Cancer incidence in a cohort of Danish firefighters: An extended long-term follow-up 1968-2021.

OBJECTIVES: To update and extend the examination of cancer incidence in a cohort of Danish firefighters, now adding 7 years of follow-up and 2766 additional firefighters. The primary focus was directed toward cancer sites that recently contributed to the hazard evaluation conducted by the International Agency for Research on Cancer (IARC). METHODS: The updated cohort consisted of 11,827 male Danish firefighters who were followed up for cancer from 1968 to 2021. Cohort cancer morbidity was compared with a working population reference group, and standardized incidence ratios (SIR) were used for estimation of relative risks, along with 95% confidence intervals (95% CI). RESULTS: Among full-time firefighters, SIR of skin melanoma was 1.30 (95% CI: 1.02-1.66), and SIR = 1.37 (95% CI: 1.02-1.85) for over 5 years of employment. Slightly positive associations were also observed for cancer of the urinary bladder (SIR = 1.16; 95% CI: 0.93-1.45), prostate (SIR = 1.11; 95% CI: 0.97-1.28), and testis (SIR = 1.11; 95% CI: 0.75-1.63). CONCLUSIONS: This updated study provides evidence indicating an elevated risk of skin melanoma in firefighters. Consistent with IARC's evaluation, we also identified positive associations for urinary bladder, prostate, and testis cancer. In contrast, our findings did not suggest an increased risk of colon cancer, non-Hodgkin lymphoma, and mesothelioma. The latter may be due to small numbers in our still relatively young cohort. Continuous follow-up for cancer in firefighters is warranted, including assessment of influence from surveillance bias.

Health perspectives and handling of PFAS contamination in Denmark.

Per- and polyfluorinated alkyl substances (PFAS) are a group of man-made extremely persistent chemicals that have been spread worldwide since the 1950s due to their properties as effective water- and grease-repellent and heat- and temperature-resistant. They are associated with an increasing number of health effects including immune and hormonal disturbances and some types of cancer. We present a review of PFAS pollution in Denmark, the current human exposure, suspected health effects, and patient management in environmental medicine.

Higher Maternal Cortisol Associated With Lower Blood Pressure in Offspring From 3 Months to 5 Years of Age in the Odense Child Cohort.

BACKGROUND: Synthetic glucocorticoid exposure in late pregnancy may be associated with higher blood pressure in offspring. We hypothesized that endogenous cortisol in pregnancy relates to offspring blood pressure (OBP). OBJECTIVE: To investigate associations between maternal cortisol status in third trimester pregnancy and OBP. METHODS: We included 1317 mother-child pairs from Odense Child Cohort, an observational prospective cohort. Serum (s-) cortisol and 24-hour urine (u-) cortisol and cortisone were assessed in gestational week 28. Offspring systolic blood pressure and diastolic blood pressure were measured at age 3, 18 months, and 3 and 5 years. Associations between maternal cortisol and OBP were examined by mixed effects linear models. RESULTS: All significant associations between maternal cortisol and OBP were negative. In boys in pooled analyses, 1 nmol/L increase in maternal s-cortisol was associated with average decrease in systolic blood pressure (ß=-0.003 mmHg [95% CI, -0.005 to -0.0003]) and diastolic blood pressure (ß=-0.002 mmHg [95% CI, -0.004 to -0.0004]) after adjusting for confounders. At 3 months of age, higher maternal s-cortisol was significantly associated with lower systolic blood pressure (ß=-0.01 mmHg [95% CI, -0.01 to -0.004]) and diastolic blood pressure (ß=-0.010 mmHg [95% CI, -0.012 to -0.011]) in boys after adjusting for confounders, which remained significant after adjusting for potential intermediate factors. CONCLUSIONS: We found temporal sex dimorphic negative associations between maternal s-cortisol levels and OBP, with significant findings in boys. We conclude that physiological maternal cortisol is not a risk factor for higher blood pressure in offspring up to 5 years of age.

Self-Reported Asthma Is Associated with Reduced Sperm Count-A Cross-Sectional Study of More than 6000 Young Men from the General Population.

Asthma is driven by an inflammatory response that may impact testicular function. In this cross-sectional study, we investigated the association between self-reported asthma and testicular function (semen parameters, reproductive hormone levels), and determined whether potential further inflammation due to self-reported allergy modified this association. A total of 6177 men from the general population completed a questionnaire including information on doctor-diagnosed asthma or allergy, had a physical examination, delivered a semen sample, and had a blood sample drawn. Multiple linear regression analyses were performed. A total of 656 (10.6%) men reported having ever been diagnosed with asthma. Generally, self-reported asthma was consistently associated with a poorer testicular function; however, few estimates were statistically significant. Specifically, self-reported asthma was associated with statistically significant lower total sperm count [median: 133 vs. 145 million; adjusted ß (95% CI): -0.18 (-0.33 to -0.04) million on cubic-root-transformed scale] and borderline statistically significant lower sperm concentration compared with no self-reported asthma. The association between asthma and total sperm count was of similar magnitude among men with and without allergy. In conclusion, men with self-reported asthma had poorer testicular function than men without asthma. However, the cross-sectional design of the study limits ascertainment of causality.

Prenatal paraben exposures and birth size: Sex-specific associations in a healthy population - A study from the Odense Child Cohort.

OBJECTIVES: To investigate the sex-specific associations between maternal paraben concentrations in second trimester urine and birth size of the offspring. METHODS: A prospective cohort study of 529 mother-child pairs within the Odense Child Cohort. Pregnant women were recruited to the cohort from 2010 to 2012 and provided fasting spot urine samples in second trimester (median 28.7 weeks). Concentrations of methylparaben (MeP), ethylparaben (EtP), iso-propylparaben (i-PrP), n-propylparaben (n-PrP), n-butylparaben (n-BuP) and benzylparaben (BzP) were analyzed by isotope diluted liquid-chromatography tandem-mass-spectrometry and osmolality adjusted. Exposures were categorized into tertiles or above/below level of detection. Data on maternal and birth characteristics were extracted from hospital records. Sex-stratified multiple linear regression analyses were performed according to relevant birth outcomes (length, weight, head/abdominal circumference) adjusting for a priori defined confounders. RESULTS: Higher paraben levels were detected in pregnant women who were older, more obese, who smoked and were primigravidae. Generally, higher maternal paraben exposure was consistently associated with lower birth size in female but not in male offspring, but with few substantial or statistically significant. Higher maternal exposure to n-BuP during pregnancy was associated with a statistically significant lower birth size in female offspring only [birth weight: -137 g (95 % CI -256; -19), head circumference: -0.48 cm (95 % CI -0.90; -0.05), abdominal circumference: -0.65 cm (95 % CI -1.21; -0.08)]. No differences in birth size were observed for other parabens. CONCLUSION: Higher maternal exposure to n-butylparaben was associated with lower birth size in female but not male offspring.

Prenatal Androgen Exposure and Traits of Autism Spectrum Disorder in the Offspring: Odense Child Cohort.

Fetal androgen exposure may be associated with autism spectrum disorder (ASD). We studied 1777 mother-child pairs in the prospective Odense Child Cohort. Prenatal androgen exposure was assessed by maternal 3rd trimester testosterone concentrations, maternal polycystic ovary syndrome (PCOS), and 3 months offspring anogenital distance. ASD traits were assessed at age 3 years with the ASD-symptom scale of the Child Behavior Checklist for ages 1½-5 years. Maternal testosterone was positively associated with traits of ASD in boys (p < 0.05). Maternal PCOS was associated with increased offspring ASD traits (p = 0.046), but became non-significant after excluding parental psychiatric diagnosis. Offspring anogenital distance was not linked to ASD traits. Higher prevalence of ASD in boys could be linked to higher susceptibility to fetal androgen exposure.

Prenatal and early childhood predictors of intelligence quotient (IQ) in 7-year-old Danish children from the Odense Child Cohort.

BACKGROUND: Cognitive development measured as intelligence quotient can predict socioeconomic markers in adulthood. It is therefore of interest to determine predictors of childhood intelligence quotient. AIM: To assess intelligence quotient scores based on standardised Danish age-appropriate scores and to evaluate potential predictors of intelligence quotient. MATERIALS: At 7 years of age children in the Odense Child Cohort completed an abbreviated version of the Wechsler intelligence scale for children 5th edition consisting of four subtests (vocabulary, similarities, block design and matrix reasoning) from which the full scale intelligence quotient and verbal comprehension index were estimated. Potential predictors from pregnancy through childhood were collected from questionnaires, birth records and clinical examinations. METHODS: Intelligence quotient scores were investigated through descriptive statistics and linear regression models. RESULTS: The mean full scale intelligence quotient among 1375 children was 99.1 (95% confidence interval 98.5; 99.8) points. Higher full scale intelligence quotient scores were observed in girls 100.8 (95% confidence interval 100.0; 101.8) compared to boys 97.6 (96.7; 98.4), and in children of mothers with high and intermediate education 101.7 (100.4; 103.1) and 99.6 (98.7; 100.5), respectively, compared to low education 96.1 (94.9; 97.3). In linear regression analyses, longer maternal education and child sex (girls) remained strong predictors of intelligence quotient at age 7 years. In addition, paternal education, child head circumference and longer duration of breastfeeding were associated with higher intelligence quotient, whereas maternal overweight and obesity before pregnancy was associated with lower intelligence quotient. CONCLUSIONS: Mean intelligence quotient scores were comparable to the standardised mean intelligence quotient of 100 point of Danish peers. It is important to follow up these children to determine which predictors persist into adulthood.

Elevated blood pressure in pregnant women with gestational diabetes according to the WHO criteria: importance of overweight.

OBJECTIVE: Hypertension before and during early pregnancy has been associated with an increased risk of gestational diabetes mellitus (GDM) in retrospective analyses. We aimed to investigate the prospective blood pressure trackings in a population-based cohort of pregnant women, who were stratified according to their metabolic status in early third trimester. METHODS: We recorded blood pressure longitudinally during pregnancy in 1230 women from the Odense Child Cohort, Denmark. Fasting glucose and insulin were measured at gestational weeks 28-30. Metabolic status was evaluated according to the WHO 2013 threshold for GDM (GDM-WHO: fasting plasma glucose ≥5.1 mmol/l), insulin and homeostatic model assessment of insulin resistance (HOMA-IR). Relationships between metabolic status in third trimester and blood pressure trajectories were evaluated with adjusted linear mixed models. Trajectory was defined as blood pressure records in pregnancy per 4 weeks interval. RESULTS: Prevalence of GDM-WHO was 40% (498/1230). GDM-WHO was associated with 1.46 (0.22-2.70) mmHg higher SBP and 1.04 (0.07-2.01) mmHg higher DBP trajectories in the overall cohort. The associations were driven by differences in the overweight group, with 3.14 (1.05-5.25) mmHg higher SBP and 1.94 (0.42-3.47) mmHg higher DBP per 4 weeks in women with GDM-WHO compared with women without GDM-WHO. GDM-WHO was not associated with blood pressure in women with normal weight. Blood pressure trajectories were elevated across quartiles of insulin resistance. CONCLUSION: GDM-WHO is associated with higher blood pressure in pregnancy, and there appears to be a stronger effect in overweight women.

Aryl hydrocarbon receptor activity in human breast milk and cryptorchidism: A case-control study within the prospective Norwegian HUMIS cohort.

BACKGROUND: The etiology of cryptorchidism remains poorly understood. Endocrine disrupting chemicals can impact estrogen signaling by interacting with aryl hydrocarbon receptor (AhR) activity. OBJECTIVE: To evaluate whether AhR activity in breast milk samples is associated with cryptorchidism. METHOD: We conducted a case-control study based on 199 mother-child pairs (n = 91 cases/108 controls) selected from the Norwegian Human Milk Study (2002-2009). We defined cases for cryptorchidism based on maternal reports at 1-, 6-, 12-, and 24- months after birth. Chemically- and biologically stable AhR activity (pg 2,3,7,8-TCDD equivalent (TEQ)/g lipid) was determined by DR- CALUX® assay in the mothers' milk collected at a median of 33 (10th-90th percentile: 18-57) days after delivery. We used multivariate logistic regression to compare AhR activity levels between cases and controls, and linear regression separately, to establish the relationship with the presence of 27 potential EDCs measured in breast milk and AhR activity. RESULTS: The average estimated daily intake (EDI) of dioxin and (dioxin-like (dl)-compounds via breast milk is 33.7 ± 17.9 pg TEQ/kg bodyweight per day among Norwegian children. There were no significant differences in AhR activation in breast milk samples between cases with cryptorchidism and controls. Among the 27 chemicals measured in breast milk, AhR activity was (borderline) significantly associated with all dl-PCBs, three non-dioxin-like (ndl)-PCBs (PCB-74, PCB-180, PCB-194) and two organochlorine pesticides (OCPs; HCB, ß-HCH). No associations between AhR activity and brominated flame retardants (PBDEs) or poly- and perfluoroalkyl substances (PFASs). CONCLUSION: No association between AhR activity and cryptorchidism was found among Norwegian boys. The average EDI of dioxin and dl-compounds in exclusively breastfed Norwegian infants remains above the safety threshold and, therefore requires further reduction measures. Consistent with a possible role in the observed AhR activity, all dl-PCBs were associated with AhR activity whereas the association was null for either PBDEs or PFASs.

Anti-androgenic compounds in breast milk and cryptorchidism among Norwegian boys in the HUMIS birth cohort.

The prevalence of cryptorchidism has increased over the past decades, yet its origins remain poorly understood. Testis descent is dependent on androgens and likely affected by endocrine disrupting compounds (EDCs), targeting the androgen receptor (AR). We investigated the association between anti-androgenic activity, not derived from natural hormones, in maternal breast milk and impaired testis descent among boys. We performed a case-control study based on 199 breast milk samples from 94 mothers of cryptorchid boys and 105 random non-cryptorchid boys participating in the Norwegian HUMIS (Human Milk Study) cohort. For each participant, apolar, and polar fractions were extracted, and combined to reconstitute a mixture. Anti-androgenic activity was measured in all three fractions using the human cell-based in vitro anti-AR CALUX® assay and expressed in µg of flutamide equivalent, a well-known antiandrogen. Results from fraction analyses were compared among boys with cryptorchidism and controls using multiple logistic regression, controlling for appropriate confounders identified using a directed acyclic graph. Children's daily exposure to anti-androgenic EDCs through breastfeeding was estimated to 78 µg flutamide eq./kg of body weigh/day. The activity was higher in the polar fraction (1.48 ± 1.37 µg flutamide eq./g of milk) mainly representing non-persistent chemicals, in contrast to other fractions. However, the activity in the polar extracts was decreased when in mixtures with the apolar fraction, indicating synergistic interactions. No significant difference in the activity was observed according to cryptorchid status for polar, apolar or mixed breast milk fractions. The study showed anti-androgenic activity in nearly all human milk samples, and at levels higher than the advisory threshold. However, no significant association was observed between cryptorchidism and antiandrogenic activity measured in either polar, apolar, or mixture fractions derived from breast milk.

Maternal polycystic ovary syndrome and attention deficit hyperactivity disorder in offspring at 3 years of age: Odense Child Cohort.

INTRODUCTION: Previous data suggested a link between maternal polycystic ovary syndrome (PCOS) and offspring attention deficit hyperactivity disorder (ADHD), which could be mediated by higher prenatal androgen exposure. MATERIAL AND METHODS: The study was part of the prospective Odense Child Cohort and included 1776 pregnant women, 165 (9%) with PCOS and 1607 (91%) controls. ADHD symptoms at 3 years of age were defined using the parent-reported questionnaire Child Behavior Checklist/1.5-5 (scores >90th centile of Danish national standard). Maternal blood samples were collected in the third trimester measuring total testosterone by mass spectrometry, sex hormone-binding globulin, and calculated free testosterone. Offspring anogenital distance was measured at 3 months of age. Regression models were performed with presence of ADHD symptoms as the dependent variable and adjusted for maternal age, body mass index, parity, smoking status, educational level, and parental psychiatric diagnoses. RESULTS: ADHD symptoms were present in 105/937 (11%) boys and 72/839 (9%) girls. In boys, maternal PCOS was positively associated with ADHD symptoms (unadjusted odds ratio [OR] 1.91, 95% CI 1.07-3.43, p = 0.03, adjusted OR 2.20, 95% CI 1.20-4.02, p = 0.01), whereas maternal PCOS was not associated with ADHD symptoms in girls. Maternal total testosterone, free testosterone, and offspring anogenital distance were not associated with higher risk of ADHD symptoms in the offspring. CONCLUSIONS: Higher risk of ADHD in boys born of mothers with PCOS were not associated with maternal third-trimester testosterone levels or offspring anogenital distance.

Reference intervals for trace elements in the general Danish population and their dependence on serum proteins.

Reference intervals that indicate the anticipated results of clinical chemistry parameters in a healthy background population are essential for the proper interpretation of laboratory data. In the present study, we analysed major trace elements in blood samples from 400 randomly selected members of the general Danish population. Reference intervals were established for trace elements in both whole blood and serum, and associations with major plasma transport proteins were investigated. In the case of a statistically significant correlation, a corresponding protein-adjusted reference interval was established for comparison with the unadjusted interval. While several trace elements correlated with albumin, ferritin and transferrin, the overall impact of transport proteins was minor and resulted in only marginal changes in the reference intervals. In conclusion, the updated reference intervals for trace elements can be employed without adjusting for plasma protein concentrations.

A case-cohort study of perinatal exposure to potential endocrine disrupters and the risk of cryptorchidism in the Norwegian HUMIS study.

BACKGROUND: Exposure to endocrine-disrupting chemicals (EDCs) during the critical period of testicular descent may increase the risk of cryptorchidism and male fertility. OBJECTIVE: To investigate 27 potential EDCs measured in breast milk as a proxy for perinatal exposure and the risk of cryptorchidism in a prospective cohort. METHOD: The Norwegian Human Milk Study (2002-2009) enrolled 2606 mother-infant pairs, of which 1326 were mother-son pairs. In a case-cohort design, we studied 641 male infants who had 27 EDCs already quantified in milk samples: 5 organochlorine pesticides, 14 polychlorinated biphenyls (PCBs), 6 brominated flame retardants, and 2 poly- and perfluoroalkyl substances. We defined cases of congenital, recurrent, persistent and ever-reported cryptorchidism based on questionnaires mothers completed when children were 1, 6, 12 and 24 months old. Variable selection via elastic net logistic regression identified the best cryptorchidism predictors while multivariable logistic regression models determined their effect estimates. RESULTS: The prevalence of reported congenital cryptorchidism was 6.1%, with half spontaneously descending within six months of birth, after which prevalence stabilized between 2.2 and 2.4%. The ever-reported prevalence of cryptorchidism at 1, 6, 12, or 24 months was 12.2%. Elastic net models identified PCB-74 (OR = 1.31, 95% CI: 1.001-1.703), PCB-114 (OR = 1.36, 95% CI: 1.05-1.77), PCB-194 (OR = 1.28, 95% CI: 1.03-1.53) and ß-HCH (OR = 1.26, 95% CI: 1.03-1.53 (per interquartile range increase in concentration of EDCs) as best predictors of congenital cryptorchidism. No EDCs were selected for either recurrent or persistent cryptorchidism, and only PCB-194 was selected by elastic net for ever-reported cryptorchidism (OR = 1.23, 95% CI: 1.01-1.51), in contrast to unpenalized multivariable logistic regression, where most of the individual congeners of PCBs showed significant associations. CONCLUSION: In the largest multi-pollutant analysis to date considering potential confounding from co-exposure to other chemicals, perinatal exposure to PCB-74, PCB-114, PCB-194 and ß-HCH were associated with increased odds of congenital cryptorchidism. Many PCBs may falsely be associated with cryptorchidism when assessed individually, due to confounding by highly correlated chemicals. Experimental studies are warranted to confirm our findings.

Exposure to perfluoroalkylated substances (PFAS) in relation to fitness, physical activity, and adipokine levels in childhood: The european youth heart study.

BACKGROUND: perfluoroalkylated substances (PFAS) are highly persistent chemicals that are able to alter the human metabolism - potentially via disruption of cell signaling pathways mediated by adipokines. Both adiponectin and leptin are influenced by and exert influence on energy storage and energy expenditure, wherefore associations between PFAS and adipokines may be mediated by fitness and fat mass. OBJECTIVES: the aim of this cross-sectional study was to investigate the association between childhood exposure to PFAS and adipokines (adiponectin and leptin), while considering associations between PFAS and children's level of fitness, physical activity and fat mass to elucidate potential mediation by fitness, physical activity and fat mass. METHODS: 9-year old children from Danish public schools were recruited in the European Youth Heart Study in 1997. For this study only children with valid measures on PFAS (PFOS, PFOA, PFNA, PFDA and PFHxS), adipokines (adiponectin and leptin), fitness, fat mass and co-variates (parity and maternal income) were included (N = 242). Multiple linear regression models with and without conditioning and causal mediation analysis were applied. RESULTS: this study found inverse associations between PFOA, PFDA and PFHxS and leptin. PFOA was positively associated with adiponectin, whereas PFHxS was inversely associated with adiponectin in boys. Latter association seemed to be mediated by fat mass. Associations with leptin showed indirect effects of fitness and fat mass but were unable to demonstrate significant mediation. Neither PFOS nor PFNA were associated with the outcome. DISCUSSION: these results may indicate a favorable leptin profile with increasing PFAS, although the results could be driven by residual negative confounding from socio-economic factors and mediation by fitness and fat mass.

Parental comorbidity and medication use in the USA: a panel study of 785 000 live births.

STUDY QUESTION: How prevalent is paternal medication use and comorbidity, and are rates of these rising? SUMMARY ANSWER: Paternal medication use and comorbidity is common and rising, similar to trends previously described in mothers. WHAT IS KNOWN ALREADY: Maternal medication use and comorbidity has been rising for the past few decades. These trends have been linked to potential teratogenicity, maternal morbidity and mortality and poorer fetal outcomes. STUDY DESIGN, SIZE, DURATION: This is a Panel (trend) study of 785 809 live births from 2008 to 2016. PARTICIPANTS/MATERIALS, SETTING, METHODS: We used the IBM© Marketscan®™ database to gather data on demographic information and International Classification of Diseases codes and Charlson comorbidity index (CCI) during the 12 months prior to the estimated date of conception for mothers and fathers. We similarly examined claims of prescriptions in the 3 months prior to conception. We performed companion analyses of medications used for >90 days in the 12 months prior to conception and of any medication use in the 12 months prior to conception. MAIN RESULTS AND THE ROLE OF CHANCE: We confirmed that both maternal medication use and comorbidity (e.g. hypertension, diabetes, hyperlipidemia) rose over the study period, consistent with prior studies. We found a concurrent rise in both paternal medication use 3 months prior to conception (overall use, 31.5-34.9% during the study period; P < 0.0001) and comorbidity (CCI of ≥1 and 10.6-18.0% over study period; P < 0.0001). The most common conditions seen in the CCI were chronic obstructive pulmonary disease for mothers (6.6-11.6%) and hyperlipidemia for fathers (8.6-13.7%). Similar trends for individual medication classes and specific comorbidities such as hypertension, diabetes and hyperlipidemia were also seen. All primary result trends were statistically significant, making the role of chance minimal. LIMITATIONS, REASONS FOR CAUTION: As this is a descriptive study, the clinical impact is uncertain and no causal associations may be made. Though the study uses a large and curated database that includes patients from across the USA, our study population is an insured population and our findings may not be generalizable. Mean parental age was seen to slightly increase over the course of the study (<1 year) and may be associated with increased comorbidity and medication use. WIDER IMPLICATIONS OF THE FINDINGS: As parental comorbidity and certain medication use may impact fecundability, temporal declines in parental health may impact conception, pregnancy and fetal outcomes. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: N/A.

Psychological stress, stressful life events, male factor infertility, and testicular function: a cross-sectional study.

OBJECTIVE: To assess the association between psychological stress and male factor infertility as well as testicular function (semen quality, serum reproductive hormones) and erectile dysfunction. DESIGN: Cross-sectional study. SETTING: University Hospital-based research center. PATIENTS: Men with impaired semen quality were included from infertile couples, and men with naturally conceived pregnant partners were used as a reference population. INTERVENTIONS: Participants completed a questionnaire on health and lifestyle, including a 14-item questionnaire about self-rated psychological stress symptoms and stressful life event (SLEs), had a physical examination performed, delivered a semen sample and had a blood sample drawn. MAIN OUTCOMES: Differences in stress scores (calculated from self-reported stress symptoms) and SLEs between infertile and fertile men were assessed in crude and fully adjusted linear regression models. Secondary outcomes were semen quality, serum reproductive hormones, and erectile dysfunction. RESULTS: Of 423 men, 176 (41.6%) experienced at least one SLE in the 3 months prior to inclusion (50.4%/36.9%: infertile/fertile men, P = .03); ß-coefficient and 95% confidence interval for the difference between the groups on the transformed scale in fully adjusted linear regression models was 0.18 (0.06, 0.30). However, there were no differences in psychological stress symptoms between the two groups (ß-coefficient and 95% confidence interval) on the transformed scale (0.14; -0.02, 0.30). No association between stress (self-reported stress symptoms and SLEs) and testicular function or with erectile dysfunction was found in any of the men. CONCLUSION: Infertile men reported a higher number of SLEs than fertile men but did not report more psychological stress symptoms. Distress and SLEs were not associated with reduced male reproductive function.

Association of Dietary Patterns With Testicular Function in Young Danish Men.

Importance: Diet may play a role in testicular function, but data on how adherence to different diet patterns influences human testicular function are scarce. Objective: To determine whether adherence to specific dietary patterns is associated with testicular function in young men. Design, Setting, and Participants: This cross-sectional study included 2935 young Danish men unselected regarding fertility status who were enrolled from April 1, 2008, through May 31, 2017. Data were analyzed from July 1, 2017, to January 30, 2019. Exposures: Dietary patterns identified with principal component analysis based on responses to a validated food frequency questionnaire. Main Outcomes and Measures: Standard semen quality assessment; serum concentrations of testosterone, free testosterone, estradiol, inhibin B, follicle-stimulating hormone, luteinizing hormone, and sex hormone-binding globulin; and testicular volume measured with ultrasonography. Results: Among the 2935 participants included in the analysis, median age was 19 (interquartile range, 19-20) years and 2290 (78.0%) had normal body mass index. The 4 dietary patterns identified included Western, prudent, open-sandwich (a traditional Danish eating pattern), and vegetarianlike. The greatest adherence to the prudent pattern was associated with the highest total sperm count (median, 167 [95% CI, 146-183] million), followed by adherence to vegetarianlike (median, 151 [95% CI, 134-168] million) and open-sandwich (median, 146 [95% CI, 131-163] million) patterns. Adherence to the Western pattern was associated with the lowest total sperm count (median, 122 [95% CI, 109-138] million), which was significantly lower than sperm count in the other 3 diet patterns. After adjusting for confounders, the median total sperm count for men in the highest quintile of adherence to the Western pattern was 26 million lower (95% CI, -42 to -9 million) than for men in the lowest quintile of adherence to this pattern. Conversely, the median total sperm count of men in the highest quintile of adherence to the prudent pattern was 43 million (95% CI, 23-63 million) higher than that of men in the lowest quintile. Men with the highest adherence to the Western pattern had a lower median ratio of inhibin B to follicle-stimulating hormone (-12 [95% CI, -20 to -3]) and higher median ratio of free testosterone to luteinizing hormone (10 [95% CI, 2-19]) compared with men with lowest adherence to this pattern. Conclusions and Relevance: In this cross-sectional study, adherence to generally healthy diet patterns was associated with better semen quality, with potentially more favorable fertility potential among adult men.

Higher circulating plasma polychlorinated biphenyls (PCBs) in fit and lean children: The European youth heart study.

BACKGROUND: Lipophilic compounds such as polychlorinated biphenyls (PCBs) are primarily stored in adipose tissue, but exercise-induced lipolysis is able to release PCBs from the adipose tissue into the circulation. The plasma concentration, distribution and metabolism of PCBs can thus vary much among individuals due to inter-human variations in lifestyle behavior and pharmacokinetics. OBJECTIVES: We examined the observational relationship of circulating plasma PCB concentrations with cardiorespiratory fitness, engagement in vigorous physical activity and fat mass in a healthy Danish child population. METHODS: Data on ∑PCB (PCB138, PCB153 and PCB180), cardiorespiratory fitness, skinfold thickness and objectively measured physical activity of 509 children derived from the Danish sub-study of The European Youth Heart Study. RESULTS: Higher fitness and greater leanness were associated with elevated plasma ∑PCB in both boys and girls. The associations were independent of each other and persisted after controlling for socio-economic status and duration of breastfeeding. We observed an almost three-fold increase in plasma ∑PCB level in the most fit/least fat children relative to the least fit/most fat children. The association between fatness and ∑PCB was strongest for boys as girls, and especially pubertal girls, displayed lower decrease in plasma ∑PCB with higher fat mass. DISCUSSION: Our findings suggest that increased lipolysis stimulates the release of PCBs into the vasculature. The consequence is higher plasma levels of PCB in very fit and lean subjects. This scenario is likely to cause negative confounding in epidemiological observations of PCB and cardio-metabolic health. At the same time adipose tissue may play a dual role in promoting adverse health and providing a relatively safe place to store PCB.