1,110 results on '"Main, Katharina"'
Search Results
202. Populations, decreasing fertility, and reproductive health
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Skakkebaek, Niels E, primary, Jørgensen, Niels, additional, Andersson, Anna-Maria, additional, Juul, Anders, additional, Main, Katharina M, additional, Jensen, Tina Kold, additional, and Toppari, Jorma, additional
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- 2019
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203. Variations in repeated serum concentrations of UV filters, phthalates, phenols and parabens during pregnancy
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Assens, Maria, primary, Frederiksen, Hanne, additional, Petersen, Jørgen Holm, additional, Larsen, Torben, additional, Skakkebæk, Niels E., additional, Juul, Anders, additional, Andersson, Anna-Maria, additional, and Main, Katharina M., additional
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- 2019
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204. Lower birth weight and increased body fat at school age in children prenatally exposed to modern pesticides: a prospective study
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Grandjean Philippe, Jensen Tina K, Boas Malene, Schmidt Ida M, Main Katharina M, Wohlfahrt-Veje Christine, Skakkebæk Niels E, and Andersen Helle R
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pesticides ,prenatal exposure ,birth weight ,body composition ,maternal smoking ,Industrial medicine. Industrial hygiene ,RC963-969 ,Public aspects of medicine ,RA1-1270 - Abstract
Abstract Background Endocrine disrupting chemicals have been hypothesized to play a role in the obesity epidemic. Long-term effects of prenatal exposure to non-persistent pesticides on body composition have so far not been investigated. The purpose of this study was to assess possible effects of prenatal exposure to currently used pesticides on children's growth, endocrine and reproductive function. Methods In a prospective study of 247 children born by women working in greenhouses in early pregnancy, 168 were categorized as prenatally exposed to pesticides. At three months (n = 203) and at 6 to11 years of age (n = 177) the children underwent a clinical examination and blood sampling for analysis of IGF-I, IGFBP3 and thyroid hormones. Body fat percentage at age 6 to11 years was calculated from skin fold measurements. Pesticide related associations were tested by linear multiple regression analysis, adjusting for relevant confounders. Results Compared to unexposed children birth weight and weight for gestational age were lower in the highly exposed children: -173 g (-322; -23), -4.8% (-9.0; -0.7) and medium exposed children: -139 g (-272; -6), -3.6% (-7.2; -0.0). Exposed (medium and highly together) children had significantly larger increase in BMI Z-score (0.55 SD (95% CI: 0.1; 1.0) from birth to school age) and highly exposed children had 15.8% (0.2; 34.6) larger skin folds and higher body fat percentage compared to unexposed. If prenatally exposed to both pesticides and maternal smoking (any amount), the sum of four skin folds was 46.9% (95% CI: 8.1; 99.5) and body fat percentage 29.1% (95% CI: 3.0; 61.4) higher. There were subtle associations between exposure and TSH Z-score -0.66(-1.287; -0.022) and IGF-I Z-score (girls: -0.62(-1.0; -0.22), boys: 0.38(-0.03; 0.79)), but not IGFBP3. Conclusions Occupational exposure to currently used pesticides may have adverse effects in spite of the added protection offered to pregnant women. Maternal exposure to combinations of modern, non-persistent pesticides during early pregnancy was associated with affected growth, both prenatally and postnatally. We found a biphasic association with lower weight at birth followed by increased body fat accumulation from birth to school age. We cannot rule out some residual confounding due to differences in social class, although this was adjusted for. Associations were stronger in highly exposed than in medium exposed children, and effects on body fat content at school age was potentiated by maternal smoking in pregnancy.
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- 2011
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205. Growth hormone, insulin-like growth factor I and its binding proteins 1 and 3 in last trimester intrauterine growth retardation with increased pulsatility index in the umbilical artery
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Larsen, Torben, Main, Katharina, Andersson, Anne Marie, Juul, Anders, Greisen, Gorm, and Skakkebæk, Niels Erik
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- 1996
206. A longitudinal study of urinary phthalate excretion in 58 full-term and 67 preterm infants from birth through 14 months
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Frederiksen, Hanne, Kuiri-Hanninen, Tanja, Main, Katharina M., Dunkel, Leo, and Sankilampi, Ulla
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Infants -- Physiological aspects -- Health aspects ,Phthalates -- Health aspects -- Physiological aspects ,Pediatric research ,Environmental issues ,Health - Abstract
Background: Some phthalates have shown antiandrogenic effects in rat offspring. Premature infants may be exposed to high amounts of specific phthalates during hospitalization, and thus are potentially at risk. Objective: We evaluated longitudinal phthalate exposure and metabolism in full-term (FT) and preterm (PT) infants. Methods: Fifty-eight FT and 67 PT (gestational age, 24.7-36.6 weeks) infants were recruited at birth and followed until 14 months (nine times). Urinary concentrations of metabolites of diethyl phthalate (DEP), dibutyl phthalate isomers (DiBP and DnBP), butylbenzyl phthalate (BBzP), di(2-ethylhexyl) phthalate (DEHP), and diisononyl phthalate (DiNP) were measured in 894 samples. Daily intake and a hazard index for antiandrogenic effects were estimated, and excretion patterns of DEHP and DiNP metabolites were analyzed. ResulTS: Metabolites of BBzP, DiNP, and DEHP were 5-50 times higher at day 7 (D7) and month 1 (M1) in PT than in FT infants. Thereafter, metabolite concentrations were similar between the two groups. The estimated hazard index for combined DiBP, DnBP, BBzP, and DEHP exposures 7 days after birth exceeded the antiandrogenic threshold in > 80% of PT and > 30% of FT infants, and after M2, in 30% of all infants. The excretion pattern of DEHP and DiNP metabolites changed with age. Conclusion: Most PT infants and approximately one-third of healthy FT newborns were exposed to phthalates during early life at a potentially harmful level according to the European Food Safety Authority's recommended limits of daily exposure. Changes in the relative proportions of secondary phthalate metabolites over time were consistent with maturation of infant metabolic pathways during the first year of life. Further research is needed on the health effects of phthalate exposures and the influence of changes in metabolic capacity in neonates and infants. http://dx.doi.org/10.1289/ehp.1307569, Introduction Phthalates are widely used as plasticizers in, for example, toys, cosmetics, food packaging, medical equipment, and building materials (Wittassek et al. 2011). Some of the most commonly used phthalates [...]
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- 2014
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207. Urinary bisphenol A levels in young men: association with reproductive hormones and semen quality
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Lassen, Tina Harmer, Frederiksen, Hanne, Jensen, Tina Kold, Petersen, Jorgen Holm, Joensen, Ulla N., Main, Katharina M., Skakkebaek, Niels E., Juul, Anders, Jorgensen, Niels, and Andersson, Anna-Maria
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Environmental health -- Research ,Environment -- Research ,Young men -- Health aspects ,Urine -- Health aspects ,Bisphenol-A -- Health aspects -- Environmental aspects ,Environmental issues ,Health - Abstract
BACKGROUND: Few human studies have examined bisphenol A (BPA) exposure in relation to semen quality and reproductive hormones in men, and results are divergent. OBJECTIVES: We examined associations between urinary BPA concentration and reproductive hormones, as well as semen quality, in young men from the general population. METHODS: Our study population consisted of 308 young men from the general population. Urinary BPA concentration was measured by isotope dilution TurboFlow-liquid chromatography- tandem mass spectrometry. We used multiple linear regression analysis to estimate associations between BPA concentration and reproductive hormones and semen quality, adjusting for confounding factors. RESULTS: We found that 98% of the men had detectable urinary levels of BPA. Median (5th-95th percentiles) BPA concentration was 3.25 ng/mL (0.59-14.89 ng/mL). Men with BPA concentrations above the lowest quartile had higher concentrations of serum testosterone, luteinizing hormone (LH), estradiol, and free testosterone compared with the lowest quartile ([p.sub.trend] ≤ 0.02). Men in the highest quartile of BPA excretion had on average 18% higher total testosterone (95% CI: 8, 28%), 22% higher LH (95% CI: 6, 39%), and 13% higher estradiol (95% CI: 4, 24%) compared with lowest quartile. Men in the highest quartile of BPA also had significantly lower percentage progressive motile spermatozoa compared with men in the lowest quartile (-6.7 percentage points, 95% CI: -11.76, -1.63). BPA was not associated with other semen parameters. Adjusting for dietary patterns did not influence the results. CONCLUSIONS: The pattern of associations between BPA and reproductive hormones could indicate an antiandrogenic or antiestrogenic effect, or both, of BPA on the hypothalamic-pituitary-gonadal hormone feedback system, possibly through a competitive inhibition at the receptor level. However, additional research is needed to confirm our findings and to further test the suggested potential mechanisms. Environ Health Perspect 122:478-484; http://dx.doi.org/10.1289/ehp.1307309, Introduction Concern has been raised about the endocrine-disrupting effects of exposure to the widely used chemical bisphenol A (BPA) including its effects on male reproductive health (Richter et al. 2007; [...]
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- 2014
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208. The AMH genotype (rs10407022 T>G) is associated with circulating AMH levels in boys, but not in girls
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Greiber, Iben Katinka, Hagen, Casper P, Busch, Alexander Siegfried, Mieritz, Mikkel Grunnet, Aksglæde, Lise, Main, Katharina, Almstrup, Kristian, Juul, Anders, Greiber, Iben Katinka, Hagen, Casper P, Busch, Alexander Siegfried, Mieritz, Mikkel Grunnet, Aksglæde, Lise, Main, Katharina, Almstrup, Kristian, and Juul, Anders
- Abstract
OBJECTIVE: Fetal anti-Müllerian hormone (AMH) is responsible for normal male sexual differentiation, and circulating AMH is used as a marker of testicular tissue in newborns with disorders of sex development. Little is known about the mechanism of action in postnatal life. A recent genome wide association study (GWAS) reported genetic variation of AMH affecting AMH levels in young men. This study investigated the effect of genetic variation of AMH and AMH type II receptor (AMHR2) (AMHrs10407022 T>G and AMHR2rs11170547 C>T) on circulating reproductive hormone levels and pubertal onset in boys and girls.DESIGN AND METHODS: This study is a combined longitudinal and cross-sectional study in healthy Danish boys and girls from the general population. We included 658 boys aged 5.8-19.8 years and 320 girls aged 5.6-16.5 years. The main outcome measures were genotyping of AMH and AMHR2, pubertal staging and serum levels of reproductive hormones.RESULTS: AMHrs10407022T>G was associated with higher serum levels of AMH in prepubertal boys (TT: 575 pmol/L vs TG: 633 pmol/L vs GG: 837 pmol/L, P = 0.002) and adolescents (TT: 44 pmol/L vs TG: 58 pmol/L vs GG: 79 pmol/L, P < 0.001). Adolescent boys carrying the genetic variation also had lower levels of LH (TT: 3.0 IU/L vs TG: 2.8 IU/L vs GG: 1.8 IU/L, P = 0.012). Hormone levels in girls and pubertal onset in either sex did not seem to be profoundly affected by the genotypes.CONCLUSION: Our findings support recent GWAS results in young adults and expand our understanding of genetic variation affecting AMH levels even in boys prior to the pubertal decline of circulating AMH.
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- 2018
209. Prenatal pesticide exposure associated with glycated haemoglobin and markers of metabolic dysfunction in adolescents
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Andersen, Helle Raun, Tinggaard, Jeanette, Grandjean, Philippe, Jensen, Tina K., Dalgård, Christine, Main, Katharina M., Andersen, Helle Raun, Tinggaard, Jeanette, Grandjean, Philippe, Jensen, Tina K., Dalgård, Christine, and Main, Katharina M.
- Abstract
Background: Pesticide exposure has been associated with increased risk of diabetes mellitus in adults, but potential effects of prenatal exposure on glucose regulation have not been investigated. The aim of this study was to investigate if maternal occupational pesticide exposure in pregnancy was associated with glycated haemoglobin A1c (HbA1c) in adolescents and whether an association was modified by sex and paraoxonase-1 (PON1) Q192R polymorphism. Methods: A prospective cohort study of children whose mothers were either occupationally exposed or unexposed to pesticides in early pregnancy. At age 10-to-16 years, the children (n = 168) underwent clinical examinations including pubertal stage assessment (accepted by 141 children) and blood sampling. PON1 Q192R genotype was available for 139 children and 103 mothers. The main outcome measure was HbA1c but other relevant biomarkers were also included. Results: Prenatal pesticide exposure was associated with a 5.0% (95% confidence interval: 1.8; 8.2) higher HbA1c compared to unexposed children after adjustment for confounders. After stratification, the association remained significant for girls (6.2% (1.6; 11.1)) and if the child or the mother had the PON1 192R-allele (6.1% (1.6; 10.8) and 7.1% (2.0; 12.6), respectively). Besides, an exposure-related increase was seen for the leptin-to-adiponectin ratio, for plasminogen activator inhibitor type-1 in girls, and for interleukin-6 in children whose mothers had the R-allele. Conclusion: Prenatal pesticide exposure was associated with higher HbA1c and changes in related biomarkers in adolescents. Our results suggest an adverse effect on glucose homeostasis and support previous findings from this cohort of an exposure-associated metabolic risk profile with higher susceptibility related to female sex and the PON1 192R-allele.
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- 2018
210. Sex Differences in Reproductive Hormones During Mini-Puberty in Infants With Normal and Disordered Sex Development
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Johannsen, Trine Holm, Main, Katharina Maria, Ljubicic, Marie Lindhardt, Jensen, Tina Kold, Andersen, Helle Raun, Andersen, Marianne Skovsager, Petersen, Jørgen Holm, Andersson, Anna-Maria, Juul, Anders, Johannsen, Trine Holm, Main, Katharina Maria, Ljubicic, Marie Lindhardt, Jensen, Tina Kold, Andersen, Helle Raun, Andersen, Marianne Skovsager, Petersen, Jørgen Holm, Andersson, Anna-Maria, and Juul, Anders
- Abstract
Context The early activation of the hypothalamic-pituitary-gonadal axis during infancy can be used in the evaluation of infants suspected of disorders of sex development (DSD). However, few data exist on sex-specific reference ranges for these hormones during early life. Objective To evaluate sex differences in reproductive hormone concentrations in serum from healthy infants to define sex-specific cutoff values and to apply these in infants with DSD. Design A cross-sectional study. Setting A tertiary center for pediatric endocrinology at the University Hospital of Copenhagen. Patients or Other Participants Healthy infants (1840) and patients with DSD (27), aged 2 to 5 months. Main Outcome Measures Serum concentrations of LH, FSH, testosterone (T), estradiol, sex hormone–binding globulin (SHBG), inhibin B, anti-Müllerian hormone (AMH), dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), 17-hydroxyprogesterone (17-OHP), androstenedione, and LH/FSH ratio. Results LH and FSH concentrations showed overlap between sexes, with LH being highest in boys and FSH being highest in girls. The LH/FSH ratio separated infant boys from girls with minimal overlap at a cutoff value of 0.32. Inhibin B and AMH concentrations were markedly higher in boys compared with girls, with minimal or no overlap. In infants with Klinefelter syndrome, 45,X/46,XY mosaicism and male phenotype, and Turner syndrome, the LH/FSH ratio matched the gender of rearing. However, infants with complete androgen insensitivity syndrome had LH/FSH ratios within the male range. Conclusions Reference ranges for reproductive hormones and LH/FSH ratio during mini-puberty were established in this study. The classifiers that best separated sex in mini-puberty were AMH, LH/FSH ratio, and T. Use of the LH/FSH ratio may add valuable information in the workup of infants suspected of DSD.
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- 2018
211. Adrenal Suppression in Infants Treated with Topical Ocular Glucocorticoids
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Bangsgaard, Regitze, Main, Katharina M, Boberg-Ans, Gøril, la Cour, Morten, Forman, Julie Lyng, Haargaard, Birgitte, Kiilgaard, Jens Folke, Bangsgaard, Regitze, Main, Katharina M, Boberg-Ans, Gøril, la Cour, Morten, Forman, Julie Lyng, Haargaard, Birgitte, and Kiilgaard, Jens Folke
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PURPOSE: To analyze the incidence of adrenal suppression and the glucocorticoid (GC) dose per kilogram body weight given in infants treated with standard protocol for topical ophthalmic GCs after congenital cataract surgery.DESIGN: Retrospective, consecutive case series.PARTICIPANTS: All children younger than 2 years of age who underwent operation for congenital cataract between January 2011 and May 2015 in 1 center.METHODS: Patient charts were reviewed to collect data on results and timing of a standard corticotropin (adrenocorticotropic hormone [ACTH]) stimulation test and GC dose per kilogram body weight.MAIN OUTCOME MEASURES: Incidence of adrenal suppression in children tested on GC treatment. Glucocorticoid dose per kilogram body weight.RESULTS: Among 26 consecutive infants, 15 (58%) were tested while they were still on GC treatment. Ten of these 15 infants (67%) had adrenal suppression, 2 of whom had obvious clinical signs of Cushing's syndrome and 1 of whom had signs of Addisonian crises during general anesthesia. Eleven of the 26 infants (42%) were tested at a median time of 21 days (range, 6-89) after treatment cessation, and they all had normal test results. Children with suppressed adrenal function had received cumulative GC doses per body weight that were significantly higher the last 5 days before testing compared with children with normal test results. Infants with adrenal suppression were treated with hydrocortisone replacement therapy. Adrenal function recovered after a median of 3.1 months (range, 2.3 months to 2.3 years).CONCLUSIONS: Two thirds of the infants tested during treatment with a standard GC protocol after congenital cataract surgery showed adrenal suppression. There was a significant association between the cumulative daily dose of GCs and the test result. Because adrenal suppression is a serious but treatable condition, we recommend a systematic assessment of adrenal function in infants treat
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- 2018
212. A complex phenotype in a family with a pathogenic SOX3 missense variant
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Jelsig, Anne M, Diness, Birgitte R, Kreiborg, Sven, Main, Katharina, Larsen, Vibeke A, Hove, Hanne, Jelsig, Anne M, Diness, Birgitte R, Kreiborg, Sven, Main, Katharina, Larsen, Vibeke A, and Hove, Hanne
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Duplications and deletions of Xq26-27 including SOX3 (Xq27.1) have been associated with X-linked mental retardation and isolated growth hormone deficiency (OMIM 300123) or X-linked panhypopituitarism (OMIM 312000). Yet, pathogenic point mutations seem to be extremely rare. We report a family with three affected males with several clinical features including mild intellectual disability, microphthalmia, coloboma, hypopituitarism, facial dysmorphology and dental anomalies, including microcephaly, retrognathia and a solitary median maxillary central incisor amongst other features. Using Whole Exome Sequencing a missense variant in SOX3, NM_005634.2:c.449C>A; p.(Ser150Tyr) was identified. Segregation analysis in the family demonstrated that the variant was inherited through healthy females with its origin in the maternal grandmother showing germline mosaicism. Thus, we report one of the first cases of a pathogenic variant in SOX3 and germline mosaicism of this variant.
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- 2018
213. The possible impact of antenatal exposure to ubiquitous phthalates upon male reproductive function at 20 years of age
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Hart, Roger J., Frederiksen, Hanne, Doherty, Dorota A., Keelan, Jeffrey A., Skakkebaek, Niels E., Minaee, Noviani S., McLachlan, Robert, Newnham, John P., Dickinson, Jan E., Pennell, Craig E., Norman, Robert J., Main, Katharina M., Hart, Roger J., Frederiksen, Hanne, Doherty, Dorota A., Keelan, Jeffrey A., Skakkebaek, Niels E., Minaee, Noviani S., McLachlan, Robert, Newnham, John P., Dickinson, Jan E., Pennell, Craig E., Norman, Robert J., and Main, Katharina M.
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Phthalates are ubiquitous environmental endocrine-disrupting chemicals suspected to interfere with developmental androgen action leading to adverse effects on male reproductive function. Prenatal exposure studies in rodents show cryptorchidism, hypospadias and reduced testicular volume (TV), testosterone and anogenital distance in males. It is postulated that there is a developmental window in utero when phthalate exposure has the most potent adverse effects. Some human studies show associations between prenatal phthalate exposure and reduced calculated "free" serum testosterone in infant boys and shorter anogenital distance. However, there are no data available yet which link antenatal exposure to long-term effects in men. We aimed to correlate antenatal phthalate exposure with adult TV, semen parameters and serum reproductive hormone concentrations. 913 men from the Western Australian (Raine) Pregnancy Cohort were contacted aged 20-22 years. 423 (56%) agreed to participate; 404 underwent testicular ultrasound examination; 365 provided semen samples, and reproductive hormones were measured in 384. Maternal antenatal serum phthalate metabolite measurements were available for 185 and 111 men, who provided serum and semen, respectively. Maternal serum collected at 18 and 34 weeks gestation, stored at -80°C, was pooled and analyzed for 32 phthalate metabolites by liquid chromatography-tandem mass spectrometry. TV was calculated, semen analysis performed by WHO approved methods, and serum concentrations of gonadotrophins, inhibin B, and testosterone measured. Eleven phthalate metabolites were detected. Primary and secondary metabolites of di-(2-ethyl-hexyl) phthalate (DEHP) and di-iso-nonyl phthalate (DiNP) were positively correlated. After correction for adult height, BMI, presence of a varicocele and exposure to maternal smoking mono-iso-nonyl phthalate (MiNP) (r = -0.22) and sums of DEHP and DiNP metabolites (r = -0.24) and the sum of the metabolites of the high m
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- 2018
214. Association of in Utero Persistent Organic Pollutant Exposure with Placental Thyroid Hormones
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Li, Zhong Min, Hernandez-Moreno, David, Main, Katharina Maria, Skakkebæk, Niels Erik, Kiviranta, Hannu, Toppari, Jorma, Feldt-Rasmussen, Ulla, Shen, Heqing, Schramm, Karl Werner, De Angelis, Meri, Li, Zhong Min, Hernandez-Moreno, David, Main, Katharina Maria, Skakkebæk, Niels Erik, Kiviranta, Hannu, Toppari, Jorma, Feldt-Rasmussen, Ulla, Shen, Heqing, Schramm, Karl Werner, and De Angelis, Meri
- Abstract
In utero exposure to persistent organic pollutants (POPs) can result in thyroid function disorder, leading to concerns about their impact on fetal and neonatal development. The associations between placental levels of various POPs and thyroid hormones (THs) were investigated. In a prospective Danish study initially established for assessing congenital cryptorchidism, 58 placenta samples were collected from mothers of boys born with (n =28) and without (n =30) cryptorchidism. The concentrations of polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs), organotin chemicals (OTCs), organochlorine pesticides (OCPs), T 4, T 3, and rT 3 were measured. The associations between placental THs and various POPs were analyzed using multiple linear regression. Five PBDEs, 35 PCBs, 14 PCDD/Fs, 3 OTCs, 25 OCPs, T 4, T 3, and rT 3 were measured. No correlation between THs and the odds of cryptorchidism was found. Several POPs were significantly associated with THs: (1) T 4 was inversely associated with BDEs 99, 100, Σ PBDE, and 2378-TeCDD, and positively associated with 1234678-HpCDF; (2) T 3 was positively associated with 2378-TeCDF and 12378-PeCDF; and (3) rT 3 was positively associated with PCB 81, 12378-PeCDF, and 234678-HxCDF, and inversely associated with tributyltin, Σ OTC, and methoxychlor. These results revealed that POP exposures were associated with TH levels in placenta, which may be a possible mechanism for the impacts of POP exposures on children's growth and development. This study provides new insight into the complexity of thyroid-disrupting properties of POPs. More research is needed to elucidate the biological consequences of POP exposures.
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- 2018
215. Postnatal Changes in Testicular Position Are Associated With IGF-I and Function of Sertoli and Leydig Cells
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Koskenniemi, Jaakko J, Virtanen, Helena E, Wohlfahrt-Veje, Christine, Löyttyniemi, Eliisa, Skakkebaek, Niels E, Juul, Anders, Andersson, Anna-Maria, Main, Katharina M, Toppari, Jorma, Koskenniemi, Jaakko J, Virtanen, Helena E, Wohlfahrt-Veje, Christine, Löyttyniemi, Eliisa, Skakkebaek, Niels E, Juul, Anders, Andersson, Anna-Maria, Main, Katharina M, and Toppari, Jorma
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Context: Despite clinical guidelines calling for repetitive examination of testicular position during childhood, little is known of normal changes in testicular position during childhood, let alone factors that control it.Objective: To assess changes in and factors associated with testicular position during childhood.Design: Testicular position (the distance from the pubic bone to the upper pole of the testes) at birth, 3 months, 18 months, 36 months, and 7 years and reproductive hormones at 3 months were measured.Setting: Prenatally recruited, prospective longitudinal birth cohort.Participants: A total of 2545 boys were recruited prenatally in a Danish-Finnish birth cohort and had a testicular position examination available. A subset of 680 Danish and 362 Finnish boys had serum reproductive hormone concentrations and insulin-like growth factor I (IGF-I) determined at 3 months.Main Outcome Measures: Testicular distance to pubic bone (TDP), serum reproductive hormone, and IGF-I concentrations.Results: TDP increased from birth to 3 months and decreased thereafter. Length, gestational age, weight for gestational age, and penile length were positively associated with larger TDP and thus lower testicular position in a linear mixed-effect model. Furthermore, IGF-I concentration, inhibin B/follicle-stimulating hormone ratio, and testosterone/luteinizing hormone ratio were all independently and positively associated with longer TDP.Conclusions: We provide longitudinal data on postnatal changes in TDP. TDP is dynamic and associated with Leydig and Sertoli cell function as well as with IGF-I levels during the first months of life at mini-puberty of infancy. TDP may thus be a useful biomarker of postnatal testicular function.
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- 2018
216. Morbidity, Mortality, and Socioeconomics in Females With 46,XY Disorders of Sex Development:A Nationwide Study
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Berglund, Agnethe, Johannsen, Trine H, Stochholm, Kirstine, Viuff, Mette H, Fedder, Jens, Main, Katharina M, Gravholt, Claus H, Berglund, Agnethe, Johannsen, Trine H, Stochholm, Kirstine, Viuff, Mette H, Fedder, Jens, Main, Katharina M, and Gravholt, Claus H
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Context: Little is known about long-term health outcomes in phenotypic females with 46,XY disorders of sex development (XY females), and the socioeconomic profile has not been described in detail.Objective: To describe morbidity, mortality, and socioeconomic status in XY females in a comparison to the general population.Design: Nationwide registry study with complete follow-up.Setting: Uniform public health care system.Participants: A total of 123 XY females karyotyped in Denmark during 1960 to 2012 and a randomly selected age-matched control cohort of 12,300 females and 12,300 males from the general population.Main Outcome Measures: Overall mortality and morbidity as well as cause-specific morbidity; medicine use and socioeconomics (education, income, cohabitation, motherhood, and retirement).Results: Compared with female controls, overall morbidity was increased in XY females [hazard ratio (HR), 1.72; 95% confidence interval (CI), 1.43 to 2.08] but not when excluding diagnoses associated with the specific disorder of sex development (DSD) diagnosis or pregnancy and birth (HR, 1.13; CI, 0.93 to 1.37). Mortality was similar to controls (HR, 0.79; CI, 0.35 to 1.77). Cohabitation (HR, 0.44; CI, 0.33 to 0.58) and motherhood (HR, 0.10; CI, 0.05 to 0.18) were reduced in XY females but education (HR, 0.92; CI, 0.61 to 1.37) was similar to controls. Income was higher than among controls in the older years.Conclusions: Morbidity was not increased in XY females when excluding diagnoses associated to the DSD condition per se. Judged on education and income, XY females perform well in the labor market. However, DSD seems to impact on the prospects of family life.
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- 2018
217. Interaction between prenatal pesticide exposure and a common polymorphism in thegene on DNA methylation in genes associated with cardio-metabolic disease risk-an exploratory study
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Declerck, Ken, Remy, Sylvie, Wohlfahrt-Veje, Christine, Main, Katharina M, Van Camp, Guy, Schoeters, Greet, Vanden Berghe, Wim, Andersen, Helle R, and Cardio-vascular diseases
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Male ,DNA methylation ,Genotype ,Aryldialkylphosphatase ,pesticides ,gene-environment interaction ,Maternal Exposure ,Prenatal Exposure Delayed Effects ,Journal Article ,Humans ,Female ,Disease Susceptibility ,pregnancy ,Prospective Studies ,Child ,METABOLIC SYNDROME ,Oligonucleotide Array Sequence Analysis - Abstract
BACKGROUND: Prenatal environmental conditions may influence disease risk in later life. We previously found a gene-environment interaction between the paraoxonase 1 (PON1) Q192R genotype and prenatal pesticide exposure leading to an adverse cardio-metabolic risk profile at school age. However, the molecular mechanisms involved have not yet been resolved. It was hypothesized that epigenetics might be involved. The aim of the present study was therefore to investigate whether DNA methylation patterns in blood cells were related to prenatal pesticide exposure level,PON1Q192R genotype, and associated metabolic effects observed in the children. METHODS: Whole blood DNA methylation patterns in 48 children (6-11 years of age), whose mothers were occupationally unexposed or exposed to pesticides early in pregnancy, were determined by Illumina 450 K methylation arrays. RESULTS: A specific methylation profile was observed in prenatally pesticide exposed children carrying thePON1192R-allele. Differentially methylated genes were enriched in several neuroendocrine signaling pathways including dopamine-DARPP32 feedback (appetite, reward pathways), corticotrophin releasing hormone signaling, nNOS, neuregulin signaling, mTOR signaling, and type II diabetes mellitus signaling. Furthermore, we were able to identify possible candidate genes which mediated the associations between pesticide exposure and increased leptin level, body fat percentage, and difference in BMIZscore between birth and school age. CONCLUSIONS: DNA methylation may be an underlying mechanism explaining an adverse cardio-metabolic health profile in children carrying thePON1192R-allele and prenatally exposed to pesticides.
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- 2017
218. The effects of long-term opioid treatment on the immune system in chronic non-cancer pain patients: A systematic review.
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Diasso, Pernille D. K., Birke, Hanne, Nielsen, Susanne D., Main, Katharina M., Højsted, Jette, Sjøgren, Per, and Kurita, Geana P.
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THERAPEUTIC use of narcotics ,CHRONIC pain ,ANALGESICS ,SYSTEMATIC reviews ,IMMUNE system - Abstract
Background and Objective: Opioids have been increasingly prescribed for chronic non-cancer pain (CNCP). An association between long-term opioid treatment (L-TOT) of CNCP patients and suppression of both the innate and the adaptive immune system has been proposed. This systematic review aims at investigating the effects of L-TOT on the immune system in CNCP patients.Databases and Data Treatment: A systematic search of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and the CINAHL for relevant articles was performed. Studies examining measures of both the innate and the adaptive immune system in adult CNCP patients in L-TOT (≥4 weeks of intake) were included. Outcomes and the level of evidence were analysed.Results: A total of 382 studies were identified; however, 376 were excluded (352 inappropriate methodology, 21 duplicates, three full-text could not be obtained) and one randomized controlled trial (RCT) and five cross-sectional studies were included and analysed. L-TOT compared with no treatment was associated with a lower percentage of natural killer (NK) cells, a lower absolute number of CD56bright NK cells, a higher absolute number of IL-2-activated NK cells and a higher concentration of IL-1β as a response to toll-like receptor (TLR) agonists stimulation (Pam3CSK4, LPS, Imiquimod). No other significant differences were reported. Generalizability of the results was limited due to inconsistency of outcomes and an overall low quality of the studies.Conclusions: L-TOT may alter the immune system in CNCP patients, but the level of evidence is still weak. More studies are needed to clarify the impact of L-TOT on immune system function.Significance: This systematic review found indication that long-term opioid treatment alters the immune system in chronic non-cancer pain patients. These alterations involved the NK cells and IL-1β production. However, the level of evidence is weak. [ABSTRACT FROM AUTHOR]- Published
- 2020
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219. Prenatal pesticide exposure associated with glycated haemoglobin and markers of metabolic dysfunction in adolescents
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Andersen, Helle Raun, primary, Tinggaard, Jeanette, additional, Grandjean, Philippe, additional, Jensen, Tina K., additional, Dalgård, Christine, additional, and Main, Katharina M., additional
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- 2018
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220. Adrenal Suppression in Infants Treated with Topical Ocular Glucocorticoids
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Bangsgaard, Regitze, primary, Main, Katharina M., additional, Boberg-Ans, Gøril, additional, la Cour, Morten, additional, Forman, Julie Lyng, additional, Haargaard, Birgitte, additional, and Kiilgaard, Jens Folke, additional
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- 2018
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221. Association of In Utero Persistent Organic Pollutant Exposure With Placental Thyroid Hormones
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Li, Zhong-Min, primary, Hernandez-Moreno, David, additional, Main, Katharina Maria, additional, Skakkebæk, Niels Erik, additional, Kiviranta, Hannu, additional, Toppari, Jorma, additional, Feldt-Rasmussen, Ulla, additional, Shen, Heqing, additional, Schramm, Karl-Werner, additional, and De Angelis, Meri, additional
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- 2018
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222. Low-saturated-fat and low-cholesterol diet does not alter pubertal development and hormonal status in adolescents
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Sadov, Sergey, primary, Virtanen, Helena E., additional, Main, Katharina M., additional, Andersson, Anna-Maria, additional, Juul, Anders, additional, Jula, Antti, additional, Raitakari, Olli T., additional, Pahkala, Katja, additional, Niinikoski, Harri, additional, and Toppari, Jorma, additional
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- 2018
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223. Sex Differences in Reproductive Hormones During Mini-Puberty in Infants With Normal and Disordered Sex Development
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Johannsen, Trine Holm, primary, Main, Katharina Maria, additional, Ljubicic, Marie Lindhardt, additional, Jensen, Tina Kold, additional, Andersen, Helle Raun, additional, Andersen, Marianne Skovsager, additional, Petersen, Jørgen Holm, additional, Andersson, Anna-Maria, additional, and Juul, Anders, additional
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- 2018
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224. The Possible Impact of Antenatal Exposure to Ubiquitous Phthalates Upon Male Reproductive Function at 20 Years of Age
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Hart, Roger J., primary, Frederiksen, Hanne, additional, Doherty, Dorota A., additional, Keelan, Jeffrey A., additional, Skakkebaek, Niels E., additional, Minaee, Noviani S., additional, McLachlan, Robert, additional, Newnham, John P., additional, Dickinson, Jan E., additional, Pennell, Craig E., additional, Norman, Robert J., additional, and Main, Katharina M., additional
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- 2018
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225. Association of placental thyroid hormone concentrations with congenital cryptorchidism
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Li, Zhong-Min, primary, Hernandez-Moreno, David, additional, Main, Katharina Maria, additional, Skakkebaek, Niels Erik, additional, Kiviranta, Hannu, additional, Toppari, Jorma, additional, Feldt-Rasmussen, Ulla, additional, Shen, Heqing, additional, Schramm, Karl-Werner, additional, and De, Angelis Meri, additional
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- 2018
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226. A validated LC-Q-TOF-MS method for quantitative analysis of thyroxine and metabolites in placenta
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Li, Zhong-Min, primary, Giesert, Florian, additional, Vogt-Weisenhorn, Daniela, additional, Main, Katharina, additional, Skakkebaek, Niels, additional, Kiviranta, Hannu, additional, Toppari, Jorma, additional, Feldt-Rasmussen, Ulla, additional, Shen, Heqing, additional, Schramm, Karl-Werner, additional, and Angelis, Meri De, additional
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- 2018
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227. A complex phenotype in a family with a pathogenic SOX3 missense variant
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Jelsig, Anne M., primary, Diness, Birgitte R., additional, Kreiborg, Sven, additional, Main, Katharina M., additional, Larsen, Vibeke A., additional, and Hove, Hanne, additional
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- 2018
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228. Postnatal Changes in Testicular Position Are Associated With IGF-I and Function of Sertoli and Leydig Cells
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Koskenniemi, Jaakko J, primary, Virtanen, Helena E, additional, Wohlfahrt-Veje, Christine, additional, Löyttyniemi, Eliisa, additional, Skakkebaek, Niels E, additional, Juul, Anders, additional, Andersson, Anna-Maria, additional, Main, Katharina M, additional, and Toppari, Jorma, additional
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- 2018
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229. The AMH genotype (rs10407022 T>G) is associated with circulating AMH levels in boys, but not in girls
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Greiber, Iben Katinka, primary, Hagen, Casper P, additional, Busch, Alexander Siegfried, additional, Mieritz, Mikkel Grunnet, additional, Aksglæde, Lise, additional, Main, Katharina, additional, Almstrup, Kristian, additional, and Juul, Anders, additional
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- 2018
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230. Determination of thyroid hormones in placenta using isotope-dilution liquid chromatography quadrupole time-of-flight mass spectrometry
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Li, Zhong-Min, primary, Giesert, Florian, additional, Vogt-Weisenhorn, Daniela, additional, Main, Katharina Maria, additional, Skakkebæk, Niels Erik, additional, Kiviranta, Hannu, additional, Toppari, Jorma, additional, Feldt-Rasmussen, Ulla, additional, Shen, Heqing, additional, Schramm, Karl-Werner, additional, and De Angelis, Meri, additional
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- 2018
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231. ESPE and PES International Survey of Centers and Clinicians Delivering Specialist Care for Children and Adolescents with Gender Dysphoria
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Skordis, Nicos, primary, Butler, Gary, additional, de Vries, Martine C., additional, Main, Katharina, additional, and Hannema, Sabine E., additional
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- 2018
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232. Anogenital distance as a phenotypic signature through infancy
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Priskorn, Lærke, primary, Petersen, Jørgen H, additional, Jørgensen, Niels, additional, Kyhl, Henriette B, additional, Andersen, Marianne S, additional, Main, Katharina M, additional, Andersson, Anna-Maria, additional, Skakkebaek, Niels E, additional, and Jensen, Tina K, additional
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- 2017
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233. Morbidity, Mortality, and Socioeconomics in Females With 46,XY Disorders of Sex Development: A Nationwide Study
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Berglund, Agnethe, primary, Johannsen, Trine H, additional, Stochholm, Kirstine, additional, Viuff, Mette H, additional, Fedder, Jens, additional, Main, Katharina M, additional, and Gravholt, Claus H, additional
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- 2017
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234. Genetic variation of follicle-stimulating hormone action is associated with age at testicular growth in boys
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Busch, Alexander S., Hagen, Casper P., Main, Katharina M., Pereira, Anita, Corvalan, Camila, Almstrup, Kristian, Mericq, Veronica, Juul, Anders, Busch, Alexander S., Hagen, Casper P., Main, Katharina M., Pereira, Anita, Corvalan, Camila, Almstrup, Kristian, Mericq, Veronica, and Juul, Anders
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Context: Although genetic factors play a pivotal role inmale pubertal timing, genome-wide association studies have identified only a few loci. Genetic variation of follicle-stimulating hormone (FSH) action affects adult reproductive parameters and female pubertal timing. Objective: To investigate whether genetic variation affecting FSH action is associated with onset of puberty in boys. Design: Cross-sectional and longitudinal study of two cohorts of healthy boys. Setting: This was a population-based study. Patients or Other Participants: Danish (n = 1130) and Chilean (n = 424) boys were followed through puberty and genotyped for FSHB c.-211G>T, FSHR c.-29A>G, and FSHR c.2039>A. Main Outcome Measures: Clinical pubertal staging including orchidometry, anthropometry, and serum gonadotropin levels. Results: Although the cohorts differed markedly (e.g., body composition and genotype frequencies), genetic variation affecting FSH production (FSHB c.-211G>T) was associated with age at pubertal onset, as assessed by testicular enlargement, in both cohorts. The effect appeared further modified by coexistence of genetic variation affecting FSH sensitivity (FSHR c.-29G>A): After correcting for body mass index (BMI), boys with a ligand-receptor variant combination resulting in weak FSH action (i.e., FSHB c.-211GT/TT and FSHR c.-29AA) entered puberty 0.64 years [95%confidence interval (CI), 0.12 to 1.17 years; Denmark] and 0.94 years (95% CI, 0.00 to 1.88 years; Chile) later than boys with the most effective FSH action. Effects explained 1.7% (Denmark) and 1.5% (Chile) of the variance. In addition, BMI z score was negatively associated with pubertal timing (b = 20.35 years in both cohorts), explaining 17.2% (Denmark) and 7.2% (Chile) of the variance. Conclusion: In two ethnically distinct populations, we independently identified an association of two genetic loci with male pubertal timing.
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- 2017
235. Interaction between prenatal pesticide exposure and a common polymorphism in the PON1 gene on DNA methylation in genes associated with cardio-metabolic disease risk:an exploratory study
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Declerck, Ken, Remy, Sylvie, Wohlfahrt-Veje, Christine, Main, Katharina M, Van Camp, Guy, Schoeters, Greet, Vanden Berghe, Wim, Andersen, Helle R, Declerck, Ken, Remy, Sylvie, Wohlfahrt-Veje, Christine, Main, Katharina M, Van Camp, Guy, Schoeters, Greet, Vanden Berghe, Wim, and Andersen, Helle R
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BACKGROUND: Prenatal environmental conditions may influence disease risk in later life. We previously found a gene-environment interaction between the paraoxonase 1 (PON1) Q192R genotype and prenatal pesticide exposure leading to an adverse cardio-metabolic risk profile at school age. However, the molecular mechanisms involved have not yet been resolved. It was hypothesized that epigenetics might be involved. The aim of the present study was therefore to investigate whether DNA methylation patterns in blood cells were related to prenatal pesticide exposure level, PON1 Q192R genotype, and associated metabolic effects observed in the children.METHODS: Whole blood DNA methylation patterns in 48 children (6-11 years of age), whose mothers were occupationally unexposed or exposed to pesticides early in pregnancy, were determined by Illumina 450 K methylation arrays.RESULTS: A specific methylation profile was observed in prenatally pesticide exposed children carrying the PON1 192R-allele. Differentially methylated genes were enriched in several neuroendocrine signaling pathways including dopamine-DARPP32 feedback (appetite, reward pathways), corticotrophin releasing hormone signaling, nNOS, neuregulin signaling, mTOR signaling, and type II diabetes mellitus signaling. Furthermore, we were able to identify possible candidate genes which mediated the associations between pesticide exposure and increased leptin level, body fat percentage, and difference in BMI Z score between birth and school age.CONCLUSIONS: DNA methylation may be an underlying mechanism explaining an adverse cardio-metabolic health profile in children carrying the PON1 192R-allele and prenatally exposed to pesticides.
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- 2017
236. Anthropometry, DXA and leptin reflect subcutaneous but not visceral abdominal adipose tissue by MRI in 197 healthy adolescents
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Tinggaard, Jeanette, Hagen, Casper P, Christensen, Anders N, Mouritsen, Annette, Mieritz, Mikkel G, Wohlfahrt-Veje, Christine, Helge, Jørn W, Beck, Thomas N, Fallentin, Eva, Larsen, Rasmus, Jensen, Rikke B, Juul, Anders, Main, Katharina M, Tinggaard, Jeanette, Hagen, Casper P, Christensen, Anders N, Mouritsen, Annette, Mieritz, Mikkel G, Wohlfahrt-Veje, Christine, Helge, Jørn W, Beck, Thomas N, Fallentin, Eva, Larsen, Rasmus, Jensen, Rikke B, Juul, Anders, and Main, Katharina M
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BACKGROUND: Abdominal fat distribution is associated with development of cardio-metabolic disease, independently of BMI. We assessed anthropometry, serum adipokines and DXA as markers of abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) by MRIMETHODS:We performed a cross-sectional study including 197 healthy adolescents (114 boys) aged 10-15 years nested within a longitudinal population-based cohort. Clinical examination, blood sampling, DXA and abdominal MRI was performed. SAT% and VAT% was adjusted to total abdominal volume.RESULTS: Girls had a higher SAT% than boys in early and late puberty (16 vs. 13%, P<0.01 and 20 vs. 15%, P=0.001, respectively), whereas VAT% was comparable (7% in both genders, independent of puberty). DXA android fat% (Standard Deviation Score [SDS]), suprailliac skinfold thickness (SDS), leptin, BMI (SDS), waist-to-height ratio (WHtR) and waist circumference (SDS) correlated strongly with SAT% (descending order: r=0.90 to r=0.55, all P<0.001), but weaker to VAT% (r=0.49 to r=0.06). Suprailiac skinfold was the best anthropometric marker of SAT% (girls: R(2)=48.6%, boys: R(2)=65.0%, P<0.001) and VAT% in boys (R(2)=16.4%, P<0.001). WHtR was the best marker of VAT% in girls (R(2)=7.6%, P=0.007).CONCLUSIONS: Healthy girls have a higher SAT% than boys, whereas VAT% is comparable, independent of puberty. Anthropometry and circulating leptin are valid markers of SAT%, but not VAT%.Pediatric Research accepted article preview online, 12 June 2017. doi:10.1038/pr.2017.138.
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- 2017
237. Maternal use of mild analgesics during pregnancy associated with reduced anogenital distance in sons:a cohort study of 1027 mother-child pairs
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Lind, Dorte Vesterholm, Main, Katharina Maria, Kyhl, Henriette Boye, Kristensen, David Møbjerg, Toppari, Jorma, Andersen, Helle Raun, Skovsager Andersen, Marianne, Skakkebæk, Niels Erik, Jensen, Tina Kold, Lind, Dorte Vesterholm, Main, Katharina Maria, Kyhl, Henriette Boye, Kristensen, David Møbjerg, Toppari, Jorma, Andersen, Helle Raun, Skovsager Andersen, Marianne, Skakkebæk, Niels Erik, and Jensen, Tina Kold
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STUDY QUESTION: Is maternal use of mild analgesics in pregnancy associated with anogenital distance (AGD)-the distance from the anus to the genitals-in the offspring?SUMMARY ANSWER: Maternal use of mild analgesics [especially simultaneous use of paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDs)] during pregnancy was associated with a shorter AGD in boys whereas no effect was found in girls.WHAT IS KNOWN ALREADY: Mild analgesics including paracetamol (acetaminophen) and NSAIDs (e.g. ibuprofen and acetyl salicylic acid) have endocrine disrupting properties and in utero exposure reduces AGD in male rats. In humans, maternal exposure has been associated with cryptorchidism and hypospadias in male offspring but no studies have examined AGD.STUDY DESIGN, SIZE, DURATION: A prospective birth cohort study. Between 2010 and 2012, 2500 pregnant women were recruited from the Odense Child Cohort. Children were examined 3 months after the expected date of birth.PARTICIPANTS/MATERIALS, SETTING, METHODS: Pregnant women were asked about use of medication including mild analgesics (paracetamol and NSAID) during pregnancy at recruitment (gestational age (GA) week 10-27) and at GA week 28. AGD and penile width were measured 3 months after expected date of birth by trained personnel. A total of 1027 women answered both questionnaires and their children were examined. Associations between prenatal exposure to mild analgesics and AGD and penile width were estimated using multivariable linear regression adjusting for age and weight-for-age SD score.MAIN RESULTS AND THE ROLE OF CHANCE: A total of 40% of the women reported use of paracetamol and/or NSAIDs (4.4%) during the first 28 weeks of pregnancy. Exposure to analgesics during pregnancy was associated with a reduced AGD in boys, although statistically significant only for NSAIDs. The association was significant among 20 boys exposed to both paracetamol and NSAIDs (AGD -4.1 mm; CI 95%: -6.
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- 2017
238. Migration of phthalates on culture plates – an important challenge to consider for in vitro studies
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Hansen, Juliana Frohnert, Boas, Malene, Brorson, Marianne Møller, Frederiksen, Hanne, Marie-Louise Hartoft-Nielsen, Rasmussen, Åse Krogh, Main, Katharina M., and Feldt-Rasmussen, Ulla
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Phthalates are endocrine disruptors of the reproductive system and suspected to influence many other organ and hormone systems. They are also semi-volatile organic compounds present in the gas phase in the environment. Their mode of action has been investigated in numerous in vitro studies. Multi-well culture plates are typically used to study phthalates in cell cultures. In a pilot study, we observed evidence of phthalate migration in 24-well culture plates. As this has not previously been described, we investigated the phenomenon in more detail. Primary human thyroid epithelial cell cultures (n = 8 cultures) were exposed to either di-ethyl phthalate (DEP), di-n-butyl phthalate (DnBP), mono-n-butyl phthalate (MnBP) or di-(2-ethylhexyl) phthalate (DEHP). Measurement of phthalate metabolites by mass spectrometry demonstrated that the short-branched DEP was able to migrate to adjacent wells when added to cell culture plates. DnBP also seemed to be able to migrate, unlike the long-branched DEHP or the monoester MnBP which did not seem to have this ability. High background levels of phthalate metabolites were also observed, which might compromise results from low dose phthalate studies. In conclusion, the migration of phthalates which is probably caused by their volatile properties might lead to false interpretation of study results.
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- 2016
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239. Differential Impact of Genetic Loci on Age at Thelarche and Menarche in Healthy Girls
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Busch, Alexander S, primary, Hagen, Casper P, additional, Assens, Maria, additional, Main, Katharina M, additional, Almstrup, Kristian, additional, and Juul, Anders, additional
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- 2017
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240. Anthropometry, DXA, and leptin reflect subcutaneous but not visceral abdominal adipose tissue on MRI in 197 healthy adolescents
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Tinggaard, Jeanette, primary, Hagen, Casper P, additional, Christensen, Anders N, additional, Mouritsen, Annette, additional, Mieritz, Mikkel G, additional, Wohlfahrt-Veje, Christine, additional, Helge, Jørn W, additional, Beck, Thomas N, additional, Fallentin, Eva, additional, Larsen, Rasmus, additional, Jensen, Rikke B, additional, Juul, Anders, additional, and Main, Katharina M, additional
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- 2017
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241. Interaction between prenatal pesticide exposure and a common polymorphism in the PON1 gene on DNA methylation in genes associated with cardio-metabolic disease risk—an exploratory study
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Declerck, Ken, primary, Remy, Sylvie, additional, Wohlfahrt-Veje, Christine, additional, Main, Katharina M., additional, Van Camp, Guy, additional, Schoeters, Greet, additional, Vanden Berghe, Wim, additional, and Andersen, Helle R., additional
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- 2017
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242. Genetic Variation of Follicle-Stimulating Hormone Action Is Associated With Age at Testicular Growth in Boys
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Busch, Alexander S., primary, Hagen, Casper P., additional, Main, Katharina M., additional, Pereira, Anita, additional, Corvalan, Camila, additional, Almstrup, Kristian, additional, Mericq, Veronica, additional, and Juul, Anders, additional
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- 2017
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243. Corrigendum to “Challenges in Interpretation of Thyroid Function Tests in Pregnant Women with Autoimmune Thyroid Disease”
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Feldt-Rasmussen, Ulla, primary, Bliddal, Sofie, additional, Rasmussen, Åse Krogh, additional, Boas, Malene, additional, Hilsted, Linda, additional, and Main, Katharina, additional
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- 2017
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244. Maternal use of mild analgesics during pregnancy associated with reduced anogenital distance in sons: a cohort study of 1027 mother–child pairs
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Lind, Dorte Vesterholm, primary, Main, Katharina M., additional, Kyhl, Henriette Boye, additional, Kristensen, David Møbjerg, additional, Toppari, Jorma, additional, Andersen, Helle Raun, additional, Andersen, Marianne Skovsager, additional, Skakkebæk, Niels E., additional, and Jensen, Tina Kold, additional
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- 2016
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245. Glandular breast tissue volume by magnetic resonance imaging in 100 healthy peripubertal girls:evaluation of clinical Tanner staging
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Fugl, Louise, Hagen, Casper P, Mieritz, Mikkel G, Tinggaard, Jeanette, Fallentin, Eva, Main, Katharina M, Juul, Anders, Fugl, Louise, Hagen, Casper P, Mieritz, Mikkel G, Tinggaard, Jeanette, Fallentin, Eva, Main, Katharina M, and Juul, Anders
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BACKGROUND: Appearance of glandular breast tissue may be difficult to distinguish from fat tissue by palpation, especially in obese girls. To our knowledge, validation of the clinical assessment of pubertal breast stages by magnetic resonance imaging (MRI) has never been performed. Our objective was to report normative data of glandular breast tissue volume and validate the clinical evaluation of pubertal breast staging by MRI of breast tissue and to evaluate circulating reproductive hormone levels and estrogen-dependent transabdominal ultrasound (TAUS) parameters as markers of glandular breast tissue.METHODS: Glandular breast tissue volume quantified by MRI and breast stage evaluation was performed in 100 healthy peripubertal girls. Circulating levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), inhibin B, and estradiol were measured by immunoassays. Ovarian volume, uterine volume, and endometrial thickness were assessed by TAUS.RESULTS: Glandular breast tissue volume was positively associated with Tanner stages (r = 0.858, P < 0.001). The sensitivity and specificity of breast palpation to detect presence of glandular breast tissue using MRI as gold standard were 96 and 95%, respectively. The best parameters to distinguish prepubertal girls from girls with breast development were: LH (area under the curve (AUC) by receiver operating characteristic analysis = 0.871), inhibin B (AUC = 0.847) and estradiol (AUC = 0.830).CONCLUSION: Clinical palpation reliably detects the presence of glandular breast tissue.
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- 2016
246. Incidence, Prevalence, Diagnostic Delay, and Clinical Presentation of Female 46,XY Disorders of Sex Development
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Berglund, Agnethe, Johannsen, Trine H, Stochholm, Kirstine, Viuff, Mette H, Fedder, Jens, Main, Katharina M, Gravholt, Claus H, Berglund, Agnethe, Johannsen, Trine H, Stochholm, Kirstine, Viuff, Mette H, Fedder, Jens, Main, Katharina M, and Gravholt, Claus H
- Abstract
CONTEXT: The prevalence of phenotypic females with a 46,XY karyotype is low, thus current knowledge about age and clinical presentation at diagnosis is sparse even for the most frequent conditions, androgen insensitivity syndrome (AIS), and gonadal dysgenesis.OBJECTIVE: To estimate incidence, prevalence, age at diagnosis, and clinical presentation at diagnosis in 46,XY females.DESIGN AND SETTING: A nationwide study covering all known females with a 46,XY karyotype in Denmark since 1960. The diagnosis of 46,XY disorder of sex development (DSD) was determined by medical record evaluation, data from the Danish National Patient Registry, and genetic testing, if available.PATIENTS: A total of 166 females registered as 46,XY females in the Danish Cytogenetic Central Registry were identified.RESULTS: A total of 124 females were classified as having 46,XY DSD, 78 with AIS and 25 with gonadal dysgenesis, whereas the remaining subjects had a variety of different diagnoses. The prevalence of 46,XY females was 6.4 per 100 000 live born females, and for AIS and gonadal dysgenesis, it was 4.1 and 1.5 per 100 000, respectively. Median age at diagnosis was 7.5 years (95% confidence interval, 4.0-13.5; range, 0-34 y) in AIS and 17.0 years (95% confidence interval, 15.5-19.0; range, 0-28 y) in gonadal dysgenesis (P = .001). Clinical presentation was dependent on cause of DSD.CONCLUSIONS: The first estimate on prevalence of 46,XY females is 6.4 per 100 000 live born females. The presentation of AIS and gonadal dysgenesis is distinctly different, with AIS being diagnosed during childhood and gonadal dysgenesis during pubertal years. The presenting phenotype is dependent on the cause of 46,XY DSD.
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- 2016
247. Genetic variations in FSH action affect sex hormone levels and breast tissue size in infant girls:A pilot study
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Henriksen, Louise Scheutz, Hagen, Casper P, Assens, Maria, Busch, Alexander S., Skakkebæk, Niels E., Almstrup, Kristian, Main, Katharina M., Henriksen, Louise Scheutz, Hagen, Casper P, Assens, Maria, Busch, Alexander S., Skakkebæk, Niels E., Almstrup, Kristian, and Main, Katharina M.
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Context: Single nucleotide polymorphisms altering FSH action (FSHB -211G>T, FSHR -29G>A, and FSHR 2039A>G) are associated with peripubertal and adult levels of reproductive hormones and age at pubertal onset in girls. Objective: To investigate whether genetic polymorphisms altering FSH action affect serum levels of female reproductive hormones and breast development as early as during minipuberty. Design: Longitudinal study. Setting: Population-based cohort study. Participants: A total of 402 healthy girls at 3 months of age. Main Outcome Measures: Analyses of single nucleotide polymorphisms by PCR using Kompetitive Allele Specific PCR genotyping assays; identification of glandular breast tissue by palpation and measurement of the diameter. Serum levels of anti-Müllerian hormone, FSH, LH, estradiol, inhibin B, and sex hormone-binding globulin were assessed by immunoassays. Results: FSHR -29G>A was associated with both FSH and anti-Müllerian hormone levels with an A allele effect size of -0.8 IU/L (P = .005) and 1.4 nmol/L (P = .003), respectively. FSHR 2039A>G correlated with breast tissue size with a negative additive effect of minor alleles (P=.021), whereas the effect on estradiol levels was only present in homozygotes. FSHB -211T carriers had smaller breast tissue size than girls who without a minor allele; GT+TT 10.5 (confidence interval 9.4 -11.5) mm vs GG 12.1 (confidence interval 11.4-12.8) mm, P = .014. Conclusions: Our study indicates that 3 genetic polymorphisms altering FSH action, especially FSHR -29G>A and FSHR 2039A>G, affect female hormone profile and glandular breast tissue development already during minipuberty. Thus, genetic variations of FSH signaling appear to determine the individual set point of the hypothalamic-pituitary-gonadal axis already early in life.
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- 2016
248. Phthalates Are Metabolised by Primary Thyroid Cell Cultures but Have Limited Influence on Selected Thyroid Cell Functions In Vitro
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Hansen, Juliana Frohnert, Brorson, Marianne Møller, Boas, Malene, Frederiksen, Hanne, Nielsen, Claus Henrik, Lindström, Emma Sofie, Hofman-Bang, Jacob, Hartoft-Nielsen, Marie-Louise, Frisch, Thomas, Main, Katharina M, Bendtzen, Klaus, Rasmussen, Åse Krogh, Feldt-Rasmussen, Ulla, Hansen, Juliana Frohnert, Brorson, Marianne Møller, Boas, Malene, Frederiksen, Hanne, Nielsen, Claus Henrik, Lindström, Emma Sofie, Hofman-Bang, Jacob, Hartoft-Nielsen, Marie-Louise, Frisch, Thomas, Main, Katharina M, Bendtzen, Klaus, Rasmussen, Åse Krogh, and Feldt-Rasmussen, Ulla
- Abstract
Phthalates are plasticisers added to a wide variety of products, resulting in measurable exposure of humans. They are suspected to disrupt the thyroid axis as epidemiological studies suggest an influence on the peripheral thyroid hormone concentration. The mechanism is still unknown as only few in vitro studies within this area exist. The aim of the present study was to investigate the influence of three phthalate diesters (di-ethyl phthalate, di-n-butyl phthalate (DnBP), di-(2-ethylhexyl) phthalate (DEHP)) and two monoesters (mono-n-butyl phthalate and mono-(2-ethylhexyl) phthalate (MEHP)) on the differentiated function of primary human thyroid cell cultures. Also, the kinetics of phthalate metabolism were investigated. DEHP and its monoester, MEHP, both had an inhibitory influence on 3'-5'-cyclic adenosine monophosphate secretion from the cells, and MEHP also on thyroglobulin (Tg) secretion from the cells. Results of the lactate dehydrogenase-measurements indicated that the MEHP-mediated influence was caused by cell death. No influence on gene expression of thyroid specific genes (Tg, thyroid peroxidase, sodium iodine symporter and thyroid stimulating hormone receptor) by any of the investigated diesters could be demonstrated. All phthalate diesters were metabolised to the respective monoester, however with a fall in efficiency for high concentrations of the larger diesters DnBP and DEHP. In conclusion, human thyroid cells were able to metabolise phthalates but this phthalate-exposure did not appear to substantially influence selected functions of these cells.
- Published
- 2016
249. Growth and pubertal development
- Author
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Koch, Göran, Poulsen, Sven, Espelid, Ivar, Haubek, Dorte, Juul, A., Kreiborg, Sven, Main, Katharina M, Koch, Göran, Poulsen, Sven, Espelid, Ivar, Haubek, Dorte, Juul, A., Kreiborg, Sven, and Main, Katharina M
- Published
- 2016
250. Testicular Growth During Puberty in Boys With and Without a History of Congenital Cryptorchidism
- Author
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Sadov, Sergey, Koskenniemi, Jaakko J, Virtanen, Helena E, Perheentupa, Antti, Petersen, Jørgen H, Skakkebaek, Niels E, Main, Katharina M, Toppari, Jorma, Sadov, Sergey, Koskenniemi, Jaakko J, Virtanen, Helena E, Perheentupa, Antti, Petersen, Jørgen H, Skakkebaek, Niels E, Main, Katharina M, and Toppari, Jorma
- Abstract
CONTEXT: The pattern of testicular growth during puberty may provide important information about early testicular damage and reproductive potential in adulthood.OBJECTIVE: To evaluate pubertal testicular growth in boys with congenital cryptorchidism and controls.DESIGN: Longitudinal case-control study.SETTING: Andrological Research Center, University of Turku.PARTICIPANTS: Altogether, 119 boys participated: 51 cases with a history of congenital cryptorchidism and 65 controls fulfilled the inclusion criteria.INTERVENTION: None.MAIN OUTCOME MEASURES: Testicular volume by an orchidometer (mL) and ultrasound (mL), testicular length by a ruler (mm), and onset of pubertal testicular growth (y). Longitudinal testicular growth was analyzed with a nonlinear mixed-effect model.RESULTS: The mean age of the onset of pubertal testicular growth (age at the attainment of >3 mL by orchidometer) was 11.7 and 11.8 years in cryptorchid cases and controls, respectively. The difference between cases and controls was not significant. Modeled postpubertal testicular size was smaller among bilaterally and unilaterally undescended testis than in controls. There was a high level of agreement between testicular sizes of 3 mL by orchidometer and 25 mm by ruler as cut-offs in definition of the onset of puberty. An orchidometer size of 3 mL and ruler length of 25 mm corresponded to 1.6 and 1.7 mL by ultrasound (with Lambert's formula), respectively.CONCLUSIONS: Testicular growth in puberty was impaired in congenitally cryptorchid boys. This suggests a poor perinatal development of the cryptorchid testis. The timing of the onset of pubertal testicular growth, however, did not differ which suggests an intact hypothalamic-pituitary axis.
- Published
- 2016
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