VITamin D and OmegA-3 TriaL (VITAL) bone health ancillary study: clinical factors associated with trabecular bone score in women and men.

We investigated the association of clinical variables with TBS at baseline in the bone health sub-cohort of the VITamin D and OmegA-3 TriaL (VITAL). Lower TBS was associated with female sex, aging, BMI ≥ 25 kg/m2, SSRI use, high alcohol intake, and presence of diabetes; there was a trend towards significance between lower TBS and history of fragility fractures. INTRODUCTION: We investigated whether TBS differs by sex, race, body mass index (BMI), and other clinical variables. METHODS: The VITamin D and OmegA-3 TriaL (VITAL) is determining effects of vitamin D3 and/or omega-3 fatty acid (FA) supplements in reducing risks of cancer and cardiovascular disease. In the VITAL: Effects on Bone Structure/Architecture ancillary study, effects of these interventions on bone will be investigated. Here, we examine the associations of clinical risk factors with TBS assessments at baseline in the bone health sub-cohort, comprised of 672 participants (369 men and 303 women), mean (± SD) age 63.5 ± 6.0 years; BMI ≤ 37 kg/m2, no bisphosphonates within 2 years or other bone active medications within 1 year. RESULTS: TBS was greater in men than women (1.311 vs. 1.278, P < 0.001) and lower with elevated BMIs (P < 0.001), higher age (P = 0.004), diabetes (P = 0.008), SSRI use (P = 0.044), and high alcohol intake (P = 0.009). There was a trend for history of fragility fractures (P = 0.072), and lower TBS. TBS did not vary when analyzed by race, smoking, history of falls, and multivitamin or caffeine use. CONCLUSIONS: Lower TBS was associated with female sex, aging, BMI ≥ 25 kg/m2, SSRI use, alcohol use, and presence of diabetes; there was a trend between lower TBS and history of fragility fractures. TBS may be useful clinically to assess structural changes that may be associated with fractures among patients who are overweight or obese, those on SSRIs, or with diabetes. Ongoing follow-up studies will clarify the effects of supplemental vitamin D3 and/or FA's on TBS and other bone health measures. TRIAL REGISTRATION: NCT01747447.

Systematic review with meta-analysis: the comparative effectiveness of aspirin vs. screening for colorectal cancer prevention.

BACKGROUND: Both aspirin use and screening with flexible sigmoidoscopy or guaiac faecal occult blood testing (FOBT) may reduce mortality from colorectal cancer, but comparative effectiveness of these interventions is unknown. AIM: To compare aspirin to guaiac FOBT screening with regard to incidence and mortality of colorectal cancer in a network meta-analysis. METHODS: We searched Medline, EMBASE and the COCHRANE central register (CENTRAL) for relevant randomised trials identified until 31 October 2015. Randomised trials in average-risk populations that reported colorectal cancer mortality, colorectal cancer incidence, or both, with a minimum follow-up of 2 years, and more than 100 randomised individuals were included. Three investigators independently extracted data. We calculated relative risks [RR with 95% predictive intervals (PrIs)] for the comparison of the interventions by frequentist network meta-analyses. RESULTS: The effect of aspirin on colorectal cancer mortality was similar to FOBT (RR 1.03; 95% PrI 0.76-1.39) and flexible sigmoidoscopy (RR 1.16; 95% PrI 0.84-1.60). Aspirin was more effective than FOBT (RR 0.36; 95% PrI 0.22-0.59) and flexible sigmoidoscopy (RR 0.37; 95% PrI 0.22-0.62) in preventing death from or cancer in the proximal colon. Aspirin was equally effective as screening in reducing colorectal cancer incidence, while flexible sigmoidoscopy was superior to FOBT (RR 0.84; 95% PrI 0.72-0.97). CONCLUSIONS: Low-dose aspirin seems to be equally effective as flexible sigmoidoscopy or guaiac FOBT screening to reduce colorectal cancer incidence and mortality, and more effective for cancers in the proximal colon. A randomised comparative effectiveness trial of aspirin vs. screening is warranted.

Estimates of benefits and harms of prophylactic use of aspirin in the general population.

BACKGROUND: Accumulating evidence supports an effect of aspirin in reducing overall cancer incidence and mortality in the general population. We reviewed current data and assessed the benefits and harms of prophylactic use of aspirin in the general population. METHODS: The effect of aspirin for site-specific cancer incidence and mortality, cardiovascular events was collated from the most recent systematic reviews. Studies identified through systematic Medline search provided data regarding harmful effects of aspirin and baseline rates of harms like gastrointestinal bleeding and peptic ulcer. RESULTS: The effects of aspirin on cancer are not apparent until at least 3 years after the start of use, and some benefits are sustained for several years after cessation in long-term users. No differences between low and standard doses of aspirin are observed, but there were no direct comparisons. Higher doses do not appear to confer additional benefit but increase toxicities. Excess bleeding is the most important harm associated with aspirin use, and its risk and fatality rate increases with age. For average-risk individuals aged 50-65 years taking aspirin for 10 years, there would be a relative reduction of between 7% (women) and 9% (men) in the number of cancer, myocardial infarction or stroke events over a 15-year period and an overall 4% relative reduction in all deaths over a 20-year period. CONCLUSIONS: Prophylactic aspirin use for a minimum of 5 years at doses between 75 and 325 mg/day appears to have favourable benefit-harm profile; longer use is likely to have greater benefits. Further research is needed to determine the optimum dose and duration of use, to identify individuals at increased risk of bleeding, and to test effectiveness of Helicobacter pylori screening-eradication before starting aspirin prophylaxis.

Low-dose aspirin and breast cancer risk: results by tumour characteristics from a randomised trial.

The Women's Health Study trial previously reported no overall effect of low-dose aspirin (100 mg every other day) on invasive breast cancer over an average of 10 years of treatment. The present subgroup analyses further show no effects by tumour characteristics at diagnosis, suggesting that low-dose aspirin has no preventive effect on breast cancer.

HbA1c measured in stored erythrocytes and mortality rate among middle-aged and older women.

AIMS/HYPOTHESIS: Diabetes is known to increase mortality rate, but the degree to which mild hyperglycaemia may be associated with the risk of death is uncertain. We examined the association between HbA1c measured in stored erythrocytes and mortality rate in women with and without diabetes. METHODS: We conducted a cohort study of 27,210 women>or=45 years old with no history of cardiovascular disease or cancer who participated in the Women's Health Study, a randomised trial of vitamin E and aspirin. RESULTS: Over a median of 10 years of follow-up, 706 women died. Proportional hazards models adjusted for age, smoking, hypertension, blood lipids, exercise, postmenopausal hormone use, multivitamin use and C-reactive protein were used to estimate the relative risk of mortality. Among women without a diagnosis of diabetes and HbA1c<5.60%, those in the top quintile (HbA1c 5.19-5.59%) had a relative risk of mortality of 1.28 (95% CI 0.98-1.69, p value for linear trend=0.14) compared with those with HbA1c 2.27-4.79%. Women with HbA1c 5.60-5.99% and no diagnosis of diabetes had a 54% increased risk of mortality (95% CI 1-136%) compared with those with HbA1c 2.27-4.79%. HbA1c was significantly associated with mortality across the range 4.50-7.00% (p value for linear trend=0.02); a test of deviation from linearity was not statistically significant (p=0.67). Diabetic women had more than twice the mortality risk of non-diabetic women. CONCLUSIONS/INTERPRETATION: This study provides further evidence that chronic mild hyperglycaemia, even in the absence of diagnosed diabetes, is associated with increased risk of mortality. ClinicalTrials.gov ID no.: NCT00000479.

Imputation strategies for blood pressure data nonignorably missing due to medication use.

BACKGROUND: Underlying or untreated blood pressure (BP) is often an outcome of interest, but is unobservable when study participants are on anti-hypertensive medications. Untreated levels are not missing at random but would be higher among those on such medication. In such cases, standard methods of analysis may lead to bias. PURPOSE: BPs obtained at the private physician's office (out-of-study BPs) at the time of prescription of anti-hypertensive medications were available from Phase II of the Trials of Hypertension Prevention (TOHP) and were used to adjust for the potential bias. METHODS: Observed out-of-study BPs were used to estimate the conditional expectation and variance of the unobserved unmedicated study BPs. For those with no physician data, imputation from bootstrap samples of out-of-study BPs was used. An iterative method based on the EM algorithm was used to estimate the unknown study parameters in a random-effects model using multiple imputations. This was compared to an alternative model for the out-of-study BPs based on a theoretical truncated normal distribution, and to standard analyses, including both multivariate repeated measures and last-observation-carried-forward (LOCF) analyses, using data from Phase II of TOHP. RESULTS: Differences between methods were seen in the decline in BP over time in the reference group, where the changes from baseline to 36 months were 3.0 in univariate analyses, 2.4 using LOCF, and 2.6 in the multivariate analysis, compared to 2.0 or 1.7 in the imputation analyses, depending on the number of physician visits. Estimated intervention effects tended to be slightly larger using the imputation methods. LIMITATIONS: out-of-study measures may not be available for other studies. CONCLUSIONS: Because the proposed strategy was based on an empirically observed distribution for out-of-study BP, fewer assumptions about the missing data were made. These data may be useful in suggesting imputation strategies for other studies.

Cross-sectional correlates of fasting hyperinsulinaemia in post-menopausal women of different ethnic origin.

AIMS: In a large ethnically diverse nationwide sample of post-menopausal women we explored the relationship between fasting insulin levels, ethnicity, and a wide range of anthropometric, socio-economic, and lifestyle factors. METHODS: Subjects were post-menopausal women aged 50-79 years without diagnosed diabetes mellitus comprising a subsample (n = 3500) of the Women's Health Initiative (WHI) Clinical Trial and Observational Study. In a cross-sectional survey at baseline, we analysed the association between ethnicity and fasting insulin using analysis of covariance procedures and identified independent correlates of hyperinsulinaemia, defined by the 75th percentile cut point for each ethnic group. RESULTS: Fasting insulin levels were higher among African-American and Hispanic women than among non-Hispanic White or Asian women. These differences persisted after adjustment for age, educational attainment, total and central body obesity, adult weight change, family history of diabetes, smoking status, alcohol consumption, use of menopausal hormone therapy and physical activity. Higher levels of body mass index, waist-hip ratio, adult weight gain, and lower levels of total and moderate or strenuous recreational activity were independent correlates of fasting hyperinsulinaemia. Habitual walking was also inversely associated with fasting insulin. CONCLUSIONS: In this cross-sectional analysis, fasting insulin levels were higher among African-American and Hispanic post-menopausal women as compared with non-Hispanic White and Asian women. In addition, obesity, adult weight gain, and low levels of moderate or strenuous physical activity were independently associated with hyperinsulinaemia.

Multi-locus candidate gene polymorphisms and risk of myocardial infarction: a population-based, prospective genetic analysis.

BACKGROUND: Polymorphisms in candidate genes related to lipid metabolism, thrombosis, hemostasis, cell-matrix adhesion, and inflammation have been suggested clinically useful in risk assessment of cardiovascular disease. METHODS: We evaluated a panel of 92 candidate gene polymorphisms, using a multiplex polymerase chain reaction-immobilized probe assay amongst 523 individuals who subsequently developed myocardial infarction (MI), and amongst 2092 individuals who remained free of reported cardiovascular disease over a mean follow-up period of 13.2 years. RESULTS: Of the 92 polymorphisms tested, three that we previously reported on were associated with risk of MI, [pro12ala in the peroxisome proliferator activated-receptor gamma gene (odds ratio, OR = 0.75, P = 0.02); thr164ile in the beta-2 adrenergic receptor gene (OR = 0.14, P = 0.007); and ala23thr polymorphism in the eotaxin gene (OR = 1.87, P = 0.01)]. However, when adjusted for the other 89 polymorphisms evaluated, these findings were no longer statistically significant. Further, in contrast to reports from other investigators, we found little evidence for association of a C677T polymorphism in the 5,10-methylenetetrahydrofolate reductase gene, the angiotensin-I-converting enzyme 1 insertion/deletion polymorphism, a 4G/5G polymorphism in the serine/cysteine proteinase inhibitor-clade E-member 1 gene, the factor V Leiden mutation, the G20210A factor II mutation, a -455G>A polymorphism in the beta-fibrinogen gene, the cys112arg/arg158cys apolipoprotein E gene polymorphism, a gly460trp polymorphism in the alpha-adducin gene, and a -629C>A polymorphism in the cholesteryl ester transfer protein gene with risk of MI. CONCLUSIONS: After correction for multiple comparisons, the addition of genetic information observed in the present study had little impact on risk prediction models for MI. The present investigation highlights the importance of replication and validation of findings from genetic association studies.

Association of common CRP gene variants with CRP levels and cardiovascular events.

C-reactive protein (CRP) is a well-documented marker of atherosclerotic cardiovascular disease risk. We resequenced CRP to identify a comprehensive set of common SNP variants, then studied and replicated their association with baseline CRP level among apparently healthy subjects in the Women's Health Study (WHS; n = 717), Pravastatin Inflammation/CRP Evaluation trial (PRINCE; n = 1,110) and Physicians' Health Study (PHS; n = 509) cohorts. The minor alleles of four SNPs were consistently associated in all three cohorts with higher CRP, while the minor alleles of two SNPs were associated with lower CRP (p < 0.05 for each). Single marker and haplotype analysis in all three cohorts were consistent with functional roles for the 5'-flanking triallelic SNP -286C>T>A and the 3'-UTR SNP 1846G>A. None of the SNPs associated with higher CRP were associated with risk of incident myocardial infarction (MI) or ischemic stroke in a prospective, nested case-control study design from the PHS cohort (610 case-control pairs). One SNP, -717A>G, was unrelated to CRP levels but associated with decreased risk of MI (p = 0.001). Taken together, these data imply significant interactions between both genetic and environmental contributions to the increased CRP levels that predict a greater risk of future atherothrombotic events in epidemiological studies.

The Tidal Model as experienced by patients and nurses in a regional forensic unit.

The Tidal Model has been implemented in Rangipapa, a regional secure mental health forensic unit in New Zealand. A phenomenological study was undertaken to obtain reflective description of the nursing care experience from the perspective's of four Registered Nurses and four Special Patients. Five major themes were identified that appeared to capture the experiences of the participants. The themes show changes to the unit's unique culture and values following implementation of the model. These changes engendered a sense of hope, where nurses felt they were making a difference and patients were able to communicate in their own words their feelings of hope and optimism. Levelling was experienced as an effect emerging from individual and group processes whereby a shift in power enhanced a sense of self and connectedness in their relationships. These interpersonal transactions were noted by the special patients as being positive for their recovery. This enabled effective nurse-patient collaboration expressed simply as working together. The participants reported a feeling of humanity, so that there was a human face to a potentially objectifying forensic setting. Implications arising from this study are that the use of the model enables a synergistic interpersonal process wherein nurses are professionally satisfied and patients are validated in their experience supporting their recovery.

Migraine, headache, and the risk of stroke in women: a prospective study.

BACKGROUND: Migraine and headache in general have been associated with subsequent risk of stroke, primarily in retrospective case-control studies. Prospective data evaluating the association between specific headache forms and stroke are sparse. METHODS: A prospective cohort study was conducted among 39,754 US health professionals age 45 and older participating in the Women's Health Study with an average follow-up of 9 years. Incident stroke was self-reported and confirmed by medical record review. RESULTS: A total of 385 strokes (309 ischemic, 72 hemorrhagic, and 4 undefined) occurred. Compared with nonmigraineurs, participants who reported migraine overall or migraine without aura had no increased risk of any stroke type. Participants who reported migraine with aura had increased adjusted hazards ratios (HRs) of 1.53 (95% CI 1.02 to 2.31) for total stroke and 1.71 (95% CI 1.11 to 2.66) for ischemic stroke but no increased risk for hemorrhagic stroke. Participants with migraine with aura who were <55 years old had a greater increase in risk of total (HR 1.75; 95% CI 1.02 to 3.00) and ischemic (HR 2.25; 95% CI 1.30 to 3.91) stroke. Compared with participants without headache, headache in general and nonmigraine headache were not associated with total, ischemic, or hemorrhagic stroke. CONCLUSIONS: In these prospective data, migraine was not associated with total, ischemic, or hemorrhagic stroke. In subgroup analyses, we found increased risks of total and ischemic stroke for migraineurs with aura. The absolute risk increase was, however, low, with 3.8 additional cases per year per 10,000 women.

Sodium reduction for hypertension prevention in overweight adults: further results from the Trials of Hypertension Prevention Phase II.

Sodium reduction is efficacious for primary prevention of hypertension, but the feasibility of achieving this effect is unclear. The objective of the paper is detailed analyses of adherence to and effects of the sodium reduction intervention among overweight adults in the Trials of Hypertension Prevention, Phase II. Sodium reduction (comprehensive education and counselling about how to reduce sodium intake) was tested vs no dietary intervention (usual care) for 36-48 months. A total of 956 white and 203 black adults, ages 30-54 years, with diastolic blood pressure 83-89 mmHg, systolic blood pressure (SBP) <140 mmHg, and body weight 110-165% of gender-specific standard weight were included in the study. At 36 months, urinary sodium excretion was 40.4 mmol/24 h (24.4%) lower in sodium reduction compared to usual care participants (P<0.0001), but only 21% of sodium reduction participants achieved the targeted level of sodium excretion below 80 mmol/24 h. Adherence was positively related to attendance at face-to-face contacts. Net decreases in SBP at 6, 18, and 36 months of 2.9 (P<0.001), 2.0 (P<0.001), and 1.3 (P=0.02) mmHg in sodium reduction vs usual care were associated with an overall 18% lower incidence of hypertension (P=0.048); were relatively unchanged by adjustment for ethnicity, gender, age, and baseline blood pressure, BMI, and sodium excretion; and were observed in both black and white men and women. From these beneficial but modest results with highly motivated and extensively counselled individuals, sodium reduction sufficient to favourably influence the population blood pressure distribution will be difficult to achieve without food supply changes.

Dose-response of sodium excretion and blood pressure change among overweight, nonhypertensive adults in a 3-year dietary intervention study.

A cross-sectional dose-response relationship between sodium intake and blood pressure (BP) has been demonstrated, but evidence for a graded longitudinal effect is limited. Evaluation of BP response to sodium reduction was assessed in a 3-year lifestyle dietary intervention trial. BP changes at 18 and 36 months after enrollment were analysed according to concurrent quantitative changes in sodium excretion and by categories of success in sodium reduction among 1157 men and women, ages 30-54 years, with a diastolic BP (DBP) 83-89 mmHg, systolic BP (SBP) <140 mmHg, body weight 110-165% of sex-specific standard weight, and valid baseline urinary sodium excretion. Participants were randomized to a Sodium Reduction intervention (n=581) or Usual Care (n=576). From a 187 mmol/24 h baseline mean sodium excretion, net decreases were 44 mmol/24 h at 18 months and 38 mmol/24 h at 36 months in Sodium Reduction vs Usual Care. Corresponding net decreases in SBP/DBP were 2.0/1.4 mmHg at 18 months, and 1.7/0.9 mmHg at 36 months. Significant dose-response trends in BP change over quintiles of achieved sodium excretion were seen at both 18 (SBP and DBP) and 36 (SBP only) months; effects appeared stronger among those maintaining sodium reduction. Estimated SBP decreases per 100 mmol/24 h reduction in sodium excretion at 18 and 36 months were 2.2 and 1.3 mmHg before and 7.0 and 3.6 mmHg after correction for measurement error, respectively. DBP changes were smaller and nonsignificant at 36 months. In conclusion, incremental decreases in BP with lower sodium excretion were observed in these overweight nonhypertensive individuals.

C-reactive protein gene polymorphisms and the risk of venous thromboembolism: a haplotype-based analysis.

C-reactive protein (CRP) is a risk predictor for future athero-thrombotic events, and its plasma concentration has a heritable component. CRP has also been suggested to play a role in the pathophysiology of venous thromboembolism. To date, no genetic-epidemiological data are available on the relation of CRP gene variants with the risk of venous thromboembolism. The present study was carried out to investigate the possible association of two previously characterized (an exonic 1059G-->C, and an intronic T-->A) CRP gene polymorphisms in a prospective, matched case-control sample from the Physicians Health Study. Allele, genotype, and haplotype distributions were similar between 130 cases and 130 matched controls. Genotype distributions were in Hardy-Weinberg equilibrium. Further investigation using a haplotype-based matched logistic regression analysis, adjusting for age, smoking, randomized treatment group (likelihood ratio test: X(2)2df = 0.19, P = 0.91) or with further controlling for body mass index, hypertension, and diabetes (likelihood ratio test: X(2)2df = 0.66, P = 0.72) yielded similar null findings. In conclusion, we found no evidence for an association between the CRP polymorphisms/haplotypes tested and the risk of venous thromboembolism.

An autosomal genome scan for loci influencing longitudinal burden of body mass index from childhood to young adulthood in white sibships: The Bogalusa Heart Study.

OBJECTIVE: To examine genetic loci linked to a long-term burden and trend of obesity traits, such as body mass index (BMI), from childhood to adulthood. DESIGN: : Longitudinal study using serial measurements of BMI from childhood. SUBJECTS: A total of 782 unselected white siblings (representing 521 full and 39 half sib-pairs) from 342 families enrolled in the Bogalusa Heart Study. MEASUREMENTS: A total of 357 microsatellite markers with an average spacing of 9.0 cM spanning the 22 autosomal chromosomes were typed. A quadratic growth curve was developed using a random effects model based on serial measurements of BMI from childhood to adulthood. The serial changes in BMI were measured in terms of long-term burden (area under the curve (AUC) divided by follow-up years) and the long-term trend (incremental AUC, calculated as total AUC-baseline AUC). RESULTS: Heritability estimates of long-term measures were 0.78 for total AUC and 0.43 for incremental AUC. In a variance-component-based multipoint linkage analysis with SOLAR, linkage to the long-term measures of BMI was observed on chromosomes 1, 5, 7, 12, 13 and 18. For total AUC, LOD scores were 3.0 at 110 cM on chromosome 12, 2.9 at 26 cM and 2.4 at 52 cM on chromosome 7, and 2.2 at 126 cM on chromosome 5. For incremental AUC, LOD scores were 2.9 at 26 cM, 2.1 at 97 cM and 2.3 at 110 cM on chromosome 12, 2.2 at 69 cM on chromosome 7, 2.2 at 91 cM and 2.5 at 150 cM on chromosome 1, 2.0 at 119 cM on chromosome 5, 2.0 at 54 cM on chromosome 13 and 2.0 at 7 cM on chromosome 18. Several important obesity-related candidate genes are located in the regions or near the markers showing positive linkage. CONCLUSION: Linkage evidence found in this study indicates that regions on these chromosomes might harbor genetic loci that affect the propensity to develop obesity from childhood.

Randomised beta-carotene supplementation and incidence of cancer and cardiovascular disease in women: is the association modified by baseline plasma level?

In a nested case-control study of 513 women with cancer; 130 with cardiovascular disease and equal numbers of controls, we found no effect of randomised beta-carotene on risk of cancer or cardiovascular disease within any quartile of baseline plasma beta-carotene, nor was there a trend across quartiles (P for trend 0.15 and 0.62, respectively).

Lifetime physical activity and risk of breast cancer.

We conducted a case-control study of 394 women with breast cancer and 788 control women (91% response) to investigate the association of lifetime physical activity with mainly menopausal breast cancer risk. After controlling for potential confounders, the odds ratios (95% confidence intervals) for increasing quartiles of lifetime physical activity were 1.00 (referent), 0.91 (0.60-1.37), 0.91 (0.60-1.39), and 1.10 (0.73-1.67), respectively; P, trend = 0.47. We also separately examined physical activity at ages 12-18, 19-34, 35-49 and > or =50 years; no significant trends were observed in any age group. These data do not support a role of physical activity in preventing breast cancer.

Obesity and renal cell cancer--a quantitative review.

Obesity has been associated with an increased risk of renal cell cancer among women, while the evidence for men is considered weaker. We conducted a quantitative summary analysis to evaluate the existing evidence that obesity increases the risk of renal cell cancer both among men and women. We identified all studies examining body weight in relation to kidney cancer, available in MEDLINE from 1966 to 1998. The quantitative summary analysis was limited to studies assessing obesity as body mass index (BMI, kg m(-2)), or equivalent. The risk estimates and the confidence intervals were extracted from the individual studies, and a mixed effect weighted regression model was used. We identified 22 unique studies on each sex, and the quantitative analysis included 14 studies on men and women, respectively. The summary relative risk estimate was 1.07 (95% CI 1.05-1.09) per unit of increase in BMI (corresponding to 3 kg body weight increase for a subject of average height). We found no evidence of effect modification by sex. Our quantitative summary shows that increased BMI is equally strongly associated with an increased risk of renal cell cancer among men and women.

Low-dose aspirin for migraine prophylaxis in women.

Although migraine is more common among women than men, the only two large, randomized trials of low-dose aspirin for migraine prophylaxis have been conducted in men. As part of the Women's Health Study, an ongoing randomized trial of low-dose aspirin and vitamin E among 39 876 female health professionals aged 45 and older, 1001 women with frequent migraine attacks were assigned to 100 mg of aspirin every other day (n = 525) or aspirin placebo (n = 476). Migraine frequency, as well as severity, duration, and degree of incapacitation, were assessed by self-report on questionnaires 12 months and 36 months after randomization, and also by monthly diaries kept before and after randomization. Women assigned to aspirin reported small and consistent decreases in migraine frequency (59.6% vs. 56.4% assigned to placebo reporting improvement at 36 months; odds ratio 1.13, 95% confidence interval, 0.86--1.48), as well as decreases in severity, duration, and migraine-related incapacitation. These reductions were not, however, statistically significant. These data are compatible with a small treatment effect of low-dose aspirin in the prophylaxis of migraine among middle-aged women.