Prepubertal organochlorine pesticide concentrations and age of pubertal onset among Russian boys.
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ABSTRACT: Background
In animal studies, organochlorine pesticide (OCP) exposure alters pubertal development; however, epidemiological data are limited and inconsistent.Objective
To evaluate the associations of serum OCP concentrations [hexachlorobenzene (HCB), β-hexachlorocyclohexane (β-HCH), and p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE)] with male pubertal onset.Methods
In Chapaevsk, Russia, a town environmentally contaminated with OCPs, 350 8-9 year old boys with measured OCPs were enrolled during 2003-2005 and were followed annually for eight years. We evaluated three measures of pubertal onset: testicular volume (TV)>3 mL in either testis, or stage 2 or greater for genitalia (G2+), or pubic hair (P2+). We used multivariable interval-censored models to evaluate associations of OCPs (quartiles) with physician-assessed pubertal onset.Results
In adjusted models, boys with higher HCB concentrations had later mean ages of TV>3 mL and P2+ (but not G2+). Mean age at attaining TV>3 mL was delayed 3.6 (95% CI: -2.6, 9.7), 7.9 (95% CI: 1.7, 14.0), and 4.7 months (95% CI: -1.4, 10.9) for HCB Q2, Q3, and Q4, respectively, compared to Q1 (trend p: 0.06). Boys with higher HCB concentrations reached P2+ 0.1 months earlier (95% CI: -5.8, 5.6) for Q2, 4.7 months later (95% CI: -1.0, 10.3) for Q3 and 4.6 months later (95% CI: -1.1, 10.3) for Q4 compared to Q1 (trend p: 0.04). There were no associations of serum β-HCH and p,p'-DDE concentrations with age of pubertal onset.Conclusion
Higher prepubertal serum HCB concentrations were associated with later age of gonadarche and pubarche.
SUBMITTER: Lam T
PROVIDER: S-EPMC4194160 | biostudies-literature | 2014 Dec
REPOSITORIES: biostudies-literature
Publications
Prepubertal organochlorine pesticide concentrations and age of pubertal onset among Russian boys.
Lam Thuy T Williams Paige L PL Lee Mary M MM Korrick Susan A SA Birnbaum Linda S LS Burns Jane S JS Sergeyev Oleg O Revich Boris B Altshul Larisa M LM Patterson Donald G DG Turner Wayman E WE Hauser Russ R
Environment international 20140810
<h4>Background</h4>In animal studies, organochlorine pesticide (OCP) exposure alters pubertal development; however, epidemiological data are limited and inconsistent.<h4>Objective</h4>To evaluate the associations of serum OCP concentrations [hexachlorobenzene (HCB), β-hexachlorocyclohexane (β-HCH), and p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE)] with male pubertal onset.<h4>Methods</h4>In Chapaevsk, Russia, a town environmentally contaminated with OCPs, 350 8-9 year old boys with measured ...[more]
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Project description:BackgroundFew human studies have evaluated the impact of childhood exposure to organochlorine pesticides (OCP) on pubertal development.ObjectiveWe evaluated associations of serum OCP concentrations [hexachlorobenzene (HCB), ?-hexachlorocyclohexane (?HCH), and p,p-dichlorodiphenyldichloroethylene (p,p´-DDE)] with age at attainment of sexual maturity among boys.MethodsFrom 2003 through 2005, 350 8- to 9-year-old boys from Chapaevsk, Russia, with measured OCPs were enrolled and followed annually for 8 years. We used multivariable interval-censored models to evaluate associations of OCPs (quartiles) with three physician-assessed measures of sexual maturity: Tanner stage 5 for genitalia growth, Tanner stage 5 for pubic hair growth, or testicular volume (TV) ? 20 mL in either testis.ResultsIn adjusted models, boys with higher HCB concentrations achieved sexual maturity reflected by TV ? 20 mL a mean of 3.1 months (95% CI: -1.7, 7.8), 5.3 months (95% CI: 0.6, 10.1), and 5.0 months (95% CI: 0.2, 9.8) later for quartiles Q2, Q3, and Q4, respectively, compared with Q1 (p trend = 0.04). Tanner stage 5 for genitalia growth was attained a mean of 2.2 months (95% CI: -3.1, 7.5), 5.7 months (95% CI: 0.4, 11.0), and 3.7 months (95% CI: -1.7, 9.1) later for quartiles Q2, Q3, and Q4, respectively, of ?HCH compared with Q1 (p trend = 0.09). Tanner stage 5 for pubic hair growth occurred 6-9 months later on average for boys in the highest versus lowest quartile for HCB (p trend < 0.001), ?HCH (trend p = 0.01), and p,p´-DDE (p trend = 0.04). No associations were observed between p,p´-DDE and Tanner stage 5 for genitalia growth or TV ? 20 mL.Conclusions and relevanceHigher prepubertal serum HCB and ?HCH concentrations were associated with a later age at attainment of sexual maturity. Only the highest quartile of serum p,p´-DDE was associated with later pubic hair maturation.CitationLam T, Williams PL, Lee MM, Korrick SA, Birnbaum LS, Burns JS, Sergeyev O, Revich B, Altshul LM, Patterson DG Jr, Hauser R. 2015. Prepubertal serum concentrations of organochlorine pesticides and age at sexual maturity in Russian boys. Environ Health Perspect 123:1216-1221; http://dx.doi.org/10.1289/ehp.1409022.
| S-EPMC4629743 | biostudies-literature
Project description:BackgroundFew studies have evaluated predictors of childhood exposure to organochlorine pesticides (OCPs), a class of lipophilic persistent chemicals.ObjectivesOur goal was to identify predictors of serum OCP concentrations-hexachlorobenzene (HCB), ?-hexachlorocyclohexane (?-HCH), and p,p-dichlorodiphenyldichloroethylene (p,p´-DDE)-among boys in Chapaevsk, Russia.MethodsBetween 2003 and 2005, 499 boys 8-9 years of age were recruited in a prospective cohort. The initial study visit included a physical examination; blood collection; health, lifestyle, and food-frequency questionnaires; and determination of residential distance from a local factory complex that produced HCB and ?-HCH. Fasting serum samples were analyzed for OCPs at the U.S. Centers for Disease Control and Prevention. General linear regression models were used to identify predictors of the boys' serum HCB, ?-HCH, and p,p´-DDE concentrations.ResultsAmong 355 boys with OCP measurements, median serum HCB, ?-HCH, and p,p´-DDE concentrations were 158, 167, and 284 ng/g lipid, respectively. Lower body mass index, longer breastfeeding duration, and local dairy consumption were associated with higher concentrations of OCPs. Boys who lived < 2 km from the factory complex had 64% (95% CI: 37, 96) and 57% (95% CI: 32, 87) higher mean HCB and ?-HCH concentrations, respectively, than boys who lived ? 5 km away. Living > 3 years in Chapaevsk predicted higher ?-HCH concentrations, and having parents who lacked a high school education predicted higher p,p´-DDE concentrations.ConclusionsAmong this cohort of prepubertal Russian boys, predictors of serum OCPs included consumption of local dairy products, longer local residence, and residential proximity to the local factory complex.
| S-EPMC3855511 | biostudies-literature
Project description:BackgroundAnimal data demonstrate associations of dioxin, furan, and polychlorinated biphenyl (PCB) exposures with altered male gonadal maturation. It is unclear whether these associations apply to human populations.ObjectivesWe investigated the association of dioxins, furans, PCBs, and corresponding toxic equivalent (TEQ) concentrations with pubertal onset among boys in a dioxin-contaminated region.MethodsBetween 2003 and 2005, 499 boys 8-9 years of age were enrolled in a longitudinal study in Chapaevsk, Russia. Pubertal onset [stage 2 or higher for genitalia (G2+) or testicular volume (TV) > 3 mL] was assessed annually between ages 8 and 12 years. Serum levels at enrollment were analyzed by the Centers for Disease Control and Prevention, Atlanta, Georgia, USA. We used Cox proportional hazards models to assess age at pubertal onset as a function of exposure adjusted for potential confounders. We conducted sensitivity analyses excluding boys with pubertal onset at enrollment.ResultsThe median (range) total serum TEQ concentration was 21 (4-175) pg/g lipid, approximately three times higher than values in European children. At enrollment, boys were generally healthy and normal weight (mean body mass index, 15.9 kg/m2), with 30% having entered puberty by G2+ and 14% by TV criteria. Higher dioxin TEQs were associated with later pubertal onset by TV (hazard ratio = 0.68, 95% confidence interval, 0.49-0.95 for the highest compared with the lowest quartile). Similar associations were observed for 2,3,7,8-tetrachlorodibenzo-p-dioxin and dioxin concentrations for TV but not G2+. Results were robust to sensitivity analyses.ConclusionsFindings support an association of higher peripubertal serum dioxin TEQs and concentrations with later male pubertal onset reflected in delayed testicular maturation.
| S-EPMC3230396 | biostudies-literature
Project description:BackgroundLimited human data suggest an association of organochlorine pesticides (OCPs) with adverse effects on children's growth.ObjectiveWe evaluated the associations of OCPs with longitudinally assessed growth among peripubertal boys from a Russian cohort with high environmental OCP levels.MethodsA cohort of 499 boys enrolled in the Russian Children's Study between 2003 and 2005 at 8-9 years of age were followed prospectively for 4 years. At study entry, 350 boys had serum OCPs measured. Physical examinations were conducted at entry and annually. The longitudinal associations of serum OCPs with annual measurements of body mass index (BMI), height, and height velocity were examined by multivariate mixed-effects regression models for repeated measures, controlling for potential confounders.ResultsAmong the 350 boys with OCP measurements, median serum hexachlorobenzene (HCB), ?-hexachlorocyclohexane (?HCH), and p,p´-dichlorodiphenyldichloroethylene (p,p´-DDE) concentrations were 159 ng/g lipid, 168 ng/g lipid, and 287 ng/g lipid, respectively. Age-adjusted BMI and height z-scores generally fell within the normal range per World Health Organization standards at entry and during follow-up. However, in adjusted models, boys with higher serum HCB, ?HCH, and p,p´-DDE had significantly lower mean [95% confidence interval (CI)] BMI z-scores, by -0.84 (-1.23, -0.46), -1.32 (-1.70, -0.95), and -1.37 (-1.75, -0.98), respectively, for the highest versus lowest quintile. In addition, the highest quintile of p,p´-DDE was associated with a significantly lower mean (95% CI) height z-score, by -0.69 (-1.00, -0.39) than that of the lowest quintile.ConclusionsSerum OCP concentrations measured at 8-9 years of age were associated with reduced growth, particularly reduced BMI, during the peripubertal period, which may affect attainment of optimal adult body mass and height.
| S-EPMC3279441 | biostudies-literature
Project description:BackgroundAlthough phthalate exposures have been associated with adverse effects on male reproductive health, few studies have explored longitudinal associations with male pubertal development.ObjectivesWe examined the association of prepubertal urinary concentrations of phthalate metabolites with age at pubertal onset in a prospective cohort of Russian boys.MethodsAt enrollment at ages 8-9 years, medical history, dietary, and demographic information was collected. At entry and annually, physical examinations and pubertal staging [Genitalia (G), Pubarche (P), and testicular volume (TV, in ml)] were conducted and spot urines were collected. Prepubertal urine samples (defined as either TV = 1, 2 and G = 1, 2 or TV = 3 and G = 1) were pooled for each boy and phthalate metabolite concentrations were quantified using isotope dilution LC-MS/MS at Moscow State University. We measured 15 metabolites including those from anti-androgenic parent phthalates (AAPs) such as di (2-ethylhexyl) (DEHP) and di-isononyl (DiNP) phthalates as well as monobenzyl (MBzP), mono-n-butyl (MnBP), and mono-isobutyl (MiBP) metabolites. We calculated the molar sums of DEHP (∑DEHP), DiNP (∑DiNP), and AAP (∑AAP) metabolites. Separate interval-censored models were used to assess associations of quartiles of prepubertal phthalate metabolites with each pubertal onset indicator, G2+, P2+ and TV > 3 mL, adjusted for covariates and urine specific gravity.Results304 boys had 752 prepubertal urine samples (median 2, range: 1-6) for pooling. In adjusted models, higher urinary AAPs were consistently associated with later pubertal onset (P2) with mean shifts ranging from 8.4 to 14.2 months for the highest versus lowest quartiles. Significantly later onset for G2 and TV > 3 mL was observed for higher versus lower quartiles of MiBP, MBzP, ∑DEHP and ∑DiNP.ConclusionsOn average, boys with higher concentrations of prepubertal urinary AAPs had later pubertal onset by six months to over a year. The impact of AAPs on timing of male puberty may be attributable to disruption of androgen-dependent biological pathways.
| S-EPMC9310051 | biostudies-literature
Project description:BackgroundPeripubertal concentrations of serum dioxins and polychlorinated biphenyls (PCBs) have demonstrated associations with altered age of pubertal onset and sexual maturity in boys, but associations with pubertal progression have received less attention.MethodsThe Russian Children's Study is a prospective cohort of 516 boys enrolled in 2003-2005 at age 8 or 9 and followed annually up to 19 years of age. Serum concentrations of dioxin-like toxic equivalents (TEQs), polychlorinated dibenzodioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and non-dioxin-like PCBs (NDL-PCBs) and whole blood lead levels (BLLs) were quantified from blood samples collected at study entry (age 8-9). Testicular volume (TV) was assessed annually using a Prader orchidometer. Pubertal trajectories were identified by applying Group-Based Trajectory Models (GBTMs) to TV measured from ages 8-19. Associations of peripubertal serum TEQs, PCDDs, PCDFs, and NDL-PCBs with specific progression trajectories were modeled using multinomial logistic regression, adjusting for each boy's birthweight, and for BLL, body mass index and nutritional factors at study entry.ResultsAmong 489 eligible boys with available exposure measures, we identified three pubertal trajectories using GBTMs: slower (34% of boys), moderate (48%) and faster (18%). Boys with higher peripubertal serum TEQs had higher adjusted odds of being in the moderate versus faster trajectory (adjusted odds ratio (aOR) 1.79, 95% CI 1.01, 3.13) and the slower versus faster trajectory (aOR 1.52, 95% CI 0.82, 2.78) per 1 log unit increase in serum TEQs. Boys with higher peripubertal serum PCDFs had higher adjusted odds of being in the moderate compared to the faster trajectory (aOR 1.92, 95% CI 1.20, 3.03) and of being in the slower versus the faster trajectory (aOR 1.42, 95% CI 0.91, 2.33) per 1 log unit increase. Boys with higher NDL-PCBs had higher adjusted odds of being in the faster trajectory versus the moderate (aOR 2.56, 95% CI 0.91-7.20) or slower (aOR 3.31, 95% CI 1.07, 10.25) trajectory. Boys with higher blood lead levels also had higher adjusted odds of being in the slower trajectory of pubertal progression, compared to either the faster (aOR 1.47, 95% CI 0.89, 2.44) or moderate (aOR 1.20, 95% CI 0.83, 1.75) trajectories, per 1 log unit increase in BLL, although these associations did not attain statistical significance.ConclusionBoys' peripubertal exposure to dioxins and certain PCBs may alter pubertal progression.
| S-EPMC10653680 | biostudies-literature
Project description:Dioxins, furans, and polychlorinated biphenyls (PCBs), dioxin-like and non-dioxin-like, have been linked to alterations in puberty.We examined the association of peripubertal serum levels of these compounds [and their toxic equivalents (TEQs)] with pubertal onset and maturity among Russian boys enrolled at ages 8-9 years and followed prospectively through ages 17-18 years.At enrollment, 473 boys had serum dioxin-like compounds and PCBs measured. At the baseline visit and annually until age 17-18 years, a physician performed pubertal staging [genitalia (G), pubarche (P), and testicular volume (TV)]. Three hundred fifteen subjects completed the follow-up visit at 17-18 years of age. Pubertal onset was defined as TV > 3 mL, G2, or P2. Sexual maturity was defined as TV ? 20 mL, G5, or P5. Multivariable interval-censored models were used to evaluate associations of lipid-standardized concentrations with pubertal timing.Medians (interquartile ranges) of the sum of dioxin-like compounds, TEQs, and non-dioxin-like PCBs were 362 pg/g lipid (279-495), 21.1 pg TEQ/g lipid (14.4-33.2), and 250 ng/g lipid (164-395), respectively. In adjusted models, the highest compared to lowest TEQ quartile was associated with later pubertal onset [TV = 11.6 months (95% CI: 3.8, 19.4); G2 = 10.1 months (95% CI: 1.4, 18.8)] and sexual maturity [TV = 11.6 months (95% CI: 5.7, 17.6); G5 = 9.7 months (95% CI: 3.1, 16.2)]. However, the highest compared to the lowest quartile of non-dioxin-like PCBs, when co-adjusted by TEQs, was associated with earlier pubertal onset [TV = -8.3 months (95% CI:-16.2, -0.3)] and sexual maturity [TV = -6.3 months (95% CI:-12.2, -0.3); G5 = -7.2 months (95% CI:-13.8, -0.6)]; the non-dioxin-like PCB associations were only significant when adjusted for TEQs. TEQs and PCBs were not significantly associated with pubic hair development.Our results suggest that TEQs may delay, while non-dioxin-like PCBs advance, the timing of male puberty. Citation: Burns JS, Lee MM, Williams PL, Korrick SA, Sergeyev O, Lam T, Revich B, Hauser R. 2016. Associations of peripubertal serum dioxin and polychlorinated biphenyl concentrations with pubertal timing among Russian boys. Environ Health Perspect 124:1801-1807;?http://dx.doi.org/10.1289/EHP154.
| S-EPMC5089876 | biostudies-other
Project description:Exposure to dioxins has been associated with delayed pubertal onset in both epidemiologic and animal studies. Whether genetic polymorphisms may modify this association is currently unknown. Identifying such genes could provide insight into mechanistic pathways. This is one of the first studies to assess genetic susceptibility to dioxins.We evaluated whether common polymorphisms in genes affecting either molecular responses to dioxin exposure or pubertal onset influence the association between peripubertal serum dioxin concentration and male pubertal onset.In this prospective cohort of Russian adolescent boys (n = 392), we assessed gene-environment interactions for 337 tagging single-nucleotide polymorphisms (SNPs) from 46 candidate genes and two intergenic regions. Dioxins were measured in the boys' serum at age 8-9 years. Pubertal onset was based on testicular volume and on genitalia staging. Statistical approaches for controlling for multiple testing were used, both with and without prescreening for marginal genetic associations.After accounting for multiple testing, two tag SNPs in the glucocorticoid receptor (GR/NR3C1) gene and one in the estrogen receptor-? (ESR1) gene were significant (q < 0.2) modifiers of the association between peripubertal serum dioxin concentration and male pubertal onset defined by genitalia staging, although not by testicular volume. The results were sensitive to whether multiple comparison adjustment was applied to all gene-environment tests or only to those with marginal genetic associations.Common genetic polymorphisms in the glucocorticoid receptor and estrogen receptor-? genes may modify the association between peripubertal serum dioxin concentration and pubertal onset. Further studies are warranted to confirm these findings.
| S-EPMC3546349 | biostudies-literature
Project description:ObjectiveTo examine the associations of bone and bone-secreted factors with measures of energy metabolism in prepubertal and early pubertal boys.Study designParticipants in this cross-sectional, observational study included 37 (69% black, 31% white) boys, aged 7-12 years (Tanner stage <III). Dual-energy X-ray absorptiometry was used to measure bone mineral content (BMC) and percent body fat. Indirect calorimetry was used to assess resting energy expenditure (REE). Fasting blood levels of osteocalcin (OCN), fibroblast growth factor 23 (FGF23), insulin, glucose, precursor product of type I collagen (N-terminal pro-peptide) and type I collagen, and C-terminal cross-linked telopeptide were measured. Pearson correlations were performed to evaluate relationships among BMC, OCN, FGF23, fasting insulin and glucose, and REE. Multiple linear regression models were used to test associations between OCN and BMC (independent variables) with fasting insulin and glucose and with REE, adjusting for bone turnover markers and further adjusted for percent body fat.ResultsBMC was correlated with REE and insulin. OCN was correlated with glucose in blacks only (r = 0.45, P < .05). FGF23 was not correlated with any markers of energy metabolism. BMC was associated with insulin level in blacks (β = 0.95, P = .001), which was attenuated by percent body fat (β = 0.47, P = .081). BMC was associated with REE in whites (β = 0.496.7, P < .05) and blacks (β = 619.5, P < .0001); but accounting for percent body fat attenuated the association in whites (β = 413.2, P = .078).ConclusionOur findings suggest that BMC is a determinant of fasting insulin and REE, and that the contribution of body fat appears to be race-specific. Endocrine effects of FGF23 and OCN on energy metabolism were not apparent.Trial registrationRegistered with ClinicalTrials.gov: NCT02040740, NCT02040727, and NCT01410643.
| S-EPMC4446221 | biostudies-literature
Project description:BackgroundOrganochlorine pesticides (OCPs) are lipophilic persistent organic pollutants associated with adverse health outcomes. Black women have higher body burdens compared with other U.S. populations and research on their correlates is limited.MethodsUsing baseline data from a prospective cohort study of Black women aged 23-35 years from the Detroit, Michigan metropolitan area (enrolled 2010-2012), we examined correlates of plasma concentrations of the following OCPs: dichlorodiphenyltrichloroethane (p,p'-DDE), hexachlorobenzene (HCB), oxychlordane, and trans-nonachlor. At enrollment, we collected non-fasting blood samples from 742 participants. We also collected data on demographic, behavioral, dietary, occupational, and medical history factors via self-administered questionnaires, telephone interviews, and in-person clinic visits. We fit linear regression models to calculate percent (%) differences across categories of each correlate and 95% confidence intervals (CIs).ResultsIn models adjusted for all other correlates, a 5-year increase in age was associated with 24% higher oxychlordane (95% CI: 12%, 38%) and 26% higher trans-nonachlor (95% CI: 12%, 42%) plasma concentrations. Heavy alcohol use was associated with 7-9% higher plasma concentrations of p,p'-DDE, oxychlordane, and trans-nonachlor. Current smoking was associated with 10-19% higher plasma concentrations of all four OCPs, and was highest for current smokers of ≥10 cigarettes/day (% differences ranged from 22 to 29%). Compared with having never been breastfed during infancy, having been breastfed for ≥3 months was associated with 15% higher concentrations of p,p'-DDE (95% CI: 6%, 25%), 14% higher oxychlordane (95% CI: 5%, 24%), and 15% higher trans-nonachlor (95% CI: 5%, 27%). Consumption of ≥5 vs. ≤2 glasses/day of tap or bottled water was associated with 8-15% higher plasma concentrations of all four OCPs, and was highest for trans-nonachlor (% difference: 15%; 95% CI: 6%, 26%). No other dietary predictors were appreciably associated with plasma OCP concentrations. Obesity, parity, higher birth order, and longer lactation duration were inversely associated with plasma OCP concentrations.ConclusionsIn Black U.S. women of reproductive age, older age was an important correlate of plasma OCP concentrations. Exposure to OCPs earlier in life appears to contribute to current blood concentrations. In addition, tobacco, alcohol, and drinking water may be important sources of exposure.
| S-EPMC8406427 | biostudies-literature