Nocturnal Hot Flashes, but Not Serum Hormone Concentrations, as a Predictor of Insomnia in Menopausal Women: Results from the Midlife Women's Health Study.

Background: Sleep disruptions are among the most common symptoms experienced during menopause and can be associated with depression, hot flashes, and fluctuating hormones. However, few studies have examined how such risk factors influence sleep in midlife women in a network-based approach that will establish the complex relationship between variables. Materials and Methods: We used a Bayesian network (BN) to examine the relationship between multiple factors known to influence sleep and depression in midlife women, including hormone concentrations, hot flashes, and menopause status among participants of the longitudinal Midlife Women's Health Study. In year 1, 762 women (45-54 years of age) answered questions regarding the frequency of insomnia, hot flashes, and depression; 389 of the same women answered similar questions at year 4. We measured serum hormones and calculated free estradiol index, free testosterone index, and ratios of estradiol:progesterone, and estradiol:testosterone. For our model, we calculated the change in frequency of insomnia, depression, and covariates (body mass index, menopause status, hot flashes at night, and present quality of life) from year 1 to 4. Results: Using a BN, we found that self-reported hot flashes at night, and no other factors, were direct predictors of self-reported insomnia in year 1. Surprisingly, we did not identify an association between hormone concentrations and self-reported insomnia. Frequency of insomnia in year 4 was only predicted by frequency of insomnia in year 1, whereas frequency of depression in year 4 was predicted by year 4 insomnia and frequency of depression in year 1. No other factors were direct predictors of insomnia or depression in our model. Conclusions: Therefore, hot flashes at night, previous insomnia, and depression are stronger predictors of how women will self-report frequency of sleep disruptions and treatment may reduce menopausal sleep complaints.

A Generic Pharmacokinetic Model for Quantifying Mother-to-Offspring Transfer of Lipophilic Persistent Environmental Chemicals.

Lipophilic persistent environmental chemicals (LPECs) can accumulate in a woman's body and transfer to her developing child across the placenta and via breast milk. To assess health risks associated with developmental exposures to LPECs, we developed a pharmacokinetic (PK) model that quantifies mother-to-offspring transfer of LPECs during pregnancy and lactation and facilitates internal dosimetry calculations for offspring. We parameterized the model for mice, rats, and humans using time-varying functions for body mass and milk consumption rates. The only required substance-specific parameter is the elimination half-life of the LPEC in the animal species of interest. We used the model to estimate whole-body concentrations in mothers and offspring following maternal exposures to hexachlorobenzene (HCB) and 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153) and compared these with measured concentrations from animal studies. We also compared estimated concentrations for humans to those generated using a previously published human LPEC PK model. Finally, we compared human equivalent doses (HEDs) calculated using our model and an allometric scaling method. Estimated and observed whole-body concentrations of HCB and PCB 153 in offspring followed similar trends and differed by less than 60%. Simulations of human exposure yielded concentration estimates comparable to those generated using the previously published model, with concentrations in offspring differing by less than 12%. HEDs calculated using our PK model were about 2 orders of magnitude lower than those generated using allometric scaling. Our PK model can be used to calculate internal dose metrics for offspring and corresponding HEDs and thus informs assessment of developmental toxicity risks associated with LPECs.

Parabens and Menopause-Related Health Outcomes in Midlife Women: A Pilot Study.

Background: Parabens are antimicrobial agents prevalently found in daily-use products that can interfere with the endocrine and reproductive systems. In this study, we examined the cross-sectional associations of parabens with hot flashes, hormone concentrations, and ovarian volume in a subsample of 101 nonsmoking, non-Hispanic 45- to 54-year-old women from the Midlife Women's Health Study. Materials and Methods: Women self-reported their hot flash history and underwent a transvaginal ultrasound to measure ovarian volume. Participants provided blood for quantification of serum hormones (by enzyme-linked immunosorbent assay or radioimmunoassay) and urine samples for measurements of urinary paraben biomarker levels (by high-performance liquid chromatography negative-ion electrospray ionization-tandem mass spectrometry). Linear or logistic regression models evaluated associations of specific gravity-adjusted paraben biomarker concentrations with hot flashes, hormone concentrations, and ovarian volume. Results: We observed marginal associations of propylparaben, methylparaben, and ∑parabens biomarkers (molar sum of four parabens) with hot flashes and follicle-stimulating hormone (FSH) concentrations, and of these paraben biomarkers and ethylparaben with ovarian volume. For example, women tended to have 32% (95% confidence intervals [CI]: 0.9 to 1.81), 40% (95% CI: 1.0 to 1.95), and 40% (95% CI: 0.98 to 2.01) higher odds of having recent, monthly, and mild hot flashes, respectively, for every two-fold increase in ∑parabens. Similarly, women tended to have 14.54% (95% CI: -0.10 to 31.32) higher FSH concentrations, but 5.67% (95% CI: -12.54 to 1.75) reduced ovarian volume for every two-fold increase in ∑parabens Conclusions: Overall, our preliminary findings suggest that urinary paraben biomarkers may be associated with menopause-related outcomes in midlife women. Additional studies in larger and diverse populations are needed to expand on these findings.

An evidence map of polychlorinated biphenyl exposure and health outcome studies among residents of the Akwesasne Mohawk Nation.

From the 1950s to the 1970s, three Superfund sites discharged polychlorinated biphenyl (PCB)-contaminated waste upstream of the Mohawk Nation at Akwesasne, resulting in PCB contamination of groundwater, soil, and sediment in the surrounding area. Given the persistence of PCBs in the environment and in human tissues, there are continued concerns regarding PCB exposures and the potential for adverse health effects in the community. We developed an evidence map of PCB research at Akwesasne in order to characterize the available data and to highlight potential research needs. Human health and exposure biomarker studies were identified from a literature search based on population, exposure, comparator, and outcome (PECO) criteria. Data extracted from references that met the inclusion criteria after full-text review included study characteristics (e.g., sample size, study design, sampling years), details on PCB measurements (e.g., analytical method, number of congeners analyzed, method detection limits), and results (e.g., PCB levels and summary of study conclusions). We identified 33 studies, conducted between 1986 and 2013, that examined PCB exposure characteristics and health effects in residents of the Akwesasne Mohawk Nation. Organizing this literature into an evidence map including information on study cohort, congener groupings, exposure biomarker characteristics, and health effects allowed us to identify research gaps and to suggest future research priorities for the community. We identified current PCB exposure levels and PCB source characterization as major uncertainties, both of which could be addressed by new studies of PCB concentrations in environmental media.

Urinary phthalate metabolite concentrations and serum hormone levels in pre- and perimenopausal women from the Midlife Women's Health Study.

BACKGROUND: Phthalate exposure is associated with altered reproductive function, but little is known about associations between phthalate and hormone levels in midlife women. METHODS: This cross-sectional analysis includes 45-54-year-old pre- and perimenopausal women from Baltimore, MD and its surrounding counties enrolled in the Midlife Women's Health Study (n = 718). Serum and urine samples were collected from participants once a week for four consecutive weeks to span the menstrual cycle. Serum samples were assayed for estradiol, testosterone, progesterone, sex hormone binding globulin (SHBG), follicle-stimulating hormone (FSH), and anti-Müllerian hormone (AMH), and geometric means were calculated for each hormone across all four weeks. Urine samples were analyzed for nine phthalate metabolites from pools of one-to-four urine samples. Phthalate metabolite concentrations were specific gravity-adjusted and assessed as individual metabolites or as molar sums of metabolites from common parents (di(2-ethylhexyl) phthalate metabolites, ∑DEHP), exposure sources (plastic, ∑Plastics; personal care products, ∑PCP), biological activity (anti-androgenic, ∑AA), and sum of all metabolites (∑Phthalates). We used linear regression models to assess overall associations of phthalate metabolites with hormones, controlling for important demographic, lifestyle, and health factors. We also explored whether associations differed by menopause status, body mass index (BMI), and race/ethnicity. RESULTS: Most participants were non-Hispanic white (67%) or black (29%), college-educated (65%), employed (80%), and had somewhat higher mean urinary phthalate metabolite concentrations than other U.S. women. Overall, the following positive associations were observed between phthalate metabolites and hormones: ∑DEHP (%Δ: 4.9; 95%CI: 0.5, 9.6), ∑Plastics (%Δ: 5.1; 95%CI: 0.3, 10.0), and ∑AA (%Δ: 7.8; 95%CI: 2.3, 13.6) with estradiol; MiBP (%Δ: 6.6; 95%CI: 1.5, 12.1) with testosterone; ∑DEHP (%Δ: 8.3; 95%CI: 1.5, 15.6), ∑Plastics (%Δ: 9.8; 95%CI: 2.4, 17.7), MEP (%Δ: 4.6; 95%CI: 0.1, 9.2), ∑PCP (%Δ: 6.0; 95%CI: 0.2, 12.2), ∑Phthalates (%Δ: 9.0; 95%CI: 2.1, 16.5), and ∑AA (%Δ: 12.9; 95%CI: 4.4, 22.1) with progesterone; and MBP (%Δ: 8.5; 95%CI: 1.2, 16.3) and ∑AA (%Δ: 9.0; 95%CI: 1.3, 17.4) with AMH. Associations of phthalate metabolites with hormones differed by menopause status (strongest in premenopausal women for estradiol, progesterone, and FSH), BMI (strongest in obese women for progesterone), and race/ethnicity (strongest in non-Hispanic white women for estradiol and AMH). CONCLUSIONS: We found that phthalate metabolites were positively associated with several hormones in midlife women, and that some demographic and lifestyle characteristics modified these associations. Future longitudinal studies are needed to corroborate these findings in more diverse midlife populations.

Association of phthalate exposure and endogenous hormones with self-reported sleep disruptions: results from the Midlife Women's Health Study.

OBJECTIVE: Follicle-stimulating hormone and estradiol (E2) have been associated with sleep in midlife women, however, few studies have examined the association of other hormones or environmental chemical exposure such as phthalates, with self-reported sleep quality. We assessed the relationship of self-reported sleep with hormones and phthalates. METHODS: In total, 762 women (aged 45-54 y, 459 premenopausal, and 303 perimenopausal) from the Midlife Women's Health Study answered self-reported questions regarding the frequency of sleep disturbances, insomnia, and restless sleep. Serum E2, progesterone, testosterone, serum hormone binding globulin, free E2 index, free testosterone index, E2:progesterone, and E2:testosterone were measured. Summary measures of phthalate mixtures, including the phthalates from plastic sources (sumPLASTIC), personal care products (sumPCP), di-(2-ethyhexyl) phthalate (sumDEHP), anti-androgenic phthalates (sumAA), and all phthalate metabolites measured (sumALL), were calculated from urinary phthalate metabolites. Ordinal logistic regression was used to fit each outcome sleep measure with all hormones and summary phthalates. RESULTS: Progesterone and testosterone were significantly negatively associated with the frequency of sleep disturbances and insomnia. Free testosterone index was also negatively associated with insomnia frequency. E2:progesterone was positively associated with frequency of sleep disturbances and restless sleep in self-reported nonsmokers. SumPCP and sumALL were significantly negatively associated with frequency of sleep disturbances, insomnia, and restless sleep. SumDEHP and sumPLASTIC were negatively associated with insomnia frequency. Further, the direction of association between phthalates and sleep appears to be dependent on the quartile of phthalate exposure. All significant associations between phthalates and sleep were in self-reported nonsmokers or former smokers. CONCLUSIONS: Our study supports previous literature that hormones beyond follicle-stimulating hormone and E2 are associated with sleep disruptions in menopause. Further, we are among the first to show that phthalate exposure is associated with sleep disruptions in midlife women.

Exposure to di(2-ethylhexyl) phthalate and diisononyl phthalate during adulthood disrupts hormones and ovarian folliculogenesis throughout the prime reproductive life of the mouse.

Di(2-ethylhexyl) phthalate (DEHP) is a phthalate commonly used for its plasticizing capabilities. Because of the wide production and use of DEHP, humans are exposed to DEHP on a daily basis. Diisononyl phthalate (DiNP) is often used as a DEHP replacement chemical, and because of the increased use of DiNP, humans are increasingly exposed to DiNP over time. Of concern is that DEHP and DiNP both exhibit endocrine disrupting capabilities, and little is known about how short-term exposure to either of these phthalates affects aspects of female reproduction. Thus, this study tested the hypothesis that short-term exposure to DEHP or DiNP during adulthood has long-lasting consequences on ovarian follicles and hormones in female mice. Female CD-1 mice aged 39-40 days were orally dosed with either vehicle control (corn oil), DEHP (20 µg/kg/day-200 mg/kg/day), or DiNP (20 µg/kg/day-200 mg/kg/day) for 10 days. Ovarian follicle populations, estradiol, testosterone, progesterone, follicle stimulating hormone (FSH), and inhibin B were analyzed at time points immediately post-dosing and 3, 6, and 9 months post-dosing. The results indicate that 10 days of exposure to DEHP and DiNP changed the distribution of ovarian follicle populations and sex steroid hormones at multiple time points, including the last time point, 9 months post-dosing. Further, FSH was increased at multiple doses up to 6 months post-dosing. Inhibin B was not affected by treatment. These data show that short-term exposure to either DEHP or DiNP has long-term consequences that persist long after cessation of exposure.

Late-life consequences of short-term exposure to di(2-ethylhexyl) phthalate and diisononyl phthalate during adulthood in female mice.

Di(2-ethylhexyl) phthalate (DEHP) is a known endocrine disruptor and diisononyl phthalate (DiNP) is a common DEHP replacement chemical. However, little is known about late-life consequences due to DEHP or DiNP exposure during adulthood. Thus, this study tested the hypothesis that adult exposure to DEHP or DiNP affects female reproductive parameters during late-life in female mice. Female CD-1 mice (age 39-40 days) were dosed with either vehicle control, DEHP (20 µg/kg/day-200 mg/kg/day), or DiNP (20 µg/kg/day-200 mg/kg/day) for 10 days and breeding trials were conducted at 12 and 15 months post-dosing. Further, ovaries and sera were collected at 12, 15, and 18 months post-dosing. DEHP and DiNP disrupted estrous cyclicity, increased pregnancy loss, decreased fertility, altered the sex ratio of pups, altered ovarian follicle populations, and disrupted hormone levels. Collectively, these data show that short-term exposure to DEHP or DiNP during adulthood has long-term consequences in late-life.

Associations of Pregnancy History with BMI and Weight Gain in 45-54-Year-Old Women.

BACKGROUND: Midlife women have a higher risk of cardiometabolic disease than younger women, but the lifelong biological/lifestyle factors responsible for this increase are unclear. OBJECTIVES: We investigated whether pregnancy history is a risk factor for midlife overweight/obesity and evaluated potential hormonal mechanisms. METHODS: The Baltimore Midlife Women's Health Study, a prospective cohort, recruited 772 women aged 45-54 y. Women reported pregnancy characteristics via questionnaires, trained staff measured weight/height to calculate midlife BMI, and serum hormones were assessed by ELISA. Logistic regression models assessed associations of pregnancy history with risk of midlife overweight/obesity and BMI gain since age 18. We additionally explored whether associations differed by menopausal status, and whether midlife hormones mediated relationships of pregnancy history and midlife BMI. RESULTS: These premenopausal or perimenopausal women were 66% Caucasian/White and 30% African American/Black, with a median of 2 live births (range: 0-11) and median age at first birth of 27 y (range: 12-46 y). Women with 0 and ≥2 live births had lower odds of overweight/obesity than those with 1 birth (OR = 0.47; 95% CI: 0.23, 0.96; P = 0.04, and OR = 0.58; 95% CI: 0.35, 0.95; P = 0.03, respectively). Women with ≥2 live births also had lower odds of BMI gain than those with 1 birth (OR = 0.66; 95% CI: 0.41, 1.06; P = 0.08). Furthermore, women who were older at their first birth had lower odds of overweight/obesity (OR = 0.96; 95% CI: 0.92, 1.00; P = 0.03) and BMI gain (OR = 0.97; 95% CI: 0.93, 1.00; P = 0.06). Number of pregnancies and age at last pregnancy were not associated with midlife overweight/obesity or BMI gain. Associations did not differ by menopausal status and were not explained by midlife hormones. CONCLUSIONS: Earlier childbirth and having 1 child increased women's risk of midlife overweight/obesity and BMI gain since age 18. Additional studies should focus on women's childbearing years as a critical determinant of midlife metabolic health.

Exposure to di-(2-ethylhexyl) phthalate transgenerationally alters anxiety-like behavior and amygdala gene expression in adult male and female mice.

Phthalates are industrial plasticizers and stabilizers commonly found in polyvinyl chloride plastic and consumer products, including food packaging, cosmetics, medical devices, and children's toys. Di-(2-ethylhexyl) phthalate (DEHP), one of the most commonly used phthalates, exhibits endocrine-disrupting characteristics and direct exposure leads to reproductive deficits and abnormalities in anxiety-related behaviors. Importantly, increasing evidence indicates that the impacts of DEHP exposure on reproduction and social behavior persist across multiple generations. In this study, we tested the hypothesis that transgenerational DEHP exposure alters anxiety-like behavior and neural gene expression in both male and female mice. Pregnant CD-1 mice were orally dosed daily with either tocopherol-stripped corn oil or DEHP (20 or 200 µg/kg/day; 500 or 750 mg/kg/day) from gestational day 10.5 until birth to produce the F1 generation. Females from each generation were bred with untreated, unrelated CD-1 males to produce subsequent generations. Behavior and gene expression assays were performed with adult, intact F3 males and females. Transgenerational DEHP exposure increased time spent in the open arm in the elevated plus maze for adult females (750 mg/kg/day lineage), but not males. In adult females, we observed a down-regulation of mRNA expression of estrogen receptor 1 in the 200 µg/kg/day and 500 mg/kg/day treatment lineages, mineralocorticoid receptor in the 200 µg/kg/day lineage, and dopamine receptor 2 in the 20 µg/kg/day and 750 mg/kg/day lineages. In adult males, we found an up-regulation of estrogen receptor 2 in the 20 and 200 µg/kg/day lineages, and dopamine receptor 1 in the 20 µg/kg/day and 750 mg/kg/day lineages. No hippocampal gene expression modifications were observed in response to treatment. These results implicate dose-specific transgenerational effects on behavior and neural gene expression in adult male and female mice.

Ovarian Metabolism of an Environmentally Relevant Phthalate Mixture.

Phthalates are synthetic chemicals with widespread human exposure due to their use as additives in consumer products. Phthalate diesters are hydrolyzed in the environment and in the body to monoesters that may be more toxic than the parent compounds. This study tested the hypothesis that adult mouse antral follicles, but not neonatal ovaries, are able to metabolize an environmentally relevant mixture of phthalates. Whole neonatal ovaries and isolated adult antral follicles from CD-1 mice were cultured in media treated with vehicle control or 0.1-10 µg/ml of a mixture composed of 35% diethyl phthalate (DEP), 21% di(2-ethylhexyl) phthalate (DEHP), 15% dibutyl phthalate (DBP), 15% diisononyl phthalate (DiNP), 8% diisobutyl phthalate (DiBP), and 5% benzylbutyl phthalate (BzBP). After 4 days of culture, media were subjected to high-performance liquid chromatography tandem mass spectrometry to measure the amounts of diester phthalates and monoester metabolites. Ovaries and follicles were collected to measure the gene and protein expression of the enzymes required for phthalate metabolism. Monoester metabolites for all phthalates except DiNP were detected in the media for both culture types at most doses. The long-chain phthalates (BzBP, DEHP, and DiNP) were metabolized less than the short-chain phthalates (DEP, DBP, and DiBP) compared with respective controls. Expression of metabolizing enzymes was observed for all treatment groups in both culture types. These data indicate that mouse ovaries are capable of metabolizing low doses of phthalates and suggest that metabolic capacity differs for follicles at different stages of development.

Subchronic Exposure to Di(2-ethylhexyl) Phthalate and Diisononyl Phthalate During Adulthood Has Immediate and Long-Term Reproductive Consequences in Female Mice.

Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer used in a variety of consumer products. This is concerning because DEHP is an endocrine disruptor and ovarian toxicant. Diisononyl phthalate (DiNP) is a DEHP replacement that is a rising human toxicant due to its increased use as a DEHP substitute. However, little is known about the effects of DEHP or DiNP exposure during adulthood on female reproduction. Thus, this study tested the hypothesis that DEHP or DiNP exposure during adulthood has long-term consequences for female reproduction in mice. Adult female CD-1 mice (39-40 days) were orally dosed with vehicle control (corn oil), DEHP (20 µg/kg/day-200 mg/kg/day), or DiNP (20 µg/kg/day-200 mg/kg/day) for 10 days. Females were paired with untreated male mice for breeding trials immediately post-dosing and again at 3 and 9 months post-dosing. Immediately post-dosing, DEHP and DiNP did not affect fertility. At 3 months post-dosing, DiNP (20 and 100 µg/kg/day and 200 mg/kg/day) significantly disrupted estrous cyclicity, and DiNP and DEHP (20 µg/kg/day) significantly reduced the ability of females to get pregnant. At 9 months post-dosing, DiNP significantly disrupted estrous cyclicity (100 µg/kg/day), reduced time to mating (100 µg/kg/day-200 mg/kg/day), and borderline reduced percent of females who produced offspring (20 mg/kg/day). At 9 months post-dosing, DEHP (200 µg/kg/day and 200 mg/kg/day) and DiNP (100 µg/kg/day and 20 and 200 mg/kg/day) increased numbers of male-biased litters. These data show that DEHP and DiNP exposure has long-term consequences for female reproduction, even long after cessation of exposure.

Hormone variability and hot flash experience: Results from the midlife women's health study.

OBJECTIVE: Hot flashes are believed to be related to hormonal changes. However, the relationship between hormonal fluctuations and hot flashes has not been studied. The objective of this study is to determine hormone measurement summaries that best explain the incidence of hot flashes in midlife women. STUDY DESIGN: In a cohort study of 798 midlife women over 1-7 years, women provided 4 weekly blood samples annually and completed a survey detailing life history, ongoing behaviors, and menopausal symptoms. Estradiol, progesterone, and testosterone were measured in all serum samples. Annual summary variables of each hormone were median, mean, maximum, minimum, variance, and range. The association of these values with hot flashes was assessed using multivariable logistic regression and Bayesian network analysis, controlling for smoking history and menopausal status. MAIN OUTCOME MEASURES: Hot flash incidence, severity, and frequency. RESULTS: For most outcomes, the best-fit model included progesterone variability; increased progesterone variance or range was correlated with decreased hot flash frequency (OR = 0.82, 95% CI = 0.74-0.91) and severity (OR = 0.82, 95% CI = 0.77-0.88). In the Bayesian network model, the maximum estradiol value was negatively correlated with many outcomes (OR for hot flashes = 0.68). Relationships between progesterone variability, maximum estradiol level, maximum progesterone level, and hot flashes indicate that the effects of progesterone variance on hot flash outcomes are likely mediated through progesterone's relationship with maximum estradiol level. CONCLUSIONS: Variability of progesterone, as opposed to mean values, should be used as an indicator of risk of hot flashes in midlife women.

Exposure to endocrine disruptors during adulthood: consequences for female fertility.

Endocrine disrupting chemicals are ubiquitous chemicals that exhibit endocrine disrupting properties in both humans and animals. Female reproduction is an important process, which is regulated by hormones and is susceptible to the effects of exposure to endocrine disrupting chemicals. Disruptions in female reproductive functions by endocrine disrupting chemicals may result in subfertility, infertility, improper hormone production, estrous and menstrual cycle abnormalities, anovulation, and early reproductive senescence. This review summarizes the effects of a variety of synthetic endocrine disrupting chemicals on fertility during adult life. The chemicals covered in this review are pesticides (organochlorines, organophosphates, carbamates, pyrethroids, and triazines), heavy metals (arsenic, lead, and mercury), diethylstilbesterol, plasticizer alternatives (di-(2-ethylhexyl) phthalate and bisphenol A alternatives), 2,3,7,8-tetrachlorodibenzo-p-dioxin, nonylphenol, polychlorinated biphenyls, triclosan, and parabens. This review focuses on the hypothalamus, pituitary, ovary, and uterus because together they regulate normal female fertility and the onset of reproductive senescence. The literature shows that several endocrine disrupting chemicals have endocrine disrupting abilities in females during adult life, causing fertility abnormalities in both humans and animals.

Phthalate metabolite levels and menopausal hot flashes in midlife women.

During the menopausal transition, a woman's reproductive capacity declines, her hormone milieu changes, and her risk of hot flashes increases. Exposure to phthalates, which can be found in personal care products, can also result in altered reproductive function. Here, we investigated the associations between phthalate metabolite levels and midlife hot flashes. Eligible women (45-54 years of age) provided detailed information on hot flashes history and donated urine samples (n=195). Urinary phthalate metabolite levels were measured by HPLC-MS/MS. A higher total sum of phthalate metabolites commonly found in personal care products was associated with an increased risk of ever experiencing hot flashes (odds ratio (OR)=1.45; 95% confidence interval (CI)=1.07-1.96), hot flashes in the past 30days (OR=1.43; 95%CI=1.04-1.96), and more frequent hot flashes (OR=1.47; 95%CI=1.06-2.05). These data suggest that some phthalate exposures from personal care products are associated with menopausal hot flashes in women.