Toxic Bodies: the history of endocrine disrupting chemicals

LIVING ON EARTH with Jeff Young and Nancy Langston

Endocrine disrupting chemicals like bisphenol A have been making news lately, with several states passing regulations limiting or banning their use. The trajectory of BPA is similar to another chemical, commonly known as DES, once prescribed for pregnant and menopausal women. Host Jeff Young talks with Professor Nancy Langston about the history of endocrine disrupting chemicals and how this history can inform future chemical regulation. Her book is called, “Toxic Bodies: Hormone Disruptors and the Legacy of DES.” (published March 19, 2010).

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Sexual differentiation of the human brain: relation to gender identity and sexual orientation

Gender identity and sexual orientation are permanently programmed in the fetal brain

A Swedish study of fishermen exposed to CB-153 and p,p′-DDE associated elevated levels of these chemicals with a higher proportion of Y-chromosome sperm, suggesting that exposure to EDCs could skew the ratio of boys to girls.

Abstract

During the intrauterine period a testosterone surge masculinizes the fetal brain, whereas the absence of such a surge results in a feminine brain. As sexual differentiation of the brain takes place at a much later stage in development than sexual differentiation of the genitals, these two processes can be influenced independently of each other. Sex differences in cognition, gender identity (an individual’s perception of their own sexual identity), sexual orientation (heterosexuality, homosexuality or bisexuality), and the risks of developing neuropsychiatric disorders are programmed into our brain during early development. There is no evidence that one’s postnatal social environment plays a crucial role in gender identity or sexual orientation. We discuss the relationships between structural and functional sex differences of various brain areas and the way they change along with any changes in the supply of sex hormones on the one hand and sex differences in behavior in health and disease on the other.

Research highlights

  • Gender identity and sexual orientation are permanently programmed in the fetal brain.
  • Testosterone in the fetal stage determines sexual differentiation of the human brain.
  • The degree of genital masculinization does not necessarily reflect that of the brain.
  • No evidence indicates social environment affect gender identity or sexual orientation.
  • Sex differences in the brain determine sex-specific prevalence of brain disorders.
Sources and more information
  • Sexual differentiation of the human brain: Relation to gender identity, sexual orientation and neuropsychiatric disorders, Sciencedirect, pii/S0091302211000252, doi:10.1016/j.yfrne.2011.02.007, 2011.
  • Gynecol Endocrinol 2004;19:301–312, full PDF, DOI: 10.1080/09513590400018231, 2004.
  • DES studies on Gender Identity and Psychological Health.

The spread of antimicrobial resistance

Antibiotic resistance genes are passed from one bacterium to another

antibiotic-resistance-comic
Antibiotic resistance genes are passed from one bacterium to another.

Antibiotic resistance occurs when bacteria that cause infection are not killed by the antibiotics taken to stop the infection. The bacteria survive and continue to multiply, causing more harm. Widespread use of antibiotics promotes the spread of antibiotic resistance. Smart use of antibiotics is the key to decreasing, or even reversing, the spread of resistance.

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Rémy Slama et les perturbateurs endocriniens

Jusqu’où doit-on interdire les perturbateurs endocriniens?

Film présenté dans l’espace Science Actualités à la Cité des sciences et de l’industrie jusqu’en avril 2015.

En savoir plus
  • Jusqu’où doit-on interdire les perturbateurs endocriniens? Ces substances, qui interfèrent avec notre système hormonal, sont en effet suspectées de poser de graves problèmes de santé publique: cancers hormono-dépendants (sein, prostate, testicule), infertilité, obésité… Y a-t-il urgence à trouver des produits de substitution?
    Entretien avec Rémy Slama, épidémiologiste (Inserm) et président du comité scientifique du Programme national de recherche sur les perturbateurs endocriniens.
  • Production : universcience.tv, Date de diffusion : 10/12/2014.

Cryptorchidism and endocrine disrupting chemicals

DES exposure has been associated with increased risk of cryptorchidism

When evaluating associations between fetal exposure to estrogenic agents and cryptorchidism in humans, exposure to DES was associated with an increased risk of cryptorchidism. Image by Alon.

2011 Study Abstract

Prospective clinical studies have suggested that the rate of congenital cryptorchidism has increased since the 1950s. It has been hypothesized that this may be related to environmental factors. Testicular descent occurs in two phases controlled by Leydig cell-derived hormones insulin-like peptide 3 (INSL3) and testosterone. Disorders in fetal androgen production/action or suppression of Insl3 are mechanisms causing cryptorchidism in rodents. In humans, prenatal exposure to potent estrogen Diethylstilbestrol (DES) has been associated with increased risk of cryptorchidism. In addition, epidemiological studies have suggested that exposure to pesticides may also be associated with cryptorchidism. Some case–control studies analyzing environmental chemical levels in maternal breast milk samples have reported associations between cryptorchidism and chemical levels. Furthermore, it has been suggested that exposure levels of some chemicals may be associated with infant reproductive hormone levels.

  • Background
  • Testicular descent
  • Animal studies
  • Human studies
    1. Exposure to estrogens/estrogenic agents
    2. Pesticides
    3. PCBs
    4. Dioxins
    5. Flame retardants
    6. Phthalates

2011 Study Conclusion

Various xenobiotics have been found to disrupt the endocrine system in animals. Reduction in the dominance of androgens to estrogens, and interference with androgen or Insl3 production or action during fetal life, are apparent mechanisms causing cryptorchidism in animals. When evaluating associations between fetal exposure to estrogenic agents and cryptorchidism in humans, exposure to DES was associated with an increased risk of cryptorchidism. Studies evaluating pesticide use in a geographical area or parental possible occupational exposure to pesticides, have suggested that also exposure to them may be associated with an increased risk of cryptorchidism in boys. Some case–control studies evaluating maternal breast milk levels of chemicals have reported associations between congenital cryptorchidism and the levels of environmental chemicals with possible endocrine disrupting activities. No clear positive association was reported in studies evaluating levels of endocrine disrupting chemicals in placenta, cord serum or maternal serum. Maternal breast milk phthalate and PBDE levels have shown anti-androgen-like associations with infant reproductive hormone levels. More studies are needed to confirm the observed associations and to evaluate associations between cryptorchidism and combined exposures.

Sources and more information

  • Cryptorchidism and endocrine disrupting chemicals, sciencedirect pii/S0303720711006782, doi:10.1016/j.mce, 2011.11.
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Prescription meds increased by over 50% in England 2004-2014

Prescriptions Dispensed in the Community,
England 2004-14

This post content was originally published by HSCICthe national provider of information, data & IT systems for commissioners, analysts and clinicians, in health and social care.

drug-prescriptions-banner
An extra 34.5 million drugs and other prescription items were given out in 2014 compared to the year before, the latest snapshot for England shows. Drugs and Prescriptions image by Seth Anderson.

Over 1.06 billion items were prescribed in 2014, an increase of 3.3 per cent (34.5 m items) on 2013, according to the Health and Social Care Information Centre (HSCIC).

The 2014 figure also represents an increase of 55.2 per cent on 2004 (378.5 million items).

The overall Net Ingredient Cost (NIC) of prescriptions in 2014 however stood at £8.85 billion, an increase of 2.6 per cent (£227.5 million) from 2013. Since 2004 this figure has increased by 9.6 per cent (£773.0 million).

The Prescriptions Dispensed in the Community 2004-2014 report looks at prescriptions dispensed in England by community pharmacists, appliance contractors, dispensing doctors and prescriptions for items administered in GP practices.

The report shows that the average net ingredient cost per prescription item dispensed in the community decreased by 29.4 per cent since 2004. The average NIC per prescription item fell to £8.32 in 2014 from £8.37 in 2013 and £11.78 in 2004.

Of all prescription items dispensed 89.9 per cent (957.1 million), were dispensed free of charge

Of which:

  • Three in five prescriptions were for patients aged 60 and over which, accounted for 51.2 per cent (£4.53 billion) of the total net ingredient cost for all prescriptions.
  • One in 20 prescriptions were for patients aged under 16 or 16 -18 and in full-time education. This age group accounted for 6.9 per cent (£612.1 million) of the total ingredient cost of all prescriptions.

Prescriptions Dispensed in the Community uses the therapeutic classifications as defined in the British National Formulary (BNF) and is structured to follow the same classifications. Within the report notable changes have been found over the last year in the following areas:

  • There was a rise in the cost of medicines used to prevent blood clots by £44.8 million (47.8 per cent) to £138.6 million. This was mainly driven by the greater use of three new oral anticoagulants, which have recently been introduced alongside warfarin.
  • The cost of medicines used to treat epilepsy also rose, by £46.6 million (10.6 per cent) to £486.5 million. The majority of this additional figure was spent on pregabalin (£36.1million) and much of the remainder on gabapentin (£9.0 million).
  • The cost of medicines used in the treatment of diabetes rose by £55.3 million (7.0 per cent) to £849.1 million.
  • The number of prescription items dispensed also rose by 2.1 million (4.8 per cent) since 2013.
  • Atorvastatin, a medicine which helps to reduce the likelihood of heart attacks and strokes, had the greatest increase in the number of items dispensed with 4.0 million more items since 2013.
  • There were 57.1 million antidepressant medicines dispensed in 2014, a 7.2 per cent increase from 53.3 million in 2013. Since 2004 the number of items dispensed has nearly doubled by 97.1 per cent from 29.0 million.

Mammography associated to breast cancer incidence increase with no reduction in mortality

Mammography does not “reduce breast cancer deaths”

Image of a mammography-plate
Mammography for detection of breast cancer does not reduce the number of deaths from the disease and may actually lead to overdiagnosis, according to a new study published in JAMA Internal Medicine. Image by Grant Hutchinson.

2015 Study Abstract

Importance
Screening mammography rates vary considerably by location in the United States, providing a natural opportunity to investigate the associations of screening with breast cancer incidence and mortality, which are subjects of debate.

Objective
To examine the associations between rates of modern screening mammography and the incidence of breast cancer, mortality from breast cancer, and tumor size.

Design, Setting, and Participants
An ecological study of 16 million women 40 years or older who resided in 547 counties reporting to the Surveillance, Epidemiology, and End Results cancer registries during the year 2000. Of these women, 53 207 were diagnosed with breast cancer that year and followed up for the next 10 years. The study covered the period January 1, 2000, to December 31, 2010, and the analysis was performed between April 2013 and March 2015.

Exposures
Extent of screening in each county, assessed as the percentage of included women who received a screening mammogram in the prior 2 years.

Main Outcomes and Measures
Breast cancer incidence in 2000 and incidence-based breast cancer mortality during the 10-year follow-up. Incidence and mortality were calculated for each county and age adjusted to the US population.

Results
Across US counties, there was a positive correlation between the extent of screening and breast cancer incidence (weighted r = 0.54; P < .001) but not with breast cancer mortality (weighted r = 0.00; P = .98). An absolute increase of 10 percentage points in the extent of screening was accompanied by 16% more breast cancer diagnoses (relative rate [RR], 1.16; 95% CI, 1.13-1.19) but no significant change in breast cancer deaths (RR, 1.01; 95% CI, 0.96-1.06). In an analysis stratified by tumor size, we found that more screening was strongly associated with an increased incidence of small breast cancers (≤2 cm) but not with a decreased incidence of larger breast cancers (>2 cm). An increase of 10 percentage points in screening was associated with a 25% increase in the incidence of small breast cancers (RR, 1.25; 95% CI, 1.18-1.32) and a 7% increase in the incidence of larger breast cancers (RR, 1.07; 95% CI, 1.02-1.12).

Conclusions and Relevance
When analyzed at the county level, the clearest result of mammography screening is the diagnosis of additional small cancers. Furthermore, there is no concomitant decline in the detection of larger cancers, which might explain the absence of any significant difference in the overall rate of death from the disease. Together, these findings suggest widespread overdiagnosis.

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What is the Community for Open Antimicrobial Drug Discovery?

CO-ADD is a not-for-profit initiative led by academics for academics

The Community for Open Antimicrobial Drug Discovery (CO-ADD) is a global initiative inviting chemists across the world to submit compounds for screening for antimicrobial activity.

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Urogenital tract abnormalities in sons of women treated with diethylstilbestrol

Urogenital abnormalities in men exposed to DES in utero, 1976

image of son-in-arms
In this 1976 survey, a large proportion of DES- exposed boys had experienced problems in passing urine and abnormalities of the penile urethra. Can’t let go image by Paolo Marconi.

1976 Study Abstract

Since in utero exposure to Diethylstilbestrol (DES) is known to cause abnormalities of the female genital tract later in life, exposed male offspring were located, surveyed by mail, and compared with unexposed male offspring from the same period and medical practices.

The exposed and unexposed respondents appeared comparable and did not differ in their response to most medical questions. However, a larger proportion of exposed than of unexposed boys had experienced problems in passing urine (12.9% vs. 1.8%, P = .0003) and abnormalities of the penile urethra (4.4% vs. 0%; P = .017).

Sources and more information

  • Urogenital tract abnormalities in sons of women treated with diethylstilbestrol, Pediatrics. NCBI PMID: 972792, 1976 Oct;58(4):505-7.
  • Urogenital abnormalities in men exposed to diethylstilbestrol in utero: a cohort study, NCBI, PMID: 19689815, 2009 Aug 18;8:37. doi: 10.1186/1476-069X-8-37. Full text PMC2739506.
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Commercial clinical trials: how does the UK really compare with Europe?

The network supported more than 900 commercial contract studies in the NHS last year

This post content was originally published by The Guardian NIHR clinical research zoneLatest NIHR Clinical Research Network partner zone news

flags-of-european-union
The number of trials in the UK is increasing, with the Clinical Research Network playing a vital role in supporting the life-sciences industry.

The UK has had its fair share of criticism when it comes to clinical trials delivery. With European counterparts often cited as more reliable, less expensive and quicker to set up, it can be a hard sell to ensure that outdated information is consigned to the past. However, figures released last summer are helping to change perceptions. They show that the performance of commercial contract studies supported by the network is on the up, and the global life-sciences community is starting to take notice.

Medicines and Healthcare products Regulatory Agency (MHRA) figures show a decline in the number of commercial contract clinical studies up to 2011, but more recent figures show that since then, the number of commercial phase II-IV studies has risen from 497 in 2011 to 624 in 2013.

Dr Martin O’Kane is acting head of the clinical trials unit at MHRA. He believes the decline in clinical trials was never as bad in the UK as it was in the rest of Europe and that we are regarded as a proficient nation by commercial companies.

It is not the case that in the past four to five years there has been a decline in the number of commercial trials in the UK. In fact we have seen numbers rise in recent years,” he says.

The UK is currently the single largest competent authority in Europe in terms of applications received and is seen as extremely approachable and competent when it comes to delivery.”

Jonathan Sheffield, chief executive officer of the Clinical Research Network, believes the support on offer to the life-sciences industry from the network has had the upmost effect on the way the UK is viewed when it comes to commercial research.

The network has led the transformation of the clinical research landscape,” he says. “It has made game changing progress for commercial contract research with industry partners telling us that there is a real uplift in the number of commercial studies being awarded to the UK.

The annual statistics released by the network [last] June showed that last year the network was supporting more than 900 commercial contract studies in the NHS – a 31% increase on the previous year and nearly 10 times the number in 2008-09. This is a phenomenal turnaround in a relatively short period of time and one that shows the commercial world that we are here and ready to deliver.”

Continue reading the full article in the NIHR Clinical Research Network’s Insight magazine, Issue 1, December 2014.