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OBJECTIVE: To evaluate revised criteria for polycystic ovarian morphology (PCOM) in the diagnosis of polycystic ovary syndrome (PCOS) in anovulatory infertility.DESIGN: Prospective cohort study.PATIENTS: WHO Group II anovulatory infertile women (n = 75).MEASUREMENTS: Clinical, sonographic and endocrine parameters, including anti-Müllerian hormone (AMH).RESULTS: The Rotterdam criteria for PCOM (antral follicle count (AFC) ≥12 and/or ovarian volume >10 ml) were fulfilled in 93% of the women. The PCOM prevalence was 68% when increasing the threshold to AFC >20 and 76% according to an AMH-based threshold of >35 pmol/l. The most recently proposed AFC ≥ 25 threshold reduced the PCOM prevalence to 52% (n = 39), leaving 48% (n = 36) without features of PCOM. Comparing the 36 women with non-PCOM with the 39 women in the PCOM group according to AFC ≥ 25, 22% vs 59% (P = 0·001) had serum LH >10 IU/l, 11% vs 41% (P = 0·003) had an LH/FSH ratio >2 and 19% vs 41% (P = 0·04) had hirsutism and/or elevated total testosterone, free testosterone, and/or androstenedione. The non-PCOM group included significantly more women with secondary infertility. The median AMH in the non-PCOM group was 47 pmol/l, which was twofold lower than in the PCOM group but above the upper limit of normo-ovulatory women.CONCLUSIONS: According to a revised threshold of 25 follicles, almost half the anovulatory infertile women do not have PCOM. The characteristics of these women may be compatible with hypothalamic anovulation, but according to AMH levels, the ovaries remain multifollicular.PERSPECTIVES: A better distinction between hypothalamic amenorrhoea and PCOS could improve treatment strategies for anovulatory infertility.

Context: Physiological gynaecomastia is common and affects a large proportion of otherwise healthy adolescent boys. It is thought to be caused by an imbalance between estrogen and testosterone, though this is rarely evident in analyses of serum. Objective: This study aimed to describe the frequency of physiological gynaecomastia, and to determine possible etiological factors (e.g. auxology and serum hormone levels) in a longitudinal set-up. Design, Settings and Participants: A prospective cohort study of 106 healthy Danish boys (5.8–16.4 years) participated in the longitudinal part of “the COPENHAGEN Puberty Study”. The boys were examined every six months during an eight year follow-up. Median number of examinations was 10 (2–15). Main outcome measurements: Blood samples and analysed for FSH, LH, testosterone, estradiol, SHBG, inhibin B, AMH, IGF-I and IGFBP-3 by immunoassays. Auxological parameters, pubertal development and the presence of gynaecomastia were evaluated at each visit. Results: 52 of 106 boys (49 developed gynaecomastia of which 10 (19 presented with intermittent gynaecomastia. Boys with physiological gynaecomastia reached peak height velocity at a significantly younger age than boys who did not develop gynaecomastia (13.5 vs 13.9 years, p = 0.027), and they had significantly higher serum levels of IGF-I (p = 0.000), estradiol (p = 0.013), free-testosterone (p <0.001) and FSH (p = 0.030) during pubertal transition. However, no differences in serum LH or in the estradiol to testosterone ratio were found. Conclusions: Gynaecomastia is frequent in pubertal boys. Increased IGF-I levels and pubertal growth appear to be associated, whereas changes in estrogen to testosterone ratio seem negligible.

Context: Few data exist on the diagnostic criteria, and on the effects of puberty induction, in boyswith constitutional delay in growth and puberty (CDGP). Objective: To develop puberty nomograms based on Danish boys with normal pubertal development.To evaluate the different diagnostic criteria and the effect of oral testosterone undecanoate(TU) in boys with CDGP. Design: A cross-sectional and longitudinal study of Danish boys with normal pubertal development(COPENHAGEN puberty study). A retrospective observational study of 451 boys evaluated fordelayed puberty between 1990 and 2013. Setting: Tertiary referral center for pediatric endocrinology. Participants: One hundred and sixty-four (36%) boys evaluated for CDGP were excluded due tomissing data, reclassification, or associated comorbidities, yielding 287 (64%) eligible for analysis. Main Outcome Measures: The number of patients with CDGP classified by the puberty nomogram(genital stage 2 SD for age) versus the classical criteria (genital stage 1 at 14 years). The effectof one year of oral TU treatment on pubertal progression, circulating hormones, height, andpredicted adult height (PAH). Results: Seventy-eight (27%) of the 287 boys had delayed pubertal onset according to the classicalcriteria, whereas 173 (60%) of the 287 boys had impaired pubertal progression according to thepuberty nomogram. Ninety-six (56%) of these 173 boys were treated with oral TU for 0.8 years (0.5;1.3) [median (25th; 75th percentiles)], which resulted in beneficial effects on pubertal progression.Height increased from 1.9 SD (2.5; 1.2) to 1.5 SD (2.1; 0.7) (P .001), and PAH increasedfrom 172.3 cm (170.3; 182.8) to 178.1 cm (171.4; 191.7) (P .001) following one year of treatment. Conclusions: The puberty nomogram evaluates both delayed pubertal onset as well as delayedpubertal progression and allows separation of normal versus abnormal pubertal development.Oral TU treatment was followed by pubertal induction and

Background: Increasing global migration has made immigrants’ health an important topic worldwide.We examined the effect of country of birth, migrant status (refugee/family-reunified) and income on coronary heart disease (CHD) incidence. Design: This was a historical prospective register-based cohort study. Methods: The study cohort consisted of immigrants above 18 years from non-Western countries who had obtained a residence permit in Denmark as a refugee (n¼29,045) or as a family-reunified immigrant (n¼28,435) from 1 January 1993–31 December 1999 and a Danish-born reference population (n¼229,918). First-time CHD incidence was identified from 1 January 1993–31 December 2007. Incidence ratios for 11 immigrant groups were estimated using Cox regression analysis. Results: Immigrants from Afghanistan, Iraq, Turkey, Eastern Europe and Central Asia, South Asia, the Former Yugoslavia, and the Middle East and North Africa had significantly higher incidences of CHD (hazard ratio (HR)¼1.36; 95% confidence interval (CI): 1.05–1.75 to HR¼2.86; 95% CI: 2.01–4.08) compared with Danish-born people. Immigrants from Somalia, South and Middle America, Sub-Saharan Africa and women from East Asia and the Pacific did not differ significantly from Danish-born people, whereas immigrant men from East Asia and the Pacific had a significantly lower incidence (HR¼0.32; 95% CI: 0.17–0.62). When also including migrant status, the higher incidences were reduced. Refugee men (HR¼1.35; 95% CI: 1.11–1.65) and women (HR¼1.33; 95% CI: 1.08–1.65) had a significantly higher incidence of CHD than family-reunified immigrants. When migrant status and income were included simultaneously, the incidences decreased to an insignificant level for most immigrant groups. Conclusions: Most non-Western immigrant groups had a higher incidence of CHD than Danish-born people. The study revealed that migrant status and income are important unde, Background: Increasing global migration has made immigrants’ health an important topic worldwide. We examined the effect of country of birth, migrant status (refugee/family-reunified) and income on coronary heart disease (CHD) incidence. Design: This was a historical prospective register-based cohort study. Methods: The study cohort consisted of immigrants above 18 years from non-Western countries who had obtained a residence permit in Denmark as a refugee (n = 29,045) or as a family-reunified immigrant (n = 28,435) from 1 January 1993–31 December 1999 and a Danish-born reference population (n = 229,918). First-time CHD incidence was identified from 1 January 1993–31 December 2007. Incidence ratios for 11 immigrant groups were estimated using Cox regression analysis. Results: Immigrants from Afghanistan, Iraq, Turkey, Eastern Europe and Central Asia, South Asia, the Former Yugoslavia, and the Middle East and North Africa had significantly higher incidences of CHD (hazard ratio (HR) = 1.36; 95% confidence interval (CI): 1.05–1.75 to HR = 2.86; 95% CI: 2.01–4.08) compared with Danish-born people. Immigrants from Somalia, South and Middle America, Sub-Saharan Africa and women from East Asia and the Pacific did not differ significantly from Danish-born people, whereas immigrant men from East Asia and the Pacific had a significantly lower incidence (HR = 0.32; 95% CI: 0.17–0.62). When also including migrant status, the higher incidences were reduced. Refugee men (HR = 1.35; 95% CI: 1.11–1.65) and women (HR = 1.33; 95% CI: 1.08–1.65) had a significantly higher incidence of CHD than family-reunified immigrants. When migrant status and income were included simultaneously, the incidences decreased to an insignificant level for most immigrant groups. Conclusions: Most non-Western immigrant groups had a higher incidence of CHD than Danish-born people. The study revealed that migrant status and income are important underlying mechanisms of the effect of coun

The influence of sex, age, pubertal development and oral contraceptives on dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), 17α-hydroxyprogesterone (17-OHP), Δ4-androstenedione (Adione), testosterone (T), calculated free testosterone (fT), free androgen index (FAI) and selected ratios in 1798 serum samples from healthy children, adolescents and young adults was evaluated. Samples were analyzed by Turboflow-LC-MS/MS. Sex hormone-binding globulin was analyzed by immunoassay. All steroid metabolite concentrations were positively associated with age and pubertal development in both sexes and generally higher in males than in females except for Adione. The pubertal rise in T in males was more pronounced compared to females, reflecting contribution from the testes. Ratios between steroid metabolites varied and depended on sex and age. All ratios were lower during infancy compared to later in life. Use of oral contraceptives significantly lowered serum concentrations of all steroid metabolites, fT, FAI, the 17-OHP/Adione, the Adione/T and the DHEA/Adione ratios, but not the DHEA/DHEAS ratio. We provide reference ranges for DHEA, DHEAS, 17-OHP, Adione, T, fT, FAI and selected ratios in relation to sex, age and pubertal development. Use of oral contraceptives strongly influences adrenal steroidogenesis and should be considered when diagnosing and monitoring treatment of patients with disorders of sex development.

Age at pubertal onset varies substantially in healthy girls. Although genetic factors are responsible for more than half of the phenotypic variation, only a small part has been attributed to specific genetic polymorphisms identified so far. Follicle-stimulating hormone (FSH) stimulates ovarian follicle maturation and estradiol synthesis which is responsible for breast development. We assessed the effect of three polymorphisms influencing FSH action on age at breast deveopment in a population-based cohort of 964 healthy girls. Girls homozygous for FSHR -29AA (reduced FSH receptor expression) entered puberty 7.4 (2.5–12.4) months later than carriers of the common variants FSHR -29GG+GA, p = 0.003. To our knowledge, this is the strongest genetic effect on age at pubertal onset in girls published to date.

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 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 sug

AIM: To construct new Danish growth charts for 0- to 20-year-olds and to compare them with Danish references from 1982 and with World Health Organization (WHO) standards for children aged 0-5 years from 2006, by applying similar inclusion and exclusion criteria.METHODS: Anthropometric data from three contemporary Danish population-based studies were combined. References for height were based on healthy Caucasian children born at term. A total of 12,671 height measurements (8055 in boys and 4616 in girls) were included. Reference charts were developed using the generalised additive models for location, scale and shape.RESULTS: From prepubertal ages, a secular increase in height was observed for both genders. The differences were most pronounced in puberty, and final heights were increased by 1.4 cm in boys and 2.9 cm in girls compared to 1982 references. In boys, but not girls an upward shift in body mass index (BMI) above median levels was found. Reference curves for height were superimposable with standard curves based on the selective WHO criteria. Danish children were longer/taller and heavier and they had larger head circumferences than those reported in the recent multiethnic WHO standards.CONCLUSION: We recommend national implementation of these contemporary 2014 Danish references for anthropometric measurements.

BACKGROUND: Antidepressant (AD) therapy is recommended for patients 4-12 months after remission from depression. The aim was to examine whether immigrants (refugees or family reunited immigrants) from non-Western countries are at greater risk than Danish-born residents of 1) not initiating AD therapy after discharge and 2) early AD discontinuation.METHODS: A cohort of immigrants from non-Western countries (n = 132) and matched Danish-born residents (n = 396) discharged after first admission with moderate to severe depression between 1 January 1996 and 31 May 2008 was followed in the Danish registries.Logistic regression models were applied to explore AD initiation within 30 days after discharge, estimating odds ratio (OR) for immigrants versus Danish-born residents.Early discontinuation was explored by logistic regression, estimating OR for no AD dispensing within 180 days after the first dispensing, and by Cox regression, estimating hazard ratio (HR) for discontinuation (maximum drug supply gap) within 180 days.RESULTS: Immigrants had higher odds for not initiating AD treatment after discharge than Danish-born residents (OR = 1.55; 95% CI: 1.01-2.38). When income was included in the model, the strength of the association was attenuated. Odds for early discontinuation was non-significantly higher among immigrants than Danish-born residents (OR = 1.80; 0.87-3.73). Immigrants also had a non-significantly higher hazard of early discontinuation (HR = 1.46; 95% CI: 0.87-2.45). Including income had only minor impact on these associations.CONCLUSION: Immigrants seem less likely to receive the recommended AD treatment after hospitalization with depression. This may indicate a need for a better understanding of the circumstances of this vulnerable group.

INTRODUCTION: The aim of this study was to compare cancer mortality among migrant patients with cancer mortality in Danish-born patients. MATERIAL AND METHODS: This was a historical prospective cohort study. All non-Western migrants (n = 56,273) who were granted a right to residency in Denmark between 1 January 1993 and 31 December 1999 were included and matched 1:4 on age and sex with Danish-born patients. Cancer patients in the cohort were identified through the Danish Cancer Registry and deaths and emigrations through the Central Population Register. Using a Cox regression model, mean sex-specific hazard ratio (HR) for all-cause mortality were estimated by ethnicity; adjusting for age, income, co-morbidity and disease stage. RESULTS: No significant differences were observed in mortality for gynaecological cancers between migrant women (HR = 1.12; 95% confidence interval (CI): 0.70-1.80) and Danish-born women. Correspondingly, migrant women (HR = 0.76; 95% CI: 0.49-1.17) showed no significant differences in breast cancer mortality compared with Danish-born women. Regarding lung cancer, neither migrant women (HR = 0.79; 95% CI: 0.45-1.40) nor men (HR = 0.73; 95% CI: 0.53-1.14) presented statistical variances in mortality rates compared with Danish-born patients. Similarly, for colorectal cancer, migrant women (HR = 0.64; 95% CI: 0.27-1.55) and men (HR = 1.58; 95% CI: 0.75-3.36) displayed no significant differences compared with Danish-born patients. CONCLUSION: Different trends were observed according to cancer type, but cancer mortality did not differ significantly between migrants and Danish-born patients. This may imply that the Danish health-care system provides equity in cancer care.

This chapter first discusses the use of item response theory (IRT) model for the analysis of agreement between raters in a situation where all raters have supplied dichotomous ratings of the same cases in a sample. Next, the chapter describes two approaches to the quantification of the rater variation in the Rasch model. The approaches are fixed-effect approach, and random effects approach. The models allow raters to have different propensities to score a given set of individuals positively or negatively. Further, the chapter presents a study of umbilical artery Doppler velocimetry used by obstetricians to asses the status of a fetus. Meta analyses of the randomized clinical trials have shown a 49% reduction in perinatal mortality on using the technique on high-risk pregnancies. It is clear from these considerations that the variations in effects of using the ultrasound technique may in part be attributed to the considerable rater variation.

AIM: The aim of this study is to determine the factors responsible for differences in the prevalence of diabetes mellitus (DM) in subjects of different social class in an urban South Indian population. MATERIALS AND METHODS: Analyses were based on the cross-sectional data from the Chennai Urban Rural Epidemiology Study of 1989 individuals, aged ≥20 years. Entered in the analyses were information obtained by self-report on (1) household income; (2) family history of diabetes; (3) physical activity; (4) smoking status; (5) alcohol consumption. Biochemical, clinical and anthropometrical measurements were performed and included in the analyses. Social class was classified based on income as low (Rs. <2000) intermediate (Rs. 2000-5000`) and high (Rs. 5000-20000). RESULTS: The prevalence rates of DM were 12.0%, 18.4% and 21.7% in low, intermediate and high social class, respectively (P < 0.001). A significant increase in the risk of diabetes was found with ascending social class (Intermediate class: Odds ratio [OR], 1.7 [confidence interval [CI], 1.2-2.3]; High class: OR, 2.0 [CI-1.4-2.9]). The multivariable adjusted logistic regression analysis revealed that the effect of social class on the risk of diabetes remained significant (P = 0.016) when age, family history of diabetes and blood pressure were included. However, with the inclusion of abdominal obesity in the model, the significant effect of social class disappeared (P = 0.087). CONCLUSION: An increased prevalence of DM was found in the higher social class in this urban South Indian population, which is explained by obesity. KEYWORDS: Asian Indians; South Asians; diabetes; obesity; social class; socio-economic status; urban

IGF1 plays an important role in growth and metabolism during puberty. IGF1 levels are increased in girls with central precocious puberty (CPP). However, the relationship with insulin before and during gonadal suppression is unknown. In addition, the influence of the exon 3-deleted GH receptor gene (GHRd3) on IGF1 levels was evaluated.

Objectives Considerable interest and controversy over a possible decline in semen quality during the 20th century raised concern that semen quality could have reached a critically low level where it might affect human reproduction. The authors therefore initiated a study to assess reproductive health in men from the general population and to monitor changes in semen quality over time. Design Cross-sectional study of men from the general Danish population. Inclusion criteria were place of residence in the Copenhagen area, and both the man and his mother being born and raised in Denmark. Men with severe or chronic diseases were not included. Setting Danish one-centre study. Participants 4867 men, median age 19 years, included from 1996 to 2010. Outcome measures Semen volume, sperm concentration, total sperm count, sperm motility and sperm morphology. Results Only 23% of participants had optimal sperm concentration and sperm morphology. Comparing with historic data of men attending a Copenhagen infertility clinic in the 1940s and men who recently became fathers, these two groups had significantly better semen quality than our study group from the general population. Over the 15 years, median sperm concentration increased from 43 to 48 million/ml (p=0.02) and total sperm count from 132 to 151 million (p=0.001). The median percentage of motile spermatozoa and abnormal spermatozoa were 68% and 93%, and did not change during the study period. Conclusions This large prospective study of semen quality among young men of the general population showed an increasing trend in sperm concentration and total sperm count. However, only one in four men had optimal semen quality. In addition, one in four will most likely face a prolonged waiting time to pregnancy if they in the future want to father a child and another 15% are at risk of the need of fertility treatment. Thus, reduced semen quality seems so frequent that

Phthalates are a group of chemicals present in numerous consumer products. They have anti-androgenic properties in experimental studies and are suspected to be involved in human male reproductive health problems. A few studies have shown associations between phthalate exposure and changes in pubertal timing among girls, although controversies exist. We determined the concentration of 12 phthalate metabolites in first morning urine samples from 725 healthy Danish girls (aged 5.6-19.1 years) in relation to age, pubertal development (breast and pubic hair stage) and reproductive hormone levels (luteinizing hormone, oestradiol and testosterone). Furthermore, urinary phthalates were determined in 25 girls with precocious puberty (PP). In general, the youngest girls with less advanced pubertal development had the highest first morning urinary concentration of the monobutyl phthalate isoforms (¿MBP((i+n)) ), monobenzyl phthalate (MBzP), metabolites of di-(2-ethylhexyl) phthalate (¿DEHPm) and of di-iso-nonyl phthalate (¿DINPm). After stratification of the urinary phthalate excretion into quartiles, we found that the age at pubarche was increasing with increasing phthalate metabolite quartiles (except for MEP). This trend was statistically significant when all phthalate metabolites (except MEP) were summarized and expressed as quartiles. No association between phthalates and breast development was observed. In addition, there were no differences in urinary phthalate metabolite levels between girls with PP and controls. We demonstrated that delayed pubarche, but not thelarche, was associated with high phthalate excretion in urine samples from 725 healthy school girls, which may suggest anti-androgenic actions of phthalates in our study group of girls.

Rationale Several studies suggest a role for neuropeptide Y (NPY) in addiction to drugs of abuse, including cocaine. However, the NPY receptors mediating addiction-related effects remain to be determined. Objectives To explore the potential role of Y5 NPY receptors in cocaine-induced behavioural effects. Methods The Y5 antagonist L-152,804 and Y5-knockout (Y5-KO) mice were tested in two models of cocaine addiction-related behaviour: acute self-administration and cocaine-induced hyperactivity. We also studied effects of Y5 receptor antagonism on cocaine-induced c-fos expression and extracellular dopamine with microdialysis as well as dopamine transporter-mediated uptake of dopamine in vitro. Immunocytochemistry was used to determine whether dopamine neurons express Y5-like immunoreactivity. Results In self-administration, L-152,804 prominently decreased nose-poking for the peak dose of cocaine and shifted the dose–response curve for cocaine downward. Y5-KO mice also showed modestly attenuated selfadministration. Cocaine-induced hyperactivity was attenuated by L-152,804 and in Y5-KO mice. Cocaine failed to increase c-fos expression in the nucleus accumbens and striatum of L-152,804-treated mice, indicating that the Y5 antagonist could act by influencing neural activity in these regions. Accordingly, the cocaine-induced increase in accumbal extracellular dopamine was attenuated by L- 152,804 and in Y5-KO mice, suggesting that Y5 antagonism influences cocaine-induced behaviour by regulating dopamine. Consistent with this concept, dopamine neurons in the ventral tegmental area appeared to contain Y5 receptors. In contrast, neither L-152,804 nor NPY influenced dopamine transporter-mediated dopamine uptake. Conclusions The present data indicate that Y5 antagonism may attenuate cocaine-induced behavioural effects, su

The Hubble constant enters big bang cosmology by quantifying the expansion rate of the universe. It is shown that the standard technique for estimation of Hubble's constant is statistically inconsistent and results in a systematically too low value. An alternative, consistent estimator of Hubble’s constant is presented resulting in a change in estimate of 1.2%. The new estimate implies that the universe is 170 million years younger than previously thought.

BACKGROUND More than half of pregnant women in the Western world report intake of mild analgesics, and some of these drugs have been associated with anti-androgenic effects in animal experiments. Intrauterine exposure to anti-androgens is suspected to contribute to the recent increase in male reproductive problems, and many of the anti-androgenic compounds are like the mild analgesics potent inhibitors of prostaglandin synthesis. Therefore, it appears imperative to further investigate the potential endocrine disrupting properties of mild analgesics. METHODS In a prospective birth cohort study, 2297 Danish and Finnish pregnant women completed a questionnaire and 491 of the Danish mothers participated in a telephone interview, reporting on their use of mild analgesics during pregnancy. The testicular position of newborns was assessed by trained paediatricians. In rats, the impact of mild analgesics on anogenital distance (AGD) after intrauterine exposure was examined together with the effect on ex vivo gestational day 14.5 testes. RESULTS In the Danish birth cohort, the use of mild analgesics was dose-dependently associated with congenital cryptorchidism. In particular, use during the second trimester increased the risk. This risk was further increased after the simultaneous use of different analgesics. The association was not found in the Finnish birth cohort. Intrauterine exposure of rats to paracetamol led to a reduction in the AGD and mild analgesics accordingly reduced testosterone production in ex vivo fetal rat testes. CONCLUSION There was an association between the timing and the duration of mild analgesic use during pregnancy and the risk of cryptorchidism. These findings were supported by anti-androgenic effects in rat models leading to impaired masculinization. Our results suggest that intrauterine exposure to mild analgesics is a risk factor for development of male reproductive disorders.

Organophosphates and carbamates (OPs/CMs) are known for their acetylcholinesterase inhibiting character. A cross-sectional study of pesticide handling practices and self-perceived symptoms of acute pesticide poisoning was conducted using questionnaire-based interviews with 89 pesticide sprayers in Boeung Cheung Ek (BCE) Lake, Phnom Penh, Cambodia. The study showed that 50% of the pesticides used belonged to WHO class I + II and personal protection among the farmers were inadequate. A majority of the farmers (88%) had experienced symptoms of acute pesticide poisoning, and this was significantly associated with the number of hours spent spraying with OPs/CMs (OR = 1.14, CI 95%: 1.02-1.28). The higher educated farmers reduced their risk of poisoning by 55% for each extra personal protective measure they adapted (OR = 0.45, CI 95%: 0.22-0.91). These findings suggest that improving safe pesticide management practices among the farmers and enforcing the effective banning of the most toxic pesticides will considerably reduce the number of acute pesticide poisoning episodes.

In the 1990s, the American population-based study NHANES III renewed the focus on possible secular trends in male puberty. However, no conclusions could be made on pubertal onset due to the lack of compatible data.

Context: Anti-Mullerian hormone (AMH), which is secreted by immature Sertoli cells, triggers the involution of the fetal Mullerian ducts. AMH is a testis-specific marker used for diagnosis in infants with ambiguous genitalia or bilateral cryptorchidism. Aim: The aim of the study was to describe the ontogeny of AMH secretion through life in healthy males. Setting:This was a population-based study of healthy volunteers. Participants: Participants included 1027 healthy males from birth (cord blood) to 69 yr. A subgroup was followed up longitudinally through the infantile minipuberty [(in cord blood, and at 3 and 12 months), n = 55] and another group through puberty [(biannual measurements), n = 83]. Main Outcome Measures: Serum AMH was determined by a sensitive immunoassay. Serum testosterone, LH, and FSH were measured, and pubertal staging was performed in boys aged 6 to 20 yr (n = 616). Results: Serum AMH was above the detection limit in all samples with a marked variation according to age and pubertal status. The median AMH level in cord blood was 148 pmol/liter and increased significantly to the highest observed levels at 3 months (P <0.0001). AMH declined at 12 months (P <0.0001) and remained at a relatively stable level throughout childhood until puberty, when AMH declined progressively with adults exhibiting 3-4% of infant levels. Conclusion: Based on this extensive data set, we found detectable AMH serum levels at all ages, with the highest measured levels during infancy. At the time of puberty, AMH concentrations declined and remained relatively stable throughout adulthood. The potential physiological role of AMH and clinical applicability of AMH measurements remain to be determined

We present a new model-based approach to the analysis of agreement between raters in a situation where all raters have supplied dichotomous ratings of the same cases in a sample. The model is a logistic regression model with random effects - a Rasch model. In the rater setting, the Rasch model includes parameters that allow raters to have different propensities to score a given set of individuals positively or negatively - the rater bias. An exact score test of the hypothesis of no rater bias is proposed and is shown to be an exact generalised McNemar's test. Based on the model, we suggest quantifying the rater variation as a suitable measure of the variation of the rater odds ratios. An important example that will serve to motivate and illustrate the proposed model, is the study of Umbilical artery Doppler velocimetry used by obstetricians to assess the status of a foetus. The purpose of the assessment is to improve the foetus' chance of survival by choosing the optimal time of elective delivery. In the study, data related to 139 perinatal deaths were sent to 32 experts who were asked whether the use of Doppler velocimetry might have prevented each death.

In adult women, anti-Müllerian hormone (AMH) is related to the ovarian follicle pool. Little is known about AMH in girls.

Udgivelsesdato: 2009-Aug, A conceptually simple two-dimensional conditional reference curve is described. The curve gives a decision basis for determining whether a bivariate response from an individual is "normal" or "abnormal" when taking into account that a third (conditioning) variable may influence the bivariate response. The reference curve is not only characterized analytically but also by geometric properties that are easily communicated to medical doctors - the users of such curves. The reference curve estimator is completely non-parametric, so no distributional assumptions are needed about the two-dimensional response. An example that will serve to motivate and illustrate the reference is the study of the height/weight distribution of 7-8-year-old Danish school girls born in 1930, 1950, or 1970.