Girls with idiopathic central precocious puberty did not display substatial changes in body mass index after treatment with gonadotropin-releasing hormone analogues.

AIM: To evaluate changes in body mass index (BMI) in girls during and after treatment for idiopathic central precocious puberty (iCPP). METHODS: We studied 123 girls receiving gonadotropin-releasing hormone analogue (GnRHa)treatment for iCPP from 2009 to 2019. Pubertal and anthropometric measurements were monitored at routine clinical visits. BMI standard deviation scores (SDS) were estimated at baseline and followed in two stages from baseline to end of treatment (median 18.9 months) and from end of treatment to end of follow-up (median 18.2 months). The influence of baseline BMI SDS and the frequency and dose of treatment was evaluated using BMI trajectories and latent class mixed models. RESULTS: The median age at treatment initiation was 8.5 years. The median BMI SDS at baseline was 0.7, corresponding to a median BMI of 17.4 kg/m2. Overall, no changes in BMI SDS were observed during treatment. According to baseline BMI subgroups, an increasing trend in BMI trajectories during treatment was observed for girls in the lowest BMI group. After treatment, most girls maintained stable BMI levels. CONCLUSION: Our retrospective study did not provide evidence that GnRHa treatment for iCPP had a significant impact on BMI trajectories in girls.

Is male gynaecomastia associated with an increased risk of death? A nationwide register-based cohort study.

OBJECTIVE: Recent evidence supports that gynaecomastia may predict long-term morbidity, but evidence on the association with death and causes of death in males with gynaecomastia is lacking. The objective of this work is to estimate the risk of death in men diagnosed with gynaecomastia and evaluate whether this was conditional on underlying aetiologies of gynaecomastia. DESIGN: A nationwide register-based cohort study. SETTING: Nationwide Danish national health registries. PARTICIPANTS: Males were diagnosed with incident gynaecomastia (n=23 429) from 1 January 1995 to 30 June 2021, and each was age and calendar matched to five randomly population-based males without gynaecomastia (n=117 145). INTERVENTIONS: Not applicable. PRIMARY AND SECONDARY OUTCOMES: Gynaecomastia was distinguished between males without (idiopathic) and males with a known pre-existing risk factor. Cox regression models and Kaplan-Meier analyses estimated associations between gynaecomastia and death (all cause/cause specific). RESULTS: We identified a total of 16 253 males with idiopathic gynaecomastia and 7176 with gynaecomastia and a known pre-existing risk factor. Of these, 1093 (6.7%) and 1501 (20.9%) died during follow-up, respectively. We detected a 37% increased risk of all-cause death in males with gynaecomastia in the entire cohort (HR 1.37; 95% CI 1.31 to 1.43). Death risk was highest in males diagnosed with gynaecomastia and a known pre-existing risk factor (HR 1.75; 95% CI 1.64 to 1.86) compared with males with idiopathic gynaecomastia (HR 1.05; 95% CI 0.98 to 1.13). Specific causes of increased death were malignant neoplasms and circulatory, pulmonary and gastrointestinal diseases. Of the latter, an over fivefold risk of death from liver disease was detected (HR 5.05; 95% CI 3.97 to 6.42). CONCLUSIONS: Males diagnosed with gynaecomastia are at higher risk of death, observed mainly in males with a known pre-existing risk factor of gynaecomastia. These findings will hopefully stimulate more awareness among healthcare providers to potentially apply interventions that aid in alleviating underlying risk factors in males with this condition.

Cotinine concentrations in maternal serum and amniotic fluid during pregnancy and risk of testicular germ cell cancer in the offspring: A prospective nested case-control study.

Maternal smoking in pregnancy may increase the risk of testicular germ cell cancer (TGCC) in offspring, but current evidence remains inconclusive. We performed a nested case-control study using cotinine measurements in maternal serum and amniotic fluid as a biomarker for tobacco exposure during pregnancy. A total of 654 males with maternal serum (n = 359, ncases/controls = 71/288) and/or amniotic fluid (n = 295, ncases/controls = 66/229) samples were included. Data on TGCC diagnoses and relevant covariates were derived from nationwide Danish health registries. Cotinine was quantified by liquid chromatography tandem mass spectrometry. An adapted cox regression model estimated the risk of TGCC considering active and inactive tobacco use defined according to cotinine concentrations of <, ≥15 ng/ml. Overall, the concentrations of cotinine were comparable in maternal serum and amniotic fluid (medianserum/amniotic fluid : 2.1/2.6 ng/ml). A strong statistically significant correlation was detected in 14 paired samples (Spearman rho: 0.85). Based on maternal serum cotinine concentrations, exposure to active tobacco use was not associated with risk of TGCC in offspring (HR 0.88, 95% CI 0.51; 1.52). Similarly, based on amniotic fluid cotinine concentrations, exposure to active tobacco use was not associated with risk of TGCC (HR 1.11, 95% CI 0.64; 1.95). However, different risks were observed for seminomas and nonseminomas in both matrices, but none were statistically significant. Our findings did not provide convincing evidence supporting that exposure to tobacco during pregnancy is associated with TGCC.

Evaporation of serum after long-term biobank storage: A chemical analysis of maternal serum from a large Danish pregnancy screening registry.

BACKGROUND: Relying on freezer stored biospecimens is preferred in epidemiolocal studies exploring environmental pregnancy exposures and later offspring health. Storage duration may increase the pre-analytical variability, potentially adding measurement uncertainty. We investigated evaporation of maternal serum after long-term biobank storage using ions (sodium, Na+; chloride, Cl-) recognized for stability and relatively narrow normal biological reference ranges in human serum. METHODS: A chemical analysis study of 275 biobanked second trimester maternal serum from a large Danish pregnancy screening registry. Serum samples were collected between 1985-1995 and stored at -20°C. Ion concentrations were quantified with indirect potentiometry using a Roche Cobas 6000 analyzer and compared according to storage time and normal biological ranges in second trimester. Ion concentrations were also compared with normal biological variation assessed by baseline Na+ and Cl- serum concentrations from a separate cohort of 24,199 non-pregnant women measured before freezing with the same instrument. RESULTS: The overall mean ion concentrations in biobanked serum were 147.5 mmol/L for Na+ and 109.7 for Cl-. No marked linear storage effects were observed according to storage time. Ion concentrations were consistently high across sampling years, especially for specific sampling years, and a relatively large proportion were outside respective normal ranges in second trimester: 38.9% for Na+ and 43.6% for Cl-. Some variation in concentrations was also evident in baseline serum used as quality controls. CONCLUSIONS: Elevated ion concentrations suggest evaporation, but independent of storage duration in the present study (27-37 years). Any evaporation may have occurred prior to freezer storage or during the first 27 years. Other pre-analytical factors such as low serum volume have likely influenced the concentrations, particularly given the high within year variability. Overall, we consider the biobanked serum samples internally comparable to enable their use in epidemiological studies.

Risk of Fracture After Bilateral Oophorectomy.

Fragility fractures, resulting from low-energy trauma, occur in approximately 1 in 10 Danish women aged 50 years or older. Bilateral oophorectomy (surgical removal of both ovaries) may increase the risk of fragility fractures due to loss of ovarian sex steroids, particularly estrogen. We investigated the association between bilateral oophorectomy and risk of fragility fracture and whether this was conditional on age at time of bilateral oophorectomy, hormone therapy (HT) use, hysterectomy, physical activity level, body mass index (BMI), or smoking. We performed a cohort study of 25,853 female nurses (≥45 years) participating in the Danish Nurse Cohort. Nurses were followed from age 50 years or entry into the cohort, whichever came last, until date of first fragility fracture, death, emigration, or end of follow-up on December 31, 2018, whichever came first. Cox regression models with age as the underlying time scale were used to estimate the association between time-varying bilateral oophorectomy (all ages, <51/≥51 years) and incident fragility fracture (any and site-specific [forearm, hip, spine, and other]). Exposure and outcome were ascertained from nationwide patient registries. During 491,626 person-years of follow-up, 6600 nurses (25.5%) with incident fragility fractures were identified, and 1938 (7.5%) nurses had a bilateral oophorectomy. The frequency of fragility fractures was 24.1% in nurses who were <51 years at time of bilateral oophorectomy and 18.1% in nurses who were ≥51 years. No statistically significant associations were observed between bilateral oophorectomy at any age and fragility fractures at any site. Neither HT use, hysterectomy, physical activity level, BMI, nor smoking altered the results. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Depression in Mid- and Later-Life and Risk of Dementia in Women: A Prospective Study within the Danish Nurses Cohort.

BACKGROUND: Depression and dementia confer substantial global health burdens, particularly in women. Understanding the association between depression and dementia may inform new targets for prevention and/or early intervention. OBJECTIVE: To investigate the association between depression in mid- and later-life and dementia (all-cause, Alzheimer's disease (AD) or vascular dementia (VaD)) in women. METHODS: A prospective study design. Nurses were followed from age 60 years or entry into the cohort, whichever came last, until date of dementia, death, emigration, or end of follow-up, whichever came first. Cox regression models with age as the underlying timeline were used to estimate the associations between time-varying depression and incident dementia. RESULTS: The study included 25,651 female Danish nurses (≥45 years) participating in the Danish Nurse Cohort. During an average of 23 years of follow-up, 1,232 (4.8%) nurses developed dementia and 8,086 (31.5%) were identified with at least two episodes of treated depression. In adjusted analyses, nurses with depression were at a statistically significant 5.23-fold higher risk of all-cause dementia (aHR 5.23:95% CI, 4.64-5.91) compared to those with no history of depression. The differential effects of depression were greater for VaD (aHR 7.96:95% CI, 5.26-12.0) than AD (aHR 4.64:95% CI, 3.97-5.42). Later life depression (>60 years) (aHR 5.85:95% CI, 5.17-6.64) and recurrent depression (aHR 3.51:95% CI, 2.67-4.61) elevated dementia risk. Severe depression tripled the risk of all cause dementia (aHR 3.14:95% CI, 2.62-3.76). CONCLUSION: Both later life and severe depression substantially increase dementia risk in women, particularly VaD.

Maternal Exposure to Cigarette Smoke during Pregnancy and Testicular Cancer in Offspring: A Systematic Review and Meta-Analysis.

BACKGROUND: Maternal exposure to cigarette smoke in pregnancy may play a role in the development of testicular cancer in offspring. An updated and comprehensive systematic review of the available evidence is needed. OBJECTIVE: To identify and evaluate current evidence on maternal exposure to cigarette smoke during pregnancy and testicular cancer in offspring. METHODS: A systematic search of English peer-reviewed original literature in PubMed through a block search approach. Publications were considered if assessing maternal exposure to cigarette smoke and the risk of testicular cancer in offspring. RESULTS: Among the 636 identified records, 14 publications were eligible for review and 10 for meta-analysis. Quality assessment of the publications was conducted. Most included publications were case-control studies (n = 11, 79%), while the remaining were ecological studies (n = 3, 21%). Completeness of reporting was high, but more than half were considered subject to potential bias. The trend synthesis showed that half (n = 7) of the included publications demonstrated a higher risk of testicular cancer in the sons of mothers exposed to cigarette smoke during pregnancy. The meta-analysis generated an overall summary risk estimate of 1.00 (95% CI: 0.88; 1.15) (n = 10 publications), with a lower risk for seminoma (0.79, 95% CI: 0.59; 1.04) and nonseminoma (0.96, 95% CI: 0.74; 1.26) (n = 4 publications). CONCLUSIONS: This systematic review did not provide evidence of an association between maternal exposure to cigarette smoke and risk of testicular cancer in offspring. An overall positive trend was suggested, but it had low statistical precision. The methodological limitations across publications encourage further research based on valid exposure data.

Increased Morbidity in Males Diagnosed With Gynecomastia: A Nationwide Register-based Cohort Study.

CONTEXT: Evidence on the long-term and general health of males with gynecomastia is lacking. OBJECTIVES: To assess health before and following a diagnosis of gynecomastia. METHODS: A register-based cohort study of 140 574 males, of which 23 429 were diagnosed with incident gynecomastia and age- and calendar-matched (1:5) to 117 145 males without gynecomastia from the background population. Males with gynecomastia were stratified into males without (idiopathic) or with a known preexisting risk factor (disease/medication). Cox and logistic regression models investigated associations of disease risk according to International Classification of Diseases 10th revision sections following and before gynecomastia diagnosis. RESULTS: A total of 16 253 (69.4%) males in the cohort were identified with idiopathic gynecomastia. These males had a statistically significant higher risk of future disease across all included disease chapters (hazard ratio [HR], 1.19-1.89), with endocrine diseases representing the greatest disease risk (HR, 1.89; 95% CI, 1.76-2.03). The highest subchapter disease risk was observed for disorders of the endocrine glands (odds ratio [OR], 7.27; 95% CI, 6.19-8.54). Similarly, the ORs of comorbidities were higher across all included disease sections (OR, 1.05-1.51), except for psychiatric disease (OR, 0.72; 95% CI, 0.68-0.78), with the highest association with musculoskeletal/connective tissue (OR, 1.51; 95% CI, 1.46-1.57) and circulatory (OR, 1.36; 95% CI, 1.29-1.43) diseases. CONCLUSIONS: The presence of idiopathic gynecomastia is an important first clinical symptom of an underlying disease and a significant predictor of future disease risk. These findings should stimulate more awareness among health care providers to increase identification of gynecomastia and its causes in males.

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

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

Maternal Serum α-Fetoprotein Levels during Pregnancy and Testicular Cancer in Male Offspring: A Cohort Study within a Danish Pregnancy Screening Registry.

Testicular cancer is believed to originate from disruptions of normal androgen-estrogen balance in-utero. α-fetoprotein (AFP) may modify fetal response to estrogens via estrogen interaction. In a cohort study, we investigated the association between circulating maternal pregnancy AFP and testicular cancer risk in offspring. Of the 56,709 live-born males from a pregnancy screening registry in 1980-1995, our study included 50,519 singleton males with available second trimester blood samples from their mothers and complete covariate ascertainment. Testicular cancer diagnoses and covariate data were obtained from nationwide Danish health registries. Cox regression and Kaplan-Meier analyses estimated the prospective risk of testicular cancer (all, seminoma, nonseminoma) by AFP multiples of the median. During follow-up, 163 (0.3%) of the included males developed testicular cancer, of which 89 (54.6%) were nonseminomas. Maternal serum AFP levels greater than/equal to the median were associated with a relative risk of testicular cancer close to unity (RR 1.04, 95% CI 0.76; 1.41) compared to AFP below the median. Associations differed by type of testicular cancer (RRseminoma 0.81, 95% CI 0.51; 1.29, RRnonseminoma 1.31, 95% CI 0.85; 2.02). On balance, our findings do not support that serum AFP in pregnancy can be used as a predictor of testicular cancer in offspring.

Sex-specific associations between maternal exposure to parabens, phenols and phthalates during pregnancy and birth size outcomes in offspring.

Current evidence on the effects of prenatal exposure to endocrine disrupting chemicals on birth size remains largely inconclusive. We aimed to investigate sex-specific associations between maternal exposure to parabens, phenols and phthalates during pregnancy and birth weight, length and head/abdominal circumferences. We performed a prospective study of 88 pregnant women who underwent amniocentesis in the period 2012 to 2014. Maternal urine samples were collected during pregnancy in weeks 12 to 36 (median: 18 weeks). The concentrations of parabens, phenols and individual phthalate diester metabolites were analyzed by isotope-diluted liquid chromatography-tandem mass spectrometry and osmolality adjusted. Linear regression models estimated the associations between urinary levels of selected compounds (tertile(T2-T3)medium/high versus T1low exposure) and birth size, stratified by offspring sex. A total of three parabens, two phenols, four individual phthalate metabolites and four sums of diester metabolites were detectable above limits of detection in at least 60% of urine samples. Overall, we observed few statistically significant associations, but medium/high exposure to bisphenol A (BPA) in male offspring was associated with statistically significant lower birth size across most outcomes [birth weight: -428 g (95% CI -756 to -99.4); birth length: -1.76 cm (95% CI -3.28 to -0.25); abdominal circumference: -1.97 cm (95% CI -3.55 to -0.39)]. Similarly, medium/high exposure to methyl paraben (MeP) in male offspring was associated with lower birth weight (-661 g, 95% CI -1251 to -70.7) and length (-3.11 cm, 95% CI -5.76 to -0.46) compared to low exposure. None of these associations were statistically significant in female offspring. Across all compounds, individual exposures were associated with more negative estimates of birth weight for male than for female offspring. Our study indicates that prenatal exposure to BPA and MeP may negatively affect birth size outcomes, with a possible sex effect. Given the small sample size, these findings need to be replicated in future larger studies.

Oophorectomy and rate of dementia: a prospective cohort study.

OBJECTIVE: Globally, dementia disproportionally affects women, which is not fully explained by higher female longevity. Oophorectomy at any age leads to the permanent loss of ovarian sex steroids, potentially increasing the risk of dementia. We aimed to investigate the association between oophorectomy and dementia and whether this was conditional on age at oophorectomy, hysterectomy or use of hormone therapy (HT). METHODS: A prospective study of 24,851 female nurses from the Danish Nurse Cohort. Nurses were followed from age 60 years or entry into the cohort, whichever came last, until date of dementia, death, emigration or end of follow-up (December 31, 2018), whichever came first. Poisson regression models with log-transformed person-years as offset were used to estimate the associations. RESULTS: During 334,420 person-years of follow-up, 1,238 (5.0%) nurses developed dementia and 1,969 (7.9%)/ 1,016 (4.1%) contributed person-time after bilateral-/unilateral oophorectomy. In adjusted analyses, an 18% higher rate of dementia was observed following bilateral oophorectomy (aRR 1.18: 95% CI, 0.89-1.56) and 13% lower rate (aRR 0.87: 95% CI, 0.59-1.23) following unilateral oophorectomy compared to nurses who retained their ovaries. Similar effects were detected after stratification according to age at oophorectomy. No statistically significant modifying effects of hysterectomy or HT were detected (Pinteraction≥0.60). CONCLUSIONS: Bilateral, but not unilateral, oophorectomy was associated with an increased rate of incident dementia. We were unable to establish whether this association was conditional on hysterectomy or HT use. Although an increase in dementia after bilateral oophorectomy is biologically plausible, limited statistical power hampers the precision of the estimates.

Presence of parabens, phenols and phthalates in paired maternal serum, urine and amniotic fluid.

OBJECTIVE: To examine whether selected endocrine disrupting chemicals were present in pregnant women and passed through the placental barrier to amniotic fluid, potentially exposing the developing fetus. METHODS: Paired samples of maternal serum, urine and amniotic fluid were concurrently collected (<1 h) from 200 pregnant women (age >18 years) with a singleton pregnancy and undergoing amniocentesis between gestational weeks 12 - 36. The concentration of six different parabens, seven phenols, 31 metabolites from 15 phthalate diesters and the polychlorinated substance triclocarban were analyzed by isotope diluted TurboFlow-liquid chromatography-tandem mass spectrometry. RESULTS: Concentrations of all included compounds were highest in maternal urine followed by serum, and lowest in amniotic fluid. Of the six parabens measured in amniotic fluid, methylparaben (MeP) and ethylparaben (EtP) were detectable most often (87% and 33% of the samples, respectively). Of the seven phenols measured, three (2,4-dichlorphenol, 2,5-dichlorphenol, 2-propylphenol) were detectable in the range of 14-21% of the amniotic fluid samples, at low concentrations (<0.12 ng/ml). Two secondary phthalates metabolites, mono-(2-carboxymethyl-hexyl) phthalate and mono-carboxy-iso-octyl phthalate were each present in ≤15% of the amniotic fluid samples at concentrations 2-5 times lower than in maternal serum and 20-100 times lower than in maternal urine. A modest statistically significant correlation between the levels of MeP and EtP was detected in paired maternal urine-amniotic fluid samples was detected (Spearman rMeP: 0.246; rEtP: 0.364). Likewise, the concentration of mono-ethyl phthalate (MEP) in paired maternal urine and amniotic fluid samples indicated a modest statistically significant correlation (Spearman rMEP: 0.264), driven by detectable levels of MEP in only 3% of the amniotic fluid samples. CONCLUSIONS: In general, the included parabens, phenols and phthalates were effectively metabolized and excreted via the urine, which was the matrix that reflected the highest detectable levels. The detectable levels of several included parabens and phthalates in human amniotic fluid calls for further investigations of the toxicokinetic and potential endocrine disrupting properties of individual and multiple endocrine disruptors in order to better assess the risk to the developing fetus.

Prenatal antibiotic exposure and birth weight.

BACKGROUND/OBJECTIVES: Current research suggests an association between antibiotic use in early life and later obesity. Less is known about prenatal antibiotic exposure and foetal growth. We investigated the association between prenatal antibiotic exposure and birth weight. METHODS: Data from the Danish National Birth Cohort were linked to the Danish National Medical Birth Registry. Exposure was self-reported antibiotic use in pregnancy. Outcome was registered birth weight. Multivariable linear regression models were adjusted for confounders defined a priori. RESULTS: A total of 63 300 mother-child dyads from 1996 to 2002 were included. Overall, prenatal antibiotic exposure was not associated with birth weight (-8.90 g, 95%CI: -19.5- +1.64 g, p = 0.10). Findings were similar for those born term and preterm. Antibiotic exposure in second to third trimester, compared to no exposure, was associated with lower birth weight (-12.6 g, 95%CI: -24.1 to -1.1 g, p = 0.03). In sex-stratified analyses, there were no observed associations between antibiotics and birth weight. With further stratifications, prenatal antibiotic exposure and birth weight were associated in boys who were preterm (+91.0 g, 95%CI: +6.8 g- +175.2 g, p = 0.03) but not among girls who were preterm (-44.0 g, 95%CI: -128.1 to +40.0 g, p = 0.30). CONCLUSIONS: Prenatal antibiotic exposure is not consistently associated with birth weight.

Cardiovascular mortality after bilateral oophorectomy: a prospective cohort study.

OBJECTIVES: Bilateral oophorectomy permanently reduces endogenous estrogen exposure and may increase cardiovascular mortality in women. This study aimed to investigate the association between bilateral oophorectomy and cardiovascular mortality and whether this association was conditional on hysterectomy or on the use of hormone therapy at the time of study entry. METHODS: A prospective cohort study of 25,338 female nurses aged ≥ 45 years within the Danish Nurse Cohort. Nurses were enrolled in 1993 or 1999 and followed until death, emigration, or end of follow-up on December 31, 2018, whichever came first. Exposure was bilateral oophorectomy. Outcome was cardiovascular mortality. Associations were estimated using Poisson regression models with log person-years as the offset. RESULTS: A total of 2,040 (8.1%) participants underwent bilateral oophorectomy. During a mean follow-up of 21.2 (SD: 5.6) years, 772 (3.0%) nurses died from cardiovascular disease. In adjusted analyses, a 31% higher rate of cardiovascular mortality was observed after bilateral oophorectomy (aMRR 1.31; 95% CI, 0.88-1.96) compared with women who retained their ovaries. No evidence of effect modification by use of hormone therapy at baseline or by hysterectomy on the association between bilateral oophorectomy and cardiovascular mortality was observed. CONCLUSION: Bilateral oophorectomy may be associated with cardiovascular mortality in women, but the estimate was not statistically significant. Additionally, we were unable to make firm conclusions regarding the possible modifying role of hormone therapy and hysterectomy on this potential association. Additional studies are needed to replicate this work.

Endocrine Disrupting Chemicals and Risk of Testicular Cancer: A Systematic Review and Meta-analysis.

The incidence of many hormone-dependent diseases, including testicular cancer, has sharply increased in all high-income countries during the 20th century. This is not fully explained by established risk factors. Concurrent, increasing exposure to antiandrogenic environmental endocrine disrupting chemicals (EDCs) in fetal life may partially explain this trend. This systematic review assessed available evidence regarding the association between environmental EDC exposure and risk of testicular cancer (seminomas and nonseminomas). Following PRISMA guidelines, a search of English peer-reviewed literature published prior to December 14, 2020 in the databases PubMed and Embase® was performed. Among the 279 identified records, 19 were eligible for quality assessment and 10 for further meta-analysis. The completeness of reporting was high across papers, but over 50% were considered subject to potential risk of bias. Mean age at diagnosis was 31.9 years. None considered effects of EDC multipollutant mixtures. The meta-analyses showed that maternal exposure to combined EDCs was associated with a higher risk of testicular cancer in male offspring [summary risk ratios: 2.16, (95% CI:1.78-2.62), 1.93 (95% CI:1.49-2.48), and 2.78 (95% CI:2.27-3.41) for all, seminoma, and nonseminoma, respectively]. Similarly, high maternal exposures to grouped organochlorines and organohalogens were associated with higher risk of seminoma and nonseminoma in the offspring. Summary estimates related to postnatal adult male EDC exposures were inconsistent. Maternal, but not postnatal adult male, EDC exposures were consistently associated with a higher risk of testicular cancer, particularly risk of nonseminomas. However, the quality of studies was mixed, and considering the fields complexity, more prospective studies of prenatal EDC multipollutant mixture exposures and testicular cancer are needed.

Antibiotic exposure during pregnancy and childhood asthma: a national birth cohort study investigating timing of exposure and mode of delivery.

OBJECTIVE: To investigate whether antibiotic exposure during pregnancy was associated with childhood asthma and if this relationship was conditional on timing of exposure and mode of delivery. DESIGN: A cohort study using multivariable logistic regression models adjusting for a priori defined confounders. Pregnant women were recruited from 1996 to 2002. SETTING: The Danish National Birth Cohort. PATIENTS: Of the 96 832 children in the cohort, 32 651 children were included in the study population. MAIN OUTCOME MEASURE: Parent-reported childhood asthma at 11 years. RESULTS: A total of 5522 (17%) children were born to mothers exposed to antibiotics during pregnancy. In adjusted analyses, children born to exposed mothers had higher odds of asthma (OR 1.14, 95% CI 1.05 to 1.24). There was no association with antibiotic exposure in the first trimester (OR 1.02, 95% CI 0.83 to 1.26), but higher odds were observed for antibiotic exposure in the second to third trimester (OR 1.17, 95% CI 1.06 to 1.28), compared with unexposed children. The overall association between antibiotics during pregnancy and childhood asthma was only observed in vaginally born children (OR 1.17, 95% CI 1.07 to 1.28) but not in caesarean section born children (planned caesarean section: OR 0.95, 95% CI 0.66 to 1.37; caesarean emergency: OR 0.96, 95% CI 0.73 to 1.28). In exposed vaginally born children, the odds for childhood asthma requiring treatment during the preceding year were 34% higher (OR 1.34, 95% CI 1.21 to 1.49), compared with unexposed vaginally born children. CONCLUSIONS: Antibiotic exposure in mid-to-late pregnancy is associated with higher odds of childhood asthma in vaginally born children. Mode of delivery may modify the association.

"Trading daughters for livestock": An ethnographic study of facilitators of child marriage in Lira district, Northern Uganda.

Child marriage remains a significant challenge in Uganda despite national policies, legislation and programs for improved rights of girls. This ethnographic study aimed to explore underlying drivers of child marriage in Lira district, Northern Uganda. We applied a triangulation of qualitative methods; in-depth interviews, focus group discussions, key informant interviews and observations. Data were analysed using qualitative thematic content analysis. Our study findings showed that child marriage is still prevalent in the study area and the practice was also carried out at designated markets, at which girls were traded in exchange of livestock. The main drivers of child marriage were identified as poverty and survival strategies; socio-cultural beliefs and norms; and school dropouts. Determined efforts are needed to address the socio-cultural drivers of child marriage, keep girls in school, address poverty through targeting the family and individual level with appropriate incentives to address the economic needs of girls and families to delay marriage, enforce laws prohibiting the practice of child marriage, equip teenagers with accurate information on SRHR and ensure that parents support their daughters to be educated and responsible adults.

Perceived barriers to utilization of antenatal care services in northern Uganda: A qualitative study.

OBJECTIVE: Antenatal care (ANC) utilization remains a challenge in efforts to reduce maternal mortality and improve maternal health in Uganda. This study aimed to identify perceived barriers to utilization of ANC services in a rural post-conflict area in northern Uganda. METHODS: A qualitative study using in-depth interviews and focus group discussions of seventeen participants (pregnant women, health workers and a traditional birth attendant). The study was informed through a phenomenological approach to capture perceived barriers to utilization of ANC. The study was carried out in post-conflict Awach sub-county, Gulu District, northern Uganda. Data was analyzed using inductive conventional content analysis. RESULTS: The main perceived barriers to ANC utilization were identified as: poor quality of care, including poor attitude of health workers; socio-cultural practices not being successfully aligned to ANC; and lack of support from the husband, including difficulties in encouraging him to attend ANC. Additionally, institutional structures and procedures at the health centers in terms of compulsory HIV testing and material requirements and transportation were perceived to prevent some pregnant women from attending ANC. CONCLUSIONS: Identifying local barriers to ANC utilization are important and should be considered when planning ANC programs. We propose that future efforts should focus on how to ensure a good patient-provider relationship and perceived quality of care, and further how to improve inter-spousal communication and sensitization of husbands for increased involvement in ANC. We recommend more research on how socio-cultural context can meaningfully be aligned to ANC to improve maternal health and reduce maternal mortality.