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

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

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

Several retrospective case-control studies suggested that insulin-like growth factor 1 (IGF-1) or insulin-like growth factor binding protein 3 (IGFBP-3) was associated with endometriosis. However, results are inconsistent and no prospective study exists. We prospectively evaluated associations between plasma levels of IGF-1 and IGFBP-3 and laparoscopically confirmed endometriosis in a case-control study nested within the Nurses' Health Study II. Between blood collections in 1996-1999 and 2007, we ascertained 310 premenopausal women with incident endometriosis and 615 matched controls. We estimated incidence rate ratios and 95% confidence intervals using multivariable conditional logistic regression. We observed no statistically significant associations between endometriosis and IGF-1 (incidence rate ratio (IRR) = 0.88, 95% confidence interval (CI): 0.61, 1.27; Ptrend = 0.48), IGFBP-3 (IRR = 1.12, 95% CI: 0.80, 1.57; Ptrend = 0.51), and the IGF-1:IGFBP-3 molar ratio (IRR = 0.94, 95% CI: 0.66, 1.34; Ptrend = 0.64), comparing the top with the bottom tertile. IGF-1, IGFBP-3, and the molar ratio appeared to be positively associated with endometriosis risk among women aged <40 years at blood draw (IGF-1: IRR = 1.60, 95% CI: 0.86, 2.98; IGFBP-3: IRR = 1.85, 95% CI: 1.08, 3.16; IGF-1:IGFBP-3: IRR = 1.57, 95% CI: 0.85, 2.88) but not among women aged ≥40 years at blood draw (all Pheterogeneity ≤ 0.05). Overall, these data suggest that, if IGF-1 or IGFBP-3 plays a role in the etiology of endometriosis, it is minimal and perhaps only among younger women. [ABSTRACT FROM AUTHOR]

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

Background Moderate to severe premenstrual syndrome (PMS) affects 8-20 percent of premenopausal women. Previous studies suggest that high dietary vitamin D intake may reduce risk. However, vitamin D status is influenced by both dietary vitamin D intake and sunlight exposure and the association of vitamin D status with PMS remains unclear. Methods We assessed the relation of plasma 25-hydroxyvitamin D (25OHD), total calcium and parathyroid hormone levels with risk of PMS and specific menstrual symptoms in a case- control study nested within the prospective Nurses' Health Study II. Cases were 401 women free from PMS at baseline who developed PMS during follow-up (1991-2005). Controls were women not experiencing PMS (1991-2005), matched 1:1 with cases on age and other factors. Timed luteal phase blood samples were collected between 1996 and 1999 from cases and controls. We used conditional logistic regression to model the relation of 25OHD levels with risk of PMS and individual menstrual symptoms. Results In analyses of all cases and controls, 25OHD levels were not associated with risk of PMS. However, results differed when the timing of blood collection vs. PMS diagnosis was considered. Among cases who had already been diagnosed with PMS at the time of blood collection (n = 279), 25OHD levels were positively associated with PMS, with each 10 nmol/L change in 25OHD associated with a 13% higher risk. Among cases who developed PMS after blood collection (n = 123), 25OHD levels were unrelated to risk of PMS overall, but inversely related to risk of specific menstrual symptoms. For example, each 10 nmol/L increase was associated with a significant 21% lower risk of breast tenderness (P = 0.02). Total calcium or parathyroid hormone levels were unrelated to PMS. Conclusions 25OHD levels were not associated with overall risk of PMS. The positive association observed among women already experiencing PMS at the time of 25OHD measurement is likely due to confounding by indication related to use of dietary supplements to treat menstrual symptoms. Results from prospective analyses, which were less likely influenced by this bias, suggest that higher 25OHD levels may be inversely related to the development of specific menstrual symptoms. [ABSTRACT FROM AUTHOR]

The article presents a study associating physical activity with breast cancer risk among postmenopausal women. Variation across levels of other risk factors is examined. Findings suggest that moderate physical activity including brisk walking, may reduce postmenopausal breast cancer risk. Body mass index (BMI), weight change since 18 years of age and use of postmenopausal hormones (PMH) were taken into account.

Background: Relatively little is known about factors that influence the initial development of premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD), although these conditions are common in reproductive age women and are associated with substantial impairment. Previous studies have observed higher alcohol use in prevalent PMS/PMDD patients compared with controls, but it is unknown if drinking predisposes women to developing these disorders or is instead influenced by symptom experience. Methods: To address this, we conducted a case-control study nested within the prospective Nurses' Health Study II (NHS2). Participants were a subset of women aged 27–44 and free from PMS at baseline (1991), including 1057 women who developed PMS over 10 years of follow-up, 762 of whom also met criteria consistent with PMDD, and 1968 control women. Alcohol use at various time periods, before and after onset of menstrual symptoms, was assessed by questionnaire. Results: Overall, alcohol use was not strongly associated with the incidence of PMS and probable PMDD. Relative risks (RR) for women with the highest cumulative alcohol use vs. never drinkers were 1.19 (95% confidence interval [CI] 0.84-1.67) for PMS and 1.28 (95% CI 0.86-1.91) for PMDD, although results did suggest a positive relationship in leaner women ( p trend = 0.002). Women who first used alcohol before age 18 had an RR of PMS of 1.26 (95% CI 0.91-1.75) compared with never drinkers; the comparable RR for PMDD was 1.35 (95% CI 0.93-1.98). Conclusions: These findings suggest alcohol use is not strongly associated with the development of PMS and PMDD, although early age at first use and long-term use may minimally increase risk. [ABSTRACT FROM AUTHOR]

Abstract: Multiple lines of evidence support a central role of hormones in the etiology of breast cancer. In epidemiologic studies, considerable effort has focused on delineating the role of endogenous hormones in risk of breast cancer among postmenopausal women. Recently, substantial additional data has accrued from prospective studies where endogenous hormones are measured in study subjects prior to disease diagnosis. In this review, the epidemiologic evidence linking sex steroids—estrogens, testosterone, and progesterone, specifically—with subsequent risk of breast cancer in both premenopausal and postmenopausal women is summarized. Overall, a strong positive association between breast cancer risk and circulating levels of both estrogens and testosterone has now been well confirmed among postmenopausal women; women with hormone levels in the top 20% of the distribution (versus bottom 20%) have a two- to three-fold higher risk of breast cancer. Evidence among premenopausal women is more limited, though increased risk associated with higher levels of testosterone is consistent. However, both positive and null associations have been observed with estrogens and progesterone and clearly more evaluation is needed. [Copyright &y& Elsevier]

Abstract: Prolactin, a hormone involved in normal breast development and lactation, has been hypothesized to be important in the etiology of breast cancer. This review summarizes in vitro, animal, and epidemiologic data supporting this hypothesis. Experimental evidence indicates that prolactin can promote cell proliferation and survival, increase cell motility, and support tumor vascularization. Animal data suggest that prolactin can increase tumor growth rates and the number of metastases, as well as induce both estrogen receptor +(ER) and ER− tumors in a transgenic mouse model in which ER+ tumors are very rare. Epidemiologic data for premenopausal women are sparse; however a recent study with 235 cases reported a significant positive association between plasma prolactin levels and breast cancer risk. Studies in postmenopausal women have reported a positive association as well, and in the largest study (n=851 cases) the association was strongest for ER+ tumors. Overall, the available data support the hypothesis that prolactin increases risk of breast cancer. Future research directions include better characterizing the potential interplay between prolactin and estrogen and determining whether genetic variability in prolactin-related genes is associated with breast cancer risk. [Copyright &y& Elsevier]

The article describes the relation between the use of estrogen and testosterone therapies and breast cancer in postmenopausal women. Epidemiologic studies suggest that endogenous testosterone levels are positively associated with breast cancer risk in women experiencing postmenopausal symptoms. Findings reveal that women using estrogen and testosterone therapies significantly increased risk of invasive breast cancer.

Abstract: Objective: Moderate alcohol consumption is associated with substantially lower risk of cardiovascular disease (CVD). We assessed the relationship between alcohol intake and inflammatory markers to partially explain this beneficial effect. Methods and results: From two large prospective studies, we sampled 959 healthy male and 473 healthy female health professionals with reported alcohol intake. Markers of inflammation were soluble tumor necrosis factor-alpha receptors 1 and 2 (sTNF-R1 and sTNF-R2), C-reactive protein (CRP), and interleukin-6 (IL-6). We found significant inverse linear trends for sTNF-R1 (p-trend<0.001 men; 0.03 women) and sTNF-R2 (p-trend=0.002 men; 0.08 women) with increasing alcohol intake. Compared to non-drinkers, men who consumed on average 1–2drinks/day had 26% lower CRP (−0.66mg/L, p =0.13), and 36% lower IL-6 (−1.12pg/ml, p =0.02) levels. Among women, a similar though stronger association was observed at half drink per day. Compared to non-drinkers, both men and women who consumed 1–2drinks/drinking day had significantly lower sTNF-R1 (−9% in men, −6% in women) and sTNF-R2 (−7% in men, −6% in women) levels as well as lower CRP (−10% in men, −32% in women) and IL-6 (−45% in men, −27% in women) levels. Conclusions: Alcohol in moderation is associated with lower levels of inflammatory markers and may lower risk of CVD through these mechanisms. [Copyright &y& Elsevier]

Multiple lines of evidence support a central role of hormones in the etiology of breast cancer. In epidemiologic studies, considerable effort has focused on delineating the role of endogenous hormones in risk of breast cancer among postmenopausal women. Recently, substantial additional data has accrued from prospective studies where endogenous hormones are measured in study subjects prior to disease diagnosis. In this review, the epidemiologic evidence linking sex steroids, prolactin and insulin-like growth factors (IGF) with subsequent risk of breast cancer in postmenopausal women is summarized and evaluated. Overall, a strong positive association between breast cancer risk and circulating levels of both estrogens and androgens has now been well confirmed; women with hormone levels in the top 20% of the distribution (versus bottom 20% have a 2- to 3-fold higher risk of breast cancer. Accumulating data also indicate a significant positive association with prolactin levels, although additional confirmation is needed. In contrast, no important link has been found between circulating levels of IGF-I (and its binding protein, IGFBP-3) and breast cancer risk in postmenopausal women. [ABSTRACT FROM AUTHOR]

Background Growing evidence suggests that type 2 diabetes mellitus and hyperinsulinemia may be related to diminished cognition. To help differentiate between the effects of diabetes and insulin, we examined the relation of insulin to cognitive function among nondiabetic participants of the Nurses’ Health Study. Methods We measured the C peptide level, representing insulin secretion, in blood samples provided by 718 women from June 14, 1989, to October 4, 1990, when they were aged 61 to 69 years. We administered telephone interviews an average of 10 years after blood collection, testing general cognition, verbal memory, category fluency, and attention; second cognitive assessments were conducted 2 years later. The primary outcomes were global cognitive function across all tests and verbal memory. We used regression models to estimate multivariable-adjusted mean differences in cognitive function and cognitive decline, and odds of cognitive impairment, across C peptide levels. Results Cognitive function was worse among women in the fourth C peptide quartile compared with those in the first quartile (eg, on the global score combining all cognitive tests, the multivariable-adjusted mean difference was -1.7 standard units [95% confidence interval, -2.9 to -0.6 standard units]; P = .002); the odds of cognitive impairment (defined as the worst 10% of the distribution) were 3-fold higher among women in the fourth vs first quartile (95% confidence interval, 1.3-7.8). On verbal memory, women in the fourth quartile scored significantly worse than those in the first quartile; the odds of impairment were 2.8-fold higher (95% confidence interval, 1.1-7.0). Consistent findings were observed for cognitive decline. Conclusion Higher insulin secretion may be related to worse cognition, even among those without diabetes. [ABSTRACT FROM AUTHOR]

Exposure to light at night suppresses melatonin production, and night-shift work (a surrogate for such exposure) has been associated with an increased risk of breast cancer. However, the association between circulating melatonin levels and breast cancer risk is unclear. In a prospective case-control study nested within the Nurses' Health Study Ii cohort, we measured the concentration of the major melatonin metabolite, 6-sulphatoxymelatonin (aMT6s), in the first morning urine of 147 women with invasive breast cancer and 291 matched control subjects. in logistic regression models, the relative risk (reported as the odds ratio [OR]) of invasive breast cancer for women in the highest quartile of urinary aMT6s compared with those in the lowest was 0.59 (95% confidence interval [CI] = 0.36 to 0.97). This association was essentially unchanged after adjustment for breast cancer risk factors or plasma sex hormone levels but was slightly weakened when the analysis included 43 case patients with in situ breast cancer and their 85 matched control subjects (OR = 0.70, 95% CI = 0.47 to 1.06). The exclusion of women who had a history of night-shift work left our findings largely unchanged. These prospective data support the hypothesis that higher melatonin levels, as measured in first morning urine, are associated with a lower risk of breast cancer. [ABSTRACT FROM AUTHOR]

The erbB2 (HER2/neu) gene is found amplified in tumours. A single nucleotide polymorphism at codon 655 (Ile655Val) has been studied in a number of case-control studies with respect to breast cancer risk, with conflicting results. The aim of the present study was to examine the association between this polymorphism and breast cancer risk in a prospective, predominantly Caucasian cohort of women, the Nurses' Health Study. We genotyped the Ile655Val single nucleotide polymorphism (rs1801200) in 1271 incident breast cancer cases, and 1667 controls who were selected from the Nurses' Health Study blood cohort. Controls were matched to cases on age, menopausal status, fasting status and postmenopausal hormone use at blood draw. An inverse association was observed between the Val/Val genotype and breast cancer risk (Val/Val versus Ile/Ile odds ratio=0.68, 95% confidence interval 0.47-0.98). We conclude that this polymorphism is not associated with an increase in breast cancer risk, and may in fact be associated with a modest decrease in risk. [ABSTRACT FROM AUTHOR]

Background Premenstrual syndrome (PMS) is one of the most common disorders of premenopausal women. Studies suggest that blood calcium and vitamin D levels are lower in women with PMS and that calcium supplementation may reduce symptom severity, but it is unknown whether these nutrients may prevent the initial development of PMS. Methods We conducted a case-control study nested within the prospective Nurses’ Health Study II cohort. Participants were a subset of women aged 27 to 44 years and free from PMS at baseline in 1991, including 1057 women who developed PMS over 10 years of follow-up and 1968 women reporting no diagnosis of PMS and no or minimal menstrual symptoms. Intake of calcium and vitamin D was measured in 1991, 1995, and 1999 by a food frequency questionnaire. Results After adjustment for age, parity, smoking status, and other risk factors, women in the highest quintile of total vitamin D intake (median, 706 IU/d) had a relative risk of 0.59 (95% confidence interval, 0.40-0.86) compared with those in the lowest quintile (median, 112 IU/d) (P = .01 for trend). The intake of calcium from food sources was also inversely related to PMS; compared with women with a low intake (median, 529 mg/d), participants with the highest intake (median, 1283 mg/d) had a relative risk of 0.70 (95% confidence interval, 0.50-0.97) (P = .02 for trend). The intake of skim or low-fat milk was also associated with a lower risk (P<.001). Conclusions A high intake of calcium and vitamin D may reduce the risk of PMS. Large-scale clinical trials addressing this issue are warranted. Given that calcium and vitamin D may also reduce the risk of osteoporosis and some cancers, clinicians may consider recommending these nutrients even for younger women. [ABSTRACT FROM AUTHOR]

The Nurses' Health Study has grown from a simple questionnaire-based study initiated in 1976 to a rich resource of information collected over 29 years. Important details about lifestyle have been collected throughout the study and, as the study has progressed, blood samples and DNA from buccal cells have been collected and stored. Tumour samples have also been collected from participants who developed cancer. Through analyses that integrate information from these various sources we are advancing our understanding of the causes of cancer and the potential for prevention. [ABSTRACT FROM AUTHOR]

Objective: To investigate the relation between the fetal environment and endometriosis. Design: Prospective cohort study. Setting: Nurses'' Health Study II with 10 years of follow-up. Participant(s): Eighty-four thousand, four hundred forty-six women aged 25–42 who had never been diagnosed with endometriosis, infertility, or cancer at baseline in 1989. Main outcome measure(s): Incidence of laparoscopically confirmed endometriosis according to birthweight, prematurity, multiple gestation, diethylstilbestrol (DES) exposure, and having been breastfed. Result(s): During 566,250 woman-years of follow-up, 1,226 cases of laparoscopically-confirmed endometriosis were reported among women with no past infertility. After adjusting for age, calendar time, parity, race, and body mass index at age 18, we observed a linear increase in the incidence rate with decreasing birthweight (rate ratio [RR] = 1.3 for birthweight <5.5 pounds versus 7.0–8.4 pounds, 95% confidence interval [CI] = 1.0–1.8, P value, test for trend = .01). In addition, women who were born as one of a multiple gestation (i.e., twins or greater number) were at increased risk even after controlling for birthweight (RR = 1.7, CI = 1.2–2.5). The rate of endometriosis was also 80% greater among women exposed to diethylstilbestrol in utero (RR = 1.8, CI = 1.2–2.8). Neither premature delivery nor having been breastfed were associated with the incidence of endometriosis. None of these effect estimates were modified by infertility status at the time of endometriosis diagnosis. Conclusion(s): The fetal environment is associated with subsequent laparoscopically confirmed endometriosis in this cohort of US women. [Copyright &y& Elsevier]

OBJECTIVE: To clarify the temporal complexities of the relation between reproductive factors and endometriosis. METHODS: We analyzed 10 years of prospective data from the Nurses' Health Study II cohort. Information was obtained through questionnaires sent every 2 years to 116,678 women aged 25-42 years when enrolled in 1989. Cox proportional hazards models were used to adjust for age, calendar time, and confounding variables. RESULTS: During 726,205 woman-years of follow-up, 1,721 cases of laparoscopically confirmed endometriosis were reported among women with no past infertility. Greater incidence was observed among women with an earlier age at menarche (rate ratio of 1.3 comparing menarche at age < 10 to age 12 years; 95% confidence interval [CI] 1.0-1.8; P value, test for trend < .001) and shorter cycle length during late adolescence (rate ratio of 1.3 comparing < 26 days to 26-31 days; 95% CI 1.1-1.5). Time to cycle regularity was not associated with risk. Among parous women, a linear decrease in risk was observed with number of live-born children (rate ratio of 0.5 comparing > 3 with 2 children; 95% CI 0.4-0.7; P value, test for trend < .001) and lifetime duration of lactation if time since last birth was less than 5 years (rate ratio of 0.2 comparing > 23 months with never; 95% CI 0.1-0.4; P value, test for trend < .001). CONCLUSION: Hormonal and anatomical changes associated with menstruation and pregnancy may affect the rate of laparoscopically confirmed endometriosis. Within this cohort, risk was greatest among nulliparous women with earlier age at menarche and shorter menstrual cycles. Among parous women, parity and lifetime duration of lactation were associated with decreased risk. [ABSTRACT FROM AUTHOR]

Evidence from epidemiology studies of the association of insulin-like growth factors with breast cancer risk has been rapidly accruing over the past few years, indicating a potential role of IGFs in breast carcinogenesis. However, several limitations that stem from both the size and design of the studies as well as from other methodological issues such as laboratory methods currently limit our ability to draw firm conclusions from published data. Nonetheless, bearing these shortcomings in mind, there is increasing evidence that an association exists between circulating IGF-I levels and risk of breast cancer, and that this relation differs by menopausal status. The prospective studies have been consistent in observing no association between circulating IGF-I levels and breast cancer risk among postmenopausal women. In contrast, four of five prospective studies have observed a relatively strong, positive association among premenopausal women. While findings from the retrospective case-control studies have not been consistent, likely due in part to the small size of many of the studies, the larger and more carefully conducted case-control studies have tended to observe similar associations of IGF-I levels with breast cancer risk. The recent reports of a correlation between IGF levels and mammographic density (a strong risk factor for breast cancer) in premenopausal women also provide indirect support for a relation with breast cancer. This review summarizes the evidence regarding IGF-I and breast cancer risk that has been generated through observational studies and discusses future research needs. [ABSTRACT FROM AUTHOR]

Evaluates the factors to the design and execution of epidemiologic studies. Description of an innovative technology to follow the progression of cancer tissues; Collection protocol minimizing the sources of variation in hormone levels; Reproducibility and validity of hormone assays.

Data from laboratory and epidemiologic studies support a relationship between endogenous hormones and the increased risk of several female cancers. In epidemiologic studies, consistent associations have been observed between risk of breast, ovarian and endometrial cancers and reproductive and hormonal risk factors such as high postmenopausal body mass index (BMI) and postmenopausal hormone use, which suggest the importance of endogenous hormones in the etiology of these diseases. The relationship between circulating estrogen levels in postmenopausal women and the risk of breast cancer is well established, with an approximately 2-fold higher risk among women in the top 20–25% (versus bottom 20–25%) of levels. However, data evaluating the relationship between endogenous estrogens and premenopausal breast cancer risk are more limited and less consistent. Two studies to date have evaluated the relationship between circulating estrogens and breast cancer risk by menstrual cycle phase at blood collection and only one study has examined this relationship by menopausal status at diagnosis. Three prospective studies have evaluated circulating estrogen levels and endometrial cancer risk in postmenopausal women, with consistent strong positive associations reported (with relative risks of 2–4 comparing high versus low hormone levels), while this relationship has not been studied in premenopausal women. Compared to breast and endometrial cancers, reproductive and hormonal characteristics such as postmenopausal hormone use are generally weaker and less consistent risk factors for ovarian cancer, and the only small prospective study conducted to date indicated a non-significant positive relationship between circulating estrogen levels and ovarian cancer risk. In this review, we summarize current evidence and identify key areas to be addressed in future epidemiologic studies of endogenous estrogens and the risk of breast, endometrial, and ovarian cancers. [ABSTRACT FROM AUTHOR]

Background: In animal studies, prolactin has been found to be important for mammary epithelial development and its administration has been shown consistently to increase the rate of mammary tumor formation. Previous epidemiologic studies of prolactin and breast cancer risk in postmenopausal women have been limited in size, and the results have been inconsistent. We conducted a nested case-control study within the prospective Nurses' Health Study cohort to better determine the relationship between plasma prolactin levels and postmenopausal breast cancer risk.Methods: Blood samples were collected from cohort members during the period from 1989 through 1990. Prolactin levels were measured by use of a microparticle enzyme immunoassay. Included in this analysis were 306 postmenopausal women who were diagnosed with breast cancer after blood donation but before June 1994. One or two postmenopausal control subjects were matched per case subject on the basis of age, postmenopausal hormone use, and time of day and month of blood collection; the study included a total of 448 control subjects.Results: In conditional logistic regression analyses, a significant positive association was observed between plasma level of prolactin and postmenopausal breast cancer risk (highest versus lowest quartile, multivariate relative risk = 2.03; 95% confidence interval = 1.24-3.31; two-sided P for trend = .01). The relationship was independent of plasma sex steroid hormone levels and was similar after excluding case subjects diagnosed in the first 2 years after blood collection.Conclusions: These prospective data suggest that higher plasma prolactin levels are associated with an increased risk of breast cancer in postmenopausal women. [ABSTRACT FROM AUTHOR]

Purpose: To study the possible association of silicone-breast-implant exposure and immunologic abnormalities within the Nurses' Health Study, an ongoing prospective cohort study of women.Subjects and Methods: From this cohort, we randomly selected 200 women who had been exposed to silicone breast implants and who had never reported connective tissue diseases during 14 years of follow-up, and 500 age-matched, nonexposed women, including 100 with definite connective tissue diseases validated by medical record review, 100 with at least one symptom of a connective tissue disease, 100 with diabetes, and 200 healthy controls. Assays for antinuclear antibodies (ANA), including anti-dsDNA, anti-ssDNA, anti-Sm/RNP/Ro/La, and anti-Scl-70, rheumatoid factor, immunoglobulins, serum complement, and C-reactive protein level, and anticardiolipin, antithyroglobulin, antithyroid microsomal, and antisilicone antibodies were performed by standard techniques in blood samples collected in 1989 or 1990 before collection of silicone-breast-implant exposure data in 1992.Results: ANA was positive (> or = 1:40) in 14% of women with silicone breast implants compared with 20% of healthy women (P = 0.11). Rheumatoid factor was positive (> or = 1:40) in 5% of women with silicone breast implants and 2% of healthy women (P = 0.16). Women with silicone breast implants had a significantly higher frequency of anti-ssDNA antibodies than healthy women (41% and 29%, P = 0.012). Duration of implant was associated with a higher frequency of anti-ssDNA antibodies (P = 0.03) but not with ANA or rheumatoid factor. No other significant differences in the frequencies of autoantibodies were observed in silicone breast implant-exposed women. Antisilicone antibodies were not found in any sample.Conclusion: We found no increased frequency of any immunologic abnormalities in women exposed to silicone breast implants, except for anti-ssDNA, which has unknown clinical relevance. [ABSTRACT FROM AUTHOR]

Background: A positive relationship has generally been observed between plasma estrogen levels and breast cancer risk in postmenopausal women, but most of these studies have been small and few have evaluated specific estrogen fractions (such as percent bioavailable estradiol). In addition, few studies have evaluated plasma androgen levels in relation to breast cancer risk, and their results have been inconsistent. We prospectively evaluated relationships between sex steroid hormone levels in plasma and risk of breast cancer in postmenopausal women by use of a case-control study nested within the Nurses' Health Study.Methods: Blood samples were collected during the period from 1989 through 1990. Among postmenopausal women not using hormone replacement therapy at blood collection (n = 11,169 women), 156 women were diagnosed with breast cancer after blood collection but before June 1, 1994. Two control subjects were selected per case subject and matched with respect to age, menopausal status, month and time of day of blood collection, and fasting status at the time of blood collection.Results: From comparisons of highest and lowest (reference) quartiles, we observed statistically significant positive associations with risk of breast cancer for circulating levels of estradiol (multivariate relative risk [RR] = 1.91; 95% confidence interval [CI] = 1.06-3.46), estrone (multivariate RR = 1.96; 95% CI = 1.05-3.65), estrone sulfate (multivariate RR = 2.25; 95% CI = 1.23-4.12), and dehydroepiandrosterone sulfate (multivariate RR = 2.15; 95% CI = 1.11-4.17). We found no substantial associations with percent free or percent bioavailable estradiol, androstenedione, testosterone, or dehydroepiandrosterone. The positive relationships were substantially stronger among women with no previous hormone replacement therapy.Conclusion: Our data, in conjunction with past epidemiologic and animal studies, provide strong evidence for a causal relationship between postmenopausal estrogen levels and the risk of breast cancer. [ABSTRACT FROM AUTHOR]

Determines plasma hormone levels and its relation to alcohol consumption, height and adiposity among postmenopausal women. Samples and data used; Positive association of body mass index and alcohol use to postmenopausal plasma estrogen and estrone sulfate levels; Implications for breast cancer treatment.

Examines whether tubal ligation and hysterectomy affect subsequent risk of ovarian cancer. Prospective cohort study with 12 years of followup involving female registered nurses; Observance of inverse association between tubal ligation and ovarian cancer which persisted after adjustment for age, oral contraceptive use, parity and other ovarian risk factors.

Examines prospectively the association between cigarette smoking and the risk of cataract extraction in women. Conclusion that smoking appears to increase the risk of cataract extraction; The Nurses' Health Study; Cataract as an important cause of visual impairment worldwide; Relative risk of cataract smoking by smoking status; Analysis by specific type of cataract; More.

Considers how breast cancer is a major cause of mortality among women. Details of study which examines the relationship between body mass index (BMI) at the age of 18 years and at midlife with breast cancer incidence and mortality; Design; Setting; Main outcome measure; Results.

Reports on a study which tested whether high circulating insulin-like growth factor (IGF)-I would be associated with an increased risk of breast cancer. Methods; Finding that there was no association between IGF-I concentrations and breast-cancer risk in the whole study group; Interpretation of the findings.

Examines the association between the dietary intake of supplements and cataract extraction in women in the United States. Participation of female registered nurses in the study; Incidence of extraction of senile cataracts; Support of the findings to the antioxidant hypothesis of cataract prevention.

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

Background: Recent experimental work has shown that phthalates may increase inflammation. Prior research has not examined the role of exposure to phthalates in relation to inflammatory status among postmenopausal women who are at higher risk of developing inflammation-related chronic disorders.Objectives: We aimed to examine the associations of urinary phthalate biomarker concentrations with circulating levels of c-reactive protein [CRP] and interleukin-6 [IL-6] among 443 postmenopausal women selected into a breast cancer case-control study nested within the Women's Health Initiative (WHI).Methods: A total of 13 phthalate metabolites were measured in urine samples provided at WHI enrollment from 1993 to 1998. We also measured baseline levels of CRP and IL-6 in these women's serum or plasma samples. Multivariable linear models were used to investigate the role of each phthalate biomarker in relation to CRP and IL-6, adjusting for potential confounding factors and specifically evaluating the role of BMI.Results: In adjusted models we observed positive associations of monocarboxynonyl phthalate (MCNP) with CRP (β = 0.092; 95% CI 0.026, 0.158) and IL-6 (β = 0.108; 95% CI 0.013, 0.204). These positive associations were attenuated and non-significant, however, after further adjustment for body mass index (BMI). In contrast, we observed inverse associations of monoethyl phthalate (MEP) (β = -0.019; 95% CI -0.036, -0.001) and monobenzyl phthalate (MBzP) (β = -0.034; 95% CI -0.058, -0.010) with CRP levels only after adjustment for BMI. Other phthalate biomarkers examined were not significantly associated with either CRP or IL-6 levels.Conclusions: Overall, these results do not suggest an important role for phthalates in promoting an inflammatory response. Future prospective studies are warranted to improve understanding of these associations, particularly in clarifying the role of BMI. [ABSTRACT FROM AUTHOR]

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

The article presents a commentary on the study "Use of archived specimens in evaluation of prognostic and predictive biomarkers" published in a 2009 issue. It notes that evidence from nonrandomized studies is important in the clinical translation of biomarker research. It also notes the shortcomings of studies based on clinical trials and prospective observational studies. It points out a need to analyze for bias in the context of the studied association.

• Plasma metabolite profiles capture metabolic signatures of depression and anxiety. • Metabolomic profiles of chronic distress can predict future heart disease. • C-reactive protein mediates the metabolic path linking mental health to heart health. Chronic psychological distress is associated with increased risk of cardiovascular disease (CVD) and investigators have posited inflammatory factors may be centrally involved in these relationships. However, mechanistic evidence and molecular underpinnings of these processes remain unclear, and data are particularly sparse among women. This study examined if a metabolite profile linked with distress was associated with increased CVD risk and inflammation-related risk factors. A plasma metabolite-based distress score (MDS) of twenty chronic psychological distress-related metabolites was developed in cross-sectional, 1:1 matched case-control data comprised of 558 women from the Nurses' Health Study (NHS; 279 women with distress, 279 controls). This MDS was then evaluated in two other cohorts: the Women's Health Initiative Observational Cohort (WHI-OS) and the Prevención con Dieta Mediterránea (PREDIMED) trial. We tested the MDS's association with risk of future CVD in each sample and with levels of C-reactive protein (CRP) in the WHI-OS. The WHI-OS subsample included 944 postmenopausal women (472 CHD cases; mean time to event = 5.8 years); the PREDIMED subsample included 980 men and women (224 CVD cases, mean time to event = 3.1 years). In the WHI-OS, a 1-SD increase in the plasma MDS was associated with a 20% increased incident CHD risk (odds ratio [OR] = 1.20, 95% CI: 1.04 – 1.38), adjusting for known CVD risk factors excluding total and HDL cholesterol. This association was attenuated after including total and HDL cholesterol. CRP mediated an average 12.9% (95% CI: 4.9% – 28%, p < 10-15) of the total effect of MDS on CHD risk when adjusting for matching factors. This effect was attenuated after adjusting for known CVD risk factors. Of the metabolites in the MDS, tryptophan and threonine were inversely associated with incident CHD risk in univariate models. In PREDIMED, each one SD increase in the MDS was associated with an OR of 1.19 (95% CI: 1.00 – 1.41) for incident CVD risk, after adjusting all risk factors. Similar associations were observed in men and women. Four metabolites in the MDS were associated with incident CVD risk in PREDIMED in univariate models. Biliverdin and C36:5 phosphatidylcholine (PC) plasmalogen had inverse associations; C16:0 ceramide and C18:0 lysophosphatidylethanolamine (LPE) each had positive associations with CVD risk. Our study points to molecular alterations that may underlie the association between chronic distress and subsequent risk of cardiovascular disease in adults. [ABSTRACT FROM AUTHOR]

Editorial. Comments on a study which concluded an inverse association between total plasma carotenoids and subsequent risk of coronary heart disease. Caution against solely attributing beneficial effects of carotenoids to beta carotene; Differences in structures and biological properties of antioxidants; Assessment of specific food sources of carotenoids.

Objective: To prospectively examine whether the association between tubal ligation, hysterectomy, unilateral oophorectomy, and ovarian cancer varied by patient, tumor, and surgical characteristics.Design: Two prospective cohort studies (Nurses' Health Study and Nurses' Health Study II).Setting: Not applicable.Patient(s): A cohort of 121,700 married US female nurses, aged 30-55 years at baseline and another cohort of 116,430 US female nurses aged 25-42 years at baseline.Intervention(s): We obtained data on gynecologic surgeries and ovarian cancer incidence through biennial questionnaires. We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for known and suspected ovarian cancer risk factors.Main Outcome Measure(s): Confirmed incident epithelial ovarian cancer.Result(s): Overall, tubal ligation was associated with a decreased risk of ovarian cancer (HR, 0.76; 95% CI 0.64-0.90). The inverse association was stronger for nonserous tumors (HR, 0.57; 95% CI 0.40-0.82) and among women younger than 35 years at surgery (HR, 0.67; 95% CI 0.49-0.90). Hysterectomy was associated with a decreased risk of ovarian cancer (HR, 0.80; 95% CI 0.66-0.97) and was somewhat stronger for nonserous tumors (HR, 0.70; 95% CI 0.49-1.02). Unilateral oophorectomy was associated with a 30% lower risk (HR, 0.70; 95% CI 0.53-0.91), which did not differ by histologic subtype.Conclusion(s): Our study provides further support that tubal ligation reduces the risk of ovarian cancer, particularly for nonserous tumors and when conducted before the age of 35 years. The inverse association with hysterectomy, along with the stronger associations for nonserous tumors, supports shared biologic mechanisms for tubal ligation and hysterectomy. [ABSTRACT FROM AUTHOR]

Objective: To prospectively examine whether the association between tubal ligation, hysterectomy, unilateral oophorectomy, and ovarian cancer varied by patient, tumor, and surgical characteristics. Design: Two prospective cohort studies (Nurses' Health Study and Nurses' Health Study II). Setting: Not applicable. Patient(s): A cohort of 121,700 married US female nurses, aged 30–55 years at baseline and another cohort of 116,430 US female nurses aged 25–42 years at baseline. Intervention(s): We obtained data on gynecologic surgeries and ovarian cancer incidence through biennial questionnaires. We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for known and suspected ovarian cancer risk factors. Main Outcome Measure(s): Confirmed incident epithelial ovarian cancer. Result(s): Overall, tubal ligation was associated with a decreased risk of ovarian cancer (HR, 0.76; 95% CI 0.64–0.90). The inverse association was stronger for nonserous tumors (HR, 0.57; 95% CI 0.40–0.82) and among women younger than 35 years at surgery (HR, 0.67; 95% CI 0.49–0.90). Hysterectomy was associated with a decreased risk of ovarian cancer (HR, 0.80; 95% CI 0.66–0.97) and was somewhat stronger for nonserous tumors (HR, 0.70; 95% CI 0.49–1.02). Unilateral oophorectomy was associated with a 30% lower risk (HR, 0.70; 95% CI 0.53–0.91), which did not differ by histologic subtype. Conclusion(s): Our study provides further support that tubal ligation reduces the risk of ovarian cancer, particularly for nonserous tumors and when conducted before the age of 35 years. The inverse association with hysterectomy, along with the stronger associations for nonserous tumors, supports shared biologic mechanisms for tubal ligation and hysterectomy. [ABSTRACT FROM AUTHOR]

Background: Moderate to severe premenstrual syndrome (PMS) affects 8-20 percent of premenopausal women. Previous studies suggest that high dietary vitamin D intake may reduce risk. However, vitamin D status is influenced by both dietary vitamin D intake and sunlight exposure and the association of vitamin D status with PMS remains unclear.Methods: We assessed the relation of plasma 25-hydroxyvitamin D (25OHD), total calcium and parathyroid hormone levels with risk of PMS and specific menstrual symptoms in a case-control study nested within the prospective Nurses' Health Study II. Cases were 401 women free from PMS at baseline who developed PMS during follow-up (1991-2005). Controls were women not experiencing PMS (1991-2005), matched 1:1 with cases on age and other factors. Timed luteal phase blood samples were collected between 1996 and 1999 from cases and controls. We used conditional logistic regression to model the relation of 25OHD levels with risk of PMS and individual menstrual symptoms.Results: In analyses of all cases and controls, 25OHD levels were not associated with risk of PMS. However, results differed when the timing of blood collection vs. PMS diagnosis was considered. Among cases who had already been diagnosed with PMS at the time of blood collection (n = 279), 25OHD levels were positively associated with PMS, with each 10 nmol/L change in 25OHD associated with a 13% higher risk. Among cases who developed PMS after blood collection (n = 123), 25OHD levels were unrelated to risk of PMS overall, but inversely related to risk of specific menstrual symptoms. For example, each 10 nmol/L increase was associated with a significant 21% lower risk of breast tenderness (P = 0.02). Total calcium or parathyroid hormone levels were unrelated to PMS.Conclusions: 25OHD levels were not associated with overall risk of PMS. The positive association observed among women already experiencing PMS at the time of 25OHD measurement is likely due to confounding by indication related to use of dietary supplements to treat menstrual symptoms. Results from prospective analyses, which were less likely influenced by this bias, suggest that higher 25OHD levels may be inversely related to the development of specific menstrual symptoms. [ABSTRACT FROM AUTHOR]

Purpose: Although physical activity is an established risk factor for chronic disease prevention, the specific mechanisms underlying these relationships are poorly understood. We examined the associations between total activity counts and moderate-vigorous physical activity (MVPA) measured by accelerometer, and physical activity energy expenditure measured by doubly labeled water, with plasma levels of proinsulin, insulin, c-peptide, insulin growth factor binding protein-3, insulin growth factor-1, adiponectin, leptin, and leptin-sR. Methods: We conducted a cross-sectional analysis of 526 healthy US women in the Women's Lifestyle Validation Study, 2010 to 2012. We performed multiple linear regression models adjusting for potential lifestyle and health-related confounders to assess the associations between physical activity, measured in quartiles (Q) and biomarkers. Results: Participants in Q4 versus Q1 of total activity counts had lower proinsulin (-20%), c-peptide (-7%), insulin (-31%), and leptin (-46%) levels, and higher adiponectin (55%), leptin-sR (25%), and insulin growth factor-1 (9.6%) levels (all P trend ≤ 0.05). Participants in Q4 versus Q1 of MVPA had lower proinsulin (-26%), c-peptide (-7%), insulin (-32%), and leptin (-40%) levels, and higher adiponectin (31%) and leptin-sR (22%) levels (all P trend ≤ 0.05). Further adjustment for body mass index (BMI) attenuated these associations, but the associations with adipokines remained significant. Those in Q4 versus Q1 of physical activity energy expenditure had lower leptin (-21%) and higher leptin-sR (10%) levels (all P trend ≤ 0.05), after additional adjustment for BMI. In the sensitivity analysis, the associations were similar but attenuated when physical activity was measured using the subjective physical activity questionnaire. Conclusions: Our data suggest that greater physical activity is modestly associated with favorable levels of cardiometabolic and endocrine biomarkers, where the strongest associations were found with accelerometer-measured physical activity. These associations may be only partially mediated through BMI, further supporting the role of physical activity in the reduction of cardiometabolic and endocrine disease risk, independent of adiposity. [ABSTRACT FROM AUTHOR]

Few studies have assessed the association between endogenous steroid hormone levels and a subsequent diagnosis of endometriosis. We prospectively evaluated premenopausal plasma sex hormone levels and the risk of laparoscopically confirmed endometriosis in a nested case-control study within Nurses' Health Study II. Between blood collection (1996–1999) and 2009, we ascertained 446 women with incident endometriosis and matched them to 878 controls through risk-set sampling. We conducted multivariable conditional logistic regression accounting for matching and confounders to estimate relative risks (RRs) and 95% confidence intervals (CIs). Women with greater early follicular-phase total or free estradiol levels had a nonlinear increased risk of endometriosis (early follicular total estradiol: second quartile vs. first, RR = 2.23 (95% CI: 1.44, 3.47); third quartile, RR = 1.83 (95% CI: 1.16, 2.88); fourth quartile, RR = 1.68 (95% CI: 1.05, 2.68); early follicular free estradiol: second quartile vs. first, RR = 1.63 (95% CI: 1.05, 2.54); third quartile, RR = 2.02 (95% CI: 1.31, 3.12); fourth quartile, RR = 1.04 (95% CI: 0.66, 1.65)). Free testosterone assessed in quartile categories was not associated with endometriosis, although a threshold effect was observed, with a positive association among women in the top 2% of free testosterone levels. Levels of mid–luteal-phase total and free estradiol, follicular and luteal estrone, total testosterone, progesterone, and sex hormone binding globulin were not associated with endometriosis risk. These results support the role of sex steroids in endometriosis etiology, although the relationships suggest complex threshold effects. [ABSTRACT FROM AUTHOR]

Few prospective studies have examined associations between reproductive factors and risk of renal cell cancer (RCC). The authors prospectively examined whether postmenopausal hormone (PMH) use, oral contraceptive use, parity, and other reproductive factors were associated with RCC risk among 118,219 US women in the Nurses’ Health Study. A total of 247 RCC cases were confirmed between 1976 and 2004. Multivariate relative risks, adjusted for known risk factors, were calculated using Cox proportional hazards models. Compared with 1 or 2 childbirths, the multivariate relative risks were 1.75 (95% confidence interval (CI): 1.21, 2.53) for 4 childbirths and 1.50 (95% CI: 1.00, 2.23) for ≥5 childbirths (Ptrend = 0.02). Comparing an age at first birth of ≥28 years with an age at first birth of ≤22 years, the multivariate relative risk was 0.66 (95% CI: 0.43, 1.01; Ptrend = 0.01). Compared with 1–3 childbirths and an age at first birth of ≥26 years, the multivariate relative risk was 2.17 (95% CI: 1.49, 3.14) for ≥4 childbirths and an age at first birth of <26 years. No clear associations were observed for PMH use or duration, time since last PMH use, oral contraceptive use or duration, age at menarche, age at menopause, or history of hysterectomy or oophorectomy. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in order to reply to the comment on the article "Serum lipids, lipid-lowering drugs, and the risk of breast cancer," by A. H. Eliassen and colleagues in a 2005 issue.

Objective: Adverse pregnancy outcomes (APOs) and early menopause are each associated with increased risk of cardiovascular disease (CVD); whether APOs are associated with age at menopause is unclear. We examined the association of gestational diabetes (GDM), hypertensive disorders of pregnancy (HDP), preterm birth, and multiple gestation with age at natural menopause.Study Design: Observational, prospective study within the Nurses' Health Study II cohort (1989-2019).Main Outcomes Measures: Risk of early natural menopause, defined as occurring before the age of 45 years, and age at onset of natural menopause (hazard ratio (HR) >1 indicates younger age at menopause).Results: The mean [SD] baseline age of 69,880 parous participants was 34.5 [4.7] years. Compared with participants who had a term singleton first birth, those with a term multiple-gestation first birth had higher risk of early menopause (HR: 1.65, 95% CI: 1.05, 2.60) and younger age at natural menopause (HR: 1.46, 95% CI: 1.31, 1.63). Estimates for preterm multiple gestation were of similar magnitude. Menopause occurred at a younger age for those with a preterm birth with spontaneous labor (HR: 1.08, 95% CI: 1.03, 1.14) compared to those with a term birth with spontaneous labor. Conversely, estimates for GDM (HR: 0.95, 95% CI: 0.89, 1.02) and HDP (preeclampsia, HR: 0.93, 95% CI: 0.89, 0.97) suggested an association with older age at menopause.Conclusions: In this large cohort study, several statistically significant associations between APOs and age at natural menopause were observed. A deeper understanding of the relationships among APOs, menopause, and CVD is needed to help identify people at higher risk for early menopause and later CVD. [ABSTRACT FROM AUTHOR]

Objectives. To review the contribution of the Nurses' Heath Study (NHS) and the NHS II in identifying risk and protective factors for breast cancer incidence and survival. Methods. We conducted a narrative review of NHS and NHS II articles on breast cancer incidence and survival published from 1976 to 2016, with a focus on exogenous and endogenous hormones; lifestyle factors, including diet, physical activity, and aspirin use; intermediate markers of risk; and genetic factors. Results. With the investigation of individual risk factors, as well as their incorporation into risk prediction models, the NHS has contributed to the identification of ways in which women may reduce breast cancer risk, including limiting alcohol consumption, reducing the duration of postmenopausal estrogen-plus-progestin use, avoiding weight gain, and increasing vegetable consumption. In addition, the NHS has helped elucidate the roles of several biomarkers and contributed to the identification of risk alleles. Conclusions. The NHS has contributed to our understanding of lifestyle, hormonal, and genetic risk factors for breast cancer, highlighting the importance of exposures across the life course, and has helped identify lifestyle changes that may reduce risk and improve survival after a diagnosis of breast cancer. [ABSTRACT FROM AUTHOR]

Objectives. To summarize the overall impact of the Nurses' Health Study (NHS) over the past 40 years on the health of populations through its contributions on prevention, translation, and control. Methods. We performed a narrative review of the findings of the NHS, NHS II, and NHS3 between 1976 and 2016. Results. The NHS has generated significant findings about the associations between (1) smoking and type 2 diabetes, cardiovascular diseases, colorectal and pancreatic cancer, psoriasis, multiple sclerosis, and eye diseases; (2) physical activity and cardiovascular diseases, breast cancer, psoriasis, and neurodegeneration; (3) obesity and cardiovascular diseases, numerous cancer sites, psoriasis, multiple sclerosis, kidney stones, and eye diseases; (4) oral contraceptives and cardiovascular disease, melanoma, and breast, colorectal, and ovarian cancer; (5) hormone therapy and cardiovascular diseases, breast and endometrial cancer, and neurodegeneration; (6) endogenous hormones and breast cancer; (7) dietary factors and type 2 diabetes, cardiovascular diseases, breast and pancreatic cancer, non-Hodgkin's lymphoma, neurodegeneration, multiple sclerosis, kidney stones, and eye diseases; and (8) sleep and shift work and chronic diseases. Conclusions. The NHS findings have influenced public health policy and practice both locally and globally to improve women s health. [ABSTRACT FROM AUTHOR]