Dietary patterns and urinary phthalate exposure among postmenopausal women of the Women's Health Initiative.

BACKGROUND: Phthalates are endocrine-disrupting chemicals linked to a higher risk of numerous chronic health outcomes. Diet is a primary source of exposure, but prior studies exploring associations between dietary patterns and phthalate exposure are limited. OBJECTIVES: We evaluated the associations between dietary patterns and urinary phthalate biomarkers among a subset of postmenopausal women participating in the Women's Health Initiative (WHI). METHODS: We included WHI participants selected for a nested case-control study of phthalates and breast cancer (N = 1240). Dietary intake was measured via self-administered food frequency questionnaires at baseline and year-3. We used these data to calculate scores for alignment with the Dietary Approach to Stop Hypertension (DASH), alternative Mediterranean (aMed), and Dietary Inflammatory Index (DII) diets. We measured 13 phthalate metabolites and creatinine in 2-3 urine samples per participant collected over 3-years when all participants were cancer-free. We fit multivariable generalized estimating equation models to estimate the cross-sectional associations. RESULTS: DASH and aMed dietary scores were inversely associated with the sum of di(2-Ethylhexyl) phthalate (-6.48%, 95% CI -9.84, -3.00; -5.23%, 95% CI -8.73, -1.60) and DII score was positively associated (9.00%, 95% CI 5.04, 13.11). DASH and aMed scores were also inversely associated with mono benzyl phthalate and mono-3-carboxypropyl phthalate. DII scores were positively associated with mono benzyl phthalate and the sum of di-n-butyl phthalate. DISCUSSION: Higher dietary alignment with DASH and aMed dietary patterns were significantly associated with lower concentrations of certain phthalate biomarkers, while an inflammatory diet pattern was associated with higher phthalate biomarker concentrations. These findings suggest that dietary patterns high in fruits, vegetables, and low-fat foods and low in processed foods may be useful in avoiding exposure to phthalates.

Association between urinary phthalate biomarker concentrations and adiposity among postmenopausal women.

BACKGROUND: Obesity is a leading risk factor for chronic diseases, potentially related to excess abdominal adiposity. Phthalates are environmental chemicals that have been suggested to act as obesogens, driving obesity risk. For the associations between phthalates and adiposity, prior studies have focused primarily on body mass index. We hypothesize that more refined measures of adiposity and fat distribution may provide greater insights into these associations given the role of central adiposity in chronic disease risk. OBJECTIVES: To evaluate associations between urinary phthalate biomarkers and both visceral and subcutaneous adipose tissue (VAT and SAT) among postmenopausal women enrolled in the Women's Health Initiative (WHI). METHODS: We included 1125 WHI participants with available, coincident measurements of urinary phthalate biomarkers (baseline, year 3) and VAT and SAT (baseline, year 3, year 6). VAT and SAT measurements were estimated from DXA scans. Multilevel mixed-effects models estimated the prospective associations between urinary phthalate biomarkers at baseline and VAT and SAT three years later. RESULTS: In multivariable adjusted models, we observed positive associations between some phthalate biomarkers, including the sum of di-isobutyl phthalate (ΣDiBP) biomarkers, MCNP, and ΣDEHP, with VAT three years later. For example, we observed positive associations between concentrations of ΣDiBP and VAT (Q4 vs Q1 ß = 7.15, 95% CI -1.76-16.06; Q3 vs Q1 ß = 10.94, 95% CI 3.55-18.33). Associations were generally attenuated but remained significant after additional adjustment for SAT. MBzP was positively associated with SAT. Other phthalate biomarkers investigated (MEP, MCOP, MCPP, ΣDBP) were not significantly associated with VAT or SAT. DISCUSSION: Based on robust measures of adiposity, this study provides supportive evidence that higher urinary concentrations of select phthalate compounds were associated with higher VAT levels over time in postmenopausal women. Efforts to replicate these findings are needed.

Vasomotor symptoms in midlife women with incident breast cancer: pink SWAN.

PURPOSE: We compared trajectories of vasomotor symptoms (VMS) and their risk factors in women with breast cancer (BrCa) to those of cancer-free controls. METHODS: Data were from 15 nearly annual follow-up visits (1996-2017) of the multi-racial/ethnic cohort of midlife women enrolled in the Study of Women's Health Across the Nation (SWAN). We compared women with incident BrCa to controls for patterns of VMS, controlling for risk factors identified in bivariate analyses using multivariable longitudinal analyses. RESULTS: Characteristics at study entry largely did not differ between cases (n = 151) and controls (n = 2161). Adjusted prevalence of any VMS increased significantly among cases from diagnosis to 2.75 years post diagnosis [per-year adjusted odds ratio (aOR) = 1.76, 95% confidence interval (CI) 1.39-2.24], peaking at 2.75 years post diagnosis, whereas prevalence was stable among controls in this interval [aOR = 1.04, 95% CI 0.99-1.11]. Beyond 2.75 years post diagnosis, prevalence declined significantly in cases [aOR = 0.72, 95% CI 0.61-0.84] and less in controls [aOR = 0.96, 95% CI 0.92-1.00]. Patterns were similar for frequent VMS. Adjustment for tamoxifen use slightly reduced the per-year OR for any prevalent VMS post diagnosis, partially explaining excess VMS in cases. Other treatments were unassociated with VMS. CONCLUSIONS: Patterns of prevalent VMS reporting differed significantly between cases and controls, particularly post diagnosis, the latter only partially explained by tamoxifen use among cases. Risk factors for VMS largely did not differ between cases and controls.

Anti-Müllerian hormone levels and breast cancer risk in the study of women's health across the nation.

PURPOSE: The relation of premenopausal anti-Müllerian hormone (AMH) levels with breast cancer risk has been evaluated in a few studies, but primarily in non-Hispanic White women. METHODS: We evaluated the association of AMH levels with breast cancer risk in Study of Women's Health Across the Nation (SWAN), a multi-ethnic cohort of women. At enrollment, participants had an intact uterus and ≥ 1 ovary, and ≥ 1 menstrual period in the last 3 months. AMH at first measurement was assessed in 1,529 pre- or perimenopausal women using a high-sensitivity ELISA assay; values were natural log transformed. Breast cancer diagnoses were assessed at enrollment and subsequent follow-up visits through 2018 (median 6.1 years). RESULTS: In total, 84 women reported an incident breast cancer diagnosis. In multivariable Cox regression models adjusting for age, race and ethnicity, body mass index, and other factors, higher AMH levels were associated with a non-significant increased breast cancer risk. Compared to women in the 1st quartile, the hazard ratio (95% confidence interval) for women in the 4th quartile was 1.77 (0.87-3.60). CONCLUSION: Our results did not suggest a significant association between AMH and breast cancer risk; however, estimates were consistent with prior studies that reported positive associations.

Phthalates and bone mineral density: a systematic review.

BACKGROUND: Exposure to endocrine disruptors, such as phthalates, may impact bone mineral density (BMD) through a variety of mechanisms. Studies of phthalate exposure and BMD in humans are scarce. OBJECTIVES: To synthesize published data on the association between phthalate metabolites and BMD in humans and to provide methodological suggestions for future research. METHODS: A single investigator searched PubMed for relevant studies, including observational studies of phthalate exposure and BMD in children and postmenopausal women. Twelve studies were screened with 5 meeting the eligibility criteria and included for review. A quality assessment form was used as a quality measure and key information was extracted from the included studies. RESULTS: In one prospective study among postmenopausal women, higher levels of monocarboxyoctyl phthalate (MCOP) and monocarboxynonyl phthalate (MCNP) were significantly associated with lower BMD among nonusers of hormone therapy (HT). In cross-sectional studies of postmenopausal women, monoethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), mono (3-carboxypropyl) phthalate (MCPP), and mono-benzyl phthalate (MBzP) were negatively associated with BMD, and MCNP was positively associated with BMD, but these results were not replicated across studies. In studies of fetal exposure to phthalates and childhood BMD, significant positive associations between MCPP and BMD in children at age 12 years were found in 1 study, while associations were null in the other study. CONCLUSIONS: Studies among postmenopausal women provide suggestive evidence of an association between urinary phthalate metabolite concentration and decreased BMD. Results from studies of childhood BMD are inconclusive given the limited data and their limitations. More research is needed to address limitations and further investigate the association between phthalate exposure and human BMD.

The association between anthropometric factors and anti-Müllerian hormone levels in premenopausal women.

Adiposity has been associated with several health conditions as well as timing of menopause. Prior epidemiologic studies on the association of adiposity and anti-Müllerian hormone (AMH) have been inconsistent. We evaluated the relations of anthropometric measures with AMH at two time periods in a subset of premenopausal participants in the Nurses' Health Study II. This prospective study included 795 women who provided a premenopausal sample in 1996-1999 and in 2010-2012. Current weight and height, and weight at age 18 were assessed in 1989 and weight again in 1996-1999. Waist and hip circumference were measured and reported in 1993. In linear regression models adjusted for smoking, reproductive events, and other factors, AMH was inversely related to BMI at age 18 (P = .03) and in 1996-1999 (P < .0001). Higher waist circumference was related to lower AMH levels in 1996-1999 (p = .0009). BMI in 1996-1999 was inversely associated with AMH levels in 2010-2012 (P = .005). Weight gain between age 18 and 1996-1999 was strongly inversely associated with AMH levels in 1996-1999 (P < .0001) and in 2010-2012 (P < .0001). Our results indicate that adiposity and weight gain are associated with lower AMH levels, suggesting an adverse impact on ovarian function.

Metabolic syndrome and risk of endometrial cancer in postmenopausal women: a prospective study.

BACKGROUND: Obesity is a strong risk factor for endometrial cancer, but it is unclear whether metabolic syndrome (MetS) contributes to endometrial cancer risk over and above the contribution of obesity. METHODS: We examined the association of MetS and its components with risk of endometrial cancer in a sub-cohort of 24,210 women enrolled in the Women's Health Initiative cohort study. Two variants of the National Cholesterol Education Program Adult Treatment Panel III definition of the MetS were used: one including and one excluding waist circumference (WC). Cox proportional hazards models were used to estimate the association of the study exposures with disease risk. RESULTS: When WC was included in the definition, MetS showed an approximately two-fold increase in endometrial cancer risk (HR 2.20; 95% CI 1.61-3.02); however, when WC was excluded, MetS was no longer associated with risk. We also observed that women with hyperglycemia, dyslipidemia and hypertension, in combination, had almost a twofold increased risk of endometrial cancer, independent of WC (HR 1.94; 95% CI 1.09, 3.46). Glucose, and, in particular, WC and body mass index were also positively associated with risk. CONCLUSIONS: Our findings suggest that MetS may predict risk of endometrial cancer independent of obesity among women with the remaining four Mets components.

Predictors of urinary phthalate biomarker concentrations in postmenopausal women.

BACKGROUND: Phthalates are ubiquitous endocrine disrupting chemicals present in a wide variety of consumer products. However, the personal characteristics associated with phthalate exposure are unclear. OBJECTIVES: We sought to describe personal, behavioral, and reproductive characteristics associated with phthalate metabolite concentrations in an ongoing study nested within the Women's Health Initiative (WHI). MATERIALS AND METHODS: We measured thirteen phthalate metabolites in two or three archived urine samples collected in 1993-2001 from each of 1257 WHI participants (2991 observations). We fit multivariable generalized estimating equation models to predict urinary biomarker concentrations from personal, behavioral, and reproductive characteristics. RESULTS: Older age was predictive of lower concentrations of monobenzyl phthalate (MBzP), mono-carboxyoctyl phthalate (MCOP), mono-3-carboxypropyl phthalate (MCPP), and the sum of di-n-butyl phthalate metabolites (ΣDBP). Phthalate metabolite concentrations varied by race/region, with generally higher concentrations observed among non-Whites and women from the West region. Higher neighborhood socioeconomic status predicted lower MBzP concentrations, and higher education predicted lower monoethyl phthalate (MEP) and higher concentrations of the sum of metabolites of di-isobutyl phthalate (ΣDiBP). Overweight/obesity predicted higher MBzP, MCOP, monocarboxynonyl phthalate (MCNP), MCPP, and the sum of metabolites of di(2-ethylhexyl) phthalate (ΣDEHP) and lower MEP concentrations. Alcohol consumption predicted higher concentrations of MEP and ΣDBP, while current smokers had higher ΣDBP concentrations. Better diet quality as assessed by Healthy Eating Index 2005 scores predicted lower concentrations of MBzP, ΣDiBP, and ΣDEHP. CONCLUSION: Factors predictive of lower biomarker concentrations included increased age and healthy behaviors (e.g. lower alcohol intake, lower body mass index, not smoking, higher quality diet, and moderate physical activity). Racial group (generally higher among non-Whites) and geographic regions (generally higher in Northeast and West compared to South regions) also were predictive of phthalate biomarker concentrations.

Urinary concentrations of phthalate biomarkers and weight change among postmenopausal women: a prospective cohort study.

BACKGROUND: Some phthalates are endocrine disrupting chemicals used as plasticizers in consumer products, and have been associated with obesity in cross-sectional studies, yet prospective evaluations of weight change are lacking. Our objective was to evaluate associations between phthalate biomarker concentrations and weight and weight change among postmenopausal women. METHODS: We performed cross-sectional (N = 997) and longitudinal analyses (N = 660) among postmenopausal Women's Health Initiative participants. We measured 13 phthalate metabolites and creatinine in spot urine samples provided at baseline. Participants' weight and height measured at in-person clinic visits at baseline, year 3, and year 6 were used to calculate body mass index (BMI). We fit multivariable multinomial logistic regression models to explore cross-sectional associations between each phthalate biomarker and baseline BMI category. We evaluated longitudinal associations between each biomarker and weight change using mixed effects linear regression models. RESULTS: In cross-sectional analyses, urinary concentrations of some biomarkers were positively associated with obesity prevalence (e.g. sum of di (2-ethylhexyl) phthalate metabolites [ΣDEHP] 4th vs 1st quartile OR = 3.29, 95% CI 1.80-6.03 [p trend< 0.001] vs normal). In longitudinal analyses, positive trends with weight gain between baseline and year 3 were observed for mono-(2-ethyl-5-oxohexyl) phthalate, monoethyl phthalate (MEP), mono-hydroxybutyl phthalate, and mono-hydroxyisobutyl phthalate (e.g. + 2.32 kg [95% CI 0.93-3.72] for 4th vs 1st quartile of MEP; p trend < 0.001). No statistically significant associations were observed between biomarkers and weight gain over 6 years. CONCLUSIONS: Certain phthalates may contribute to short-term weight gain among postmenopausal women.

Bisphenol-A in breast adipose tissue of breast cancer cases and controls.

We evaluated whether bisphenol-A (BPA) could be quantified in breast adipose tissue samples provided by 36 breast cancer mastectomy patients and 14 reduction mammoplasty patients. Samples of breast adipose tissue were collected and BPA concentration was quantified using HPLC-ESI-MS/MS. BPA was detectable above the limit of quantitation of 0.38 ng/g in 30.6% of samples. BPA concentrations varied within- and between breasts and were similar between cases and controls (0.39 vs 0.41 ng/g, p = 0.74).

Sleep Duration in Relation to Attention Deficit Hyperactivity Disorder in American Adults.

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental condition being diagnosed in increasing numbers. While the link between sleep and ADHD is of increasing interest, the relationship between sleep duration and ADHD remains largely uninvestigated in adult populations. We evaluated the association between self-reported sleep duration and ADHD in a cohort of American adults using data from the 2012 National Health Interview Survey (Centers for Disease Control and Prevention, 2012). Of the 30,858 participants eligible for our analyses, there were 1,122 cases of ADHD. Elevated and diminished sleep durations were both associated with increased odds of reporting ADHD (≤ 6 hr: OR = 1.50, 95% CI 1.19, 1.90; ≥ 9 hr: OR = 1.49, 95% CI 1.26, 1.75) in fully adjusted models. Future prospective studies are necessary to further examine this association in adult patients.

Antidepressant use and circulating prolactin levels.

PURPOSE: To determine whether antidepressants (AD), specifically selective serotonin reuptake inhibitors (SSRIs), are linked to elevated prolactin levels among the general population. METHODS: Circulating prolactin levels were available for 4593 healthy participants in the Nurses' Health Study (NHS) and NHS2, including 267 AD users. We fit generalized linear models to calculate and compare adjusted mean prolactin levels between AD users and non-users and further among SSRI users. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) for "elevated" prolactin levels (>11 ng/mL) comparing AD users to non-users. We evaluated AD use and change in prolactin levels among 610 NHS participants with two measurements an average of 11 years apart. RESULTS: Adjusted geometric mean prolactin levels were similar among SSRI users (13.2 ng/mL, 95 % CI 12.2-14.4), users of other classes of ADs (12.7 ng/mL, 95 % CI 11.0-14.6), and non-users (13.1 ng/mL, 95 % CI 12.8-13.4). Neither AD use (OR 1.17, 95 % CI 0.89-1.53) nor SSRI use (OR 0.95, 95 % CI 0.66-1.38) was associated with elevated prolactin levels. Change in prolactin levels was similar across women who started, stopped, consistently used, or never used ADs. CONCLUSIONS: This study does not support the hypothesis that AD use would influence breast cancer risk via altered prolactin levels. These results provide some evidence that use of ADs to treat depression or other conditions may not substantially increase prolactin levels in the majority of women.

Menopausal vasomotor symptoms and incident breast cancer risk in the Study of Women's Health Across the Nation.

PURPOSE: Two case-control studies reported a 50 % decreased breast cancer risk among women who experienced menopausal vasomotor symptoms (VMS), but one cohort study found no association. VMS may be triggered by declining estrogen levels during menopause, whereas elevated estrogen levels have been associated with increased breast cancer risk. VMS may thus be indicative of lower susceptibility to breast cancer. METHODS: We evaluated this relationship in the longitudinal Study of Women's Health Across the Nation (SWAN), using discrete survival analysis of approximately annual data on VMS and self-reported breast cancer occurrences for up to 13 years of follow-up in 3,098 women who were pre- or early perimenopausal at enrollment. RESULTS: Over an average 11.4 years of follow-up, 129 incident breast cancer cases were self-reported, and approximately 50 % of participants experienced VMS. Symptomatic women had a reduced risk of breast cancer compared to non-symptomatic women (adjusted HR 0.63, 95 % CI 0.39, 1.00). The association was stronger in the subgroup of women who fully transitioned to postmenopause during follow-up (n = 67 cases, adjusted HR 0.45, 95 % CI 0.26, 0.77). CONCLUSION: VMS appeared to be a marker of reduced breast cancer risk. Future research is needed to understand the biology underlying this relationship.

Urinary bisphenol-A, phthalate metabolites and body composition in US adults, NHANES 1999-2006.

BACKGROUND: Exposure to bisphenol-A (BPA) and phthalates is highly prevalent. Prior studies have not assessed associations between urinary levels of BPA and phthalate metabolites and body composition. METHODS: National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2006 on adults aged ≥20 were analyzed by linear regression for associations between urinary BPA, monoethyl phthalate, monobutyl phthalate (MBP), monoethylhexyl phthalate (MEHP), and monobenzyl phthalate (MBzP) and lean mass, fat mass, and percent body fat. RESULTS: BPA and phthalate metabolites were not independently associated with fat mass or percent body fat. Significant inverse associations were observed with lean mass, with the strongest association observed for BPA in men (mean lean mass 1.39 kg lower for quartile 4 vs. quartile 1, p trend = 0.02). CONCLUSIONS: BPA and some phthalates could have important, negative effects on muscle and may affect conditions related to deficits in lean mass, though additional research is needed.

Urinary melatonin concentration and the risk of breast cancer in Nurses' Health Study II.

Experimental and epidemiologic data support a protective role for melatonin in breast cancer etiology, yet studies in premenopausal women are scarce. In a case-control study nested within the Nurses' Health Study II cohort, we measured the concentration of melatonin's major urinary metabolite, 6-sulfatoxymelatonin (aMT6s), in urine samples collected between 1996 and 1999 among 600 breast cancer cases and 786 matched controls. Cases were predominantly premenopausal women who were diagnosed with incident breast cancer after urine collection and before June 1, 2007. Using multivariable conditional logistic regression, we computed odds ratios and 95% confidence intervals. Melatonin levels were not significantly associated with total breast cancer risk (for the fourth (top) quartile (Q4) of aMT6s vs. the first (bottom) quartile (Q1), odds ratio (OR) = 0.91, 95% confidence interval (CI): 0.64, 1.28; Ptrend = 0.38) or risk of invasive or in situ breast cancer. Findings did not vary by body mass index, smoking status, menopausal status, or time between urine collection and diagnosis (all Pinteraction values ≥ 0.12). For example, the odds ratio for total breast cancer among women with ≤5 years between urine collection and diagnosis was 0.74 (Q4 vs. Q1; 95% CI: 0.45, 1.20; Ptrend = 0.09), and it was 1.20 (Q4 vs. Q1; 95% CI: 0.72, 1.98; Ptrend = 0.70) for women with >5 years. Our data do not support an overall association between urinary melatonin levels and breast cancer risk.

Within-person variability of urinary bisphenol-A in postmenopausal women.

We evaluated the within-person variability of urinary BPA levels over two samples collected three years apart in 90 Women's Health Initiative participants. The intraclass correlation coefficient was 0.09 (95% CI 0.01-0.44), indicating high within-participant variability relative to the between-person variation. Concordance of BPA quartile over time was low (31.7%) and was unrelated to demographic, behavioral, or dietary factors. A single, or even several, measurements of BPA may not adequately classify long-term exposure in human studies.

Erythrocyte omega-6 and omega-3 fatty acids and mammographic breast density.

Diets low in omega-6 (n-6) polyunsaturated fatty acids (PUFAs) and high in omega-3 (n-3) PUFAs may protect against breast cancer development. Associations of PUFA intake with mammographic density, an intermediate marker of breast cancer risk, have been inconsistent; however, prior studies have relied on self-reported dietary PUFA intake. We examined the association between circulating erythrocyte n-6 and n-3 PUFAs with mammographic density in 248 postmenopausal women who were not taking exogenous hormones. PUFAs in erythrocytes were measured by gas-liquid chromatography, and mammographic density was assessed quantitatively by planimetry. Spearman's correlation coefficients and generalized linear models were used to evaluate the relationships between PUFA measures and mammographic density. None of the erythrocyte n-6 or n-3 PUFA measures were associated with percent density or dense breast area.

A Systematic Review of MRI Studies and the "Emotional paiN and social Disconnect (END)" Brain Model of Suicidal Behavior in Youth.

Introduction: Risk of suicidal ideation and suicidal behaviors greatly increases during adolescence, and rates have risen dramatically over the past two decades. However, few risk factors or biomarkers predictive of suicidal ideation or attempted suicide have been identified in adolescents. Neuroimaging correlates hold potential for early identification of adolescents at increased risk of suicidality and risk stratification for those at high risk of suicide attempt. Methods: In this systematic review, we evaluated neural regions and networks associated with suicidal ideation and suicide attempt in adolescents derived from magnetic resonance imaging (MRI) studies. A total of 28 articles were included in this review. Results: After descriptively synthesizing the literature, we propose the Emotional paiN and social Disconnect (END) model of adolescent suicidality and present two key neural circuits: (1) the emotional/mental pain circuit and (2) the social disconnect/distortion circuit. In the END model, the emotional pain circuit-consisting of the cerebellum, amygdala, and hippocampus-shows similar aberrations in adolescents with suicidal ideation as in those with a history of a suicide attempt (but to a smaller degree). The social disconnect circuit is unique to adolescent suicide attempters and includes the lateral orbitofrontal cortex (OFC), the temporal gyri, and the connections between them. Conclusion: Our proposed END brain model of suicidal behavior in youth, if confirmed by future prospective studies, can have implications for clinical goals of early detection, risk stratification, and intervention development. Treatments that target emotional pain and social disconnect may be ideal interventions for reducing suicidality in adolescents.

Perineal powder use and risk of endometrial cancer in postmenopausal women.

BACKGROUND: Most known endometrial cancer risk factors involve genetics or exposure to unopposed estrogens; less is known about risk due to environmental exposures. While several studies have found an increased risk of ovarian cancer associated with perineal powder use, only two studies have addressed perineal powder use and endometrial cancer risk. METHODS: We used Cox proportional hazards regression to examine the association between perineal powder use and endometrial cancer risk using the Women's Health Initiative Observational Study Research Materials obtained from the National Heart, Lung, and Blood Institute Biological Specimen and Data Repository Coordinating Center. RESULTS: Of the 48,526 women in our primary analysis, 25,181 (52 %) reported ever use of perineal powder. During 364,134 person-years of follow-up, 447 participants were diagnosed with endometrial cancer. Ever use of perineal powder was not associated with increased risk of endometrial cancer (multivariable-adjusted hazard ratio, 1.06; 95 % confidence interval, 0.87-1.28). External use of powder on the genitals and/or on sanitary napkins was also not significantly associated with risk of endometrial cancer. However, use of powder on a diaphragm for twenty or more years was associated with a threefold increase in risk of endometrial cancer compared to women who never used perineal powder (multivariable-adjusted hazard ratio, 3.06; 95 % CI, 2.00-4.70). CONCLUSIONS: Any duration of external use of perineal powder was not associated with increased risk of endometrial cancer; however, long-term use of powder on a diaphragm may increase the risk of endometrial cancer.

Components of metabolic syndrome and risk of breast cancer by prognostic features in the study of osteoporotic fractures cohort.

PURPOSE: Metabolic syndrome (MetS) and most of its components have been previously associated with increased breast cancer risk. We hypothesized that increasing number of MetS components would be positively associated with breast cancer risk. METHODS: Data were obtained from the Study of Osteoporotic Fractures, a prospective cohort of women aged ≥65 enrolled between 1986 and 1988 and still being followed prospectively (n = 8,956). MetS components evaluated at baseline were elevated waist circumference, hypertension, and diabetes. Data were not available on hyperlipidemia. Incident breast cancers were confirmed by pathology report. We compared women with 0, 1, and 2 or 3 MetS components. We used Cox proportional hazards regression to calculate associations for breast cancer overall and classified by prognostic features. RESULTS: At baseline, 28.8 % of participants had 2 or 3 MetS components. Over an average follow-up of 14.4 years, 551 breast cancer cases were identified. Compared to those with no components, women with 2 or 3 components had increased breast cancer risk (hazard ratio (HR), 1.30; 95 % confidence interval (CI), 1.01-1.68) and increased risk of ER+ (HR, 1.48; 95 % CI, 1.09-2.03) and PR+ (HR, 1.56; 95 % CI, 1.10-2.20) cancer, adjusting for age, hormone use, and family history of breast cancer. These results became attenuated and not statistically significant when additionally adjusted for body mass index. CONCLUSIONS: MetS is associated with increased postmenopausal breast cancer risk, especially for ER+ and PR+ cancers, though this effect may not be independent of the effect of body mass index. Managing the components of MetS could be efficacious for breast cancer risk reduction.