Olive oil and risk of breast cancer: a systematic review and dose-response meta-analysis of observational studies.

Olive oil consumption has been suggested to be inversely associated with breast cancer risk, probably due to its high MUFA and polyphenol content. The purpose of this meta-analysis was to assess the association between olive oil and breast cancer risk, including assessing the potential for a dose-response association. We performed a systematic search of PubMed, Web of Science, CINAHL and Cochrane Central Register of Controlled Trials through June 2020, identifying ten observational studies (two prospective studies and eight case-control studies) for meta-analysis. We estimated summary OR and 95 % CI for the highest v. lowest olive oil intake category across studies using random effect models and assessed the dose-response relationship between olive oil and breast cancer risk using restricted cubic splines. The summary OR comparing women with the highest intake to those with the lowest category of olive oil intake was 0·48 (95 % CI 0·09, 2·70) in prospective studies and 0·76 (95 % CI 0·54, 1·06) in case-control studies, with evidence of substantial study heterogeneity (prospective I2 = 89 %, case-control I2 = 82 %). There was no significant dose-response relationship for olive oil and breast cancer risk; the OR for a 14 g/d increment was 0·93 (95 % CI 0·83, 1·04). There may be a potential inverse association between olive oil intake and breast cancer; however, since the estimates are non-significant and the certainty level is very low, additional prospective studies with better assessment of olive oil intake are needed.

Plasma B-vitamin and one-carbon metabolites and risk of breast cancer before and after folic acid fortification in the United States.

Prior epidemiologic findings for plasma folate and B-vitamins and breast cancer risk are inconsistent and have not assessed the influence of folic acid fortification. Therefore, we examined the associations of plasma folate, B12 , pyridoxal 5'-phosphate (PLP), homocysteine, cysteine and cysteinylglycine with breast cancer risk, before and after fortification. We conducted a nested case-control study within the prospective Nurses' Health Study. In 1989-1990 (pre-fortification), 32,826 women donated a blood sample and 18,743 donated an additional blood sample in 2000-2001 (post-fortification). Between the first blood collection and 2006, 1874 incident breast cancer cases with at least one blood sample and 367 with two were 1:1 matched to controls. Conditional logistic regression was used to estimate relative risks (RR) and 95% confidence intervals (CI) adjusting for breast cancer risk factors. Overall, higher plasma folate, B12 , PLP, homocysteine, cysteine and cysteinylglycine levels were not associated with breast cancer risk. Associations did not vary by in situ/invasive, hormone receptor status, or tumor molecular subtype. Additionally, associations were null before and after fortification. For example, the RR (95% CI) for the highest versus lowest tertile of 1990 (pre-fortification) plasma folate with 1990-2000 follow-up was 0.93 (0.75-1.16) and for the 2000 plasma folate (post-fortification) with 2000-2006 follow-up the RR (95% CI) was 1.17 (0.79-1.74). Plasma folate, B12 , PLP, homocysteine, cysteine and cysteinylglycine were not significantly associated with breast cancer overall, before and after fortification, or with specific tumor molecular subtypes. However, long term associations (>8 years) after the implementation of fortification could not be examined.

Plasma B-vitamins and one-carbon metabolites and the risk of breast cancer in younger women.

PURPOSE: We examined the association of plasma B-vitamins and metabolites, and related genetic variants, with risk of breast cancer among predominantly premenopausal women. METHODS: We conducted a nested case-control study within the Nurses' Health Study II. From blood samples collected in 1996-1999 and follow-up through 2007, plasma measures were available for 610 cases and 1207 controls. Unconditional multivariable logistic regression was used to estimate relative risks (RR) of breast cancer and 95% confidence intervals (CIs). We examined whether associations varied by methylenetetrahydrofolate reductase (MTHFR) and dihydrofolate reductase polymorphisms, breast cancer risk factors, or tumor characteristics. RESULTS: Plasma vitamin B12 was associated with a 64% higher risk of breast cancer comparing the highest versus lowest quintile (95% CI 1.17-2.29, p-trend = 0.02). Plasma folate (comparable RR = 1.18, 95% CI 0.84-1.66), pyridoxal 5'-phosphate (RR = 1.18, 95% CI 0.85-1.64), homocysteine (RR = 0.93, 95% CI 0.67-1.28), cysteine (RR = 1.14, 95% CI 0.81-1.62), and cysteinylglycine (RR = 0.93, 95% CI 0.66-1.31) were not associated with overall breast cancer risk. Folate was significantly positively associated with invasive and estrogen receptor-positive/progesterone receptor-positive breast cancer, and this association was suggestively stronger for bloods collected post-fortification. Several nutrient/breast cancer associations varied across subgroups defined by age, smoking, alcohol, multivitamin use, and MTHFR status (p-interaction < 0.05). CONCLUSIONS: Overall, plasma B-vitamins and metabolites were not associated with lower breast cancer risk. Plasma vitamin B-12 was positively associated with higher risk of overall breast cancer, and plasma folate was positively associated with risk of invasive breast cancer. Additionally, there may be associations in subgroups defined by related genetic variants, breast cancer risk factors, and tumor factors. Further studies in younger women and in the post-fortification era are needed to confirm these findings.

Protein intake and the risk of premenstrual syndrome.

OBJECTIVE: To examine the relationship between protein intake and the risk of incident premenstrual syndrome (PMS). DESIGN: Nested case-control study. FFQ were completed every 4 years during follow-up. Our main analysis assessed protein intake 2-4 years before PMS diagnosis (for cases) or reference year (for controls). Baseline (1991) protein intake was also assessed. SETTING: Nurses' Health Study II (NHS2), a large prospective cohort study of registered female nurses in the USA.ParticipantsParticipants were premenopausal women between the ages of 27 and 44 years (mean: 34 years), without diagnosis of PMS at baseline, without a history of cancer, endometriosis, infertility, irregular menstrual cycles or hysterectomy. Incident cases of PMS (n 1234) were identified by self-reported diagnosis during 14 years of follow-up and validated by questionnaire. Controls (n 2426) were women who did not report a diagnosis of PMS during follow-up and confirmed experiencing minimal premenstrual symptoms. RESULTS: In logistic regression models adjusting for smoking, BMI, B-vitamins and other factors, total protein intake was not associated with PMS development. For example, the OR for women with the highest intake of total protein 2-4 years before their reference year (median: 103·6 g/d) v. those with the lowest (median: 66·6 g/d) was 0·94 (95 % CI 0·70, 1·27). Additionally, intakes of specific protein sources and amino acids were not associated with PMS. Furthermore, results substituting carbohydrates and fats for protein were also null. CONCLUSIONS: Overall, protein consumption was not associated with risk of developing PMS.

Intake of dietary fat and fat subtypes and risk of premenstrual syndrome in the Nurses' Health Study II.

Approximately 8-20 % of reproductive-aged women experience premenstrual syndrome (PMS), substantially impacting quality of life. Women with PMS are encouraged to reduce fat intake to alleviate symptoms; however, its role in PMS development is unclear. We evaluated the association between dietary fat intake and PMS development among a subset of the prospective Nurses' Health Study II cohort. We compared 1257 women reporting clinician-diagnosed PMS, confirmed by premenstrual symptom questionnaire and 2463 matched controls with no or minimal premenstrual symptoms. Intakes of total fat, subtypes and fatty acids were assessed via FFQ. After adjustment for age, BMI, smoking, Ca and other factors, intakes of total fat, MUFA, PUFA and trans-fat measured 2-4 years before were not associated with PMS. High SFA intake was associated with lower PMS risk (relative risk (RR) quintile 5 (median=28·1 g/d) v. quintile 1 (median=15·1 g/d)=0·75; 95 % CI 0·58, 0·98; P trend=0·07). This association was largely attributable to stearic acid intake, with women in the highest quintile (median=7·4 g/d) having a RR of 0·75 v. those with the lowest intake (median=3·7 g/d) (95 % CI 0·57, 0·97; P trend=0·03). Individual PUFA and MUFA, including n-3 fatty acids, were not associated with risk. Overall, fat intake was not associated with higher PMS risk. High intake of stearic acid may be associated with a lower risk of developing PMS. Additional prospective research is needed to confirm this finding.

Impact of 8 lifestyle factors on mortality and life expectancy among United States veterans: The Million Veteran Program.

BACKGROUND: Lifestyle medicine has been proposed as a way to address the root causes of chronic disease and their associated health care costs. OBJECTIVE: This study aimed to estimate mortality risk and longevity associated with individual lifestyle factors and comprehensive lifestyle therapy. METHODS: Age- and sex-specific mortality rates were calculated on the basis of 719,147 veterans aged 40-99 y enrolled in the Veteran Affairs Million Veteran Program (2011-2019). Hazard ratios and estimated increase in life expectancy were examined among a subgroup of 276,132 veterans with complete data on 8 lifestyle factors at baseline. The 8 lifestyle factors included never smoking, physical activity, no excessive alcohol consumption, restorative sleep, nutrition, stress management, social connections, and no opioid use disorder. RESULTS: On the basis of 1.12 million person-years of follow-up, 34,247 deaths were recorded. Among veterans who adopted 1, 2, 3, 4, 5, 6, 7, and 8 lifestyle factors, the adjusted hazard ratios for mortality were 0.74 (0.60-0.90), 0.60 (95% CI: 0.49, 0.73), 0.50 (95% CI: 0.41, 0.61), 0.43 (95% CI: 0.35, 0.52), 0.35 (95% CI: 0.29, 0.43), 0.27 (95% CI: 0.22, 0.33), 0.21 (95% CI: 0.17, 0.26), and 0.13 (95% CI: 0.10, 0.16), respectively, as compared with veterans with no adopted lifestyle factors. The estimated life expectancy at age 40 y was 23.0, 26.5, 28.8, 30.8, 32.7, 35.1, 38.3, 41.3, and 47.0 y among males and 27.0, 28.8, 33.1, 38.0, 39.2, 41.4, 43.8, 46.3, and 47.5 y for females who adopted 0, 1, 2, 3, 4, 5, 6, 7, and 8 lifestyle factors, respectively. The difference in life expectancy at age 40 y was 24.0 y for male veterans and 20.5 y for female veterans when comparing adoption of 8-9 lifestyle factors. CONCLUSIONS: A combination of 8 lifestyle factors is associated with a significantly lower risk of premature mortality and an estimated prolonged life expectancy.

Cardiovascular Disease Risk Assessment Using Traditional Risk Factors and Polygenic Risk Scores in the Million Veteran Program.

Importance: Primary prevention of atherosclerotic cardiovascular disease (ASCVD) relies on risk stratification. Genome-wide polygenic risk scores (PRSs) are proposed to improve ASCVD risk estimation. Objective: To determine whether genome-wide PRSs for coronary artery disease (CAD) and acute ischemic stroke improve ASCVD risk estimation with traditional clinical risk factors in an ancestrally diverse midlife population. Design, Setting, and Participants: This was a prognostic analysis of incident events in a retrospectively defined longitudinal cohort conducted from January 1, 2011, to December 31, 2018. Included in the study were adults free of ASCVD and statin naive at baseline from the Million Veteran Program (MVP), a mega biobank with genetic, survey, and electronic health record data from a large US health care system. Data were analyzed from March 15, 2021, to January 5, 2023. Exposures: PRSs for CAD and ischemic stroke derived from cohorts of largely European descent and risk factors, including age, sex, systolic blood pressure, total cholesterol, high-density lipoprotein (HDL) cholesterol, smoking, and diabetes status. Main Outcomes and Measures: Incident nonfatal myocardial infarction (MI), ischemic stroke, ASCVD death, and composite ASCVD events. Results: A total of 79 151 participants (mean [SD] age, 57.8 [13.7] years; 68 503 male [86.5%]) were included in the study. The cohort included participants from the following harmonized genetic ancestry and race and ethnicity categories: 18 505 non-Hispanic Black (23.4%), 6785 Hispanic (8.6%), and 53 861 non-Hispanic White (68.0%) with a median (5th-95th percentile) follow-up of 4.3 (0.7-6.9) years. From 2011 to 2018, 3186 MIs (4.0%), 1933 ischemic strokes (2.4%), 867 ASCVD deaths (1.1%), and 5485 composite ASCVD events (6.9%) were observed. CAD PRS was associated with incident MI in non-Hispanic Black (hazard ratio [HR], 1.10; 95% CI, 1.02-1.19), Hispanic (HR, 1.26; 95% CI, 1.09-1.46), and non-Hispanic White (HR, 1.23; 95% CI, 1.18-1.29) participants. Stroke PRS was associated with incident stroke in non-Hispanic White participants (HR, 1.15; 95% CI, 1.08-1.21). A combined CAD plus stroke PRS was associated with ASCVD deaths among non-Hispanic Black (HR, 1.19; 95% CI, 1.03-1.17) and non-Hispanic (HR, 1.11; 95% CI, 1.03-1.21) participants. The combined PRS was also associated with composite ASCVD across all ancestry groups but greater among non-Hispanic White (HR, 1.20; 95% CI, 1.16-1.24) than non-Hispanic Black (HR, 1.11; 95% CI, 1.05-1.17) and Hispanic (HR, 1.12; 95% CI, 1.00-1.25) participants. Net reclassification improvement from adding PRS to a traditional risk model was modest for the intermediate risk group for composite CVD among men (5-year risk >3.75%, 0.38%; 95% CI, 0.07%-0.68%), among women, (6.79%; 95% CI, 3.01%-10.58%), for age older than 55 years (0.25%; 95% CI, 0.03%-0.47%), and for ages 40 to 55 years (1.61%; 95% CI, -0.07% to 3.30%). Conclusions and Relevance: Study results suggest that PRSs derived predominantly in European samples were statistically significantly associated with ASCVD in the multiancestry midlife and older-age MVP cohort. Overall, modest improvement in discrimination metrics were observed with addition of PRSs to traditional risk factors with greater magnitude in women and younger age groups.

Estrogenic Activity and Risk of Invasive Breast Cancer Among Postmenopausal Women in the Nurses' Health Study.

BACKGROUND: Estrogens increase breast cancer risk through estrogen receptor (ER)-mediated pathway activation. It is unclear whether a broader assessment of plasma compounds that lead to ER activation would be more strongly related to risk than measurement of individual estrogens. METHODS: A prospective nested case-control study was conducted among postmenopausal women in the Nurses' Health Study, that included 371 cases with blood samples collected prior to breast cancer diagnosis and 731 matched controls. Total estrogen pathway activity (EA) was assessed via a luciferase reporter assay using plasma-treated T47D-Kbluc (ATCC) human breast cancer cells. We also assessed the contribution of EA to risk, independent of circulating estrone, estradiol, and estrone sulfate concentrations. Multivariable ORs and 95% confidence intervals (CI) were calculated using conditional logistic regression adjusting for breast cancer risk factors. RESULTS: Women in the highest, versus lowest EA quartile had an 86% increased risk of invasive breast cancer (ORQ4vsQ1, 1.86; 95% CI = 1.16-2.97). After accounting for estradiol only, a weaker association was observed (ORQ4vsQ1, 1.27; 95% CI = 0.75-2.17). No association was observed after accounting for all three estrogens (ORQ4vsQ1, 1.01; 95% CI = 0.56-1.84). CONCLUSIONS: A positive association between EA and breast cancer risk was observed. However, the association was substantially attenuated after accounting for levels of other estrogens. IMPACT: Our study provides a first detailed assessment of a breast cancer cell line-based EA assay and postmenopausal breast cancer risk.

Central Adiposity and Subsequent Risk of Breast Cancer by Menopause Status.

BACKGROUND: Increased body mass index (BMI) is associated with higher postmenopausal breast cancer risk and lower premenopausal breast cancer risk. Less is known about the central adiposity-breast cancer risk association, particularly for tumor subtypes. METHODS: We used prospective waist (WC) and hip circumference (HC) measures in the Nurses' Health Studies. We examined associations of WC, HC, and waist-to-hip ratio (WHR) with breast cancer independent of BMI, by menopausal status. Cox proportional hazards models estimated the hazard ratios (HRs) and 95% confidence intervals (CIs) adjusting for breast cancer risk factors, with and without BMI. RESULTS: Adjusting for BMI, WC and HC were not associated, and WHR was positively associated with premenopausal breast cancer risk (WHR, quintile 5 vs 1: HRQ5vQ1, BMI-adjusted = 1.27, 95% CI = 1.04 to 1.54; Ptrend = .01), particularly for estrogen receptor-negative (ER-) and progesterone receptor-negative (PR-) and basal-like breast cancers. Premenopausal WC, HC, and WHR were not associated with postmenopausal breast cancer risk, with or without BMI adjustment. Postmenopausal WC, HC, and WHR were each positively associated with postmenopausal breast cancer (eg, WC HRQ5vsQ1 = 1.59, 95% CI = 1.36 to 1.86); after adjustment for BMI, only WC remained statistically significant (HRQ5vsQ1, BMI-adjusted = 1.38, 95% CI = 1.15 to 1.64; Ptrend = .002). In postmenopausal women, associations were stronger among never-users of hormone therapy and for ER+/PR+ breast cancers. CONCLUSIONS: Central adiposity was positively associated with pre- and postmenopausal breast cancers independent of BMI. This suggests that mechanisms other than estrogen may also play a role in the relationship between central adiposity and breast cancer. Maintaining a healthy waist circumference may decrease pre- and postmenopausal breast cancer risk.

Social Support for Changing Multiple Behaviors: Factors Associated With Seeking Support and the Impact of Offered Support.

INTRODUCTION: Social support is important for behavior change, and it may be particularly important for the complexities of changing multiple risk behaviors (MRB). Research is needed to determine if participants in an MRB intervention can be encouraged to activate their social network to aid their change efforts. METHODS: Healthy Directions 2, a cluster-randomized controlled trial of an intervention conducted in two urban health centers, targeted five behaviors (physical activity, fruit and vegetable intake, red meat consumption, multivitamin use, and smoking). The self-guided intervention emphasized changing MRB simultaneously, focused on self-monitoring and action planning, and encouraged participants to seek support from social network members. An MRB score was calculated for each participant, with one point being assigned for each behavioral recommendation that was not met. Analyses were conducted to identify demographic and social contextual factors (e.g., interpersonal, neighborhood, and organizational resources) associated with seeking support and to determine if type and frequency of offered support were associated with changes in MRB score. RESULTS: Half (49.6%) of participants identified a support person. Interpersonal resources were the only contextual factor that predicted engagement of a support person. Compared to individuals who did not seek support, those who identified one support person had 61% greater reduction in MRB score, and participants identifying multiple support persons had 100% greater reduction. CONCLUSION: Engagement of one's social network leads to significantly greater change across multiple risk behaviors. Future research should explore strategies to address support need for individuals with limited interpersonal resources.

Carbohydrate and fiber intake and the risk of premenstrual syndrome.

BACKGROUND/OBJECTIVES: Women with premenstrual syndrome (PMS) are encouraged to reduce sugar and increase fiber intake to reduce symptoms. However, research supporting these recommendations is limited, and their role in PMS development is unclear. This study examines the relation between carbohydrate and fiber intake and the risk of PMS nested within the prospective Nurses' Health Study II cohort. SUBJECTS/METHODS: Carbohydrate and fiber intake were assessed at baseline and three additional times during follow up by food frequency questionnaire. Incident cases of PMS were identified by self-reported PMS diagnosis during 14 years of follow up and validated by supplemental questionnaire (n = 1234). Women were classified as controls if they did not report PMS diagnosis during follow up and confirmed minimal or no premenstrual symptoms (n = 2426). We estimated relative risks (RR) and 95% confidence intervals (CI) using multivariable logistic regression. RESULTS: Total carbohydrate intake 2-4 years before reference year was not associated with PMS development (RR quintile 5 versus 1 = 0.99; 95% CI = 0.74-1.33). Intakes of specific carbohydrates or fibers were not associated with PMS development, except maltose. Adjusting for body mass index, smoking, and other factors, women with the highest maltose intake (median = 3.0 g/day) had a RR of 1.45 (95% CI = 1.11-1.88) compared to those with the lowest intake (median = 1.2 g/day). CONCLUSIONS: Overall, carbohydrate and fiber consumption was not associated with risk of PMS. As this is the first study to suggest that maltose may be associated with PMS development, further replication is needed.

Premenstrual Symptom Patterns and Behavioral Risk Factors in Young Women: A Cross-Sectional Study.

BACKGROUND: Approximately 80% of reproductive age women experience physical or emotional symptoms before onset of menses. Of these women, ∼20% experience symptoms severe enough to interfere with social functioning and life activities, and meet clinical criteria for premenstrual syndrome (PMS). More than 100 different symptoms are associated with PMS. Symptom groupings tend to be stable within an individual, but vary distinctly between women. Potential differences in the etiology of symptoms suggest that PMS may have subtypes that represent distinct entities. METHODS: The goal of this study was to identify symptom patterns using factor analysis. We then used linear regression to evaluate relations between PMS risk factors with factor scores for the symptom patterns. Analysis included: (1) 414 healthy women aged 18-30 years; (2) the subgroup of these women meeting established criteria for PMS (n = 80). All participants provided information on the occurrence and severity of 26 premenstrual symptoms by validated questionnaire. RESULTS: Four distinct symptom patterns emerged, labeled Emotional, Psychological/Cognitive, Physical, and Consumption. We observed a linear relationship between body mass index and the Consumption pattern in both the total study population (p = 0.03) and the PMS subset (p = 0.04). Additionally, in the total population, physical activity was inversely associated with the Physical pattern (p = 0.04), but positively associated with the Consumption pattern (p = 0.03). Results from this study are consistent with previously identified patterns and suggest that distinct subtypes of PMS exist. CONCLUSIONS: Future studies of behavioral factors should evaluate associations with symptom patterns in addition to PMS as an aggregate disorder.

Recreational Physical Activity and Premenstrual Syndrome in Young Adult Women: A Cross-Sectional Study.

INTRODUCTION: It is estimated that up to 75% of premenopausal women experience at least one premenstrual symptom and 8-20% meet clinical criteria for premenstrual syndrome. Premenstrual syndrome substantially reduces quality of life for many women of reproductive age, with pharmaceutical treatments having limited efficacy and substantial side effects. Physical activity has been recommended as a method of reducing menstrual symptom severity. However, this recommendation is based on relatively little evidence, and the relationship between physical activity, premenstrual symptoms, and premenstrual syndrome remains unclear. METHODS: We evaluated the relationship between physical activity and premenstrual syndrome and premenstrual symptoms among 414 women aged 18-31. Usual premenstrual symptom experience was assessed with a modified version of the Calendar of Premenstrual Experiences. Total, physical, and affective premenstrual symptom scores were calculated for all participants. Eighty women met criteria for moderate-to-severe premenstrual syndrome, while 89 met control criteria. Physical activity, along with dietary and lifestyle factors, was assessed by self-report. RESULTS: Physical activity was not significantly associated with total, affective, or physical premenstrual symptom score. Compared to the women with the lowest activity, women in tertiles 2 and 3 of activity, classified as metabolic equivalent task hours, had prevalence odds ratios for premenstrual syndrome of 1.5 (95% CI: 0.6-3.7) and 0.9 (95% CI: 0.4-2.4), respectively (p-value for trend = 0.85). CONCLUSIONS: We found no association between physical activity and either premenstrual symptom scores or the prevalence of premenstrual syndrome.

Association of Premenstrual Syndrome with Blood Pressure in Young Adult Women.

OBJECTIVE: The prevalence of hypertension in premenopausal women is increasing. There is substantial need for novel strategies to identify women who would benefit from increased screening and early interventions. Several mechanisms likely contributing to premenstrual syndrome (PMS) are also involved in hypertension, including renin-angiotensin-aldosterone system dysfunction and micronutrient deficiencies. However, it is unknown whether young women with PMS have elevated blood pressure. MATERIALS AND METHODS: We evaluated the association of blood pressure, PMS, and premenstrual symptoms in a cross-sectional study of 409 young women (mean age 21 years), conducted from 2006 to 2014. Our analysis included 78 cases (19%) who met established criteria for clinically significant PMS and 88 controls (22%) experiencing few symptoms. Blood pressure was measured during the mid-luteal phase. Lifestyle, diet, anthropometry, and other factors were measured by questionnaire and/or direct measurement. RESULTS: After adjustment for smoking, body mass index, and other factors, mean diastolic blood pressure in PMS cases was 72.3 versus 69.1 mm Hg in controls (p = 0.02). Diastolic blood pressure was also significantly higher in women reporting specific symptoms; for example, mean diastolic blood pressure in women reporting moderate or severe premenstrual nausea was 77.7 mm Hg compared with 71.0 mm Hg in women without nausea (p = 0.007). Systolic blood pressure did not vary by PMS status. CONCLUSIONS: To our knowledge, this is among the first studies to suggest that diastolic blood pressure is elevated in young adult women experiencing PMS. Prospective studies are needed to determine whether PMS may be a useful sentinel for future hypertension risk in young women.

Perineal powder use and risk of ovarian cancer.

BACKGROUND: Case-control studies have reported an increased risk of ovarian cancer among talc users; however, the only cohort study to date found no association except for an increase in serous invasive ovarian cancers. The purpose of this analysis was to assess perineal powder use and risk of ovarian cancer prospectively in the Women's Health Initiative Observational Study cohort. METHODS: Perineal powder use was assessed at baseline by self-report regarding application to genitals, sanitary napkins, or diaphragms and duration of use. The primary outcome was self-reported ovarian cancer centrally adjudicated by physicians. Cox proportional hazard regression was used to estimate risk, adjusting for covariates, including person-time until diagnosis of ovarian cancer (n = 429), death, loss to follow-up, or September 17, 2012. All statistical tests were two-sided. RESULTS: Among 61576 postmenopausal women, followed for a mean of 12.4 years without a history of cancer or bilateral oophorectomy, 52.6% reported ever using perineal powder. Ever use of perineal powder (hazard ratio [HR]adj = 1.06, 95% confidence interval [CI] = 0.87 to 1.28) was not associated with risk of ovarian cancer compared with never use. Individually, ever use of powder on the genitals (HRadj = 1.12, 95% CI = 0.92 to 1.36), sanitary napkins (HRadj = 0.95, 95% CI = 0.76 to 1.20), or diaphragms (HRadj = 0.92, 95% CI = 0.68 to 1.23) was not associated with risk of ovarian cancer compared with never use, nor were there associations with increasing durations of use. Estimates did not differ when stratified by age or tubal ligation status. CONCLUSION: Based on our results, perineal powder use does not appear to influence ovarian cancer risk.