Maternal tobacco use: A third-trimester risk factor for small-for-gestational-age pregnancy outcome.

BACKGROUND: Small for gestational age (SGA) is a well-known consequence of maternal smoking. Here, we newly examine the magnitude of SGA risk by week of gestational age. METHODS: Singleton live births (N = 3,032,928) with recorded birth weight, gestational age (22-44 weeks), and maternal tobacco use (Y/N) were categorized as to SGA (Y/N), based on 10th percentile gender-specific weights-for-age. RESULTS: SGA prevalence among tobacco users (19.5%) and non-users (9.1%) yielded a significant SGA prevalence rate ratio of 2.15 (2.13-2.16) and a significant adjusted odds ratio of 2.36 (2.34-2.38). The tobacco non-users' rate was steadily near 9% across the week 22-44 gestational age range. The tobacco users' rate was steady until week 33 when it rose monotonically through week 37 to about 20% at week 38 and remained high. This pattern for SGA by gestational week was similar for prevalence rates and adjusted ORs. Tobacco use only through week 33 was not seen to be an SGA risk factor. The magnitude of tobacco use as an SGA risk factor for late third trimester births increased during the period of preterm birth and became fully evident with a two-fold risk for full term infants. CONCLUSION: We newly report the temporal pattern of tobacco-related SGA by week of gestational age. Tobacco-related SGA was only seen for late third trimester births - increasing during weeks 33-37 with a doubling during weeks 38-44. This pattern, informative for issues of mechanism, highlights the potential benefit of extending tobacco cessation programs through the third trimester of pregnancy.

Small-for-gestational age prevalence risk factors in central Appalachian states with mountain-top mining.

OBJECTIVES: To identify risk factors for small-for-gestational age (SGA) for counties in central Appalachian states (Kentucky (KY), Tennessee (TN), Virginia (VA), and West Virginia (WV)) with varied coal mining activities. MATERIAL AND METHODS: Live birth certificate files (1990-2002) were used for obtaining SGA prevalence rates for mothers based on the coal mining activities of their counties of residence, mountain-top mining (MTM) activities, underground mining activities but no mountain-top mining activity (non-MTM), or having no mining activities (non-mining). Co-variable information, including maternal tobacco use, was also obtained from the live birth certificate. Adjusted odds ratios were obtained using multivariable logistic regression comparing SGA prevalence rates for counties with coal mining activities to those without coal mining activities and comparing SGA prevalence rates for counties with coal mining activities for those with and without mountain-top mining activities. Comparisons were also made among those who had reported tobacco use and those who had not. RESULTS: Both tobacco use prevalence and SGA prevalence were significantly greater for mining counties than for non-mining counties and for MTM counties than for non-MTM counties. Adjustment for tobacco use alone explained 50% of the increased SGA risk for mining counties and 75% of the risk for MTM counties, including demographic pre-natal care co-variables that explained 75% of the increased SGA risk for mining counties and 100% of the risk for MTM. The increased risk of SGA was limited to the third trimester births among tobacco users and independent of the mining activities of their counties of residence. CONCLUSIONS: This study demonstrates that the increased prevalence of SGA among residents of counties with mining activity was primarily explained by the differences in maternal tobacco use prevalence, an effect that itself was gestational-age dependent. Self-reported tobacco use marked the population at the increased risk for SGA in central Appalachian states. Int J Occup Med Environ Health 2018;31(1):11-23.

Arsenic in Drinking Water and Lung Cancer Mortality in the United States: An Analysis Based on US Counties and 30 Years of Observation (1950-1979).

Background. To examine whether the US EPA (2010) lung cancer risk estimate derived from the high arsenic exposures (10-934 µg/L) in southwest Taiwan accurately predicts the US experience from low arsenic exposures (3-59 µg/L). Methods. Analyses have been limited to US counties solely dependent on underground sources for their drinking water supply with median arsenic levels of ≥3 µg/L. Results. Cancer risks (slopes) were found to be indistinguishable from zero for males and females. The addition of arsenic level did not significantly increase the explanatory power of the models. Stratified, or categorical, analysis yielded relative risks that hover about 1.00. The unit risk estimates were nonpositive and not significantly different from zero, and the maximum (95% UCL) unit risk estimates for lung cancer were lower than those in US EPA (2010). Conclusions. These data do not demonstrate an increased risk of lung cancer associated with median drinking water arsenic levels in the range of 3-59 µg/L. The upper-bound estimates of the risks are lower than the risks predicted from the SW Taiwan data and do not support those predictions. These results are consistent with a recent metaregression that indicated no increased lung cancer risk for arsenic exposures below 100-150 µg/L.

Are residents of mountain-top mining counties more likely to have infants with birth defects? The West Virginia experience.

BACKGROUND: Pooled 1996 to 2003 birth certificate data for four central states in Appalachia indicated higher rates of infants with birth defects born to residents of counties with mountain-top mining (MTM) than born to residents of non-mining-counties (Ahern 2011). However, those analyses did not consider sources of uncertainty such as unbalanced distributions or quality of data. Quality issues have been a continuing problem with birth certificate analyses. We used 1990 to 2009 live birth certificate data for West Virginia to reassess this hypothesis. METHODS: Forty-four hospitals contributed 98% of the MTM-county births and 95% of the non-mining-county births, of which six had more than 1000 births from both MTM and nonmining counties. Adjusted and stratified prevalence rate ratios (PRRs) were computed both by using Poisson regression and Mantel-Haenszel analysis. RESULTS: Unbalanced distribution of hospital births was observed by mining groups. The prevalence rate of infants with reported birth defects, higher in MTM-counties (0.021) than in non-mining-counties (0.015), yielded a significant crude PRR (cPRR = 1.43; 95% confidence interval [CI] = 1.36-1.52) but a nonsignificant hospital-adjusted PRR (adjPRR = 1.08; 95% CI = 0.97-1.20; p = 0.16) for the 44 hospitals. So did the six hospital data analysis ([cPRR = 2.39; 95% CI = 2.15-2.65] and [adjPRR = 1.01; 95% CI, 0.89-1.14; p = 0.87]). CONCLUSION: No increased risk of birth defects was observed for births from MTM-counties after adjustment for, or stratification by, hospital of birth. These results have consistently demonstrated that the reported association between birth defect rates and MTM coal mining was a consequence of data heterogeneity. The data do not demonstrate evidence of a "Mountain-top Mining" effect on the prevalence of infants with reported birth defects in WV.

Discontinuity in the cancer slope factor as it passes from high to low exposure levels--arsenic in the BFD-endemic area.

BACKGROUND: The ingestion of inorganic arsenic causes bladder and lung cancers demonstrably at >400-500ug/L but questionably below 100-200ug/L. Using the standard 42-village cancer mortality dataset from the Blackfoot-disease (BFD) endemic area of southwest Taiwan (Wu et al., 1989), we examined the risk from low exposures by excluding the high exposures. METHOD: Poisson regression analyses with the sequential removal of the highest exposure village have been performed using the median, mean, or maximum village well water arsenic level and demonstrated graphically. RESULTS: Risk estimates are positive when villages with exposures of 200-400ug/L are included and significantly so when villages with >400ug/L are included. Risk estimates for exposures below 100ug/L are negative but rarely significantly so. The inflection point where the slope is no longer positive occurs in the range of 100-200ug/L, depending upon whether the exposure metric used is the median, the mean or the maximum. CONCLUSION: There is a discontinuity in the cancer slope factor or risk from arsenic exposure that occurs in the range of 100-200ug/L. Above these levels, there are significantly positive risks, while below these levels there are not. The analysis reveals within this dataset an intrinsic non-linearity in the cancer risk. The literature speaks to this discontinuity, but this is the first demonstration within a single dataset that shows the discontinuity across the full exposure range and where the low-dose data are not compromised with high-dose data.

Racial/ethnic differences in serum sex steroid hormone concentrations in US adolescent males.

OBJECTIVE: Contrary to the hypothesis that the racial/ethnic disparity in prostate cancer has a hormonal basis, we did not observe a difference in serum testosterone concentration between non-Hispanic black and white men in the Third National Health and Nutrition Examination Survey (NHANES III), although non-Hispanic black men had a higher estradiol level. Unexpectedly, Mexican-American men had the highest testosterone level. Next, we evaluated whether the same patterns are observed during adolescence, the time of prostate maturation. METHODS: We measured serum testosterone, estradiol, and sex hormone-binding globulin (SHBG) by immunoassay in 134 males aged 12-19 in NHANES III. Mean concentrations were compared by race/ethnicity adjusting for age, Tanner stage, percent body fat, waist, physical activity, tobacco smoke, and the other hormones. RESULTS: After multivariable adjustment, in the 12-15-year-old males, testosterone concentration was lower in non-Hispanic blacks than whites (p = 0.043), SHBG concentration did not significantly differ between the two groups. Mexican-Americans had the highest testosterone (versus non-Hispanic black: p = 0.002) and lowest SHBG (versus non-Hispanic white: p = 0.010; versus non-Hispanic black: p = 0.047) concentrations. Estradiol concentration was lower in non-Hispanic blacks (p = 0.11) and Mexican-Americans (p = 0.033) compared with non-Hispanic whites. After multivariable adjustment, in the 16-19-year-old males, testosterone, estradiol, and SHBG concentrations did not differ between non-Hispanic blacks and whites. Mexican-Americans had the highest testosterone concentration (versus non-Hispanic white: p = 0.08), but did not differ from the other groups on estradiol and SHBG concentrations. In both age groups, these patterns were generally present, but less pronounced after adjusting for age and Tanner stage only. CONCLUSION: In adolescent males, non-Hispanic blacks did not have a higher testosterone concentration than non-Hispanic whites, and Mexican-Americans had the highest testosterone concentration, patterns similar to adult males.

Bladder/lung cancer mortality in Blackfoot-disease (BFD)-endemic area villages with low (<150 µg/L) well water arsenic levels--an exploration of the dose-response Poisson analysis.

OBJECTIVE: To examine the analytic role of arsenic exposure on cancer mortality among the low-dose (well water arsenic level <150 µg/L) villages in the Blackfoot-disease (BFD) endemic area of southwest Taiwan and with respect to the southwest regional data. METHOD: Poisson analyses of the bladder and lung cancer deaths with respect to arsenic exposure (µg/kg/day) for the low-dose (<150 µg/L) villages with exposure defined by the village median, mean, or maximum and with or without regional data. RESULTS: Use of the village median well water arsenic level as the exposure metric introduced misclassification bias by including villages with levels >500 µg/L, but use of the village mean or the maximum did not. Poisson analyses using mean or maximum arsenic levels showed significant negative cancer slope factors for models of bladder cancers and of bladder and lung cancers combined. Inclusion of the southwest Taiwan regional data did not change the findings when the model contained an explanatory variable for non-arsenic differences. A positive slope could only be generated by including the comparison population as a separate data point with the assumption of zero arsenic exposure from drinking water and eliminating the variable for non-arsenic risk factors. CONCLUSION: The cancer rates are higher among the low-dose (<150 µg/L) villages in the BFD area than in the southwest Taiwan region. However, among the low-dose villages in the BFD area, cancer risks suggest a negative association with well water arsenic levels. Positive differences from regional data seem attributable to non-arsenic ecological factors.

Serum sex steroid hormones and frailty in older American men of the Third National Health and Nutrition Examination Survey (NHANES III).

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.

Life-style and genital human papillomavirus in a cross-sectional survey in Shanxi Province, China.

BACKGROUND: To determine the age-stratified HPV prevalence rate and the risk factors of life-style associated with HPV infection among women in rural China. METHODS: An age-stratified, cross-sectional survey of 941 women between 16-59 years old was conducted in rural China. Carcinogenic HPV infection was determined using Digene's Hybrid Capture II HPV DNA test and interviews of life-style were conducted. Odds ratios (OR) and 95% confidence interval (CI) from the logistic regression models were used to determine the risk factors associated with HPV. RESULTS: Among 941 women, 745 who had sexual intercourse underwent a cervical examination. The prevalence rate of 13 carcinogenic HPV infections among women 20-59 years old was 15.97%. the rate of HPV prevalence in the 25-34 age group was statistically lower than that in 20-24 and 35-59 age groups (X²=13.3, P=0.0013). The OR of bathing every 7-19 days, 20-180 days, less than once every 180 days vs. bathing at least once a week were 1.19, 1.83 and 2.29 respectively and they had a dose-response relationship (Trend Test: P=0.003). The OR of women aged 25-34 age group vs. 20-24 age group was 0.40 (0.16 - 0.97) and the OR of bathing once every 180 days or less vs. at least once weekly was 2.22 (1.14 - 4.33) adjusted for the other confounding factors,. CONCLUSIONS: The HPV prevalence rate was lowest among child bearing women aged 25-34 year. Also, personal hygiene is significantly associated with the HPV infection in this area, regardless of age.

Body fatness and sex steroid hormone concentrations in US men: results from NHANES III.

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 prevalence of low sex steroid hormone concentrations in men in the Third National Health and Nutrition Examination Survey (NHANES III).

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.

Hepatitis B virus infection and risk of intrahepatic cholangiocarcinoma and non-Hodgkin lymphoma: a cohort study of parous women in Taiwan.

UNLABELLED: Few studies have evaluated the risk of cancers other than hepatocellular carcinoma associated with hepatitis B virus (HBV) infection. This study aimed to estimate incidence rates of intrahepatic cholangiocarcinoma (ICC) and non-Hodgkin lymphoma (NHL) and its major subtypes in a nationwide cohort of parous women and to assess their associations with chronic HBV infection. We conducted a cohort study including 1,782,401 pregnant Taiwanese women whose HBV serostatus was obtained from the National Hepatitis B Vaccination Registry. Newly diagnosed ICCs and NHLs were ascertained through data linkage with the National Cancer Registry. Risks of ICC and NHL were assessed using Cox proportional hazards regression models. After a mean of 6.91 years of follow-up, there were 18 cases of ICC and 192 cases of NHL, including 99 cases of diffuse large B-cell lymphoma (DLBCL). Incidence rates of ICC were 0.09 and 0.43 per 100,000 person-years, respectively, among women who were hepatitis B surface antigen (HBsAg)-seronegative and HBsAg-seropositive, showing an age-adjusted hazard ratio (HR(adj) ) (95% confidence interval [CI]) of 4.80 (1.88-12.20). The incidence rates of NHL overall for HBsAg-seronegative and HBsAg-seropositive women were 1.23 and 3.18 per 100,000 person-years, respectively, with an HR(adj) (95% CI) of 2.63 (1.95-3.54). Among NHL subtypes, HBsAg-seropositive women had an increased risk of DLBCL compared with those who were HBsAg-seronegative (incidence rates: 1.81 and 0.60 per 100,000 person-years, respectively; HR(adj) [95% CI]: 3.09 [2.06-4.64]). The significantly increased risk was not observed for other specific subtypes of NHL. CONCLUSIONS: Chronic HBV infection was associated with an increased risk of ICC and DLBCL in women. Our data suggested a possible etiological role of HBV in the development of ICC and specific subtypes of NHL.

Association of serum α-tocopherol with sex steroid hormones and interactions with smoking: implications for prostate cancer risk.

BACKGROUND: Vitamin E may protect against prostate cancer, possibly only in smokers and, we hypothesize, through altered sex steroid hormones. A controlled trial in smokers showed that sex hormone levels were inversely associated with baseline serum α-tocopherol and decreased in response to vitamin E supplementation. The vitamin E-hormone relation is understudied in non-smokers. METHODS: Serum sex steroid hormones and α-tocopherol were measured for 1,457 men in NHANES III. Multivariable-adjusted geometric mean hormone concentrations by α-tocopherol quintile were estimated. RESULTS: We observed lower mean testosterone, estradiol, and SHBG concentrations with increasing serum α-tocopherol (Q1 = 5.5 and Q5 = 4.6 ng/ml, p-trend = 0.0007; Q1 = 37.8 and Q5 = 33.1 pg/ml, p-trend = 0.02; Q1 = 38.8 and Q5 = 30.6 pg/ml, p-trend = 0.05, respectively). Interactions between serum α-tocopherol and exposure to cigarette smoke for total testosterone, total estradiol, and SHBG were found with the inverse relation observed only among smokers. CONCLUSIONS: Results from this nationally representative, cross-sectional study indicate an inverse association between serum α-tocopherol and circulating testosterone, estradiol, and SHBG, but only in men who smoked. Our findings support vitamin E selectively influencing sex hormones in smokers and afford possible mechanisms through which vitamin E may impact prostate cancer risk.

Association of serum cholesterol and cholesterol-lowering drug use with serum sex steroid hormones in men in NHANES III.

PURPOSE: Low cholesterol levels and statin drugs may protect against prostate cancer with a worse prognosis. Their protective mechanism is unknown, but has been hypothesized to be related to cholesterol's role as a sex steroid hormone precursor. We evaluated whether serum testosterone and estradiol differ by cholesterol or cholesterol-lowering drug use. MATERIALS AND METHODS: Testosterone and estradiol were measured for 1,457 male participants in the Third National Health and Nutrition Examination Survey. We estimated multivariable-adjusted geometric mean hormone concentration by quintiles of cholesterol concentration and by cholesterol-lowering drugs use. RESULTS: Across quintiles of cholesterol, testosterone level did not differ (mean, 95% confidence interval (CI); Q1: 5.25, 5.02-5.49, Q5: 5.05, 4.76-5.37 ng/ml; p-trend = 0.32), whereas estradiol levels were lower (Q1: 38.7, 36.9-40.5; Q5: 33.1, 31.8-34.5 pg/ml; p-trend < 0.0001). Neither testosterone (no: 5.12, 4.94-5.30, yes: 4.91, 4.33-5.57 ng/ml, p = 0.57) nor estradiol (no: 35.9, 34.8-37.1; yes: 33.9, 29.4-39.2 pg/ml; p = 0.39) differed by cholesterol-lowering drugs use. CONCLUSION: Testosterone did not differ by cholesterol or cholesterol-lowering drug use. Estradiol was lower in men with higher cholesterol, but did not differ by cholesterol-lowering drug use. Our results suggest that the lower risk of advanced prostate cancer among statin users is not readily explained by a cholesterol-mediated effect of statins on sex hormone levels.

Mortality after chronic hepatitis B virus infection: a linkage study involving 2 million parous women from Taiwan.

BACKGROUND: Few studies have evaluated survival rates among women who have chronic hepatitis B virus infection. We investigated the overall and disease-specific mortality rates in a nationwide cohort of women after they were screened for hepatitis B surface antigen (HBsAg) during pregnancy. METHODS: HBsAg prenatal screening data were available for 2,087,994 women in Taiwan between 1 January 1986 and 31 March 2000 in the National Hepatitis B Vaccination Registry. Their vital status and cause of death were ascertained by computerized linkage with the National Death Certification Registry. Cox proportional hazards models were used to estimate the association between HBsAg status and specific causes of death. RESULTS: Overall, 14,524 deaths were identified after a mean of 11.43 years of follow-up. The age-adjusted hazard ratio for mortality among HBsAg carriers compared with noncarriers was 1.24 (95% confidence interval [CI], 1.19-1.30), 6.59 (95% CI, 5.70-7.61), and 1.09 (95% CI, 1.04-1.14) for all-cause, liver-specific, and non-liver-related deaths, respectively. In addition to liver-specific causes, a significantly increased risk of mortality from non-Hodgkin lymphoma (P < .001) and gallbladder and extrahepatic bile duct cancer (P = .01) was observed. CONCLUSIONS: Our study found an excess risk of death due to both liver-specific and non-liver-related causes for HBsAg-positive women in Taiwan. Effective prevention and treatment of hepatitis B virus infection is an important public health priority.

Sex steroid hormone concentrations and risk of death in US 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.

Hepatitis B virus infection and hepatocellular carcinoma among parous Taiwanese women: nationwide cohort study.

BACKGROUND: Few long-term studies of hepatitis B virus (HBV) infection and hepatocellular carcinoma have focused on women. We used a nationwide cohort of reproductive-aged Taiwanese women to study relationships of HBV infection and parity with hepatocellular carcinoma risk. METHODS: Prenatal test results were available for hepatitis B surface antigen (HBsAg) and e antigen (HBeAg) in the National Hepatitis B Vaccination Registry from 1 782 401 pregnant women tested from October 1, 1983, through March 31, 2000. Data from the 306 women who were diagnosed with hepatocellular carcinoma were ascertained during 15 901 722 person-years of follow-up through linkage with National Cancer Registry and National Death Certification Registry. We used Cox proportional hazards models to investigate the association of age and reproductive and serological parameters with the risk of hepatocellular carcinoma. RESULTS: Incidence rates for hepatocellular carcinoma were 0.55, 7.91, and 8.76 per 100 000 person-years among women who were HBsAg negative (ie, noncarriers), HBsAg positive plus HBeAg negative, and HBsAg positive plus HBeAg positive, respectively (compared with noncarriers, for HBsAg-positive and HBeAg-positive women, age-adjusted hazard ratio [HR] for developing hepatocellular carcinoma = 17.31, 95% confidence interval [CI] = 12.08 to 24.81; and for HBsAg-negative plus HBeAg-positive women, HR = 13.94, 95% CI = 10.34 to 18.79). Incidence rates were 0.39, 3.10, and 9.01 per 100 000 person-years, respectively, among persistent noncarriers, HBsAg-serocleared carriers, and persistent HBsAg carriers (compared with noncarriers, for HBsAg-serocleared carriers, age-adjusted HR = 7.95, 95% CI = 3.50 to 18.04; and for HBsAg persistence, HR = 23.13, 95% CI = 14.23 to 37.61). Incidence rates were 2.04, 1.55, and 1.66 per 100 000 person-years for women who had one, two, or three or more children, respectively (compared with one child, for two children, age- and HBsAg-adjusted HR = 0.68, 95% CI = 0.50 to 0.93; and for three or more children, HR = 0.63, 95% CI = 0.42 to 0.92). CONCLUSIONS: The risk for hepatocellular carcinoma was statistically significantly higher among women with chronic or active HBV infections and among those with persistent HBV infection or who underwent HBsAg seroclearance during follow-up than among HBV-unexposed women. This risk decreased as parity increased, independent of HBsAg status and age.

Association of cigarette smoking, alcohol consumption, and physical activity with sex steroid hormone levels in US men.

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.

Androgens and diabetes in men: results from the Third National Health and Nutrition Examination Survey (NHANES III).

OBJECTIVE: Low levels of androgens in men may play a role in the development of diabetes; however, few studies have examined the association between androgen concentration and diabetes in men in the general population. The objective of this study is to test the hypothesis that low normal levels of total, free, and bioavailable testosterone are associated with prevalent diabetes in men. RESEARCH DESIGN AND METHODS: The study sample included 1,413 adult men aged > or =20 years who participated in the morning session of the first phase of the Third National Health and Nutrition Examination Survey, a cross-sectional survey of the civilian, noninstitutionalized population of the U.S. Bioavailable and free testosterone levels were calculated from serum total testosterone, sex hormone-binding globulin, and albumin concentrations. RESULTS: In multivariable models adjusted for age, race/ethnicity, and adiposity, men in the first tertile (lowest) of free testosterone level were four times more likely to have prevalent diabetes compared with men in the third tertile (odds ratio 4.12 [95% CI 1.25-13.55]). Similarly, men in the first tertile of bioavailable testosterone also were approximately four times as likely to have prevalent diabetes compared with men in the third tertile (3.93 [1.39-11.13]). These associations persisted even after excluding men with clinically abnormal testosterone concentrations defined as total testosterone <3.25 ng/ml or free testosterone <0.07 ng/ml. No clear association was observed for total testosterone after multivariable adjustment (P for trend across tertiles = 0.27). CONCLUSIONS: Low free and bioavailable testosterone concentrations in the normal range were associated with diabetes, independent of adiposity. These data suggest that low androgen levels may be a risk factor for diabetes in men.