T-shaped uterus and subtle uterine variances

A need for reliable criteria, Fertility and Sterility, August 2019

Abstract

The ASRM Class VII, the ESHRE/ESGE Class U1, and the T-shaped uterus have a uniquely interesting history. The T-shaped uterus was first described as a diethylstilbestrol– (DES-) related congenital uterine anomaly based on findings from hysterosalpingography by Kaufman in 1977. Together with two similar morphologic forms of the uterus—constricting bands in the uterine cavity and a widening of the lower two-thirds of the uterus—this was included as a separate class of DES-related anomalies by the Buttram and Gibbons 1979 classification, and its further modification—the American Fertility Society classification.

In 2013, ESHRE/ESGE singled out a subtle uterine variance with a thickened lateral wall and a T-shaped uterus. As a result, the diagnosis of subtle uterine variances has increased with the designation of a T-shaped uterus or dysmorphic uterus and surgical repair is offered to enhance fertility. However, there is insufficient evidence to offer it in daily practice even in women with recurrent pregnancy loss, where historically metroplasty of the T-shaped uterus is rarely reported and its surgical correction is always questionable.

In this issue Alonso Pacheco et al. present a nicely done video using three-dimensional ultrasound and hysteroscopy in three cases of what they believe is a T-shaped uterus that is representative in distinguishing three of its subclasses. The authors used three-dimensional ultrasound and hysteroscopy to suggest that T-shaped uterus can be subclassified as T-shaped, Y-shaped, or I-shaped uterus. However, the division still remains arbitrary based on subjective impression of the presence of thickened wall and letter-shaped uterine cavities in these conditions. Discussion.

A DES-victim and hero celebrated

Alan Turing to be the face on the new £50 banknote

Homosexual acts were criminal offences in the United Kingdom in the 1950s and Alan Turing was charged with “gross indecency” under Section 11 of the Criminal Law Amendment Act 1885. Brought to trial on 31 March 1952, he was convicted and given a choice between imprisonment and probation. His probation would be conditional on his agreement to undergo hormonal physical changes designed to reduce libido. He accepted the option of injections of what was then called stilboestrol (also known as diethylstilbestrol or DES), a synthetic oestrogen; this feminization of his body was continued for the course of one year. The treatment rendered Turing impotent and caused breast tissue to form, fulfilling in the literal sense Turing’s prediction that “no doubt I shall emerge from it all a different man, but quite who I’ve not found out”.

Selected Press Releases

  • Alan Turing, World War II code-breaker castrated for being gay, is the face of Britain’s £50 note, CNN Business July 15, 2019 – Alan Turing belongs on the UK’s £50 note; now put Harriet Tubman on the $20 bill, CNN Opinion, July 16, 2019.
  • Alan Turing is crowned the most iconic figure of the 20th centurydailymail, 6 February 2019.
  • Pardon all of the estimated 49,000 men who, like Alan Turing, were convicted of consenting same-sex relations under the British “gross indecency” law (only repealed in 2003), and also all the other men convicted under other UK anti-gay lawschange.org, Feb 10, 2015.
  • The Castration of Alan Turing, Britain’s Code-Breaking WWII Herothedailybeast, 11.29.14.
  • Alan Turings name restored with film about his work, life and identity,
    oddonion, November 14, 2014.
  • Budget 2014: Alan Turing Institute to lead big data research,
    oddonion, March 19, 2014.
  • The Imitation Game, based on the real life story of Alan Turingdesdaughter, 2015/02/14.
  • Alan Turing granted Royal pardon by the Queentelegraph, 24 Dec 2013.
  • Grant a pardon to Alan Turinepetitions, Closing:23/11/2012.
  • Alan Turing: Inquest’s suicide verdict ‘not supportable’BBC Radio Science Unit, 26 June 2012.
  • ALAN TURING AND HIS MACHINES – FRESH INSIGHTS INTO THE ENIGMAindependent.co.uk, 14 June 2012.
  • How Alan Turing Finally Got a Posthumous Apologyradar, September 17, 2009.
  • PM apology after Turing petitionBBC News, 11 September 2009.
  • Gordon Brown: I’m proud to say sorry to a real war herotelegraph, 10 Sep 2009.
DES DIETHYLSTILBESTROL RESOURCES

Alan Turing to be the face on the new £50 banknote

Castrated with DES for being gay, Alan Turing will appear on the new £50 polymer note

15 July 2019 – Today, Bank of England Governor, Mark Carney, announced that Alan Turing will appear on the new £50 polymer note. Making the announcement at the Science and Industry Museum in Manchester, the Governor also revealed the imagery depicting Alan Turing and his work that will be used for the reverse of the note. The new polymer £50 note is expected to enter circulation by the end of 2021. BOE news release.

“We want to represent as best as possible all aspects of diversity within the country, from race, religion, creed, sexual orientation, disability and beyond. What we have today is a celebration of one of the greatest mathematicians and scientists in the United Kingdom and not just this country’s history but world history.”

“Turing was homosexual and was posthumously pardoned by the Queen, having been convicted of gross indecency for his relationship with a man. His legacy continues to have an impact on both science and society today.”

Turing was found guilty of gross indecency and had to decide between going to prison or undergoing chemical castration. He chose the latter, a horrifying treatment that involved (DES) hormonal injections.

“I hope it will serve as a stark and rightfully painful reminder of what we lost in Turing, and what we risk when we allow that kind of hateful ideology to win.”

“It is almost impossible to put into words the difference that Alan Turing made to society, but perhaps the most poignant example is that his work is estimated to have shortened the war by four years and saved up to 21 million lives. And yet the way he was treated afterwards remains a national embarrassment and an example of society at its absolute worst.”

Selected Press Releases

  • Alan Turing, World War II code-breaker castrated for being gay, is the face of Britain’s £50 note, CNN Business July 15, 2019 – Alan Turing belongs on the UK’s £50 note; now put Harriet Tubman on the $20 bill, CNN Opinion, July 16, 2019.
  • Alan Turing is crowned the most iconic figure of the 20th centurydailymail, 6 February 2019.
  • Pardon all of the estimated 49,000 men who, like Alan Turing, were convicted of consenting same-sex relations under the British “gross indecency” law (only repealed in 2003), and also all the other men convicted under other UK anti-gay lawschange.org, Feb 10, 2015.
  • The Castration of Alan Turing, Britain’s Code-Breaking WWII Herothedailybeast, 11.29.14.
  • Alan Turings name restored with film about his work, life and identity,
    oddonion, November 14, 2014.
  • Budget 2014: Alan Turing Institute to lead big data research,
    oddonion, March 19, 2014.
  • The Imitation Game, based on the real life story of Alan Turingdesdaughter, 2015/02/14.
  • Alan Turing granted Royal pardon by the Queentelegraph, 24 Dec 2013.
  • Grant a pardon to Alan Turinepetitions, Closing:23/11/2012.
  • Alan Turing: Inquest’s suicide verdict ‘not supportable’BBC Radio Science Unit, 26 June 2012.
  • ALAN TURING AND HIS MACHINES – FRESH INSIGHTS INTO THE ENIGMAindependent.co.uk, 14 June 2012.
  • How Alan Turing Finally Got a Posthumous Apologyradar, September 17, 2009.
  • PM apology after Turing petitionBBC News, 11 September 2009.
  • Gordon Brown: I’m proud to say sorry to a real war herotelegraph, 10 Sep 2009.
DES DIETHYLSTILBESTROL RESOURCES

Distilbene : pas encore de provision d’indemnisation pour préjudice professionnel

JT 19/20 Pays de la Loire, 28 mai 2019

Mi-avril 2019, la famille Le Cossec a entamé un troisième procès contre le laboratoire UCB Pharma ; ils veulent être reconnus comme “parents-victimes”. Fin mai 2019, le Tribunal de Grande Instance de Nanterre a refusé, de leur accorder une provision d’indemnisation pour préjudice professionnel.

28/5: Décision sanction pour la reconnaissance de notre préjudice de parents victimes du Distilbène

La juge de la mise en état du TGI de Nanterre a refusé de nous accorder une provision d’indemnisation pour préjudice professionnel. Elle indique que les questions soulevées dans cette procédure sont “un débat de fond qui devra être tranché par le tribunal et qu’il n’appartient pas au juge de la mise en état d’apprécier”.

Attendre, toujours attendre.
Nous sommes abattus face à cette décision qui après 12 ans de combat va nous contraindre à nouveau à souffrir.

20 ans qu’on se bat pour que Julien vive correctement. On s’est construits tout seuls, on n’a pas attendu le laboratoire UCB Pharma. C’est une évidence qu’il faut continuer de travailler même lorsqu’un tel bouleversement arrive dans notre vie.

On a essayé de rester debout. On nous reproche aujourd’hui d’avoir gagné nos vies au detriement de notre couple, de notre vie de famille.
On ne s’est jamais plaints, on s’est toujours battus, c’est aujourd’hui pour nous une prime de sanction.
Nous avons gardé la tête haute jusqu’en 2019 pour préserver notre couple et nos enfants mais cette décision nous effondre plus que tout notre combat au seul motif d’avoir des revenus corrects!
C’est à se demander s’il ne faut pas mieux sombrer dans la dépression pour pouvoir être reconnus comme victimes.

Mais nous ne lâcherons pas, nous irons jusqu’au bout avec les médias dont on a besoin dans ce combat tellement injuste et inéquitable de David contre Goliath.
Nous ferons appel pour que justice soit faite lors d’une nouvelle audience fixée le 15 octobre 2019.
Il est scandaleux que le laboratoire pharmaceutique UCB Pharma n’assume pas ses erreurs passées et toutes leurs conséquences. UCB cherche encore à nous asphixier avec ce sordide jeu de la montre.

On vous remercie Tous de nous avoir soutenus dans ce combat, on va encore avoir plus besoin de vous pour porter notre voix et en finir au plus vite avec UCB Pharma.

Chaleureusement.

Sylvie et Loic
Référence. Vidéo originale. Reportage Allodocteurs.

Distilbène : un couple veut être reconnu comme “parents victimes”

Le Distilbène DES, en savoir plus

Dry olive leaf extract attenuates DNA damage induced by DES in human peripheral blood cells in vitro

The protective potential of dry olive leaf extract could arise from the synergistic effect of its scavenging activity and enhancement of the cells’ antioxidant capacity

2018 Study Highlights

  • Antigenotoxic potential of DOLE was investigated on the human whole blood in vitro, using comet assay.
  • E2 and DES were used as DNA damage inducers, expressing a genotoxic effect.
  • DOLE exhibited antigenotoxic properties.

Abstract

Phenolic groups of steroidal or nonsteroidal estrogens can redox cycle, leading to oxidative stress, where creation of reactive oxygen species are recognized as the main mechanism of their DNA damage properties.

Dry olive (Olea europaea L.) leaf extract is known to contain bioactive and antioxidative components and to have an ability to modulate the effects of various oxidants in cells.

The main goal of this study was to investigate antigenotoxic potential of a standardized dry olive leaf extract on DNA damage induced by 17β-estradiol and diethylstilbestrol in human whole blood cells in vitro, using comet assay.

Our results indicated that both hormones showed a genotoxic effect at a concentration of 100 μM (P < 0.05, n = 6).

Dry olive leaf extract was efficient in reducing number of cells with estrogen-induced DNA damage at tested concentrations (0.125, 0.5 and 1 mg/mL) (P < 0.05, n = 6) and under two experimental protocols, pre-treatment and post-treatment, exhibiting antigenotoxic properties.

Analysis of antioxidant properties of the extract revealed moderate ABTS radical scavenging properties and reducing power.

Overall, our results suggested that the protective potential of dry olive leaf extract could arise from the synergistic effect of its scavenging activity and enhancement of the cells’ antioxidant capacity.

DES DiEthylStilbestrol Resources

The effects of an EDCs cocktail of BPA + DES + NP

Analysis of individual and combined estrogenic effects of bisphenol, nonylphenol and diethylstilbestrol in immature rats with mathematical models

2019 Study Abstract

Background
Traditional toxicological studies focus on individual compounds. However, this single-compound approach neglects the fact that the mixture exposed to human may act additively or synergistically to induce greater toxicity than the single compounds exposure due to their similarities in the mode of action and targets. Mixture effects can occur even when all mixture components are present at levels that individually do not produce observable effects. So the individual chemical effect thresholds do not necessarily protect against combination effects, an understanding of the rules governing the interactive effects in mixtures is needed. The aim of the study was to test and analyze the individual and combined estrogenic effects of a mixture of three endocrine disrupting chemicals (EDCs), bisphenol A (BPA), nonylphenol (NP) and diethylstilbestrol (DES) in immature rats with mathematical models.

Method
In the present study, the data of individual estrogenic effects of BPA, NP and DES were obtained in uterotrophic bioassay respectively, the reference points for BPA, NP and DES were derived from the dose-response ralationship by using the traditional no observed adverse effect (NOAEL) or lowest observed adverse effect level (LOAEL) methods, and the benchmark dose (BMD) method. Then LOAEL values and the benchmark dose lower confidence limit (BMDL10) of single EDCs as the dose design basis for the study of the combined action pattern. Mixed prediction models, the 3 × 2 factorial design model and the concentration addition (CA) model, were employed to analyze the combined estrogenic effect of the three EDCs.

Results
From the dose-response relationship of estrogenic effects of BPA, NP and DES in the model of the prepuberty rats, the BMDL10(NOAEL) of the estrogenic effects of BPA, NP and DES were 90(120) mg/kg body weight, 6 mg/kg body weight and 0.10(0.25) μg/kg body weight, and the LOAEL of the the estrogenic effects of three EDCs were 240 mg/kg body weight, 15 mg/kg body weight and 0.50 μg/kg body weight, respectively. At BMDL10 doses based on the CA concept and the factorial analysis, the mode of combined effects of the three EDCs were dose addition. Mixtures in LOAEL doses, NP and DES combined effects on rat uterine/body weight ratio indicates antagonistic based on the CA concept but additive based on the factorial analysis. Combined effects of other mixtures are all additive by using the two models.

Conclusion
Our results showed that CA model provide more accurate results than the factorial analysis, the mode of combined effects of the three EDCs were dose addition, except mixtures in LOAEL doses, NP and DES combined effects indicates antagonistic effects based on the CA model but additive based on the factorial analysis. In particular, BPA and NP produced combination effects that are larger than the effect of each mixture component applied separately at BMDL doses, which show that additivity is important in the assessment of chemicals with estrogenic effects. The use of BMDL as point of departure in risk assessment may lead to underestimation of risk, and a more balanced approach should be considered in risk assessment.

References

  • Full study (free access) : Analysis of individual and combined estrogenic effects of bisphenol, nonylphenol and diethylstilbestrol in immature rats with mathematical models, Environmental health and preventive medicine, NCBI PubMed PMC6515622, 2019 May 13.
  • Image credit Helena Yankovska.
DES DiEthylStilbestrol Resources

The James Lind Library’s Introduction to Fair Tests of Treatments

JLL Book of Essays, About Fair Tests, May 2019

Introduction

At various times in our lives and to varying levels of intensity, we all use, provide or pay for health and social care. As we decide what to do, take, offer or buy, we need evidence that is reliable, robust and trustworthy about different options. Even before James Lind’s experiment comparing possible treatments for scurvy on HMS Salisbury people had recognised that getting this evidence requires strenuous efforts to reduce bias –but that achieving this is often not straightforward. This book of essays from the James Lind Library is our attempt to illustrate some of the challenges encountered and how to overcome them.

We will take you on a journey through the sometimes stormy waters of why treatments need to be tested, rather than being based on assumptions that “it must work” before the treatment has even been tried, or based on impressions after it has been used a few times, through to the need for fair tests comparing alternative treatment options. We will show why genuine uncertainties must be identified and addressed, and how research to find the most effective and appropriate treatments need to build on research to identify the most effective and appropriate methods for doing that research. We will navigate through the reasons why comparisons need to be fair at the outset, and then kept fair as the treatments being tested are given;outcomes are measured;and results are analysed, reported, and combined in systematic reviews of all the relevant, trustworthy evidence.

We have not cluttered the chapters with references to all the source material on which we have drawn. For that level of detail, please follow the links to the fuller essays on the James Lind Library website. Instead, where we know of reviews of methodology research which are relevant to a topic, we have listed these at the end of each chapter.

By the end of the book, we hope that you will recognise how, to bring benefits of research to patients and the public, systematic reviews of fair tests are needed to provide key elements of the knowledge needed to inform decisions about health and social care, while taking into account other important factors, such as values, preferences, needs, resources and priorities. We also hope that, as you finish the book, you will share the sense of enlightenment, education and enjoyment that we have gained from preparing it.

Finally, we dedicate this book to England’s National Institute for Health Research. Without the Institute’s 16-year-long support for the James Lind Initiative, the home of the James Lind Library during that time, neither the Library nor these essays would have been possible. And we also wish to acknowledge the role the Institute plays in recognising the vital contribution of research to the delivery of health and social care that is effective and efficient, and the Institute’s leadership in ensuring that the research itself is effective, efficient and reliable, with minimal waste.

Abstract

1.3 Why treatment comparisons must be fair

Untrustworthy treatment comparisons are those in which biases, or the play of chance, or both result in misleading estimates of the effects of treatments. Fair treatment comparisons avoid biases and reduce the effects of the play of chance.

It is not only failure to test theories about treatments in practice that has caused preventable tragedies. They have also occurred because the tests used to assess the effects of treatments have been unreliable and misleading. In the 1950s, theory and poorly controlled tests yielded unreliable evidence suggesting that diethylstilboestrol (DES) helped pregnant women who had previously had miscarriages and stillbirths. Although fair tests suggested that DES was useless, theory and unreliable evidence, together with aggressive marketing, led to DES being prescribed to millions of pregnant women over the next few decades. The consequences were disastrous for the women and their children, who experienced infertility and cancers as a result. The lesson is that a treatment that has not been reliably shown to be useful should not be promoted.

Problems resulting from inadequate tests of treatments continue to occur. Again, because of unreliable evidence and aggressive marketing, millions of women were persuaded to use hormone replacement therapy (HRT). It was claimed that, not only could it reduce unpleasant menopausal symptoms, but also the chances of having heart attacks and strokes. When these claims were assessed in fair tests, the results showed that in women over 60, far from reducing the risks of heart attacks and strokes, HRT increases the risks of these life-threatening conditions, as well as having other undesirable effects.These examples of the need for fair tests of treatments are a few of many that illustrate how treatments can do more harm than good. Improved general knowledge about fair tests of treatments is needed so that –laced with a healthy dose of scepticism –we can all assess claims about the effects of treatments more critically. That way, we will all become more able to judge which treatments are likely to do more good than harm.

DES DiEthylStilbestrol Resources

Comment fonctionnent les perturbateurs endocriniens ?

Le Monde, vidéo publiée le 12 juillet 2017

Ils sont partout ! Comment perturbent-ils ?

Vidéo Le Monde, publiée le 12 juillet 2017

Le Distilbène DES, en savoir plus

DES Action Australia

DES : The wonder drug you should wonder about – In Australia

DES Action Australia formed in late 1979 and, in retrospect, it was a result of serendipity, several independent factors aligning.

Continue readingAbout DES Action Australia“.
– Watch the slideshare presentation : DES Action in Australia.
– Follow DES Action in Australia on Facebook.

DES DiEthylStilbestrol Resources

Lettre ouverte aux membres du conseil exécutif du groupe UCB Pharma

Sylvie et Loïc Le Cossec, avril 2019

Sylvie et son époux Loïc sont les parents d’un enfant lourdement handicapé, en cause, le Distilbène.

La famille Le Cossec entame un troisième procès contre le laboratoire UCB Pharma : ils veulent être reconnus comme “parents-victimes“.

Objet: Procès DES/ Parents Le Cossec:
Soyez JUSTE jusqu’au bout!

Cher Monsieur Fleurial,

En complément de notre courrier d’hier, nous souhaitions vous apporter quelques éléments supplémentaires pour votre réflexion compte-tenu du fait que vous êtes en coulisse très impliqué dans notre procès.

Nous ne reviendrons pas sur l’indemnisation de Julien que nous avons validée.
Julien va pouvoir vivre dignement malgré son handicap à vie mais après un combat judiciaire de 10 ans (pardon de ne pas vous remercier pour cette angoisse là!!!)

Mais aujourd’hui, c’est un autre combat: LE NÔTRE, celui de nos carrières abandonnées et des manques à gagner salariaux et retraite sans parler du préjudice moral pour moi et mon époux Loïc.

Et cessons de dire que les sommes versées pour le préjudice du polyhandicap de Julien couvrent ce dommage, ce qui est faux.
Pour l’Assistance par Tierce personne passée, ce sont nos soirées, nos week-ends et nos vacances consacrés à Julien qui ont été indemnisés et pour l’Assistance par Tierce Personne future, c’est la vie de Julien qui est protégée .

Mais NOUS parents victimes, dans tout ça, tout ce qui nous a été retiré: ma carrière internationale, celle de loïc: C’EST OÙ?
Et irez-vous jusqu’à continuer de dire que nous gagnons déjà bien notre vie!

Une lueur d’espoir reste dans les propos de votre propre avocat devant la presse.

Alors soyez JUSTE jusqu’au bout de ce procès!
Ne pas réparer, c’est cautionner les erreurs du passé.

Très sincèrement.

Sylvie et Loïc Le COSSEC

Référence.

Distilbène : un couple veut être reconnu comme “parents victimes”

Le Distilbène DES, en savoir plus