Determinantes de los parámetros reproductivos en varones universitarios sanos

INTRODUCCIÓN: Los compuestos disruptores endocrinos son tóxicos medioambientales ubicuos con posibles efectos sobre la función reproductiva masculina. El bisfenol A (BPA) es ampliamente utilizado en la fabricación de plásticos policarbonatos y empaquetados alimentarios. Los parabenos son sustancias que se añaden a productos de uso personal y alimentos como preservantes antimicrobianos. Los filtros ultravioletas (UV) tipo benzofenonas (BP) se utilizan en cremas de uso personal o protectores solares. La exposición a estos compuestos es común entre las poblaciones estudiadas a nivel mundial (>80%), y se ha visto que podrían tener efectos estrogénicos o anti-androgénicos. Sin embargo, existen pocos trabajos que hayan estudiado las relaciones entre la exposición a BPA, parabenos y filtros UV tipo BP y los parámetros reproductivos en hombres no seleccionados por su función testicular. El objetivo de esta Tesis fue evaluar las asociaciones entre las concentraciones urinarias de BPA, parabenos y filtros UV tipo BP y la calidad seminal y niveles de hormonas reproductivas en varones jóvenes. MATERIAL Y MÉTODO: Se llevó a cabo un estudio transversal con una muestra de 215 varones universitarios (18-23 años) de la Región de Murcia entre 2010 y 2011. El mismo día de la exploración física, los sujetos proporcionaron una muestra de orina, semen y sangre y cumplimentaron cuestionarios sobre hábitos de vida. Los compuestos medioambientales se midieron en orina después de tratar las muestras mediante microextracción dispersiva líquido-líquido y analizarlas por cromatografía líquida de alta resolución acoplada a espectrometría de masas en tándem. La calidad seminal se evaluó analizando el volumen, la concentración, el recuento total, la movilidad y la morfología espermática. Se determinaron los niveles séricos de la hormona folículo-estimulante (FSH), hormona luteinizante (LH), testosterona (T) total y libre, estradiol (E2) e inhibina B. Se utilizó la regresión linear múltiple para evaluar las asociaciones entre los distintos compuestos químicos ambientales y los parámetros seminales y niveles hormonales tras ajustar por potenciales variables confundidoras. RESULTADOS: En los modelos multivariantes se halló una asociación positiva significativa entre las concentraciones urinarias de BPA y los niveles séricos de LH (β = 0,07; IC95%: 0,02; 0,12, p-valor <0,01). Las concentraciones de BPA también se asociaron significativa e inversamente con la concentración espermática (β = − 0,04; IC95%: − 0.07; − 0.02, p-valor<0,01) y el recuento total espermático (β = − 0,05; IC95%: − 0,08; − 0,02, p-valor<0,01). No se observaron relaciones significativas entre el BPA y otros parámetros seminales u hormonales. No se hallaron asociaciones significativas entre las concentraciones urinarias de parabenos o su suma molar y ninguno de los parámetros seminales u hormonas. Se encontró una relación positiva significativa entre las concentraciones urinarias de filtros UV tipo BP-1 y BP-3 y los niveles de FSH (β=0,08; IC95%: 0,009; 0.15 y β=0,04; IC95%: 0,0002; 0,08, respectivamente). Las concentraciones de filtros UV tipo BP-1 también se asociaron positiva y significativamente con el cociente T/E2 (β=0,04; IC95%: 0,002; 0,07) y negativamente con el cociente inhibina B/FSH (β=−0.11; IC95%: −0,21; −0,006). No se observó ninguna otra relación significativa entre el resto de filtros UV tipo BP y otros parámetros seminales u hormonales. CONCLUSIONES: Nuestros resultados apoyan la hipótesis de que la exposición a BPA se asocia con una reducción de la capacidad de las células de Leydig (niveles elevados de LH) y un recuento espermático disminuido. Las concentraciones urinarias de parabenos podrían no tener un efecto adverso sobre los parámetros reproductivos en varones jóvenes. Hasta ahora, las evidencias de una asociación entre la exposición a parabenos y el potencial de fecundidad masculino son limitadas. Por último, nuestros resultados sugieren que, en hombres jóvenes, las concentraciones urinarias de filtros UV tipo BP se asociaron con una alteración moderada de algunos niveles hormonales, pero los efectos que se observan sobre la función reproductiva podrían ser menores y con una significación clínica incierta. Son necesarios más estudios para confirmar y ampliar estos hallazgos en otras poblaciones de varones. BACKGROUND: Endocrine Disrupting Chemicals are pervasive environmental toxicants with potential male reproductive function effects. Bisphenol A (BPA) is widely used in industry and commerce to manufacture polycarbonate plastics and food packaging components. Parabens are a group of alkyl esters of p-hydroxybenzoic acid that are commonly added to personal care products, and food processing as antimicrobial preservatives. Benzophenone (BP)-type ultraviolet (UV) light filters are chemicals coming from different sources generally added to personal care products and sunscreens. Exposure to these chemicals is common among the general population, with detectable concentration in more than 80% of study participants, and have been reported to have estrogenic or anti-androgenic effects. However, studies exploring associations between exposure to BPA, parabens and BP-type UV filters and reproductive parameters in men non-selected for testicular function or unaware of their fecundity are very scarce. The objective of this Thesis was to assess the relationships between urinary BPA, parabens and BP-type UV filters concentrations and semen quality and serum reproductive hormone levels in young men. MATERIAL AND METHODS: The Murcia Young Men’s Study (MYMS) is a cross-sectional study of university students 18-23 years old in the Murcia Region. A total of 215 students agreed to participate and completed the study visit between October 2010 and November 2011. All subjects provided urine, blood serum and semen samples on a single day. Environmental chemical concentrations were measured by dispersive liquid–liquid microextraction and ultrahigh performance liquid chromatography with tandem mass spectrometry detection in urine. Semen quality was evaluated by measuring volume, concentration, motility, morphology and total sperm count. Serum samples were analyzed for reproductive hormones, including follicle-stimulating hormone (FSH), luteinizing hormone (LH), total and free testosterone (T), estradiol (E2) and inhibin B. Relationships between urinary concentrations of BPA, parabens and BP-type UV filters and semen quality parameters and reproductive hormone levels were examined using multiple linear regression, adjusting for potential confounders. RESULTS: After adjustment for important covariates, there was a significant positive association between urinary BPA concentrations and serum LH levels (β = 0.07, 95%CI: 0.02; 0.12, p-value <0.01). Urinary BPA concentration was also significantly and inversely associated with sperm concentration (β = − 0.04, 95%CI: − 0.07; − 0.02, p-value<0.01) and total sperm count (β = − 0.05, 95%CI: − 0.08; − 0.02, p-value<0.01). No significant associations were found between BPA and other semen parameters or reproductive hormone levels. Urinary concentrations of parabens or their molar sum were not significantly associated with any semen parameters or reproductive hormone levels. There was a significant positive association between urinary BP-1 and BP-3 concentrations and serum FSH levels (β=0.08, 95%CI: 0.009; 0.15 and β=0.04, 95%CI: 0.0002; 0.08, respectively). Urinary BP-1 concentration was also significantly positively associated with T/E2 (β=0.04, 95%CI: 0.002; 0.07) and negatively with inhibin B/FSH (β=−0.11, 95%CI: −0.21; −0.006) ratio. No significant associations were found between other urinary BP-type UV filters and other reproductive hormone levels or any semen parameters. CONCLUSIONS: Our data support the hypothesis that exposure to BPA is associated with a reduction in Leydig cell capacity (increased LH levels) and decreased sperm count. Urinary concentrations of parabens in young men may not adversely impact reproductive function. So far, limited to no evidence of an association between concurrent urinary parabens and male potential fecundity has been found. Lastly, our results suggest that, in young men, urinary BP-type UV filters may be associated with a modest alteration of some reproductive hormones, but the effects we report on reproductive function are likely to be small, and of unclear clinical significance. Further research is needed to replicate these findings in other male population

Human epidemiological evidence about the associations between exposure to organochlorine chemicals and endometriosis: Systematic review and meta-analysis

Background: Endometriosis is a gynaecological disease characterized by the presence of ectopic endometrial tissue that affects women during their reproductive years, having a strong impact on their lives, fertility and healthcare costs. The aetiology remains largely unknown, but current evidence suggests that it is multi-causal and oestrogen-dependent. Many epidemiologic studies have explored associations between organochlorine chemicals (OCCs) and endometriosis, but the findings are inconsistent. Objectives: A systematic review (SR) and meta-analysis were conducted to gather and synthesize all the available evidence from human epidemiological studies about the associations between OCCs and endometriosis. Data sources: The searches were conducted in PubMed and Web of Science in June 2016 with a final follow-up in August 2018. Study eligibility criteria: Only human epidemiological studies were considered, independent of participant age, body mass index or life-stage. Studies reporting individual measures of exposure to OCCs were included, considering but not limited to polychlorinated dibenzodioxins and dibenzofurans (PCDD/Fs), polychlorinated bi-phenyls (PCBs), or organochlorine pesticides (OCPs). The primary health outcome was presence of endometriosis, including all sub-types. Eligibility criteria excluded articles not written in English, conference papers, reviews and studies with overlapping information. Study appraisal and synthesis methods: A SR protocol pre-registered at PROSPERO was applied in duplicate to gather and extract all eligible original papers from PUBMED and Web of Science databases. Odds ratios were pooled using the inverse variance method for random effects meta-analysis for each group of OCCs. Risk of bias was assessed using the National Toxicology Program/Office of Health Assessment and Translation (NTP/ OHAT) Risk of Bias Rating Tool for Human and Animal Studies adapted to the review question. The confidence in the body of evidence and related level of evidence was measured by using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) based NTP/ OHAT framework. The results were structured and presented in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: Of the 51 studies retained for the full-text screening, 17 provided effect sizes and metrics sufficient for pooling estimates through meta-analysis. The overall odds ratios and 95% confidence intervals were 1.65 (1.14; 2.39) for dioxins (n=10), 1.70 (1.20; 2.39) for PCBs (n=9), and 1.23 (1.13; 1.36) for OCPs (n=5). Despite being statistically significant, these estimates should be considered with caution given the notable heterogeneity and small estimated effect size. Misclassification of exposure, due to varying laboratory detection rate capabilities, and disease status, due to varying definitions of endometriosis, were identified as major sources of uncertainty. Limitations, conclusions, and implications of key findings: The level of evidence was considered to be "moderate" with "serious" risk of bias according the NTP/OHAT criteria, supporting the need for further well-designed epidemiological research to fill lingering data gaps. Given the complexity of endometriosis and lack of known biomarkers suitable for population-based research, carefully designed observational studies play an important role in better understanding the aetiology of endometriosis, as will evolving mixture modeling approaches capable of handling various environmental chemical exposures. Attention to critical windows of exposure will shed further light on the possible developmental origin of endometriosis. Considering the high economic and societal cost associated with endometriosis, further research on this field is urged

Vitamin D status is not associated with reproductive parameters in young Spanish men

European Union under grant agreement 675526-REP-BIOTECH-H2020-MSCA-Innovative Training Networks-201

Assessment of Optimism in Women with Polycystic Ovary Syndrome: A Case Control-Study

Polycystic ovary syndrome (PCOS) is a chronic endocrinopathy characterized by hyperandrogenism and anovulation that may pervade psychological dimensions such as dispositional optimism. Considering how PCOS influences mental health and the lack of studies on this matter, this research was aimed at assessing optimism and associated factors in PCOS. A case–control study of 156 patients with PCOS and 117 controls was conducted. All woman filled out the Life Orientation Test-Revised (LOT-R), a self-report questionnaire for measuring dispositional optimism. Medication, pain severity, gynecological, and sociodemographic information was also collected. Lower optimism was found in patients with PCOS compared to controls, even after covariate adjustment (LOT-R global scores: 14.1 vs. 15.9, p = 0.020). Our study provides evidence that a personality characteristic with important implications in illness prognosis may be affected in PCOS. We propose to assess dispositional optimism with the LOT-R scale in the gynecological appointment and tailor medical attention accordingly as a way to improve the comprehensive care of these patients within a multidisciplinary team

Is dispositional optimism associated with endometriomas and deep infiltrating endometriosis?

Introduction Endometriosis is a chronic painful condition characterized by high prognostic uncertainty, as well as the threat of infertility and emotional symptoms that may affect many aspects of women, including psychological characteristics like dispositional optimism. Considering the impact of endometriosis on psychological health and the paucity of papers on this topic, the aim of this study is to explore optimism and associated factors in endometriosis. Methods A case-control study was performed on a group of 95 women with endometriosis and 156 controls. All participants completed the Life Orientation Test-Revised (LOT-R), a self-administered tool for assessing dispositional optimism. Pain severity, medication, gynecological and socio-demographic information was also collected. Results Low optimism was observed for women with endometriosis compared to controls even after covariate adjustment (LOT-R global scores: 14.5 vs. 15.9 points, p = .045). Conclusions This study provides the first evidence that a personality dimension with many prognostic implications may be altered in women with endometriosis. Our findings highlight the importance of a broader understanding of this condition, treating this disorder from a biopsychosocial perspective and suggests the need for non-medical attention within a multidisciplinary team

Are Dietary Indices Associated with Polycystic OvarySyndrome and Its Phenotypes? A Preliminary Study

©. This manuscript version is made available under the CC-BY 4.0 license http://creativecommons.org/licenses/by /4.0/ This document is the Published Manuscript version of a Published Work that appeared in final form in [Nutrients]. To access the final edited and published work see[https://doi.org/10.3390/nu13020313

Maternal urinary concentrations of bisphenol A during pregnancy are associated with global DNA methylation in cord blood of newborns in the "NELA" birth cohort.

Endocrine disrupting chemicals (EDCs) set a public health risk through disruption of normal physiological processes. The toxicoepigenetic mechanisms of developmental exposure to common EDCs, such as bisphenol A (BPA), are poorly known. The present study aimed to evaluate associations between perinatal maternal urinary concentrations of BPA, bisphenol S (BPS) and bisphenol F (BPF) and LINE-1 (long interspersed nuclear elements) and Alu (short interspersed nuclear elements, SINEs) DNA methylation levels in newborns, as surrogate markers of global DNA methylation. Data come from 318 mother-child pairs of the `Nutrition in Early Life and Asthma´ (NELA) birth cohort. Urinary bisphenol concentration was measured by dispersive liquid-liquid microextraction and ultrahigh performance liquid chromatography with tandem mass spectrometry detection. DNA methylation was quantitatively assessed by bisulphite pyrosequencing on 3 LINEs and 5 SINEs. Unadjusted linear regression analyses showed that higher concentration of maternal urinary BPA in 24th week's pregnancy was associated with an increase in LINE-1 methylation in all newborns (p = 0.01) and, particularly, in male newborns (p = 0.03). These associations remained in full adjusted models [beta = 0.09 (95 % CI = 0.03; 0.14) for all newborns; and beta = 0.10 (95 % CI = 0.03; 0.17) for males], including a non-linear association for female newborns as well (p-trend = 0.003). No associations were found between maternal concentrations of bisphenol and Alu sequences. Our results suggest that exposure to environmental levels of BPA may be associated with a modest increase in LINE-1 methylation -as a relevant marker of epigenomic stability- during human fetal development. However, any effects on global DNA methylation are likely to be small, and of uncertain biological significance