Environment-wide association study to comprehensively test and validate associations between nutrition and lifestyle factors and testosterone deficiency: NHANES 1988-1994 and 1999-2004

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

Intake of heterocyclic aromatic amines and the risk of prostate cancer in the EPIC-Heidelberg cohort

BACKGROUND: Heterocyclic amines (HCA) are positively associated with prostate cancer risk in animal models. Because of mostly inconsistent results of epidemiological studies, we examined the association between intake of HCA and prostate cancer risk. METHODS: In the EPIC-Heidelberg cohort, detailed information on diet, anthropometry, and lifestyle was assessed between 1994 and 1998. Dietary HCA intake was estimated using information on meat consumption, cooking methods, and preferred degree of browning. During 104,195 person-years of follow-up, 337 incident cases of prostate cancer (123 advanced cases) were identified among 9,578 men with valid dietary information. Multivariate Cox proportional hazards regression was used to examine the association between intake 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-dimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and prostate cancer. RESULTS: Men in the highest quartiles of PhIP, MeIQx, and DiMeIQx intake, respectively, had no increased risk of prostate cancer compared with men in the lowest quartiles (HR = 0.89, 95% CI 0.66-1.22 [PhIP]; 1.06, 0.77-1.45 [MeIQx]; 0.98, 0.72-1.34 [DiMeIQx]). There were no associations between HCA intake and advanced prostate cancer or between high consumption of strongly browned meat and prostate cancer. DISCUSSION: Our data do not support the hypothesis that HCA intake as consumed in a regular diet is a risk factor for prostate cancer

Nationally Representative Estimates of Serum Testosterone Concentration in Never-Smoking, Lean Men Without Aging-Associated Comorbidities

Context Testosterone deficiency prevalence increases with age, comorbidities, and obesity. Objective To inform clinical guidelines for testosterone deficiency management and development of targets for nonpharmacologic intervention trials for these men, we determined serum testosterone in never-smoking, lean men without select comorbidities in nationally representative surveys. Design Setting Participants We used cross-sectional data for never-smoking, lean men ≥20 years without diabetes, myocardial infarction, congestive heart failure, stroke, or cancer, without use of hormone-influencing medications, and participated in morning sessions of National Health and Nutrition Examination Survey (NHANES) III (phase I 1988-1991) or continuous NHANES (1999-2004). By age, we determined median total testosterone (ng/mL) measured previously by a Food and Drug Administration-approved immunoassay and median estimated free testosterone concentration. Results In NHANES III, in never-smoking, lean men without comorbidities, median (25th, 75th percentile) testosterone was 4% to 9% higher than all men-20 to 39 years: 6.24 (5.16, 7.51), 40 to 59: 5.37 (3.83, 6.49), and ≥60: 4.61 (4.01, 5.18). In continuous NHANES, in never-smoking, lean men without comorbidities, levels were 13% to 24% higher than all men-20 to 39 years: 6.26 (5.32, 7.27), 40 to 59: 5.86 (4.91, 6.55), and ≥60: 4.22 (3.74, 5.73). In never-smoking, lean men without comorbidities, median estimated free testosterone was similar to (NHANES III) or slightly higher than (continuous NHANES) in all men. Conclusions These nationally representative data document testosterone levels (immunoassay) in never-smoking, lean men without select comorbidities 30 and 15 to 20 years ago. This information can be incorporated into guidelines for testosterone deficiency management and used to develop targets for nonpharmacologic intervention trials for testosterone deficiency

The association of urinary cadmium with sex steroid hormone concentrations in a general population sample of US adult men

<p>Abstract</p> <p>Background</p> <p>Studies investigating the association of cadmium and sex steroid hormones in men have been inconsistent, but previous studies were relatively small.</p> <p>Methods</p> <p>In a nationally representative sample of 1,262 men participating in the morning examination session of phase I (1998–1991) of the third National Health and Nutrition Examination Survey, creatinine corrected urinary cadmium and serum concentrations of sex steroid hormones were measured following a standardized protocol.</p> <p>Results</p> <p>After adjustment for age and race-ethnicity, higher cadmium levels were associated with higher levels of total testosterone, total estradiol, sex hormone-binding globulin, estimated free testosterone, and estimated free estradiol (each p-trend < 0.05). After additionally adjusting for smoking status and serum cotinine, none of the hormones maintained an association with urinary cadmium (each p-trend > 0.05).</p> <p>Conclusion</p> <p>Urinary cadmium levels were not associated with sex steroid hormone concentrations in a large nationally representative sample of US men.</p

Meat, eggs, dairy products, and risk of breast cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Background: A Western diet is associated with breast cancer risk. Objective: We investigated the relation of meat, egg, and dairy product consumption with breast cancer risk by using data from the European Prospective Investigation into Cancer and Nutrition (EPIC). Design: Between 1992 and 2003, information on diet was collected from 319,826 women. Disease hazard ratios were estimated with multivariate Cox proportional hazard models. Results: Breast cancer cases (n = 7119) were observed during 8.8 y (median) of follow-up. No consistent association was found between breast cancer risk and the consumption of any of the food groups under study, when analyzed by both categorical and continuous exposure variable models. High processed meat consumption was associated with a modest increase in breast cancer risk in the categorical model (hazard ratio: 1.10; 95% CI: 1.00, 1.20; highest compared with lowest quintile: P for trend = 0.07). Subgroup analyses suggested an association with butter consumption, limited to premenopausal women (hazard ratio: 1.28; 95% CI: 1.06, 1.53; highest compared with lowest quintile: P for trend = 0.21). Between-country heterogeneity was found for red meat (Q statistic = 18.03; P = 0.05) and was significantly explained (P = 0.023) by the proportion of meat cooked at high temperature. Conclusions: We have not consistently identified intakes of meat, eggs, or dairy products as risk factors for breast cancer. Future studies should investigate the possible role of high-temperature cooking in the relation of red meat intake with breast cancer risk. Am J Clin Nutr 2009;90:602-12

Changing geographical patterns and trends in cancer incidence in children and adolescents in Europe, 1991–2010 (Automated Childhood Cancer Information System): a population-based study

Background: A deceleration in the increase in cancer incidence in children and adolescents has been reported in several national and regional studies in Europe. Based on a large database representing 1·3 billion person-years over the period 1991–2010, we provide a consolidated report on cancer incidence trends at ages 0–19 years. Methods: We invited all population-based cancer registries operating in European countries to participate in this population-based registry study. We requested a listing of individual records of cancer cases, including sex, age, date of birth, date of cancer diagnosis, tumour sequence number, primary site, morphology, behaviour, and the most valid basis of diagnosis. We also requested population counts in each calendar year by sex and age for the registration area, from official national sources, and specific information about the covered area and registration practices. An eligible registry could become a contributor if it provided quality data for all complete calendar years in the period 1991–2010. Incidence rates and the average annual percentage change with 95% CIs were reported for all cancers and major diagnostic groups, by region and overall, separately for children (age 0–14 years) and adolescents (age 15–19 years). We examined and quantified the stability of the trends with joinpoint analyses. Findings: For the years 1991–2010, 53 registries in 19 countries contributed a total of 180 335 unique cases. We excluded 15 162 (8·4%) of 180 335 cases due to differing practices of registration, and considered the quality indicators for the 165 173 cases included to be satisfactory. The average annual age-standardised incidence was 137·5 (95% CI 136·7–138·3) per million person-years and incidence increased significantly by 0·54% (0·44–0·65) per year in children (age 0–14 years) with no change in trend. In adolescents, the combined European incidence was 176·2 (174·4–178·0) per million person-years based on all 35 138 eligible cases and increased significantly by 0·96% (0·73–1·19) per year, although recent changes in rates among adolescents suggest a deceleration in this increasing trend. We observed temporal variations in trends by age group, geographical region, and diagnostic group. The combined age-standardised incidence of leukaemia based on 48 458 cases in children was 46·9 (46·5–47·3) per million person-years and increased significantly by 0·66% (0·48–0·84) per year. The average overall incidence of leukaemia in adolescents was 23·6 (22·9–24·3) per million person-years, based on 4702 cases, and the average annual change was 0·93% (0·49–1·37). We also observed increasing incidence of lymphoma in adolescents (average annual change 1·04% [0·65–1·44], malignant CNS tumours in children (average annual change 0·49% [0·20–0·77]), and other tumours in both children (average annual change 0·56 [0·40–0·72]) and adolescents (average annual change 1·17 [0·82–1·53]). Interpretation: Improvements in the diagnosis and registration of cancers over time could partly explain the observed increase in incidence, although some changes in underlying putative risk factors cannot be excluded. Cancer incidence trends in this young population require continued monitoring at an international level. Funding: Federal Ministry of Health of the Federal German Government, the European Union's Seventh Framework Programme, and International Agency for Research on Cancer

Consumption of caffeinated beverages and serum concentrations of sex steroid hormones in US men

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