Addressing racial and ethnic disparities in US liver cancer care.

HCC, the most common form of primary liver cancer, is the fastest rising cause of cancer-related death in the United States. HCC disproportionately affects racial and ethnic minorities in the United States. A practical framework is needed to organize the complex patient, provider, health system, and societal factors that drive these racial and ethnic disparities. In this narrative review, we adapted and applied the National Institute on Minority Health and Health Disparities (NIMHD) Research Framework to the HCC care continuum, as a step toward better understanding and addressing existing HCC-related disparities. We first summarize the literature on HCC-related disparities by race and ethnicity organized by the framework's 5 domains (biological, behavioral, physical/built environment, sociocultural environment, and health care system) and 4 levels (individual, interpersonal, community, and societal) of influence. We then offer strategies to guide future research initiatives toward promotion of health equity in HCC care. Clinicians and researchers may help mitigate further inequities and better address racial and ethnic disparities in HCC care by prioritizing the following in HCC research: (1) increasing racial and ethnic minority representation, (2) collecting and reporting HCC-related data by racial and ethnic subgroups, (3) assessing the patient experience of HCC care by race and ethnicity, and (4) evaluating HCC-specific social determinants of health by race and ethnicity. These 4 priorities will help inform the development of future programs and interventions that are tailored to the unique experiences of each racial and ethnic group.

Hand-assisted laparoscopic repair of a grade IV rectal tear in a postparturient mare.

CASE DESCRIPTION: An 8-year-old multiparous Thoroughbred broodmare was admitted for evaluation of a rectal tear sustained during parturition. CLINICAL FINDINGS: On initial evaluation, the mare had mild signs of abdominal discomfort. A full-thickness rectal tear located 30 cm cranial to the anus and extending approximately 15 cm longitudinally along the surface of the small colon between the 4 and 6 o'clock positions, when viewed from behind, was diagnosed on examination per rectum. TREATMENT AND OUTCOME: Laparoscopic evaluation of the abdomen was performed to assess the tear and extent of peritoneal contamination. A hand-assisted repair via a flank incision was performed. The tear was closed in a single-layer, simple continuous pattern with size-0 polydioxanone with a handheld needle holder. Subsequently, a ventral midline celiotomy was performed, and intestinal contents were evacuated via a pelvic flexure enterotomy and a typhlotomy. Following surgery, the mare was managed with IV fluid therapy, partial parenteral nutrition, antimicrobials, and NSAIDs for 5 to 7 days before being gradually reintroduced to a complete pelleted feed and alfalfa hay. Prior to discharge, examination per rectum revealed no stricture formation associated with repair. The mare was discharged from the hospital and performed successfully as a broodmare, with the delivery of a live foal 1 year after surgery. CLINICAL RELEVANCE: Successful repair with an excellent outcome was achieved in this mare. Hand-assisted laparoscopic repair should be considered as a possible treatment option in horses with grade IV rectal tears.

Reproductive cancer risk factors among Alaska Native women: the Alaska Education and Research Towards Health (EARTH) Study.

BACKGROUND: The purpose of this study was to provide estimates for the prevalence of reproductive cancer risk factors among Alaska Native (AN) women who enrolled in the Alaska Education and Research Towards Health (EARTH) Study from 2004 to 2006. METHODS: A total of 2,315 AN women 18 years or older completed reproductive health questions as part of a comprehensive health history questionnaire. The reproductive health section included menstrual status (age at menarche and menopause), pregnancy and live birth history, use of hormonal contraception, hormone replacement therapy, and history of hysterectomy and/or oophorectomy. RESULTS: A total of 463 (20%) of women experienced menarche before age 12 with a decline in mean age at menarche by age cohort. More than 86% had been pregnant (mean number of pregnancies, 3.8; mean number of live births, 2.9). More than one half of women (58%) had their first live birth between the ages of 18 and 24. Almost 28% of participants had completed menopause, of whom 24% completed menopause after age 52. Fewer than half (43%) reported ever using hormone replacement therapy. Almost two thirds (62%) reported ever using oral contraceptives, and fewer reported ever using birth control shots (30%) or implants (10%). CONCLUSIONS: This study is unique in reporting reproductive health factors among a large group of AN women. These data show that AN women have selective protective factors for reproductive cancers, including low nulliparity rates, low use of menopausal estrogens, and common use of contraceptive hormones. However, analysis by age cohorts indicates decreasing age at menarche that might increase the risk for reproductive cancers among AN women in the future.

Zinc transporter mRNA levels in Alzheimer's disease postmortem brain.

Zinc (Zn2+) is concentrated into pre-synaptic vesicles and co-released with neurotransmitter at some synapses. Zn2+ can accelerate assembly of the amyloid-ß peptides (Aß) and tau protein central to the neuropathological changes found in Alzheimer's disease (AD). Altered protein levels of the membrane Zn2+ transporters ZnT1, ZnT4, and ZnT6 have been reported in AD postmortem brain tissue. The present study analyzed mRNA levels of five established (LIV1, ZIP1, ZnT1, ZnT4, and ZnT6) and one potential (PRNP) Zn2+ transporter in human postmortem brain tissue from Braak-staged individuals with AD and controls using quantitative real-time PCR. Four cortical regions (middle temporal gyrus, superior occipital gyrus, superior parietal gyrus, and superior frontal gyrus) and cerebellum were examined. PRNP mRNA levels were decreased by ∼30% in all four cortical regions examined in AD patients, but unchanged in the cerebellum. In contrast, some increases in mRNA levels of the other more established Zn2+ transporters (LIV1, ZIP1, ZnT1, ZnT6) were found in AD cortex. The ratios of the mRNA levels of LIV1, ZIP1, ZnT1, ZnT4, and ZnT6/mRNA level of neuron specific enolase increased significantly as the disease progressed and Braak stage increased. Significant correlations were also identified between mRNA levels of several of the Zn2+ transporters investigated. These expression changes could either reflect or cause the altered cortical Zn2+ distribution in AD, potentially increasing the likelihood of interactions between Zn2+ and Aß or tau protein.

Association of menopausal vasomotor symptoms with increased bone turnover during the menopausal transition.

The purpose of this study was to determine the longitudinal association between menopausal vasomotor symptoms (VMS) and urinary N-telopeptide level (NTX) according to menopausal stage. We analyzed data from 2283 participants of the Study of Women's Health Across the Nation, a longitudinal community-based cohort study of women aged 42 to 52 years at baseline. At baseline and annually through follow-up visit 8, participants provided questionnaire data, urine samples, serum samples, and anthropometric measurements. Using multivariable repeated-measures mixed models, we examined associations between annually assessed VMS frequency and annual NTX measurements. Our results show that mean adjusted NTX was 1.94 nM of bone collagen equivalents (BCE)/mM of creatinine higher among early perimenopausal women with any VMS than among early perimenopausal women with no VMS (p < .0001). Mean adjusted NTX was 2.44 nM BCE/mM of creatinine higher among late perimenopausal women with any VMS than among late perimenopausal women with no VMS (p = .03). Among premenopausal women, VMS frequency was not significantly associated with NTX level. When NTX values among women with frequent VMS (≥6 days in past 2 weeks) were expressed as percentages of NTX values among women without frequent VMS, the differences were 3% for premenopausal women, 9% for early perimenopausal women, 7% for late perimenopausal women, and 4% for postmenopausal women. Adjustment for serum follicle-stimulating hormone (FSH) level greatly reduced the magnitudes of associations between VMS and NTX level. We conclude that among early perimenopausal and late perimenopausal women, those with VMS had higher bone turnover than those without VMS. Prior to the final menstrual period, VMS may be a marker for risk of adverse bone health.

Reproductive hormones and obesity: 9 years of observation from the Study of Women's Health Across the Nation.

The effect of change in reproductive hormones and menopause on incident obesity (body mass index > or =30 kg/m(2)) and severe obesity (body mass index > or =35 kg/m(2)) was evaluated over 9 years in 3,260 US women recruited in the multiethnic Study of Women's Health Across the Nation in 1996-1997. After 9 years, cumulative incidences of obesity and severe obesity reached 21.8% and 12.3%, respectively. In multivariate analysis, hormone changes, chronic health conditions, lower physical activity, race/ethnicity, and age were significantly associated with incident obesity and/or severe obesity. The odds of incident severe obesity increased with surgical menopause (odds ratio (OR) = 5.07, 95% confidence interval (CI): 2.29, 11.20; P < 0.001) and initiation of hormone therapy prior to 12 months of amenorrhea (OR = 2.94, 95% CI: 1.14, 7.58; P = 0.03). Predictors of obesity included an increase in free androgen index (OR = 1.37, 95% CI: 1.12, 1.68; P = 0.002) and a decrease in sex hormone-binding globulin (OR = 0.60, 95% CI: 0.45, 0.80; P = 0.0005). Similar results were found for severe obesity. Obesity rates varied by race, but no hormone-by-race interactions were observed. These longitudinal data demonstrate that higher androgens, lower sex hormone-binding globulin, surgical menopause, and early hormone therapy use predict incident obesity and/or severe obesity in a multiracial cohort of women transitioning into menopause.

Racial differences in women who have a hysterectomy for benign conditions.

OBJECTIVE: To evaluate if there are racial differences between African-American and Caucasian women who have hysterectomy for benign conditions in terms of (1) presenting symptoms (prolapse, vaginal bleeding, pain, and known history of leiomyomas), (2) serum estradiol and testosterone levels at the visit before hysterectomy, and (3) uterine weight. METHODS: A multi-ethnic, multisite, community-based longitudinal cohort study of 3,302 women ages 42-52 at enrollment was conducted. During 9 years of follow-up, 203 African-American and Caucasian women reported a hysterectomy, 90 with evidence of uterine leiomyomas. Women were surveyed regarding their overall perceived health before and after hysterectomy, presenting symptoms, and their motivations for surgery. Serum estradiol and testosterone levels were measured. Uterine weight at time of hysterectomy and clinical pathology were determined via medical record abstraction. RESULTS: Previously diagnosed leiomyomas were presenting symptoms more frequently in African-American women than Caucasian women (85% vs. 63%; p = .02). African-American women had less prolapse than Caucasian women (0% vs. 10%; p = 0.04). Chronic pain was a more frequent reason for hysterectomy in African-American women than in Caucasian women (49% vs. 29%; p = .05). There were no differences between the groups in levels of estradiol or testosterone. African-American women had almost twice the uterine weight as that of Caucasian women (448 vs. 240 g; p = .0005). CONCLUSION: Racial differences in frequency of hysterectomy for benign conditions are consistent with differences in presenting symptoms, where African-American women seemingly have larger, more symptomatic fibroids.

A novel reciprocal and biphasic relationship between membrane cholesterol and beta-secretase activity in SH-SY5Y cells and in human platelets.

Research into the cause of Alzheimer's disease (AD) has identified strong connections to cholesterol. Cholesterol and cholesterol esters can modulate amyloid precursor protein (APP) processing, thus altering production of the Abeta peptides that deposit in cortical amyloid plaques. Processing depends on the encounter between APP and cellular secretases, and is thus subject to the influence of cholesterol-dependent factors including protein trafficking, and distribution between membrane subdomains. We have directly investigated endogenous membrane beta-secretase activity in the presence of a range of membrane cholesterol levels in SH-SY5Y human neuroblastoma cells and human platelets. Membrane cholesterol significantly influenced membrane beta-secretase activity in a biphasic manner, with positive correlations at higher membrane cholesterol levels, and negative correlations at lower membrane cholesterol levels. Platelets from individuals with AD or mild cognitive impairment (n = 172) were significantly more likely to lie within the negative correlation zone than control platelets (n = 171). Pharmacological inhibition of SH-SY5Y beta-secretase activity resulted in increased membrane cholesterol levels. Our findings are consistent with the existence of a homeostatic feedback loop between membrane cholesterol level and membrane beta-secretase activity, and suggest that this regulatory mechanism is disrupted in platelets from individuals with cognitive impairment.

Adenomyosis a variant, not a disease? Evidence from hysterectomized menopausal women in the Study of Women's Health Across the Nation (SWAN).

OBJECTIVE: Our study evaluates the symptoms commonly attributed to adenomyosis in women undergoing the menopausal transition. We hypothesized that adenomyosis is more commonly seen in women with fibroids, pelvic pain, abnormal uterine bleeding, and in the presence of endometriosis. DESIGN: Retrospective cohort. SETTING: Multisite community-based study. PATIENT(S): Enrollees in the Study of Women's Health Across the Nation who had hysterectomies. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Relationship of adenomyosis to presenting symptoms and other patient characteristics. RESULT(S): Adenomyosis was found in 48% of 137 patients. Frequencies of presenting symptoms were similar in those with and without evidence of adenomyosis. The same prevalence of fibroids was seen in the presence or absence of adenomyosis: 37% versus 43%, endometriosis, 3% versus 5%, abnormal bleeding, 27% versus 33%, or chronic pelvic pain in the presence of fibroids 12% versus 17%. CONCLUSION(S): Adenomyosis is a common diagnosis seen in hysterectomized specimens from women undergoing the perimenopausal transition. Adenomyosis is equally common in women who also have fibroids, endometriosis, pelvic pain, or abnormal uterine bleeding, and women who do not. Therefore, adenomyosis is an incidental finding, not the source of the symptomatology. It appears not to be a "disease" per se but rather a normal variant.

Sensitivity and specificity of recalled vasomotor symptoms in a multiethnic cohort.

Many epidemiologic studies include symptom checklists assessing recall of symptoms over a specified time period. Little research exists regarding the congruence of short-term symptom recall with daily self-reporting. The authors assessed the sensitivity and specificity of retrospective reporting of vasomotor symptoms using data from 567 participants in the Study of Women's Health Across the Nation (1997-2002). Daily assessments were considered the "gold standard" for comparison with retrospective vasomotor symptom reporting. Logistic regression was used to identify predictors of sensitivity and specificity for retrospective reporting of any vasomotor symptoms versus none in the past 2 weeks. Sensitivity and specificity were relatively constant over a 3-year period. Sensitivity ranged from 78% to 84% and specificity from 85% to 89%. Sensitivity was lower among women with fewer symptomatic days in the daily assessments and higher among women reporting vasomotor symptoms in the daily assessment on the day of retrospective reporting. Specificity was negatively associated with general symptom awareness and past smoking and was positively associated with routine physical activity and Japanese ethnicity. Because many investigators rely on symptom recall, it is important to evaluate reporting accuracy, which was relatively high for vasomotor symptoms in this study. The approach presented here would be useful for examining other symptoms or behaviors.

Wrong-site surgery: can we prevent it?

Wrong-site surgery happens frequently enough that it is a significant risk for many surgeons during their professional careers. But it is an event that should never happen. Most wrong-site surgery is wrong-side surgery, followed by wrong-digit and wrong-vertebral-level surgery. Wrong-site surgery results from misinformation or misperception of the patient's orientation. The key to preventing wrong-site surgery is to have multiple independent checks of critical information. Discrepancies among the operative record, consent, and the surgeon's record of the history and physical examination should ideally be resolved prior to the day of surgery to avoid time-consuming reconciliations. We noted that the preoperative verification was the most effective of the three steps of the Universal Protocol and that the patient was a more reliable source of accurate information than the documents. Marking the operative site gives patients a voice after they are sedated or anesthesia is induced. Wrong-site surgery has involved local or regional anesthesia at the wrong site when anesthesiologists did not adhere to formal time-outs for their procedures. Surgeons need to have access to all relevant information and to be engaged in the processes to prevent wrong-site surgery, particularly in the final time-out. Junior members of the operating room team must be made comfortable about speaking up if concerned. During spinal surgery, the vertebral level needs to be confirmed radiographically. Wrong-site surgical problems can occur after an operation if accurate information is not provided to accompany the specimen or if leftover labels from a previous patient are used to identify the specimen.

Identification of valid reference genes for the normalization of RT qPCR gene expression data in human brain tissue.

BACKGROUND: Studies of gene expression in post mortem human brain can contribute to understanding of the pathophysiology of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Quantitative real-time PCR (RT qPCR) is often used to analyse gene expression. The validity of results obtained using RT qPCR is reliant on accurate data normalization. Reference genes are generally used to normalize RT qPCR data. Given that expression of some commonly used reference genes is altered in certain conditions, this study aimed to establish which reference genes were stably expressed in post mortem brain tissue from individuals with AD, PD or DLB. RESULTS: The present study investigated the expression stability of 8 candidate reference genes, (ubiquitin C [UBC], tyrosine-3-monooxygenase [YWHAZ], RNA polymerase II polypeptide [RP II], hydroxymethylbilane synthase [HMBS], TATA box binding protein [TBP], beta-2-microglobulin [B2M], glyceraldehyde-3-phosphate dehydrogenase [GAPDH], and succinate dehydrogenase complex-subunit A, [SDHA]) in cerebellum and medial temporal gyrus of 6 AD, 6 PD, 6 DLB subjects, along with 5 matched controls using RT qPCR (TaqMan(R) Gene Expression Assays). Gene expression stability was analysed using geNorm to rank the candidate genes in order of decreasing stability in each disease group. The optimal number of genes recommended for accurate data normalization in each disease state was determined by pairwise variation analysis. CONCLUSION: This study identified validated sets of mRNAs which would be appropriate for the normalization of RT qPCR data when studying gene expression in brain tissue of AD, PD, DLB and control subjects.

Associations of endogenous sex hormones with the vasculature in menopausal women: the Study of Women's Health Across the Nation (SWAN).

OBJECTIVE: As associations between endogenous sex hormones and the vasculature are not well characterized, the objective was to examine the cross-sectional associations of menopausal status and endogenous sex hormones with vascular characteristics. DESIGN: Common carotid artery adventitial diameter and intima-media thickness were determined using B-mode ultrasonography among 483 middle-aged women enrolled in the Pittsburgh and Chicago sites of the Study of Women's Health Across the Nation. RESULTS: Sixty-two percent of women were pre- or early perimenopausal (<3 mo amenorrhea), 12% were late perimenopausal (3-12 mo amenorrhea), and 27% were postmenopausal (>or=12 mo amenorrhea). After adjustment for age, compared with pre-/early perimenopause, late perimenopause was associated with a 0.28-mm larger adventitial diameter (P=0.001), whereas postmenopause was associated with a 0.15-mm larger adventitial diameter (P=0.040). Adjustment for traditional cardiovascular risk factors slightly attenuated these associations, but the association with late perimenopause remained statistically significant (P=0.001). Each SD lower log estradiol value was associated with a 0.07-mm larger adventitial diameter after adjustment for traditional cardiovascular risk factors (P=0.023), whereas other endogenous hormones showed no associations. Intima-media thickness values were not significantly associated with menopausal status or endogenous sex hormones after adjustment for age. CONCLUSIONS: The menopausal transition and declining estrogen levels are associated with alterations of the peripheral vasculature, which may help to explain the increased risk of cardiovascular disease with postmenopause.

Adiposity and reporting of vasomotor symptoms among midlife women: the study of women's health across the nation.

It has long been hypothesized that increased adiposity would be associated with decreased vasomotor symptoms during menopause because of conversion of androgens to estrogens in body fat. However, recent thermoregulatory models have postulated that increased adipose tissue would be associated with a greater likelihood of vasomotor symptoms. The authors evaluated these hypotheses in the Study of Women's Health Across the Nation, a multiethnic, community-based observational study of US women transitioning through menopause. The sample included 1,776 women aged 47-59 years with an intact uterus and at least one ovary who completed bioelectrical impedance analysis for assessment of body composition at the sixth annual study visit (2002-2004). Assessments also included reported vasomotor symptoms (hot flashes, night sweats) and serum levels of follicle-stimulating hormone, estradiol, and sex hormone-binding globulin-adjusted estradiol (free estradiol index). Results indicated that a higher percentage of body fat was associated with increased odds of reporting vasomotor symptoms (per standard deviation increase in percent body fat, odds ratio = 1.27, 95% confidence interval: 1.14, 1.42) in age- and site-adjusted models. Associations persisted in fully adjusted models and were not reduced when models included reproductive hormones. These findings support a thermoregulatory model of vasomotor symptoms.

Getting surgery right.

OBJECTIVE: We sought to identify factors contributing to wrong-site surgery (wrong patient, procedure, side, or part). METHODS: We examined all reports from all hospitals and ambulatory surgical centers--in a state that requires reporting of wrong-site surgery--from the initiation of the reporting requirement in June 2004 through December 2006. RESULTS: Over 30 months, there were 427 reports of near misses (253) or surgical interventions started (174) involving the wrong patient (34), wrong procedure (39), wrong side (298), and/or wrong part (60); 83 patients had incorrect procedures done to completion. Procedures on the lower extremities were the most common (30%). Common contributions to errors resulting in the initiation of wrong-site surgery involved patient positioning (20) and anesthesia interventions (29) before any planned time-out process, not verifying consents (22) or site markings (16), and not doing a proper time-out process (17). Actions involving operating surgeons contributed to 92. Common sources of successful recovery to prevent wrong-site surgery were patients (57), circulating nurses (30), and verifying consents (43). Interestingly, 31 formal time-out processes were unsuccessful in preventing "wrong" surgery. CONCLUSIONS: Wrong-site surgery continues to occur regularly, especially wrong-side surgery, even with formal site verification. Many errors occur before the time-out; some persist despite the verification protocol. Patients and nurses are the surgeons' best allies. Verification, starting with verification of the consent, needs to occur at multiple points before the incision.

The association between mammographic breast density and bone mineral density in the study of women's health across the nation.

BACKGROUND: Bone mineral density and mammographic breast density are each associated with markers of lifetime estrogen exposure. The association between mammographic breast density and bone mineral density in early perimenopausal women is unknown. METHODS: We analyzed data from a cohort (n = 501) of premenopausal (no change in menstrual regularity) and early perimenopausal (decreased menstrual regularity in past 3 months) participants of African-American, Caucasian, Chinese, and Japanese ethnicity in the Study of Women's Health Across the Nation. Using multivariable linear regression, we examined the cross-sectional association between percent mammographic density and bone mineral density (BMD). RESULTS: Percent mammographic density was statistically significantly inversely associated with hip BMD and lumbar spine BMD after adjustment (body mass index, ethnicity, age, study site, parity, alcohol intake, cigarette smoking, physical activity, age at first childbirth) in early perimenopausal, but not premenopausal, women. In early perimenopausal women, every 0.1g/cm(2) greater hip BMD predicted a 2% lower percent mammographic density (95% confidence interval -37.0 to -0.6%, p = 0.04). CONCLUSION: Mammographic breast density is inversely associated with BMD in the perimenopausal participants of this community-based cohort. The biological underpinnings of these findings may reflect differential responsiveness of breast and bone mineral density to the steroid milieu.

Menopause transition stage and endogenous estradiol and follicle-stimulating hormone levels are not related to cognitive performance: cross-sectional results from the study of women's health across the nation (SWAN).

BACKGROUND: By one estimate, 60% of women experiencing the menopause transition perceive that they have memory problems, but most studies that have used cognitive function tests have not substantiated a relation between menopause stage and cognitive performance. We sought to describe the cross-sectional relation between menopause status, estradiol (E(2)), follicle-stimulating hormone (FSH), and measured cognitive function. METHODS: Cross sectional analysis of a community-based cohort of midlife women was used. Cognitive tests were the East Boston Memory Test, Symbol Digit Modalities, and Digits Span Backward. Menopause categories (premenopausal, early perimenopausal, late perimenopausal, and postmenopausal) were defined based on menstrual patterns. One set of general linear models assessed the relations between each cognitive test and menopause transition category, initially adjusted for age, race/ethnicity, education, symptoms, self-rated general health, and body mass index (BMI); next, these were additionally adjusted for FSH and E(2). A second set of models, stratified by menopause status, examined the possible relations between each cognitive test and either E(2) or FSH, adjusted for age, race/ethnicity, education, symptoms, self-related general health, and BMI. RESULTS: The mean age of the analytical sample (n = 1657) was 49.7 years. Only 5% of the sample had less than a high school education, 16% graduated from high school, and the rest had at least some college. The percent of women in each menopause category was premenopausal (9.0%), early perimenopausal (57.0%), late perimenopausal (13.4%), postmenopausal (20.6%). Although clinical-site adjusted models showed moderate differences between menopause transition groups and cognitive performance, no association was found between each of the measured cognitive performance tests and menopause transition status when adjusting for covariates. Similarly, no association between each cognitive test and E(2) or FSH was found. CONCLUSIONS: This study does not support a cross-sectional relation between cognitive test performance and menopause stage, FSH, or E(2).

Helping midlife women predict the onset of the final menses: SWAN, the Study of Women's Health Across the Nation.

OBJECTIVE: Women approaching menopause often ask their doctors, "When are my periods going to end?" The objective of this study was to predict time to the final menstrual period (FMP). DESIGN: This multiethnic, observational cohort study, the Study of Women's Health Across the Nation, has been ongoing since 1996. Data collected from seven annual study visits were used. The community-based cohort from seven national sites included 3,302 white, African American, Hispanic, Chinese, and Japanese women aged 42 to 52 years at baseline with a uterus and at least one ovary, who were not pregnant or taking reproductive hormones, and had at least one menstrual period within the past 3 months at baseline. The time to the FMP was defined retrospectively after 12 months of amenorrhea. Uni- and multivariable Cox proportional hazard models, hazard ratios (HRs), and 95% CIs were computed for variables of interest. RESULTS: A total of 2,662 women, of whom 706 had an observed FMP, were included. Age, menstrual cycles that had become farther apart (HR = 2.56, 95% CI = 1.94-3.39) or more variable (HR = 1.79, 95% CI = 1.45-2.21), and current smoking (HR = 1.68, 95% CI = 1.35-2.08) were all associated with shorter time to the FMP. Higher (log) follicle-stimulating hormone (HR = 2.32, 95% CI = 2.02-2.67) was related to a shorter time to the FMP, but the highest estradiol category (>or=100 pg/mL [367 pmol/L]) was associated with an earlier onset of the FMP (HR = 2.16, 95% CI = 1.63-2.89). The number of vasomotor symptoms was related to an earlier FMP, whereas higher physical activity and educational levels were associated with a later FMP. CONCLUSIONS: Age, menstrual cycle recall, smoking status, and hormone measurements can be used to estimate when the FMP will occur, allowing for more precise estimates for older midlife women: in the most extreme cases, ie, age 54, high estradiol level, current smoking, and high follicle-stimulating hormone level, the FMP can be estimated to within 1 year.