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Objective To investigate the possible associations between maternal pre-pregnancy body mass index (BMI) and daughters' age of menarche and subsequent markers of reproductive health. Methods Nine hundred eighty-five pregnant women (80 %) were enrolled at their routine 30th week examinations in 1988-1989. In 2008, a follow-up questionnaire was completed for 365 daughters (83 %), while 267 daughters (61 %) participated in a subsequent clinical examination. Main outcome measures were age of menarche, reproductive hormone profile, and ovarian follicle count in daughters. Results Daughters of mothers in the highest pre-pregnancy BMI tertile (BMI ≥ 22.0 kg/m(2)) had an adjusted 4.1 (0.3; 8.0) months earlier menarche compared with the middle tertile group (BMI 20.0-21.9 kg/m(2)). Among non-users of hormonal contraceptives, daughters of mothers in the highest pre-pregnancy BMI tertile had non-significantly lower dehydroepiandrosterone-sulphate (DHEAS), estradiol, and free estrogen index (FEI), compared to the middle BMI tertile. This was supported by a sub-analysis using the WHO classification (underweight, BMI

Background: The biopersistent organochlorine pollutants dichlorodiphenyldichloroethylene (p,p′-DDE), hexachlorobenzene (HCB) and polychlorinated biphenyls (PCBs) can be detected in humans worldwide. The chemicals can cross the placenta and may interfere with endogenous hormonal homeostasis. Objectives: To investigate effects on female reproduction following intrauterine exposure to selected biopersistent organochlorines. Methods: We used data from a Danish pregnancy cohort with follow-up on 436 eligible daughters at approximately 20 years of age. Information on age of menarche (n = 335), menstrual cycle length (n = 230) and serum concentrations of reproductive hormones (n = 243) was obtained. Number of antral follicles was counted by vaginal ultrasound (n = 147). Of 244 daughters who attended clinical examination, 170 used hormonal contraceptives and 74 were non-users. Concentrations of p,p′-DDE, HCB and six PCB congeners were analysed in maternal serum samples obtained in pregnancy week 30. Results: Age of menarche and menstrual cycle length were found not to be statistically significant associated with prenatal organochlorine exposure. Among non-users of hormonal contraceptives with information on antral follicle number (n = 43), daughters exposed to the highest tertile of p,p′-DDE had 28% (95% confidence interval (95% CI): 5; 46%) lower follicle number compared to the low-level exposed reference group. Those exposed to medium and higher levels of HCB had 30% (95% CI: 5; 48%) and 28% (95% CI: 7; 44%) lower follicle number compared to the reference group. Furthermore, maternal serum HCB concentrations were inversely associated with free androgen index among non-users of hormonal contraceptives (n = 73). These associations were not found in users of hormonal contraceptives. Conclusions: Among non-users of hormonal contraceptives, we found indications of adverse long-term effects on female reproduction following prenatal exposure to biopersistent organochlorines. These findings may have wide implications for public health as intrauterine exposure occurs worldwide. Keywords: Persistent organochlorines, Female reproduction, Ovary, Fetal development, Epidemiology

Objective The purpose of this study was to survey the impact of epilepsy and its treatment on the quality of life, development, and opportunities for children/teenagers with the condition. Methods We asked three groups—children/teenagers, parents and caregivers, and health care professionals—to complete specifically designed questionnaires containing clinical and demographic information and perceptions of the impact of epilepsy and its treatment on aspects of daily living, including education and leisure. For health care professionals, the survey included questions on area of speciality and volume of children with epilepsy seen in their clinic. Questionnaires were translated into the local written language in each participating country. Prepaid envelopes were provided for return of completed questionnaires. Responses were analyzed by an independent data analysis company. Results Two hundred twelve young people with epilepsy and 507 parents or carers of children/teenagers from 16 different countries completed the questionnaire. The majority of children were over the age of 12 (74%) and attended mainstream schools (64%). Approximately two-thirds (65%) of the children/teenagers who responded reported that their seizures caused them to lose, on average, 7 school days per year. More than one-third of the children/teenagers who responded to the survey (36%) have kept their epilepsy a secret from other people at some time for fear of being treated differently and a belief that people should not know (47%). The majority (87%) of respondents were taking epilepsy medications. More than a third of the children/teenagers who responded had experienced side effects in some form or another, with weight change (49%), headaches (46%), dizziness (41%), and shaking (33%) most commonly reported. More than one-third of the children/teenagers expected the condition to hinder their lives in the future, with impact on employment opportunities (73%), traveling and exploring (37%), and education (36%) most commonly reported. Conclusions This survey documents some of the real-life consequences of childhood epilepsy and highlights important challenges and issues faced by children/teenagers with epilepsy and their families. Although there are a number of limitations to this study relating to sample selection, ensuring that children are as free from seizures as possible and minimizing the side effects of treatment must be the primary goal of epilepsy management, but considering the wider implications of epilepsy and treatment is also important.

Introduction. Gastroesophageal reflux disease (GERD), functional dyspepsia (FD) and irritable bowel syndrome (IBS) are common functional gastrointestinal conditions with significant impact on the daily lives of individuals. The objective was to investigate the prevalence and overlap of the three conditions in a Western general population. Material and methods. A nationwide study of 100,000 individuals 20 years and above, randomly selected in the general population. A web-based questionnaire survey formed the basis of this study. Questions regarding FD and IBS were extracted from the ROME III adult questionnaire. Questions regarding GERD were developed based on the Montreal definition. Prevalence estimates for GERD, FD IBS were calculated in total and for each sex separately and for four age groups. A Venn diagram was constructed, illustrating the overlap between the three conditions. Results. The overall response rate was 52.2%. The prevalence of GERD, FD and IBS was 11.2%, 7.7% and 10.5%, respectively, and overlap between two or three of these conditions was seen among 6.5% of the respondents. Among individuals meeting the criteria of one or more of the conditions GERD, FD and IBS, 30.7% had overlap between two or all three conditions. Conclusion. GERD, FD and IBS are common conditions in the general population and the overlap between these conditions is also quite common. When diagnosing patients with GERD, FD and IBS, physicians should keep in mind that these patients could be suffering from more than one of these conditions.

Persistent organochlorine pollutants (POPs) are ubiquitous, bioaccumulative compounds with potential endocrine-disrupting effects. They cross the placental barrier thereby resulting inin uteroexposure of the developing fetus. The objective of this study was to investigate whether maternal serum concentrations of polychlorinated biphenyls (PCBs) andp,p′-dichlorodiphenyldichloroethylene (p,p′-DDE) during pregnancy are associated with son's semen quality and reproductive hormone levels. During 2008–2009, we recruited 176 male offspring from a Danish cohort of pregnant women who participated in a study in 1988–1989. Each provided semen and blood samples that were analyzed for sperm concentration, total sperm count, motility, and morphology, and reproductive hormone levels, respectively. The maternal blood samples were collected in pregnancy week 30 and were analyzed for the concentrations of six PCBs (PCB-118, -138, -153, -156, -170, and -180) andp,p′-DDE. The potential associations betweenin uteroexposure to ΣPCBs (pmol/ml), Σdioxin like-(DL) PCBs (PCB-118 and -156) (pmol/ml), andp,p′-DDE and semen quality and reproductive hormone levels were investigated using multiple regression. Maternal median (range) exposure levels of ΣPCB, ΣDL-PCB, andp,p′-DDE were 10.0 (2.1–35.0) pmol/ml, 0.8 (0.2–2.7) pmol/ml, and 8.0 (0.7–55.3) pmol/ml, respectively, reflecting typical background exposure levels in the late 1980s in Denmark. Results suggested thatin uteroexposure to ΣPCB, ΣDL-PCB, andp,p′-DDE was not statistically significantly associated with semen quality measures or reproductive hormone levels. Thus, results based on maternal PCB andp,p′-DDE concentrations alone are not indicative of long-term consequences for male reproductive health; however, we cannot exclude that these POPs in concert with other endocrine-modulating compounds may have adverse effects.

STUDY QUESTION: Does in utero exposure to constituents of cigarette smoke have a programming effect on daughters' age of menarche and markers of long-term reproductive health? SUMMARY ANSWER: In utero exposure to constituents of cigarette smoke was associated with earlier age of menarche and--to a lesser extent--changes in the testosterone profile of the young women. WHAT IS KNOWN ALREADY: Studies observe potential effects of in utero exposure to constituents of cigarette smoke on the intrauterine formation of female gonads, but the consequences on long-term reproductive health in daughters remain unclear. STUDY DESIGN, SIZE AND DURATION: A prospective cohort study was designed using data from 965 pregnant women enrolled prior to a routine 30th-week antenatal examination at a midwifery practice in Denmark from 1988 to 1989 and a follow-up of their 19-21-year-old daughters in 2008. PARTICIPANTS/MATERIALS, SETTING AND METHODS: The pregnant women provided information on lifestyle factors during pregnancy, including the exact number of cigarettes smoked per day during the first and the second trimesters. A total of 438 eligible daughters were asked to complete a web-based questionnaire on reproductive health and subsequently invited to participate in a clinical examination during 2008. Of the 367 daughters (84%) who answered the questionnaire, 267 (61%) agreed to further examination. Information on menstrual pattern was provided at examination, blood samples were drawn to be analyzed for serum levels of reproductive hormones [FSH, LH, estradiol (E(2)), sex hormone-binding globulin, anti-Müllerian hormone, dehydroepiandrosterone-sulphate (DHEAS), free testosterone and free E(2)] and number of follicles (2-9 mm) were examined by transvaginal ultrasound. The daughters were divided into three exposure groups according to the level of maternal smoking during first trimester [non-exposed (reference), low-exposed (mother smoking >0-9 cigarettes/day) and high-exposed (mother smoking ≥ 10 cigarettes/day)]. Data were analyzed by multiple regression analyses in which we adjusted for potential confounders. Both crude and adjusted test for trend were carried out using maternal smoking during the first trimester as a continuous variable. MAIN RESULTS AND THE ROLE OF CHANCE: We observed an inverse association between in utero exposure to constituents of cigarette smoke and age of menarche (P = 0.001). Daughters exposed to >0-9 cigarettes/day debuted with -2.7 [95% confidence interval (CI) -5.2 to -0.1] percentage earlier age of menarche, whereas daughters exposed to ≥ 10 cigarettes/day had -4.1 (95% CI: -6.6 to -1.5) percentage earlier age of menarche corresponding to 6.5 (95% CI: -10.7 to -2.2) months. There was a non-significant tendency towards lower levels of testosterone and DHEAS with increasing in utero exposure to constituents of cigarette smoke but no associations with follicle number, cycle length or serum levels of the other reproductive hormones were observed. LIMITATIONS AND REASONS FOR CAUTION: We collected information on age of menarche retrospectively but the recall time was relatively short (2-10 years) and the reported values were within the normal range of Caucasians. Analyses of reproductive hormones are presented only for the group of daughters who were non-users of hormonal contraceptives because users were excluded, leaving only a low number of daughters available for the analyses (n = 75), as reflected in the wide CIs. The analyses of hormones were further adjusted for menstrual phase at time of clinical examination (follicular, ovulation and luteal phase) because blood samples were not collected on a specific day of the menstrual cycle. WIDER IMPLICATIONS OF THE FINDINGS: This study supports the limited evidence of an inverse association between maternal smoking during pregnancy and age of menarche and further addresses to what extent reproductive capacity and hormones may be programmed by maternal smoking during pregnancy. A trend toward earlier maturation of females is suggested to have implications on long-term reproductive function. STUDY FUNDING/COMPETING INTEREST(S): Supported by a scholarship from The Lundbeck Foundation (R93-A8476). No conflict of interest declared.

Background and Aims: Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are man-made compounds found globally in humans. They are suspected to act as endocrine disrupters and since ...

Objective To investigate the association between serum antimullerian hormone (AMH) and other reproductive parameters in young women. Design Cross-sectional study. Setting University hospital. Patient(s) Population-based cohort of 256 women: 180 were users and 76 were nonusers of hormonal contraceptives. Intervention(s) None. Main Outcome Measure(s) Antral follicles, androgens, age at menarche, and duration and regularity of menstrual cycle. Result(s) AMH levels were lower among users of hormonal contraceptives compared to nonusers. Among nonusers, women with AMH levels in the upper tertile had 55% (95% confidence interval [CI]: 22%–99%) higher levels of total T and 8% (95% CI=2%–15%) longer menstrual cycles than women with AMH levels in the lower tertile. An increase of 1 ng/mL in AMH was associated with 45% (95% CI=6%–97%) higher prevalence of irregular menstrual cycles. These associations were not seen among users of hormonal contraceptives. A strong relationship between AMH and follicle number was found in both users and nonusers. Conclusion(s) AMH measurements were found to be applicable in evaluation of the reproductive function of young women. However, there may be differences in the way that serum AMH levels can be interpreted depending on whether the woman uses hormonal contraceptives or not.

background: According to the Rotterdam 2003 criteria, an ovary is defined as polycystic if 12 or more follicles of 2 –9 mm are present, when evaluating the ovary by ultrasonography on Days 3 –5 of the menstrual cycle in women not using hormonal contraceptives. The aim of this population-based study was to estimate the prevalence of polycystic ovaries (PCO) in a representative sample of young Danish women according to the Rotterdam criteria. methods: From a Danish pregnancy cohort established in 1988–1989, 267 (61%) young adult daughters agreed to participate in a clinical examination and 174 (40%) consented to vaginal ultrasound. Sufficient image quality in at least one ovary was obtained from 154 women. Both users and non-users of hormonal contraceptives were included and the examination was not restricted to a particular time of the menstrual cycle. results: The median (range) age was 20.1 (19.5 –21.0) years. The median follicle number per ovary was 14 (6 –30) and 12 or more follicles were counted in 104 of the 154 women. Thus, the prevalence was estimated to 68% [95% confidence interval (CI): 60– 74%]. PCO were present in 80% (95% CI: 65– 89%) of non-users (n ¼ 44) of hormonal contraceptives. Of the 104 women with PCO, 41% (95% CI: 32–51%) could be defined as having polycystic ovary syndrome. conclusions: A very large proportion of the young women had PCO according to the Rotterdam 2003 criteria. As the number of follicles is higher at a younger age, we believe the Rotterdam criteria should be revised, particularly to avoid misdiagnosis in this age group.