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Sex steroid hormones and inflammatory biomarkers are both associated with the development and progression of chronic diseases, but their interrelationship is relatively uncharacterized. We examined the association of sex hormones and sex hormone-binding globulin ( SHBG) with biomarkers of inflammation, C-reactive protein ( CRP) and white blood cell ( WBC) count. The study included data from 809 adult men in the National Health and Nutrition Examination Survey 1999-2004. Geometric means and 95% confidence intervals were estimated separately for CRP and WBC concentrations by sex steroid hormones and SHBG using weighted linear regression models. Higher concentrations of total (slope per one quintile in concentration, −0.18; p-trend, 0.001) and calculated free (slope, −0.13; p-trend, 0.03) testosterone were statistically significantly associated with lower concentrations of CRP, but not with WBC count. Men in the bottom quintile of total testosterone (≤3.3 ng/mL), who might be considered to have clinically low testosterone, were more likely to have elevated CRP (≥3 mg/L) compared with men in the top four quintiles (OR, 1.61; 95% CI, 1.00-2.61). Total and calculated free estradiol (E2) were positively associated with both CRP (Total E2: slope, 0.14; p-trend, <0.001; Free E2: slope, 0.15; p-trend, <0.001) and WBC (Total E2: slope, 0.02; p-trend, 0.08; Free E2: slope, 0.02; p-trend, 0.02) concentrations. SHBG concentrations were inversely associated with WBC count (slope, −0.03; p-trend, 0.04), but not with CRP. These cross-sectional findings are consistent with the hypothesis that higher androgen and lower oestrogen concentrations may have an anti-inflammatory effect in men. [ABSTRACT FROM AUTHOR]

Previous studies suggest that male testosterone concentrations have declined over time. To explore this in a large US population, we examined testosterone and free testosterone concentrations in National Health and Nutrition Examination Surveys (NHANES) from 1988-1991 and 1999-2004. We also examined sex hormone-binding globulin (SHBG), estradiol, and androstanediol glucuronide (3α-diol-G) over the same period. Non-Hispanic white, non-Hispanic black, and Mexican-American men from 1988-1991 and 1999-2004 NHANES surveys who were ≥20 years old and had serum from morning blood draws were included in this analysis (1988-1991: N = 1,413; 1999-2004: N = 902). Testosterone, estradiol and SHBG were measured by competitive electrochemiluminescence immunoassays and 3α-diol-G was measured by enzyme immunoassay. Free testosterone was calculated using testosterone and SHBG values. Adjusted mean hormone concentrations were estimated using linear regression, accounting for NHANES sampling weights and design, age, race/ethnicity, body mass index, waist circumference, alcohol use and smoking. Differences in adjusted mean concentrations (Δ) and two-sided p-values were calculated; p < 0.05 was statistically significant. Overall, 3α-diol-G and estradiol declined between 1988-1991 and 1999-2004, but there was little change in testosterone, free testosterone, or SHBG (Δ: 3α-diol-G = −1.83 ng/mL, p < 0.01; estradiol = −6.07 pg/mL, p < 0.01; testosterone = −0.03 ng/mL, p = 0.75; free testosterone = −0.001 ng/mL, p = 0.67; SHBG = −1.17 nmol/L, p = 0.19). Stratification by age and race revealed that SHBG and 3α-diol-G declined among whites 20-44 years old (Δ: SHBG = −5.14 nmol/L, p < 0.01; 3α-diol-G = −2.89 ng/mL, p < 0.01) and free testosterone increased among blacks 20-44 years old (Δ: 0.014 ng/mL, p = 0.03). Estradiol declined among all ages of whites and Mexican-Americans. In conclusion, there was no evidence for testosterone decline between 1988-1991 and 1999-2004 in the US general population. Subgroup analyses suggest that SHBG and 3α-diol-G declined in young white men, estradiol declined in white and Mexican-American men, and free testosterone increased in young black men. These changes may be related to the increasing prevalence of reproductive disorders in young men. [ABSTRACT FROM AUTHOR]

Population monitoring of lifestyle behaviours that are crucial as risk and protective factors for major chronic diseases is vital for the identification of priority areas for public health. In this study, we aimed to investigate the prevalence of adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) cancer prevention recommendations in Switzerland, overall and by selected sociodemographic and lifestyle characteristics. Data from the population-based, cross-sectional survey menuCH were used. We constructed a score reflecting adherence to the 2018 WCRF/AICR cancer prevention recommendations. Multinomial logistic regression models were fitted to investigate the association of sociodemographic and lifestyle characteristics with the level of adherence to the WCRF/AICR cancer prevention recommendations. The least frequently met cancer prevention recommendations were the ones on fibre intake (met by 13·7 %), red and processed meat (25·4 %), and ultra-processed food (33·3 %) consumption, while the recommendation on physical activity was met by almost 80 %. Women and individuals with tertiary education were more likely to have a score of ≥ 5 (as a reflection of adherence to the cancer prevention recommendations), compared with men or those who completed secondary education, respectively. Current smokers were less likely to have a score of ≥ 5, compared with never smokers. A high proportion of the population in Switzerland was found to not adhere closely to the WCRF/AICR cancer prevention recommendations. Differences were detected based on sociodemographic characteristics. Education and policy actions are needed to facilitate the adoption of a cancer-protective lifestyle.

Objectives: The World Cancer Research Fund (WCRF) and the American Institute for Cancer Research (AICR) established 10 lifestyle recommendations for cancer prevention. The current study examines the proportion and changes over 25 years of adherence to these recommendations and their determinants in Switzerland., Methods: On the basis of six Swiss Health Surveys (1992-2017, N = 110 478), an index reflecting adherence to the 2018 WCRF/AICR cancer-prevention recommendations was created. Multinomial logistic regression models were fitted to investigate changes over time and determinants of a cancer-protective lifestyle., Results: Adherence to cancer-prevention recommendations was moderate and higher in the years 1997-2017 compared to 1992. Higher adherence was observed among women (odds ratio [OR]high vs. low adherence ranging from 3.31 to 3.74) and participants with a tertiary education level (ORhigh vs. low adherence ranging from 1.71 to 2.18), and lower adherence among participants of the oldest age group (ORhigh vs. low adherence ranging from 0.28 to 0.44) and participants of the Switzerland (lat.: Confoederatio helvetica)-French language regions (ORhigh vs. low adherence ranging from 0.53 to 0.73)., Conclusion: Our results showed that cancer-prevention recommendations are not well followed by the general Swiss population, as the adherence to a cancer-protective lifestyle was generally moderate; however, adherence to cancer-prevention recommendations improved over the past 25 years. Sex, age group, education level, and language regions were significant determinants of adherence to a cancer-protective lifestyle. Further actions at the governmental and individual levels promoting the adoption of a cancer-protective lifestyle are needed., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

A health-conscious lifestyle may protect against breast cancer in situ. However, breast cancer in situ is mainly detected by screening, and many studies lack information on screening participation. Thus, we evaluated the association between prediagnostic lifestyle and risk of breast cancer in situ, accounting for screening participation at recruitment. A score reflecting the adherence to the World Cancer Research Fund/American Institute for Cancer Research cancer prevention recommendations was constructed, using the recommendations on healthy body weight, physical activity, consumption of plant-based foods, red and processed meat, alcohol and avoidance of sugar. Cox proportional hazards regression models were used to investigate the association between the lifestyle score and breast cancer in situ risk, while accounting for important confounders. The lifestyle score was not significantly associated with breast cancer in situ risk (HR continuous  = 0.96, 95% CI = 0.91-1.03) in the overall cohort. In participants not reporting dietary changes in the past 5 years, the lifestyle score was inversely associated with breast cancer in situ risk (HR continuous  = 0.92, 95% CI = 0.85-0.99). In those reporting dietary changes in the past 5 years due to illness or other reasons, the lifestyle score was not associated with breast cancer in situ risk (HR continuous  = 1.04, 95% CI = 0.94-1.15). Lifestyle was inversely associated with breast cancer in situ risk in women not reporting recent changes in their dietary habits. This inverse association is consistent with inverse associations reported in previous studies. Our findings suggest that breast cancer in situ and invasive breast cancer share a similar risk factor profile., (© 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Purpose: Testosterone (T) plays an important role in men's health and its deficiency is linked with poorer health. However, the role of nutritional and lifestyle factors in T regulation and production remains unclear. The objectives are to comprehensively test the cross-sectional associations of nutritional and lifestyle factors with T deficiency and to validate the associations in the NHANES survey., Methods: We performed weighted multivariable logistic regression analysis to examine the association of 173 nutritional and lifestyle factors with T deficiency (total testosterone ≤ 3.5 ng/mL) in NHANES III as the discovery set (mean age 41). We controlled for multiple comparisons with a false discovery rate (FDR) < 5% and replicated in NHANES 1999-2004 (mean age 44)., Results: We identified seven nutritional factors as being inversely associated with T deficiency in NHANES 1999-2004, namely dietary intake of vitamin A, protein, saturated fatty acids, monounsaturated fatty acids, total fats, saturated fatty acid 16:0, and phosphorus. In a multivariable model, only vitamin A intake remained significantly associated with T deficiency (OR 0.97, 95% CI 0.94-0.99). Principal component analysis suggested that the two principal components, (1) dietary fats, protein, and phosphorous and (2) total vitamin A, may be associated with T deficiency., Conclusion: Our systematic evaluation provided new insight into the modifiable factors that could play a role in the regulation of T production. This study has the potential to contribute to the current body of literature which seeks to formulate a clinical definition of T deficiency after taking into account nutritional and lifestyle factors.

Coffee consumption has been inversely associated with various diseases; however, the underlying mechanisms are not entirely clear. We used data of 17,752 Third National Health and Nutrition Examination Survey participants to investigate the association of 245 metabolites, nutrients, and lifestyle factors with coffee consumption. We used data from the first phase ( n = 8825) to identify factors with a false discovery rate of <5%. We then replicated our results using data from the second phase ( n = 8927). Regular coffee consumption was positively associated with active and passive smoking, serum lead and urinary cadmium concentrations, dietary intake of potassium and magnesium, and aspirin intake. In contrast, regular coffee consumption was inversely associated with serum folate and red blood cell folate levels, serum vitamin E and C, and beta-cryptoxanthin concentrations, Healthy Eating Index score, and total serum bilirubin. Most of the aforementioned associations were also observed for caffeinated beverage intake. In our assessment of the association between coffee consumption and selected metabolites, nutrients, and lifestyle factors, we observed that regular coffee and caffeinated beverage consumption was strongly associated with smoking, serum lead levels, and poorer dietary habits., Competing Interests: The authors declare no conflict of interest.

Background: Even though in situ breast cancer (BCIS) accounts for a large proportion of the breast cancers diagnosed, few studies have investigated potential risk factors for BCIS. Their results suggest that some established risk factors for invasive breast cancer have a similar impact on BCIS risk, but large population-based studies on lifestyle factors and BCIS risk are lacking. Thus, we investigated the association between lifestyle and BCIS risk within the European Prospective Investigation into Cancer and Nutrition cohort., Methods: Lifestyle was operationalized by a score reflecting the adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) cancer prevention recommendations. The recommendations utilized in these analyses were the ones pertinent to healthy body weight, physical activity, consumption of plant-based foods, energy-dense foods, red and processed meat, and sugary drinks and alcohol, as well as the recommendation on breastfeeding. Cox proportional hazards regression was used to assess the association between lifestyle score and BCIS risk. The results were presented as hazard ratios (HR) and corresponding 95% confidence intervals (CI)., Results: After an overall median follow-up time of 14.9 years, 1277 BCIS cases were diagnosed. Greater adherence to the WCRF/AICR cancer prevention recommendations was not associated with BCIS risk (HR = 0.98, 95% CI 0.93-1.03; per one unit of increase; multivariable model). An inverse association between the lifestyle score and BCIS risk was observed in study centers, where participants were recruited mainly via mammographic screening and attended additional screening throughout follow-up (HR = 0.85, 95% CI 0.73-0.99), but not in the remaining ones (HR = 0.99, 95% CI 0.94-1.05)., Conclusions: While we did not observe an overall association between lifestyle and BCIS risk, our results indicate that lifestyle is associated with BCIS risk among women recruited via screening programs and with regular screening participation. This suggests that a true inverse association between lifestyle habits and BCIS risk in the overall cohort may have been masked by a lack of information on screening attendance. The potential inverse association between lifestyle and BCIS risk in our analyses is consistent with the inverse associations between lifestyle scores and breast cancer risk reported from previous studies.

Background: Given the recent findings from pooled studies about a potential inverse association between selenium levels and prostate cancer risk, this cross-sectional study aimed to investigate the association between serum selenium and serum concentrations of sex steroid hormones including estradiol in a nationally representative sample of U.S. men to investigate one mechanism by which selenium may influence prostate cancer risk., Methods: The study included 1,420 men ages 20 years or older who participated in the Third National Health and Nutrition Examination Survey between 1988 and 1994. We calculated age/race-ethnicity-adjusted and multivariable-adjusted geometric mean serum concentrations of total and estimated free testosterone and estradiol, androstanediol glucuronide, and sex hormone binding globulin, and compared them across quartiles of serum selenium., Results: Adjusting for age, race/ethnicity, smoking status, serum cotinine, household income, physical activity, alcohol consumption, and percent body fat, mean total estradiol [e.g., Q1, 38.00 pg/mL (95% confidence interval (CI), 36.03-40.08) vs. Q4, 35.29 pg/mL (95% CI, 33.53-37.14); P trend = 0.050] and free estradiol [e.g., Q1, 0.96 pg/mL (95% CI, 0.92-1.01) vs. Q4, 0.90 (95% CI, 0.85-0.95); P trend = 0.065] concentrations decreased over quartiles of selenium. Stratification by smoking and alcohol consumption, showed that the latter observation was stronger for never smokers ( P interaction = 0.073) and those with limited alcohol intake ( P interaction = 0.017). No associations were observed for the other sex steroid hormones studied., Conclusions: Our findings suggests that a possible mechanism by which selenium may be protective for prostate cancer is related to estrogen., Impact: Further studies of longitudinal measurements of serum and toenail selenium in relation to serum measurements of sex steroid hormones are needed., (©2018 American Association for Cancer Research.)

Background: By modulating the levels of sex steroid hormones and sex hormone-binding globulin (SHBG), caffeine could be a factor in the development of several conditions in men, including prostate cancer. The aim of this study was to evaluate if caffeine consumption is associated with concentrations of sex steroid hormones and SHBG in men., Methods: 1,410 men aged 20 + years who attended the morning examination session of the Third National Health and Nutrition Examination Survey (1988-1991) were included in the analysis. Coffee and soft drink consumption was assessed using a food frequency questionnaire. Daily caffeine intake was estimated by multiplying caffeine content per cup times the daily frequency of coffee, tea, or soft drink consumption. Serum levels of hormones and SHBG were measured by immunoassay. Associations of frequency of beverage consumption or estimated caffeine intake with hormone levels were examined using multivariable linear regression., Results: Coffee consumption was positively associated with SHBG concentration (p = 0.045) taking lifestyle factors into account, but mutually adjusting for testosterone and estradiol attenuated the association; no association with SHBG was observed for soft drink consumption or caffeine intake. No associations between caffeinated beverage consumption and androgen or estrogen concentrations were observed., Conclusion: Men who drink coffee more frequently may have higher circulating SHBG concentration, but there were no consistent associations for soft drinks or caffeine intake.

Background: Evidence relating heterocyclic aromatic amines (HCA), associated with high-temperature cooking methods, to prostate cancer risk is inconsistent., Methods: In a large U.S. cohort study, intakes of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and a meat-derived mutagenicity (MDM) index were assessed using a cooking method questionnaire administered in 1996. Until 2010, 2,770 prostate cancer cases were observed among 26,030 participants., Results: Intake of PhIP from red meat was statistically significantly associated with total prostate cancer risk (top vs. bottom quintile HR, 1.18; 95% confidence intervals; CI, 1.03-1.35), but not other HCAs (MeIQx, 1.12; 0.98-1.27, PhIP from white meat, 1.08; 0.95-1.22, DiMeIQx, 1.09; 0.97-1.21) or MDM (1.13; 1.00-1.28). For high-grade (Gleason sum 7 with pattern 4+3 and Gleason sum 8-10, n = 483 cases) and advanced cancers (n = 281), we only observed positive associations for PhIP from red meat (top vs. bottom quintile: high grade: HR, 1.44; 95% CI, 1.04-1.98, Ptrend = 0.03; advanced: HR, 1.50; 95% CI, 0.99-2.26; Ptrend = 0.12), but associations for advanced cancers did not reach statistical significance. Observed associations remained similar after adjustment for total, unprocessed, or processed red meat intake., Conclusion: Observed positive associations between PhIP intake from red meat and prostate cancer, particularly high-grade and possibly also advanced prostate cancer, need to be confirmed in other studies., Impact: Results do not provide strong evidence that HCAs increase risk of prostate cancers., (©2015 American Association for Cancer Research.)

The aim was to examine the capacity of commonly used type 2 diabetes mellitus (T2DM) risk scores to predict overall mortality. The US-based NHANES III (n = 3138; 982 deaths) and the Swiss-based CoLaus study (n = 3946; 191 deaths) were used. The predictive value of eight T2DM risk scores regarding overall mortality was tested. The Griffin score, based on few self-reported parameters, presented the best (NHANES III) and second best (CoLaus) predictive capacity. Generally, the predictive capacity of scores based on clinical (anthropometrics, lifestyle, history) and biological (blood parameters) data was not better than of scores based solely on clinical self-reported data. T2DM scores can be validly used to predict mortality risk in general populations without diabetes. Comparison with other scores could further show whether such scores also suit as a screening tool for quick overall health risk assessment., (© The Author 2014. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.)

Purpose: Chronic inflammation has been implicated in the etiology of various chronic diseases. We previously found that certain urinary isoflavones are associated with markers of inflammation. In the present study, we examined the associations of serum C-reactive protein (CRP) and white blood cell (WBC) count with lignans, which are more frequent in the Western diet than isoflavones., Methods: Our analysis included 2,028 participants of NHANES 2005-2008 and 2,628 participants of NHANES 1999-2004 aged 18 years and older. The exposures of interest were urinary mammalian lignans (enterodiol and enterolactone). Outcome variables were two inflammatory markers (CRP [≤10 mg/L] and WBC [≥3.0 and ≤11.7 (1,000 cells/μL)]). Log-transformed CRP concentration and WBC count by log-transformed creatinine-standardized concentrations of mammalian lignans were used for linear regression., Results: Statistically significant inverse associations of urinary lignan, enterodiol, and enterolactone concentrations with circulating CRP and WBC counts were observed in the multivariate-adjusted models: In NHANES 2005-2008, per one-percent increase in lignan concentrations in the urine, CRP concentrations and WBC counts decreased by 8.1 % (95 % CI -11.5, -4.5) and 1.9 % (95 % CI -2.7; -1.2), respectively. Per one-percent increase in enterodiol and enterolactone, WBC counts decreased by 2.1 % (95 % CI -2.8, -1.3) and 1.3 % (95 % CI -1.9, -0.6), respectively. In NHANES 1999-2004, analogous results were 3.0 % (95 % CI -5.6, -0.3), 1.2 % (95 % CI -2.0; -0.4), 1.0 % (95 % CI -1.8, -0.2), and 0.8 % (95 % CI -1.4, 0.2)., Conclusions: Mammalian lignans were inversely associated with markers of chronic inflammation. Due to the cross-sectional design, our findings require confirmation in prospective studies.

Purpose: Sex steroid hormone concentrations and insulin-like growth factor (IGF) proteins have been independently associated with risk of cancer, chronic diseases, and mortality. However, studies that evaluated the inter-relation between the sex hormones and IGF pathways have provided mixed results. We examined the association between endogenous sex hormones and sex hormone-binding globulin (SHBG) with IGF-1 and IGF-binding protein 3 (IGFBP-3) in a population-based sample of US men., Methods: Data from 1,135 men aged 20 years or older participating in the third National Health and Nutrition Examination Survey (NHANES III) were analyzed. Weighted linear regression was used to estimate geometric means and 95 % confidence intervals for IGF-1 and IGFBP-3 concentrations by sex steroid hormones and SHBG after adjusting for age, race/ethnicity, body mass index, waist circumference, alcohol consumption, cigarette smoking, physical activity, diabetes, and mutually adjusting for other sex hormones and SHBG., Results: No significant association was observed between sex steroid hormones, SHBG, and IGF-1 concentrations. Total estradiol (% difference in Q5 - Q1 geometric means -9.7 %; P-trend 0.05) and SHBG (% difference -7.3 %; P-trend 0.02) were modestly inversely associated with IGFBP-3. Total testosterone was modestly inversely associated with IGFBP-3 (% difference -6.2 %; P-trend 0.01), but this association disappeared after adjustment for total estradiol and SHBG (% difference 2.6 %; P-trend 0.23). Androstanediol glucuronide was not associated with IGFBP-3., Conclusions: These findings suggest that there may be inter-relationships between circulating total estradiol, SHBG, and IGFBP-3 concentrations. Future research may consider these inter-relationships when evaluating potential joint effects of the sex hormones and IGF pathways.

Purpose: The aim of this study was to determine the association between urinary isoflavonoid (genistein, daidzein, and the daidzein metabolites O-desmethylangolensin (O-DMA) and equol) excretion and markers of inflammation in adults in the United States in National Health and Nutrition Examination Survey (NHANES) 2005-2008., Methods: The NHANES is a cross-sectional study conducted by the National Center for Health Statistics to study the health and nutritional status of people living in the United States. The analysis included 1,683 participants from study years 2005-2008 for whom urinary isoflavonoids were measured and who met inclusion criteria. Urinary isoflavonoids were measured by HPLC-APPI-MS/MS. Serum C-reactive protein (CRP) was measured by latex-based nephelometry. White blood cell (WBC) count was measured by Coulter counting. Multivariable linear regression was used to calculate the geometric mean values of the markers, and multivariable logistic regression was used to estimate the odds of high CRP (≥3 mg/L) and of high WBC count (≥7,900/μL) by quartile of urinary isoflavonoid (nmol/mg creatinine)., Results: The highest quartile of genistein (OR = 0.62; 95 % CI 0.39-0.99) was associated with significantly decreased odds of high CRP compared with the lowest quartile. The sum of daidzein and its metabolites was significantly inversely associated with serum CRP concentration (p-trend = 0.017). Equol was inversely associated with WBC count (p-trend < 0.0001). O-DMA was the only isoflavonoid whose excretion was significantly associated with a decrease in both CRP (p-trend = 0.024) and WBC count (p-trend < 0.0001)., Conclusions: Though no clear pattern emerged, higher excretion of certain soy isoflavonoids was associated with decreased CRP concentration and WBC counts, suggesting a possible inverse association between soy intake and inflammation.

Background/objectives: There is growing evidence that meat consumption is associated with total and cause-specific mortality. Our objective was to evaluate the association of meat intake and the healthy eating index (HEI) with total mortality, cancer and cardiovascular disease (CVD) mortality., Subjects/methods: Analyses are based on 17, 611 participants from Third National Health and Nutrition Examination Survey (NHANES III) (1986-2010). Meat intake was assessed using a food frequency questionnaire administrated at baseline. Adherence to the HEI was analyzed with a single 24-h dietary recall. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of mortality according to five categories of meat consumption and three categories of the HEI score., Results: During the follow-up period, 3683 deaths occurred, of which 1554 were due to CVD and 794 due to cancer. After multivariable adjustment, neither red and processed meat, nor white meat consumption were consistently associated with all-cause or cause-specific mortality. In men, white meat consumption tended to be inversely associated with total mortality (P for trend=0.02), but there was no such association among women. Significantly decreased mortality was observed in the top compared with the bottom third of the HEI score (HR=0.70, 95% CI 0.52-0.96). This association was only observed in men, but not in women., Conclusions: Meat consumption was not associated with mortality. A healthy diet according to HEI, however, was associated with a decreased total mortality in men, but not in women.

Background: Recently, some US cohorts have shown a moderate association between red and processed meat consumption and mortality supporting the results of previous studies among vegetarians. The aim of this study was to examine the association of red meat, processed meat, and poultry consumption with the risk of early death in the European Prospective Investigation into Cancer and Nutrition (EPIC)., Methods: Included in the analysis were 448,568 men and women without prevalent cancer, stroke, or myocardial infarction, and with complete information on diet, smoking, physical activity and body mass index, who were between 35 and 69 years old at baseline. Cox proportional hazards regression was used to examine the association of meat consumption with all-cause and cause-specific mortality., Results: As of June 2009, 26,344 deaths were observed. After multivariate adjustment, a high consumption of red meat was related to higher all-cause mortality (hazard ratio (HR) = 1.14, 95% confidence interval (CI) 1.01 to 1.28, 160+ versus 10 to 19.9 g/day), and the association was stronger for processed meat (HR = 1.44, 95% CI 1.24 to 1.66, 160+ versus 10 to 19.9 g/day). After correction for measurement error, higher all-cause mortality remained significant only for processed meat (HR = 1.18, 95% CI 1.11 to 1.25, per 50 g/d). We estimated that 3.3% (95% CI 1.5% to 5.0%) of deaths could be prevented if all participants had a processed meat consumption of less than 20 g/day. Significant associations with processed meat intake were observed for cardiovascular diseases, cancer, and 'other causes of death'. The consumption of poultry was not related to all-cause mortality., Conclusions: The results of our analysis support a moderate positive association between processed meat consumption and mortality, in particular due to cardiovascular diseases, but also to cancer.

Aim: The aim of this study is to evaluate racial variation in umbilical cord blood concentration of vitamin D and to explore its correlation with markers of the insulin-like growth factor axis (IGFs) and sex steroid hormones in white and black male neonates., Methods: In 2004-2005, venous umbilical cord blood samples were collected from 75 black and 38 white male neonates, along with maternal and birth characteristics from two hospitals in Maryland, United States. 25-Hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)(2)D] were measured by radioimmunoassay and testosterone, estradiol, and sex hormone-binding globulin (SHBG) by immunoassay and IGF-1, IGF-2, and IGF-binding protein-3 by ELISA. Crude and multivariable-adjusted geometric mean concentrations were computed., Results: Mean 25(OH)D levels were lower in black than in white neonates (11.44; 95 % CI 10.10-12.95 ng/mL vs. 18.24; 95 % CI 15.32-21.72 ng/mL; p < 0.0001). Black neonates were at higher risk of suboptimal vitamin D levels [25(OH)D < 20 ng/mL] than whites (84 vs. 63 %). 25(OH)D concentrations varied by season in whites but not in blacks and were significantly inversely correlated with mother's parity (number of live births) in blacks but not in whites. Mean concentration of 1,25(OH)(2)D did not differ by race. 25(OH)D and 1,25(OH)(2)D did not correlate with IGFs, sex steroid hormones, and SHBG., Conclusions: Suboptimal vitamin D levels were prevalent especially in blacks and influenced by mother's parity and by season. The observed vitamin D differences between black and white neonates warrant further evaluation of the etiology of the disparity in chronic diseases in adulthood.

Objective: To determine whether frailty is associated with circulating total and free testosterone, total and free estradiol, and sex hormone-binding globulin (SHBG) in older men., Methods: With NHANES III data of 461 men aged 60 years and older, we used logistic regression to analyze the associations between serum concentrations of sex steroid hormones, SHBG and frailty. Participants meeting any three or more of the five frailty criteria were classified as "frail", all others were considered as non-frail., Results: 2.5% of men were frail. Men with SHBG ≥66 nmol/L had three times the odds of frailty (OR = 2.97; 95% CI 1.28-6.86) compared to men with SHBG <66 nmol/L. Men with free testosterone levels below 243 pmol/L had an increased odds of frailty (OR = 3.92; 95% CI 1.29-11.89). None of these associations was statistically significant after additionally adjusting for body mass index, smoking and history of cardiovascular diseases (CVD). Total testosterone, and total and free estradiol serum levels were not statistically significantly associated with frailty., Conclusions: In this US nationally representative study of older men, low free testosterone and high SHBG serum levels were associated with a significantly increased odds of frailty after adjustment for age and race/ethnicity. These associations may, however, be explained by confounding due to obesity, smoking, and the higher prevalence of CVD in frail men or by low hormones or high SHBG mediating the association between obesity, smoking, CVD and frailty.

Background: A score based on serum concentrations of C-reactive protein (CRP), albumin, gamma-glutamyl transferase (GGT), and HDL cholesterol was positively associated with death from cancer, circulatory disease, and all-cause mortality. We replicated this in the third National Health and Nutrition Examination Survey (NHANES III), a US nationally representative survey conducted between 1988-1994., Methods: Baseline measurements of CRP, albumin, GGT, and HDL were available for participants with mortality follow-up (n=13,056). A biomarker score, ranging 0-4, was created by adding number of markers with abnormal values (cut-off: CRP>10mg/L, albumin<35mg/L, GGT>36U/L, HDL<1.04mmol/L). Its association with mortality was analyzed with multivariate Cox proportional hazards models., Results: The score was positively associated with death from all causes, cancer and circulatory disease [e.g. HR all-cause mortality: 1.21 (95% CI: 1.09, 1.35), 1.92 (1.67, 2.20), 3.38 (2.62, 4.36), and 7.93 (5.77, 10.89), for score 1, 2, 3, 4 vs.0]. These patterns were found across the Charlson Comorbidity Index (CCI). Where CCI =3, risk of cancer death was 1.09 (0.93, 1.28), 1.81 (1.43, 2.29), 4.67 (3.05, 7.14), and 6.97 (5.32, 9.14) for score 1, 2, 3, 4 vs. 0. No effect-modification by sex or race/ethnicity was observed., Conclusions: These findings correlate with results from a Swedish study. This biomarker-based score could help clinicians make decisions in prevention and disease management.

Purpose: To evaluate whether there is racial variation in venous umbilical cord blood concentrations of sex steroid hormones and the insulin-like growth factor (IGF) axis between female African-American and white neonates., Methods: Maternal and birth characteristics and venous umbilical cord blood samples were collected from 77 African-American and 41 white full-term uncomplicated births at two urban hospitals in 2004 and 2005. Cord blood was measured for testosterone, dehydroespiandrosterone-sulfate, estradiol, and sex steroid hormone-binding globulin (SHBG) by immunoassay. IGF-1, IGF-2, and IGF-binding protein-3 (IGFBP-3) were measured by ELISA. Crude and multivariable-adjusted geometric mean concentrations were computed for the hormones., Results: African-American neonates weighed less at birth (3,228 g vs. 3,424 g, p < 0.004) than whites. Birth weight was positively correlated with IGF-1, IGFBP-3, and the molar ratio of IGF-1 to IGFBP-3, but inversely correlated with the molar ratio of IGF-2 to IGFBP-3. Adjusted models showed higher testosterone (1.82 ng/ml vs. 1.47 ng/ml, p = 0.006) and the molar ratio of testosterone to SHBG (0.42 vs. 0.30, p = 0.03) in African-American compared to white female neonates. IGF-1, IGF-2, and IGFBP-3 were lower in African-American compared to white female neonates, but only the difference for IGF-2 remained significant (496.5 ng/ml vs. 539.2 ng/ml, p = 0.04)., Conclusion: We provide evidence of racial variation in cord blood testosterone and testosterone to SHBG in African-American compared to white female neonates, and higher IGF-2 in white compared to African-American female neonates. Findings suggest plausible explanations for a prenatal influence on subsequent breast cancer risk and mortality. Further work is needed to confirm these observations.

Background: Physiologic processes during ageing leading to multi-morbidity and diseases that increase risk of premature death may be influenced by ageing-associated changes in endogenous hormone production., Objective: To evaluate the decline in sex steroid hormone levels across age and estimate the number of US men 40+ years old who may have low hormone levels., Design: We measured serum testosterone, oestradiol and sex hormone binding globulin by immunoassay in 1351 men 20+ years old in Third National Health and Nutrition Examination Survey. We estimated free hormones by mass action., Results: Free testosterone declined most rapidly with age (a 2% decline in geometric mean concentration occurred after ageing 1·3 years), followed by total testosterone (2·4 years), free oestradiol (4·1 years) and total oestradiol (8·1 years). These hormone changes with age translated into 25·0% and 30·2% of men 70+ years old having low total (which we defined as <10·4 nm) and free (<0·17 nm) testosterone, respectively, and 8·3% and 23·9% having low total (<73·4 pm) and free (<2·2 pm) oestradiol. Using population size projections between the 2000 and 2010 Censuses, we estimated that 8·4 (95% CI 4·7-12·2), 6·2 (3·1-9·2) and 6·0 (3·1-9·0) million men 40+ years old may have low total testosterone, free testosterone and free oestradiol, respectively. The prevalences were only modestly lower in men without prevalent chronic diseases., Conclusion: Although no consensus exists for defining low hormone levels in ageing men, a substantial number of US men may have low sex steroid hormone levels, possibly putting them at risk for adverse health consequences and premature death., (© 2011 Blackwell Publishing Ltd.)

Objective: Obesity is associated with a variety of chronic diseases, including cancer, which may partly be explained by its influence on sex steroid hormone concentrations. Whether different measures of obesity, i.e., body mass index (BMI), waist circumference, and percent body fat were differentially associated with circulating levels of sex steroid hormones was examined in 1,265 men, aged 20-90+ years old, attending the morning examination session of the Third National Health and Nutrition Examination Survey (NHANES III)., Materials and Methods: Serum hormones were measured by immunoassay. Weight, height, and waist circumference were measured by trained staff. Percent body fat was estimated from bioelectrical impedance. Multivariate linear regression was used to estimate associations between body fatness measures and hormone levels., Results: Total and free testosterone and sex hormone binding globulin concentrations decreased, whereas total and free estradiol increased with increasing BMI, waist circumference, and percent body fat (all p trend < 0.05). The magnitude of change in these hormones was similar for a one-quartile increase in each body fatness measure., Conclusion: Measured BMI, waist circumference, and percent body fat led to similar inferences about their association with hormone levels in men.

The association of sex hormone levels with mortality over a median of 16 years of follow-up was evaluated in a prospective cohort study. The study included 1,114 US men who participated in phase 1 (1988-1991) of the Third National Health and Nutrition Examination Survey Mortality Study and had no history of cardiovascular disease or cancer at baseline. Multivariable adjusted hazard ratios for all-cause mortality associated with a decrease in hormone concentration equal to the difference between the 90th and 10th percentiles of the sex hormone distributions were estimated by using proportional hazards regression. The hazard ratios associated with low free testosterone and low bioavailable testosterone levels were 1.43 (95% confidence interval (CI): 1.09, 1.87) and 1.52 (95% CI: 1.15, 2.02), respectively, for follow-up between baseline and year 9; they were 0.94 (95% CI: 0.51, 1.72) and 0.98 (95% CI: 0.56, 1.72), respectively, for follow-up between year 9 and year 18. Men with low free and bioavailable testosterone levels may have a higher risk of mortality within 9 years of hormone measurement. Future studies should be conducted to fully characterize the association of low free and bioavailable testosterone concentrations and mortality in men and to describe the mechanism underlying the association.

Background: We evaluated the associations of smoking, alcohol consumption, and physical activity with sex steroid hormone concentrations among 1,275 men > or =20 years old who participated in the Third National Health and Nutrition Examination Survey (NHANES III)., Methods: Serum concentrations of testosterone, estradiol, and sex hormone-binding globulin (SHBG) were measured. We compared geometric mean concentrations across levels of smoking, alcohol, and physical activity using multiple linear regression., Results: Current smokers had higher total testosterone (5.42, 5.10, and 5.26 ng/ml in current, former, and never smokers), free testosterone (0.110, 0.102, and 0.104 ng/ml), total estradiol (40.0, 34.5, and 33.5 pg/ml), and free estradiol (1.05, 0.88, and 0.84 pg/ml) compared with former and never smokers (all p < or = 0.05). Men who consumed > or =1 drink/day had lower SHBG than men who drank less frequently (31.5 vs. 34.8 nmol/l, p = 0.01); total (p-trend = 0.08) and free testosterone (p-trend = 0.06) increased with number of drinks per day. Physical activity was positively associated with total (p-trend = 0.01) and free testosterone (p-trend = 0.05)., Conclusions: In this nationally representative sample of men, smoking, alcohol, and physical activity were associated with hormones and SHBG, thus these factors should be considered as possible confounders or upstream variables in studies of hormones and men's health, including prostate cancer.

Context: Sex steroid hormones may play a role in the pathogenesis of chronic kidney disease (CKD)., Objective: To determine whether sex steroid hormone concentrations are associated with kidney function or kidney damage in men in the general US population. We hypothesized that lower serum testosterone and E(2) concentrations are associated with CKD. DESIGN PATIENTS AND MEASUREMENTS: Serum sex steroid hormones were measured by electrochemiluminescence immunoassays for 1470 men who attended the morning session of Phase I of the Third National Health and Nutrition Examination Survey (NHANES III). We used two measures of CKD, estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m(2) calculated using serum creatinine or cystatin C levels and the abbreviated Modification of Diet in Renal Disease Study formulae and urinary albumin : creatinine ratio (UACR) >or= 17 mg/g., Results: Mean free testosterone concentration was higher in men with an eGFR < 60 ml/min/1.73 m(2) than in men with a higher eGFR. In multivariable adjusted models, the odds of an eGFR < 60 ml/min/1.73 m(2) or UACR >/= 17 mg/g did not differ across tertiles of hormones with the exception of free E(2); those in the highest vs. lowest tertile had an elevated odds of decreased eGFR (OR: 3.04, 95% CI (1.22, 7.57); P-trend = 0.02)., Conclusions: In a nationally representative sample of US adult men, higher free E(2) concentration was significantly associated with an eGFR < 60 ml/min/1.73 m(2) as assessed by serum creatinine or cystatin C even after multivariable adjustment. These findings are in contrast to the hypothesis that oestrogens may protect against CKD, though reverse causation cannot be ruled out. Longitudinal investigation of the role of oestrogens in kidney haemodynamics, function, and pathophysiology is warranted.

Background: Benign growth of the prostate is thought to contribute to lower urinary tract symptoms (LUTS) in older men. It is, however, unclear which factors induce prostate growth in these men. We examined the association of insulin-like growth factor (IGF)-1 and its major binding protein IGFBP-3 with LUTS in a representative US study., Methods: We included men 60 years and older who participated in the morning session of the Third National Health and Examination Survey (NHANES III) between 1988 and 1994. Men were classified as cases (n = 91) if they reported at least three of four LUTS (nocturia, incomplete emptying, hesitancy, or weak stream) but had not had non-cancer prostate surgery in the past. Controls were men without symptoms and surgery (n = 220). All results were weighted to account for sampling probability in NHANES III. IGF-1 and IGFBP-3 were measured by ELISA and IRMA, respectively., Results: After mutual adjustment, men in the highest tertile of serum IGF-1 concentration had a non-significantly higher odds of LUTS than men in the lowest tertile (odds ratio (OR) = 3.20; 95% confidence interval (CI) 0.89-11.4; p-trend = 0.09]. A high concentration of IGFBP-3 was inversely related to the odds of LUTS (OR = 0.25; 95% CI 0.08-0.81; p-trend = 0.02)., Conclusion: A high IGFBP-3 level might affect LUTS by decreasing the bioavailability of IGF-1 or independent of IGF-1 by up-regulating apoptosis, and, thus, limiting its growth promoting effects on the prostate.

Purpose: Previous epidemiological studies described suggestive positive associations between sexually transmitted infections, particularly gonorrhea and human immunodeficiency virus infection, and lower urinary tract symptoms. To our knowledge no groups have investigated other infections, such as human papillomavirus type 16, herpes simplex virus type 2, cytomegalovirus, human herpesvirus type 8, herpes simplex type 1, and hepatitis B and C virus infection, in relation to lower urinary tract symptoms. Therefore, we examined each of these associations in the Third National Health and Nutrition Examination Survey., Materials and Methods: The Third National Health and Nutrition Examination Survey is a representative, cross-sectional survey of the population in the United States that was done between 1988 and 1994. Each participant provided a blood sample and completed a computer assisted interview including questions on lower urinary tract symptoms (nocturia, incomplete emptying, hesitancy and weak stream). Blood samples were tested for IgG antibodies against each virus., Results: In younger men (ages 30 to 49 years) positive associations were observed between cytomegalovirus, human herpesvirus type 8, herpes simplex virus type 1, and hepatitis B and C virus antibody seropositivity, and lower urinary tract symptoms. In 50 to 59-year-old men positive associations were observed between human papillomavirus type 16, herpes simplex virus type 2, cytomegalovirus, human herpesvirus type 8 and hepatitis C virus antibody seropositivity and lower urinary tract symptoms. In men 60 years or older only a slight, nonsignificant positive association was observed between cytomegalovirus antibody seropositivity and lower urinary tract symptoms., Conclusions: In this cross-sectional survey of American men suggestive positive associations were observed between several viral infections and lower urinary tract symptoms, primarily in 30 to 59-year-old men. These findings provide interesting hypotheses and preliminary evidence for future etiological studies of infections and lower urinary tract symptoms.

Context: Higher testosterone in black compared with white men has been postulated to explain their higher prostate cancer incidence. Previous studies comparing hormone levels by race might have been limited by size, restricted age variation, or lack of representation of the general population., Objective: Our objective was to compare serum testosterone, estradiol, and SHBG concentrations among non-Hispanic black, non-Hispanic white, and Mexican-American men., Participants, Design, and Setting: A total of 1413 men aged 20+ yr and who attended the morning examination session of the Third National Health and Nutrition Examination Survey (NHANES III) in 1988-1991 were included in this cross-sectional study., Measurement: Serum hormone concentrations were measured by electrochemiluminescence immunoassays., Results: After applying sampling weights and adjusting for age, percent body fat, alcohol, smoking, and activity, testosterone concentrations were not different between non-Hispanic blacks (n = 363; geometric mean, 5.29 ng/ml) and non-Hispanic whites (n = 674; 5.11 ng/ml; P > 0.05) but were higher in Mexican-Americans (n = 376; 5.48 ng/ml; P < 0.05). Non-Hispanic blacks (40.80 pg/ml) had a higher estradiol concentration than non-Hispanic whites (35.46 pg/ml; P < 0.01) and Mexican-Americans (34.11 pg/ml; P < 0.01). Non-Hispanic blacks (36.49 nmol/liter) had a higher SHBG concentration than non-Hispanic whites (34.91 nmol/liter; P < 0.05) and Mexican-Americans (35.04 nmol/liter; P < 0.05)., Conclusions: Contrary to the postulated racial difference, testosterone concentrations did not differ notably between black and white men. However, blacks had higher estradiol levels. Mexican-Americans had higher testosterone than whites but similar estradiol and SHBG concentrations. Given these findings, it may be equally if not more important to investigate estradiol as testosterone in relation to diseases with racial disparity.

Objectives: To examine the association of cigarette smoking with subsequent fatal prostate cancer., Methods: Two private censuses were conducted in Washington County, Maryland, in which 26,810 adult men in 1963 and 28,292 in 1975 provided smoking information. Prostate cancer deaths through 2000 (1963 cohort, 240 deaths; and 1975 cohort, 184 deaths) were ascertained by review of the death certificates. Poisson regression analysis was used to estimate the rate ratio of prostate cancer death adjusted for age., Results: Overall, cigarette smokers in the 1963 census cohort were not more likely to die of prostate cancer than those who had never smoked cigarettes, pipes, or cigars when considering the total follow-up period. However, current smokers of 20 or more cigarettes per day (rate ratio 2.38; 95% confidence interval 0.94 to 5.99) and former smokers (rate ratio 2.75; 95% confidence interval 1.13 to 6.74) had a greater risk of death from prostate cancer during the first 10 years of follow-up. Weaker positive associations of prostate cancer death with current and former cigarette smoking were seen during the first 10 years of follow-up in the 1975 census cohort. Current cigarette smoking at baseline was not associated with the prostate cancer incidence., Conclusions: The lack of an association between cigarette smoking and prostate cancer incidence, but the tendency of greater prostate cancer mortality in former and current cigarette smokers earlier in the follow-up period is consistent with other studies in which smoking was assessed once at baseline.

Background: Nutrients with antioxidant properties or that influence cell growth and differentiation might reduce the risk of benign prostatic hyperplasia (BPH)., Objective: The objective was to evaluate the association of fruit, vegetable, and micronutrient intakes with BPH., Design: The participants were members of the Health Professionals Follow-Up Study and were aged 46-81 y in 1992. In 1992 and biennially thereafter, the men reported having surgery for an enlarged prostate, and in 1992 and on 3 subsequent questionnaires they completed the American Urological Association symptom index (AUASI). BPH cases were men who reported having surgery or who had an AUASI score of 15-35 (n = 6092). Control subjects were men who had not had surgery and never had an AUASI score >7 (n = 18 373). Men with a score of 8-14 were excluded (n = 7800). Intakes of fruit, vegetables, and antioxidants were assessed with a food-frequency questionnaire in 1986. We calculated odds ratios (ORs) of BPH and 95% CIs using logistic regression., Results: Vegetable consumption was inversely associated with BPH (fifth compared with first quintile-OR: 0.89; 95% CI: 0.80, 0.99; P for trend = 0.03), whereas fruit intake was not. Consumption of fruit and vegetables rich in beta-carotene (P for trend = 0.004), lutein (P for trend = 0.0004), or vitamin C (P for trend = 0.05) was inversely related to BPH. With increasing vitamin C intake from foods, men were less likely to have BPH (P for trend = 0.0009). Neither alpha- nor gamma-tocopherol intake from foods was associated with BPH (P for trend = 0.05 and 0.84, respectively)., Conclusion: Our findings are consistent with the hypothesis that a diet rich in vegetables may reduce the occurrence of BPH.

Objective: To evaluate the association of meat and dairy food consumption with subsequent risk of prostate cancer., Methods: In 1989, 3,892 men 35+ years old, who participated in CLUE II study of Washington County, MD, completed an abbreviated Block food frequency questionnaire. Intake of meat and dairy related foods was calculated using consumption frequency and portion size. Incident prostate cancer cases (n = 199) were ascertained through October 2004. Cox proportional hazards regression was used to calculate hazard ratios (HR) of total and advanced (SEER states three and four; n = 54) prostate cancer and 95% confidence intervals (CI) adjusted for age, BMI at age 21, and intake of energy, saturated fat, and tomato products., Results: Intakes of total mean (HR = 0.90, 95% CI 0.60-1.33, comparing highest to lowest tertile) and red meat (HR = 0.87, 95% CI 0.59-1.32) were not statistically significantly associated with prostate cancer. However, processed meat consumption was associated with a non-statistically significant higher risk of total (5+ vs. < or =1 servings/week: HR = 2.24; 95% CI 0.90-5.59) prostate cancer. There was no association across tertiles of dairy or calcium with total prostate cancer, although compared tp < or =1 servings/week consumption of 5+ servings/week of dairy foods was associated with an increased risk of prostate cancer (HR = 1.65, 98% CI 1.02-2.66)., Conclusion: Overall, consumption of processed meat, but not total meat or red meat, was associated with a possible increased risk of total prostate cancer in this prospective study. Higher intake of dairy foods but not calcium was positively associated with prostate cancer. Further investigation into the mechanisms by which processed meat and dairy consumption might increase the risk of prostate cancer is suggested.

The authors examined the association between obesity and lower urinary tract symptoms (LUTS) in the Third National Health and Nutrition Examination Survey. This 1988-1994 US cross-sectional study included 2,797 men aged > or = 60 years whose current weight, weight at age 25 years, highest weight ever, height, waist circumference, and body mass index (BMI) were assessed. LUTS cases had at least three of these symptoms: nocturia, incomplete emptying, weak stream, and hesitancy. Controls were men without symptoms or noncancer prostate surgery. Odds ratios adjusted for age and race and weighted for selection probability were estimated by logistic regression. The odds of LUTS were lower for men who were obese at age 25 years compared with men whose BMI was normal (odds ratio = 0.49, 95% confidence interval: 0.27, 0.91). An increase in BMI between age 25 years and the highest BMI ever was positively associated with LUTS (odds ratio = 1.90, 95% confidence interval: 0.89, 4.05). Men with a larger waist circumference (> or = 102 cm) were more likely to have LUTS compared with men with a smaller waist circumference (odds ratio = 1.48, 95% confidence interval: 0.87, 2.54). Results suggest that being overweight in young adulthood may be associated with a lower prevalence of LUTS later in life, whereas weight gain and central adiposity in adulthood are possibly associated with a higher prevalence of LUTS.