. Analysis of covariance was used to examine the mean α-diversity (within-sample diversity), assessed by the Shannon index (species evenness), Chao1 index (species richness), and observed operational taxonomic unit (OTU) count and the mean relative abundance of 245 bacterial taxa across alcohol consumption categories. RESULTS: Over half of the participants (67%) consumed alcohol, with 14% reporting ≥1 drink/d. The ß-diversity across categories of total alcohol consumption, but not categories of alcohol type, was statistically significantly different (P for PERMANOVA = 0.016). Mean α-diversity measures were statistically significantly higher (P < 0.05) in the highest category of total alcohol and wine consumption compared to nondrinkers; no significant associations were found for beer or liquor consumption. The relative abundance of 1 OTU, Selenomonassp._oral_taxon_133, was significantly lower in the highest level of total alcohol consumption compared to nondrinkers after adjustment for multiple comparisons. CONCLUSIONS: Alcohol consumption was associated with the diversity and composition of the subgingival microbiome.

Association between dietary patterns and periodontal disease: The OsteoPerio cohort study.

AIM: To examine the association of dietary patterns with periodontal disease (PD) and its progression over 5 years. MATERIALS AND METHODS: Analyses involved 1197 post-menopausal women from the OsteoPerio cohort. Dietary patterns assessed include Healthy Eating Index-2015 (HEI), Alternative HEI (AHEI), Dietary Approaches to Stop Hypertension (DASH) and alternate Mediterranean Diet (aMed) at baseline (the average of two food frequency questionnaires administered between 1993 and 2001). At baseline and the 5-year follow-up, periodontal assessments evaluated alveolar crestal height (ACH), probing pocket depth (PPD), clinical attachment loss (CAL), percentage of gingival sites bleeding on probing (%BOP) and missing teeth due to PD. Linear and logistic regression were used to examine the associations. RESULTS: Cross-sectionally, HEI and aMed were associated with smaller CAL and %BOP; along with DASH, they were associated with a decreased odds of teeth missing due to PD. AHEI and aMed were associated with a decreased odds of severe PD. Prospectively, AHEI was associated with greater ACH progression. This association was attenuated to the null after loss of ACH was imputed for teeth lost due to PD over follow-up, or after excluding participants with diabetes, osteoporosis, hypertension or heart disease at baseline. CONCLUSIONS: Better adherence to healthy dietary patterns was associated with better PD measures cross-sectionally but greater progression of ACH over 5 years. The latter might be explained by incident tooth loss due to PD and pre-existing comorbidities.

Proton Pump Inhibitor Use and Obesity-Associated Cancer in the Women's Health Initiative.

Proton pump inhibitors (PPIs) have off-target activity on fatty acid synthase (FASN), a critical enzyme in energy balance and cancer growth. We evaluated risk of common obesity-related cancers: breast, colorectal (CRC), and endometrial, with use of PPI and histamine-2 receptor antagonists (H2RA) in 124,931 postmenopausal women enrolled in the Women's Health Initiative. Incident cancer cases were physician-adjudicated. Cox proportional hazards models were used to estimate multivariable hazard ratios (HR) and 95% confidence intervals (CI) for cancer incidence after year 3. There were 7956 PPI ever users and 9398 H2RA only users. Ever use of either PPI or H2RA was not associated with risk of breast cancer (n = 9186) nor risk of endometrial cancer (n = 1231). The risk of CRC (n = 2280) was significantly lower in PPI users (HR = 0.75, 95% CI = 0.61-0.92), but not in H2RA users (HR = 1.13, 95% CI = 0.97-1.31). The association of PPI use with CRC was apparent regardless of BMI or NSAID use, and was stronger with longer PPI duration (p = 0.006) and potency (p = 0.005). The findings that PPI use, but not H2RA use, demonstrate an inverse dose-response relationship with risk of CRC is consistent with preclinical data showing FASN inhibition prevents colon cancer progression and supports a role of PPI in CRC prevention.

Red blood cell fatty acids and age-related macular degeneration in postmenopausal women.

PURPOSE: To evaluate the relationship between red blood cell (RBC) polyunsaturated fatty acid (PUFA) levels, and dietary PUFA and fish intake, with prevalent and incident age-related macular degeneration (AMD) in a US cohort of postmenopausal women. METHODS: This analysis included 1456 postmenopausal women from the Women's Health Initiative (WHI) Clinical Trials. RBC PUFAs were measured from fasting serum samples collected at WHI baseline. Dietary PUFAs and fish intake were assessed via food frequency questionnaires at baseline. There were 240 women who had prevalent AMD and 138 who self-reported AMD development over 9.5 years. Adjusted odds ratios and 95% confidence intervals were estimated for prevalent AMD by RBC PUFA levels, dietary PUFA intake, and frequency of fish consumption. Adjusted hazard ratios and 95% confidence intervals were estimated for incident AMD. A p-for-trend was estimated for continuous measures of dietary PUFA and fish intake. RESULTS: No significant association was found between prevalent or incident AMD and RBC docosahexaenoic acid (DHA) + eicosapentaenoic acid (EPA), EPA, DHA, alpha-linolenic acid (ALA), linoleic acid (LA), or arachidonic acid (AA). A positive association was found between dietary intake of AA and odds of prevalent AMD (p-for-trend for continuous AA intake = 0.02) and between intake of LA/ALA and incident AMD (p-for-trend for continuous ratio of LA/ALA intake = 0.03). No statistically significant associations were found between AMD and dietary intake of PUFAs or fish. CONCLUSIONS: RBC PUFAs were not associated with AMD in this cohort. Overall, dietary analyses of PUFAs supported this, excepting dietary AA intake and intake of LA in proportion to ALA of which there were trends of increased risk.

Caffeine intake from coffee and tea and invasive breast cancer incidence among postmenopausal women in the Women's Health Initiative.

Research findings remain inconsistent whether caffeine consumption is associated with invasive breast cancer. We aimed to examine the association between caffeine intake from coffee and tea and incident invasive breast cancer among postmenopausal women. We included 79 871 participants in the Women's Health Initiative Observational Study in the current analysis. Incident invasive breast cancers were identified through September 30, 2015. Caffeine intake (mg/day) from caffeinated and decaffeinated coffee and tea was estimated based on self-reported frequency (cups/day) and average caffeine amount in each beverage. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Subgroup analyses were conducted to explore whether associations of caffeine intake from coffee and tea with invasive breast cancer were different by age, race and ethnicity, smoking status, body mass index, history of hormone therapy use, alcohol intake and subtypes of breast cancer. During a median follow-up of 16.0 years, 4719 incident invasive breast cancers were identified. No significant association was found between caffeine intake from coffee and tea and invasive breast cancer incidence after adjusting for demographic, lifestyle and reproductive factors: HRs (95% CIs) for increasing quartiles of caffeine intake compared to the lowest were 1.03 (0.94, 1.12), 1.04 (0.95, 1.13) and 1.03 (0.94, 1.13), respectively (P-for-trend = .54). No significant associations of coffee and tea intake (cups/day) with overall breast cancer risk were found. Our findings are consistent with others showing no clear association of caffeine consumption with invasive breast cancer among postmenopausal women.

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.

Composition and diversity of the subgingival microbiome and its relationship with age in postmenopausal women: an epidemiologic investigation.

BACKGROUND: The extent to which the composition and diversity of the oral microbiome varies with age is not clearly understood. METHODS: The 16S rRNA gene of subgingival plaque in 1219 women, aged 53-81 years, was sequenced and its taxonomy annotated against the Human Oral Microbiome Database (v.14.5). Composition of the subgingival microbiome was described in terms of centered log(2)-ratio (CLR) transformed OTU values, relative abundance, and prevalence. Correlations between microbiota abundance and age were evelauted using Pearson Product Moment correlations. P-values were corrected for multiple testing using the Bonferroni method. RESULTS: Of the 267 species identified overall, Veillonella dispar was the most abundant bacteria when described by CLR OTU (mean 8.3) or relative abundance (mean 8.9%); whereas Streptococcus oralis, Veillonella dispar and Veillonella parvula were most prevalent (100%, all) when described as being present at any amount. Linear correlations between age and several CLR OTUs (Pearson r = - 0.18 to 0.18), of which 82 (31%) achieved statistical significance (P < 0.05). The correlations lost significance following Bonferroni correction. Twelve species that differed across age groups (each corrected P < 0.05); 5 (42%) were higher in women ages 50-59 compared to ≥70 (corrected P < 0.05), and 7 (48%) were higher in women 70 years and older. CONCLUSIONS: We identified associations between several bacterial species and age across the age range of postmenopausal women studied. Understanding the functions of these bacteria could identify intervention targets to enhance oral health in later life.

Stratified Probabilistic Bias Analysis for Body Mass Index-related Exposure Misclassification in Postmenopausal Women.

BACKGROUND: There is widespread concern about the use of body mass index (BMI) to define obesity status in postmenopausal women because it may not accurately represent an individual's true obesity status. The objective of the present study is to examine and adjust for exposure misclassification bias from using an indirect measure of obesity (BMI) compared with a direct measure of obesity (percent body fat). METHODS: We used data from postmenopausal non-Hispanic black and non-Hispanic white women in the Women's Health Initiative (n=126,459). Within the Women's Health Initiative, a sample of 11,018 women were invited to participate in a sub-study involving dual-energy x-ray absorptiometry scans. We examined indices of validity comparing BMI-defined obesity (≥30 kg/m), with obesity defined by percent body fat. We then used probabilistic bias analysis models stratified by age and race to explore the effect of exposure misclassification on the obesity-mortality relationship. RESULTS: Validation analyses highlight that using a BMI cutpoint of 30 kg/m to define obesity in postmenopausal women is associated with poor validity. There were notable differences in sensitivity by age and race. Results from the stratified bias analysis demonstrated that failing to adjust for exposure misclassification bias results in attenuated estimates of the obesity-mortality relationship. For example, in non-Hispanic white women 50-59 years of age, the conventional risk difference was 0.017 (95% confidence interval = 0.01, 0.023) and the bias-adjusted risk difference was 0.035 (95% simulation interval = 0.028, 0.043). CONCLUSIONS: These results demonstrate the importance of using quantitative bias analysis techniques to account for nondifferential exposure misclassification of BMI-defined obesity. See video abstract at, http://links.lww.com/EDE/B385.

Periodontal disease severity and cancer risk in postmenopausal women: the Buffalo OsteoPerio Study.

PURPOSE: Few prospective studies have reported on relationships between objective periodontal disease (PD) measures and cancer risk. This association was examined in 1,337 postmenopausal women participating in the Buffalo OsteoPerio Study. METHODS: Oral alveolar crestal height (ACH) was measured using oral radiographs. Incident cancers were adjudicated with medical records. Hazard ratios (HRs) and 95 % confidence intervals (CIs) for associations between ACH and incident cancer outcomes were estimated using Cox proportional hazards models. RESULTS: There were 203 confirmed total incident cancer cases during follow-up (12.2 ± 4.2 years). After adjusting for age and smoking, there were no statistically significant associations between ACH-defined PD categories and total cancer risk (mild/moderate vs. none: HR 1.33, 95 % CI 0.91-1.94; severe vs. none: HR 1.20, 95 % CI 0.77-1.86). ACH-defined PD categories were not associated with common site-specific cancers. Whole-mouth mean and worst-site ACH (per 1 mm loss) were significantly associated with increased risk of lung (adjusted HR 1.81, 95 % CI 1.30-2.54; adjusted HR 1.34, 95 % CI 1.08-1.66, respectively), but not total or other site-specific cancer. Smoking status modified the associations between continuous ACH variables and total cancer risk; measures of PD were associated with total cancer among smokers but not never smokers (interaction p = 0.02 and p < 0.01 for whole-mouth mean and worst-site ACH, respectively). CONCLUSIONS: ACH-defined PD was associated with total cancer risk in ever but not never smoking postmenopausal women. Whole-mouth mean and worst-site ACH were associated with increased lung cancer risk. However, these results need to be interpreted cautiously given the small number of lung cancer cases (n = 18). Further research utilizing a larger sample is warranted to confirm the relationships among oral bone loss, site-specific cancers, and total cancer.

Impact of incident diabetes on atherosclerotic cardiovascular disease according to statin use history among postmenopausal women.

To compare impact of incident diabetes on atherosclerotic cardiovascular disease (ASCVD) risk among postmenopausal women according to statin use. Prospective data from 120,499 postmenopausal women without prevalent diabetes or cardiovascular disease at baseline from the Women's Health Initiative were used. Incident diabetes was self-reported annually and defined as treatment with pills or injectable medication for diabetes. Current statin use was determined at enrollment and years 1, 3, 6, 9 and 13.5 in the three clinical trial arms, and at baseline, year 3, and 13.5 for the observational study. The primary outcome was incident ASCVD events, self-reported annually and adjudicated by blinded local and central physicians. Incident diabetes and statin use status were fitted as time-varying covariates in Cox regression models to assess ASCVD risk during an average follow-up of 13.6 years. For those not on statins at the time of diabetes diagnosis, there was a 42 % increased risk of ASCVD [hazard ratio (HR) 1.42, 95 % CI 1.28-1.58] among women with incident diabetes versus those without diabetes. Among women on statins, there was a 39 % increased risk of ASCVD (HR 1.39, 95 % CI 1.12-1.74) in women with incident diabetes versus those without diabetes. The increased ASCVD risk due to diabetes was similar between women before or after initiating statins (P = 0.89). Whether diabetes was diagnosed before or after statin use did not alter the increased risk of ASCVD associated with diabetes. Mitigating the increased incidence of diabetes in statin users could increase the ASCVD benefit-to-risk ratio of statins.

Associations between lifetime tobacco exposure with infertility and age at natural menopause: the Women's Health Initiative Observational Study.

BACKGROUND: Several studies have investigated the association of tobacco use with infertility and age at natural menopause, yet few have explored secondhand smoke (SHS) exposure with these outcomes. This study offers a comprehensive, quantified secondary data analysis of these issues using the Women's Health Initiative Observational Study (WHI OS). PURPOSE: This study examines associations between lifetime tobacco exposure-active smoking and SHS-and infertility and natural menopause (before age 50). METHODS: Information on smoking, lifetime fertility status, and age at natural menopause was collected and available from 93 676 postmenopausal women aged 50-79 enrolled in the WHI OS from 1993 to 1998 at 40 centres in the USA. Multivariate-adjusted regression models were used to estimate ORs and 95% CI according to levels of active smoking and SHS exposure, and trends were tested across categories. RESULTS: Overall, 15.4% of the 88 732 women included in the analysis on infertility met criteria for the condition. 45% of the 79 690 women included in the analysis on natural menopause (before age 50) met criteria for the condition. Active-ever smokers had overall OR's of 1.14 (95% CI 1.03 to 1.26) for infertility, and 1.26 (95% CI 1.16 to 1.35) for earlier menopause than never-smoking women. Never-smoking women with the highest levels of lifetime SHS exposure had adjusted OR's of 1.18 (95% CI 1.02 to 1.35) for infertility, and 1.18 (95% CI 1.06 to 1.31) for earlier menopause. Active-ever smokers reached menopause 21.7 months earlier than the mean of 49.4 years for never-smokers not exposed to SHS, and women exposed to the highest level of SHS reached menopause 13.0 months earlier. CONCLUSIONS: Active smoking and SHS exposure are associated with increased risk of infertility and natural menopause occurring before the age of 50 years.

Recruitment for longitudinal, randomised pregnancy trials initiated preconception: lessons from the effects of aspirin in gestation and reproduction trial.

BACKGROUND: Recruitment into large, preconception randomised clinical trials (RCT) is challenging. We describe clinic and community-based preconception recruitment strategies for the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial and highlight approaches that were and were not successful. This longitudinal RCT was conducted at four major sites in the US. Eligible women had one to two prior pregnancy losses and were actively trying to become pregnant. METHODS: Provider/clinic and community-based outreach strategies were utilised, and the recruitment rate and costs of methods were assessed. RESULTS: A screening questionnaire was completed by 5485 women; 42.4% (n = 2323) screened were initially eligible, of whom 50.7% (n = 1228) were randomised. Provider/clinic-based recruitment yielded the highest number eligible of those screened (30.1%) and also the most randomised participants overall (40.3%). The next highest yield came from direct mail and brochures/flyers at 13.1% and 12.5% of women randomised, respectively. However, direct mailings cost $720 per participant randomised. Other than word of mouth, provider/clinic-based recruitment was the most cost effective method, costing an average of $60 per randomised participant. Web-based recruitment yielded 4.7% of participants at a cost of $278 per randomised participant. CONCLUSIONS: Provider and clinic-based recruitment was the most effective and cost-efficient method of recruitment in a preconception intervention study of reproduction among women.

Associations of lifetime active and passive smoking with spontaneous abortion, stillbirth and tubal ectopic pregnancy: a cross-sectional analysis of historical data from the Women's Health Initiative.

OBJECTIVE: To examine the associations between tobacco exposure and adverse pregnancy outcomes using quantitative measures of lifetime active smoking and secondhand smoke (SHS) exposure. METHODS: Historical reproductive data on 80 762 women who participated in the Women's Health Initiative Observational Study were examined with a cross-sectional analysis. We assessed self-reported lifetime active and passive tobacco smoke exposure, self-reported spontaneous abortions, stillbirths and ectopic pregnancies. RESULTS: When compared with never-smoking women, participants who were ever active smokers during their reproductive years had ORs (OR) of 1.16 (95% CI 1.08 to 1.26) for 1 or more spontaneous abortions, 1.44 (95% CI 1.20 to 1.73) for 1 or more stillbirths, and 1.43 (95% CI 1.10 to 1.86) for 1 or more ectopic pregnancies. Never-smoking women participants with the highest levels of lifetime SHS exposure, including childhood >10 years, adult home >20 years and adult work exposure >10 years, when compared with never-smoking women with no SHS exposure had adjusted ORs of 1.17 (95% CI 1.05 to 1.30) for spontaneous abortion, 1.55 (95% CI 1.21 to 1.97) for stillbirth, and 1.61 (95% CI 1.16 to 2.24) for ectopic pregnancy. CONCLUSIONS: Women who were ever-smokers during their reproductive years had significantly greater estimates of risk for spontaneous abortion, stillbirth and tubal ectopic pregnancy. Never-smoking women with the highest levels of lifetime exposure to SHS had significantly increased estimates of risk for spontaneous abortion, stillbirth and tubal ectopic pregnancy.

History of periodontal disease diagnosis and lung cancer incidence in the Women's Health Initiative Observational Study.

PURPOSE: While some evidence suggests that periodontal disease (PD) might be positively associated with lung cancer, prospective studies in women are limited. Previous findings may reflect residual confounding by smoking. The study aims to determine whether history of PD diagnosis is associated with incident lung cancer in a large cohort of postmenopausal women. METHODS: Prospective analyses were conducted in a cohort of 77,485 postmenopausal women enrolled in the Women's Health Initiative Observational Study. History of PD (prevalence of 26.1 %) was self-reported, and 754 incident lung cancer cases occurred during an average 6.8 (SD ± 2.6) years of follow-up. Cox proportional hazards regression analysis was used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs). RESULTS: Overall, PD was positively associated with lung cancer risk after adjusting for detailed smoking history including smoking status and pack-years of smoking (HR 1.24, 95 % CI 1.07-1.45). There was a positive additive interaction between PD with pack-years of smoking (p = 0.02), suggesting a potential synergistic effect between PD and smoking intensity on lung cancer. The association between PD and lung cancer was stronger in former smokers. When restricted to never-smokers, PD was not associated with lung cancer (HR 1.02, 95 % CI 0.68-1.53). CONCLUSIONS: Periodontal disease was not independently associated with lung cancer in non-smoking postmenopausal women. However, smoking and PD jointly increased lung cancer risk beyond that expected from the sum of the each effect separately. The potential synergism between PD and smoking on lung cancer warrants further examination.

Defining Porphyromonas gingivalis strains associated with periodontal disease.

Porphyromonas gingivalis, a Gram-negative anaerobic bacterium commonly found in human subgingival plaque, is a major etiologic agent for periodontitis and has been associated with multiple systemic pathologies. Many P. gingivalis strains have been identified and different strains possess different virulence factors. Current oral microbiome approaches (16S or shotgun) have been unable to differentiate P. gingivalis strains. This study presents a new approach that aims to improve the accuracy of strain identification, using a detection method based on sequencing of the intergenic spacer region (ISR) which is variable between P. gingivalis strains. Our approach uses two-step PCR to amplify only the P. gingivalis ISR region. Samples are then sequenced with an Illumina sequencer and mapped to specific strains. Our approach was validated by examining subgingival plaque from 153 participants with and without periodontal disease. We identified the avirulent strain ATCC33277/381 as the most abundant strain across all sample types. The W83/W50 strain was significantly enriched in periodontitis, with 13% of participants harboring that strain. Overall, this approach can have significant implications not only for the diagnosis and treatment of periodontal disease but also for other diseases where P. gingivalis or its toxins have been implicated, such as Alzheimer's disease.

Caregiving and all-cause mortality in postmenopausal women: Findings from the Women's Health Initiative.

BACKGROUND: Caregiving is commonly undertaken by older women. Research is mixed, however, about the impact of prolonged caregiving on their health, well-being, and mortality risk. Using a prospective study design, we examined the association of caregiving with mortality in a cohort of older women. METHODS: Participants were 158,987 postmenopausal women aged 50-79 years at enrollment into the Women's Health Initiative (WHI) who provided information on current caregiving status and caregiving frequency at baseline (1993-1998) and follow-up (2004-2005). Mortality was ascertained from baseline through March of 2019. Cox regression with caregiving status defined as a time-varying exposure was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for mortality, adjusting for sociodemographic factors, smoking, and history of diabetes, hypertension, cardiovascular disease (CVD), and cancer. Stratified analyses explored whether age, race-ethnicity, depressive symptoms, frequency of caregiving, optimism, and living status modified the association between caregiver status and mortality. RESULTS: At baseline, 40.7% of women (mean age 63.3 years) self-identified as caregivers. During a mean 17.5-year follow-up, all-cause mortality (50,526 deaths) was 9% lower (multivariable-adjusted HR = 0.91, 95% CI: 0.89-0.93) in caregivers compared to non-caregivers. The inverse association between caregiving and all-cause mortality did not differ according to caregiving frequency or when stratified by age, race-ethnicity, depressive symptoms, optimism, or living status (interaction p > 0.05, all). Caregiving was inversely associated with CVD and cancer mortality. CONCLUSION: Among postmenopausal women residing across the United States, caregiving was associated with lower mortality. Studies detailing the type and amount of caregiving are needed to further determine its impact on older women.

Discontinuation of hormone therapy and bone mineral density: does physical activity modify that relationship?

OBJECTIVE: Hormone therapy can positively impact bone mineral density after menopause. We explored bone mineral density change in postmenopausal women who discontinued hormone therapy after the Women's Health Initiative landmark 2002 trial results were published. We secondarily explored whether usual physical activity modified the results. METHODS: Postmenopausal women participating in the Buffalo OsteoPerio study with information on hip bone density, hormone therapy use, and self-reported physical activity at two time points (1997-2001; 2002-2007) were included (N = 961). Hormone therapy included three groups according to use at baseline and year 5 (non/non; current/non; current/current). RESULTS: At baseline (mean age, 65.9 years; SD, 6.7 years), 480 women were not using hormone therapy, while 481 were current users. Between the baseline and 5-year visits, 336 women using hormone therapy discontinued. Baseline total hip bone density was highest in current users. After 5 years, those who continued hormone therapy exhibited no bone loss; those who discontinued exhibited the greatest loss at the total hip of -0.021 gm/cm2. Women who never used hormone therapy exhibited some loss of -0.012 gm/cm2. Usual physical activity did not appreciably impact change in bone density in any group. CONCLUSIONS: This prospective observational study explored the 5-year change in bone mineral density among older postmenopausal women after the landmark 2002 hormone therapy trial findings were released. We found bone density decreased in never-users and in women who discontinued use. Bone density was maintained in current users. Although usual physical activity did not mitigate bone loss, targeted physical activity regimens should be investigated.

Association of Artificially Sweetened Beverage Consumption and Urinary Tract Cancers in the Women's Health Initiative Observational Study.

Background: Insufficient data exist to conclude whether consumption of artificially sweetened beverages is associated with a higher risk of urinary tract cancers. Objective: We sought to investigate whether urinary tract cancer incidence differed among women who consumed various amounts of artificially sweetened beverages. Design setting and participants: This was a secondary analysis of data from the Women's Health Initiative Observational Study, a multicenter longitudinal prospective study of the health of 93 676 postmenopausal women with a mean follow-up time of 13.5 yr. Women were identified at 40 clinical centers across the USA and enrolled from 1993 to 1998. Women between the ages of 50 and 79 yr were enrolled. We included women who answered questions about artificially sweetened beverage consumption and reported no prior urinary tract cancer diagnoses. The frequency of artificially sweetened beverage consumption was categorized as follows: rare artificially sweetened beverage consumption (never to fewer than one serving per week), frequent consumption (one to six servings per week), and daily consumption (more than one servings per day). Outcome measurements and statistical analysis: The incidence of urinary tract cancer reported during subsequent visits until February 28, 2020 was recorded. Demographic characteristics were compared between those with varying levels of artificially sweetened beverage consumption. Descriptive statistics were used to report the rates of urinary tract cancer diagnosis, and Cox regression models were constructed to determine hazard ratios and adjust for potential confounders. Results and limitations: We identified 80 388 participants who met the inclusion criteria. Most participants (64%) were infrequent consumers of artificially sweetened beverages, with 13% (n = 10 494) consuming more than one servings per day. The incidence of urinary tract cancers was low, with only 804 cases identified. Cox regression models showed that frequent artificially sweetened beverage consumption was associated with a higher risk of kidney cancer (adjusted hazard ratio 1.34, 95% confidence interval 1.03-1.75). There was no significant association between artificially sweetened beverage intake and bladder cancer. Conclusions: Frequent consumption of artificially sweetened beverages may be associated with a higher risk of kidney cancer among postmenopausal women. Patient summary: A secondary analysis of the Women's Health Initiative Observational Study showed that higher consumption of artificially sweetened beverages was associated with a higher risk of kidney cancer.

Artificially sweetened beverages and urinary incontinence-a secondary analysis of the Women's Health Initiative Observational Study.

OBJECTIVE: The aim of this study was to determine if higher artificially sweetened beverage intake is associated with higher prevalence of urinary incontinence symptoms. METHODS: We conducted a secondary analysis of data from the Women's Health Initiative Observational Study. Our analytic cohort included 80,388 women. Participants who answered questions about beverage consumption and urinary incontinence symptoms at a 3-year follow-up visit were included. Demographic characteristics were compared between three groups of beverage consumers: never to less than one serving per week, one to six servings per week, and greater than or equal to one serving per day. Multivariable logistic regression models were constructed to estimate odds and type of urinary incontinence and adjust for potential confounders. RESULTS: Most participants (64%) were rare consumers of artificially sweetened beverages, with 13% ( n = 10,494) consuming greater than or equal to 1 serving per day. The unadjusted odds of reporting urinary incontinence were 10% to 12% higher in women consuming one to six servings per week (odds ratio [OR], 1.10; 95% CI, 1.06-1.14) or greater than or equal to one serving per day (OR, 1.12; 95% CI, 1.07-1.18) versus never to less than one serving per week. In multivariable analyses, women consuming greater than or equal to one serving per day (ref: never to <1 serving/wk) had 10% higher odds of reporting mixed urinary incontinence (OR, 1.10; 95% CI, 1.02-1.19). There were no significant differences for stress or urgency urinary incontinence symptoms between groups. CONCLUSIONS: When compared to never to less than one serving per week, women consuming greater than or equal to one serving per day of artificially sweetened beverages had 10% greater odds of reporting mixed urinary incontinence after adjustments. Amount of artificially sweetened beverage consumption was not associated with stress or urgency urinary incontinence symptoms.

Changes in vitamin D supplement use and baseline plasma 25-hydroxyvitamin D concentration predict 5-y change in concentration in postmenopausal women.

Few studies have prospectively examined predictors of change in plasma concentrations of 25-hydroxyvitamin D [25(OH)D]. We sought to determine the predictors of 5-y change in 25(OH)D. Plasma 25(OH)D concentrations were assessed at baseline (1997-2000) and 5 y later (2002-2005) in 668 postmenopausal women enrolled in the Osteoporosis and Periodontal Disease Study. Baseline and changes in demographic, dietary, lifestyle, and health-related factors were tested as predictors of change in 25(OH)D concentrations by using multivariable linear regression. The mean 5-y change in 25(OH)D (mean ± SD) was 7.7 ± 0.7 nmol/L (P < 0.001). In our predictive model (n = 643), predictors explained 31% of the variance in change in 25(OH)D concentrations and included baseline 25(OH)D, baseline and change in vitamin D supplementation and physical activity, change in season of blood draw, BMI, whole-body T score, and baseline hormone therapy use. Baseline 25(OH)D and change in vitamin D supplementation explained the most variation (25%) in 25(OH)D. Exploratory analyses showed a borderline significant interaction between tertiles of baseline 25(OH)D and change in vitamin D supplementation over time (P = 0.06). The greatest mean increase in 25(OH)D (22.9 ± 16.8 nmol/L), with adjustment for other statistically significant predictors, occurred in women whose baseline 25(OH)D concentration was ≤51.0 nmol/L (tertile 1) and who increased supplementation use over time. These results confirm the importance of supplementation in increasing 25(OH)D concentrations in aging women, even after other statistically significant predictors are controlled for. These data also suggest that this is especially true among aging women with inadequate 25(OH)D (e.g., <50 nmol/L).