The Intersection of Neurotoxicology and Endocrine Disruption

BPA and phthalates associations with brain sexual differentiation are reviewed and further questions noted.

Abstract

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BPA and phthalates associations with brain sexual differentiation are reviewed and further questions noted.

Endocrine disruption, the guiding theme of the 27th International Neurotoxicology Conference, merged into the neurotoxicology agenda largely because hormones help steer the process of brain development. Although the disruption motif first attracted public health attention because of reproductive anomalies in both wildlife and humans, the neurobehavioral implications had been planted decades earlier. They stemmed from the principle that sex differences in behavior are primarily the outcomes of differences in how the brain is sexually differentiated during early development by gonadal hormones (the Organizational Hypothesis). We also now understand that environmental chemicals are capable of altering these underlying events and processes. Among those chemicals, the group labeled as endocrine disrupting chemicals (EDCs) offers the clearest evidence of such selectivity, a consequence of their actions on the endogenous sex steroids, androgens and estrogens. Two EDCs in particular offer useful and intriguing examples. One is phthalate esters. The other is bisphenol A (BPA). Both agents are used extensively in plastics manufacture, and are pervasive in the environment. Both are produced in immense quantities. Both are found in almost all humans. Phthalates are considered to function in essence as anti-androgens, while bisphenol A is labeled as an estrogen. Their associations with brain sexual differentiation are reviewed and further questions noted. Both EDCs produce a wider spectrum of health effects, however, than would be extrapolated simply from their properties as anti-androgens and estrogens. Obesity is one example. Further complicating their assessment as health risks are questions about nonmonotonic dose-response functions and about transgenerational effects incurred via epigenetic mechanisms. All these facets of endocrine disruption are pieces of a puzzle that challenge neurotoxicologists for solutions.

Sources and More Information:

I Got No Idea if my Treatment for Breast Cancer was Necessary… or Not…

“One Lump or Two” talks about your (3-yearly) mammogram and the possible outcomes…

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Personal Stories – One Lump or Two by Elizabeth

This is what makes me so mad. I have no idea if my treatment was necessary or if I will go through the rest of my life maimed for nothing. I turn 50 this year and can expect to live about as much longer. My “breasts” are really abdominal tissue that has been moved. I have no feeling there at all. In eight short years, I will have been married as long without functioning breasts as I was with. I wish I had been offered the chance to just be monitored. As it is, I have suffered a HUGE loss in quality of life, perhaps for no reason.”

A comment by thissideofgaudy to Elizabeth’s post Damned if You Do, October 2013. One Lump or Two talks about your (3-yearly) mammogram and the possible outcomes… plus references…

How Humanity has changed since the Dawn of the Plastic Age

Man-made chemicals exposure and fertility decline

The Dawn of the Plastic Age infographic
Watch our selection of infographics addressing health issues on Flickr.

Sources:

On Flickr®

Choosing Wisely will Make You Happy

Choose wisely when it comes to making health care decisions

Choosing Wisely – a parody of the infectious Pharrell Williams song “Happy” – choose wisely when it comes to making health care decisions and if you choose wisely it will make you happy.

Sources

Financial Conflicts of Interest in FDA Advisory Committees

Findings point to important heterogeneities in financial ties

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Doctors on FDA panels with ties to drug companies are more likely to vote in favour of that company’s drug…

When the Food and Drug Administration creates an advisory committee to help it decide whether to approve drugs, it often asks academic physicians to serve on the committee as external experts…

A study by Genevieve Pham-Kanter published in The Milbank Quarterly concluded:
There appears to be a pro-sponsor voting bias among advisory committee members who have exclusive financial relationships with the sponsoring firm but not among members who have non-exclusive financial relation-ships (ie, those with ties to both the sponsor and its competitors). These findings point to important heterogeneities in financial ties and suggest that policy-makers will need to be nuanced in their management of financial relationships of FDA advisory committee members“.

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No Link found between Assisted Reproduction and Autism

No increase in autism-associated genetic events in children conceived by assisted reproduction

UVMCollegeofMedicine
This is the first large genetic association to concurrently examine the genotype of individuals with autism spectrum disorder in relation to their exposure to assisted reproductive technology versus natural conception, and it adds reassuring evidence to the argument that ART does not increase the risk of ASD.

When prospective parents have trouble conceiving and decide to seek medical help, they typically experience more than a little anxiety and have a host of questions:

  • What are the potential risks to the mother and the baby?
  • What kinds of diseases or other problems are associated with assisted reproduction?
  • And, is one of those problems autism?

Over the past five years, several studies have focused on infertility treatment, partly because of the coincidental rise in both the diagnosis of autism and the use of assisted reproduction. A recent study – conducted by Sean Ackerman and his team at the University of Vermont College of Medicine – examined a potential link, and concluded that there is none.

2014 Study Abstract

Objective
To understand the rate of genetic events in patients with autism spectrum disorder (ASD) who were exposed to assisted reproduction.

Design
Case control study using genetics data.

Setting
Twelve collaborating data collection sites across North America as part of the Simons Simplex Collection.

Patient(s)
2,760 children with ASD, for whom 1,994 had published copy number variation data and 424 had published gene mutation status available.

Intervention(s)
None.

Main Outcome Measure(s)
Rates of autism-associated genetic events in children with ASD conceived with assisted reproduction versus those conceived naturally.

Result(s)
No statistically significant differences in copy number variations or autism-associated gene-disrupting events were found when comparing ASD patients exposed to assisted reproduction with those not exposed to assisted reproduction.

Conclusion(s)
This is the first large genetic association to concurrently examine the genotype of individuals with ASD in relation to their exposure to ART versus natural conception, and it adds reassuring evidence to the argument that ART does not increase the risk of ASD.

Sources and More Information:

  • Ackerman Study Examines Potential Link Between Assisted Reproduction and Autism,
    University of Vermont, News ID 19138, 09-09-2014.
  • No increase in autism-associated genetic events in children conceived by assisted reproduction,
    Fertility and Sterility, S0015-0282%2814%2900366-5, Volume 102, Issue 2, Pages 388–393, August 2014.

Selective Reporting of Analyses and Discrepancies in Clinical Trials

Evidence for the Selective Reporting of Analyses and Discrepancies in Clinical Trials: A Systematic Review of Cohort Studies of Clinical Trials

Abstract

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To ensure transparency, protocols and statistical analysis plans need to be published, and investigators should adhere to these or explain discrepancies.

Background
Most publications about selective reporting in clinical trials have focussed on outcomes. However, selective reporting of analyses for a given outcome may also affect the validity of findings. If analyses are selected on the basis of the results, reporting bias may occur. The aims of this study were to review and summarise the evidence from empirical cohort studies that assessed discrepant or selective reporting of analyses in randomised controlled trials (RCTs).
Methods and Findings
A systematic review was conducted and included cohort studies that assessed any aspect of the reporting of analyses of RCTs by comparing different trial documents, e.g., protocol compared to trial report, or different sections within a trial publication. The Cochrane Methodology Register, Medline (Ovid), PsycInfo (Ovid), and PubMed were searched on 5 February 2014. Two authors independently selected studies, performed data extraction, and assessed the methodological quality of the eligible studies. Twenty-two studies (containing 3,140 RCTs) published between 2000 and 2013 were included. Twenty-two studies reported on discrepancies between information given in different sources. Discrepancies were found in statistical analyses (eight studies), composite outcomes (one study), the handling of missing data (three studies), unadjusted versus adjusted analyses (three studies), handling of continuous data (three studies), and subgroup analyses (12 studies). Discrepancy rates varied, ranging from 7% (3/42) to 88% (7/8) in statistical analyses, 46% (36/79) to 82% (23/28) in adjusted versus unadjusted analyses, and 61% (11/18) to 100% (25/25) in subgroup analyses. This review is limited in that none of the included studies investigated the evidence for bias resulting from selective reporting of analyses. It was not possible to combine studies to provide overall summary estimates, and so the results of studies are discussed narratively.

Conclusions
Discrepancies in analyses between publications and other study documentation were common, but reasons for these discrepancies were not discussed in the trial reports. To ensure transparency, protocols and statistical analysis plans need to be published, and investigators should adhere to these or explain discrepancies.

Sources and Full Report
  • Evidence for the Selective Reporting of Analyses and Discrepancies in Clinical Trials: A Systematic Review of Cohort Studies of Clinical Trials, PLOS one Collections, DOI: 10.1371/journal.pmed.1001666, June 24, 2014.

The story of the NHS: where it came from, how it was formed, how it could be destroyed

Video published on 8 Sept 2014 by 999Call for the NHS

This is the story of the NHS: where it came from, how it was formed, and how it could be destroyed.

Prescription Mortelle

Robin Cook reprend les grandes problématiques actuelles de la e-santé

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Un suspense extrêmement informé et actuel autour de la médecine du futur et des dérives engendrées par la quête effrénée de rentabilité.

George est radiologue, spécialité qu’il a choisie car il n’aime pas particulièrement le contact avec ses patients. Il a contribué à la création de l’iDoc, un smartphone qui permet d’ausculter en direct le patient, 24h sur 24h, et de lui délivrer diagnostics et ordonnances. Un petit bijou, qui permettrait de réduire les coûts de santé aux USA de façon spectaculaire. Mais c’est trop beau pour être vrai. Quand, après sa petite amie, c’est son meilleur ami qui meurt sans raison, il se pose des questions. Car tous deux participaient en fait à la phase test de l’iDoc. Quel est vraiment le but de la société Amalgamated, propriétaire d’iDoc ? Quel rôle joue son ex-petite amie Paula, principale actrice et défenseuse de l’iDoc ? Une vérité qui dérange, mais qu’il a bien l’intention de dévoiler, coûte que coûte…

  • Une application mobile peut-elle vous tuer?
  • Un suspense extrêmement informé et actuel autour de la médecine du futur et des dérives engendrées par la quête effrénée de rentabilité.
  • Un roman qui reprend les grandes problématiques actuelles de la e-santé.

Robin Cook, ancien chirurgien ophtalmique, est l’un des maîtres du thriller médical. Depuis la parution en 1992 de Avec intention de nuire, chacun de ses romans, traduits dans le monde entier, se vend à plus de 25 000 exemplaires en France.

Prescription Mortelle, en savoir plus:

Sur Flickr®

The History of DES, Lessons to be learned

Health care professionals have to know the history of DES to prevent future disasters with drugs prescribed

Abstract

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Health care professionals have to know the history of DES to prevent future disasters with drugs prescribed.

Since the 1940s, Diethylstilbestrol (DES) has been used by millions of pregnant women to prevent miscarriages and many other disorders in pregnancy. In 1971, it became clear that this apparently innocent treatment proved to be a time bomb for the infants exposed to DES during the first trimester of pregnancy. DES is now associated with an increased risk of breast cancer, clear cell adenocarcinoma (CCAC) of the vagina and cervix, and reproductive anomalies. This article summarises the potential long-term health implications of DES on the mother, DES daughters and DES sons, and the possible side effects on the third generation. Health care professionals have to know the history of DES to prevent future disasters with drugs prescribed.

Sources
  • The history of DES, lessons to be learned,
    NCBI, PMID: PubMed 16096877, 2005 Jun;27(3):139-43.
  • Full text: Springer, June 2005, Volume 27, Issue 3, pp 139-143.
More DES DiEthylStilbestrol Resources