Adverse Health Outcomes in Women Exposed In Utero to Diethylstilbestrol

Hoover, Robert N.; Hyer, Marianne; Pfeiffer, Ruth M.; Adam, Ervín; Bond, Brian; Cheville, Andrea L.; Colton, Theodore; Hartge, Patricia; Hatch, Elizabeth E.; Herbst, Arthur L.; Karlan, Beth Y.; Kaufman, Raymond H.; Noller, Kenneth L.; Palmer, Julie R.; Robboy, Stanley J.; Saal, Robert C.; Strohsnitter, William C.; Titus-Ernstoff, Linda; Troisi, Rebecca

doi:10.1056/nejmoa1013961

Cited by 383 publications

(282 citation statements)

References 33 publications

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“…L'augmentation du nombre de cancers de la thyroïde et du testicule, beaucoup moins fréquents [5], n'est pas visible ici (© Ellen Benhamou, Institut Gustave Roussy, service de biostatistiques et Hélène Sancho-Garnier). [9], la survenue d'un cancer rare du vagin à petites cellules a facilité la démonstration épidémiologique de l'agent responsable, ce n'est pas le cas des cancers du sein et de la prostate.…”

Section: Perturbateurs Endocriniens Et Incidence Des Cancers Hormonodunclassified

“…une exposition précoce de nouveau-nés à de faibles doses de BPA facilite à l'âge adulte l'apparition de cancers in situ de la prostate susceptibles d'évoluer vers des cancers invasifs chez les rats plus âgés [9,14,15].…”

Section: Deux Caractéristiques Généralesunclassified

“…Ces dernières voies d'entrée échappent à l'inactivation hépatique, le BPA étant rapidement métabolisé après son absorption digestive par les enzymes de conjugaison. Les dosages du BPA libre et de ses métabolites chez l'homme (plasma, urines, lait maternel, liquide amniotique et foetus) indiquent une exposition de 80 à 90 % de la population, plus importante chez les jeunes enfants et variable avec le type d'alimentation [9,19,20]. Bien que le BPA soit inactivé par les enzymes de conjugaison, les conjugués peuvent ensuite être hydrolysés et libérer le BPA libre dans les tissus périphé-riques.…”

Section: Controverses Sur Le Degré D'exposition De La Population Humaunclassified

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Bisphénol A et cancers hormono-dépendants

Rochefort

2013

Med Sci (Paris)

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Section: Perturbateurs Endocriniens Et Incidence Des Cancers Hormonodunclassified

Section: Deux Caractéristiques Généralesunclassified

Section: Controverses Sur Le Degré D'exposition De La Population Humaunclassified

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Bisphénol A et cancers hormono-dépendants

Rochefort

2013

Med Sci (Paris)

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“…DES-exposed daughters were found to have abnormally shaped uteri, which led both to infertility problems and premature births of their offspring [17,18]. Additional follow-up of DESexposed mothers and daughters showed that each group appeared to have an increased risk of developing breast cancer [19][20][21][22].…”

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confidence: 99%

“…Most recently, National Cancer Institute (NCI) collaborative studies showed that in-utero exposure of women to DES is associated with a high lifetime risk of a broad spectrum of adverse health outcomes, including an increased risk of breast cancer in daughters 40 years of age and older [22]. For DES-exposed sons, an increased risk of cancer has not been demonstrated [23] but they do have increased prevalence of maldescent of the testes, epididymal cysts, hypotrophic testes, and varicoceles [24][25][26][27].…”

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Diethylstilbestrol (DES) Pregnancy Treatment: A Promising Widely Used Therapy with Unintended Adverse Consequences

Herbst

Anderson

2015

AMA Journal of Ethics

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Diethylstilbestrol (DES) was first synthesized in 1938 and was the first orally active nonsteroidal estrogen that could be used for human therapy [1]. At that time, endocrinology was in its infancy and this discovery was a unique and great advance. Recurrent pregnancy loss was a serious medical problem then as it is now. It was believed the problems were due to a faulty hormonal environment of the fetal-placental unit, rather than primarily to genetic causes, as we have subsequently learned. There were studies at that time indicating that compromised pregnancies had a deficient output of the hormone progesterone, and further studies conducted in the late 1940s in Boston using very crude measuring techniques suggested that this deficiency could be corrected by administering DES to the mother, which would then lead to a healthy pregnancy. These studies led to the widespread usage of the drug to prevent pregnancy loss [2][3][4].The initial examination of the newborns born to mothers treated with DES during pregnancy showed no abnormalities (C. Smith, personal communication). The treatment, however, was controversial. (A unique double-blind study conducted at the University of Chicago in the early 1950s failed to show any improved pregnancy outcome with DES therapy [5]. This study, while negative, was conducted on a healthy pregnant population, which was different than the Boston Study, which was conducted on a high-risk population with a history of bleeding in pregnancy or multiple pregnancy losses.) An additional problem is that the hormone assays in the Boston Study were later found to be faulty and not to actually measure progesterone (Louis L. Engel, PhD, personal communication). It is believed that DES continued to be heavily used in the 1960s, and it has been estimated that 2 to 4 million women in the United States took DES during pregnancy [6].Then, in the late 1960s, eight extraordinarily rare cases of clear cell adenocarcinoma (CCA) of the vagina were diagnosed and treated in women in their teens and early 20s in the Boston area [7]. No such cluster of cases in young patients had ever been seen previously. CCA of the vagina was known to be a cancer that rarely occurred even in older women. In an effort to understand the cause of this cluster, a case-control study was conducted at the Massachusetts General Hospital in 1971 that linked the appearance of these cancers to the patients' mothers having been treated with DES for pregnancy

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Endocrine Disruptors

Kougias,

Kundu

2023

Patty's Toxicology

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Endocrine disruption is a relatively new field of study, as endocrine disruptors were not formally acknowledged by regulatory agencies until 1996. Over the years, many federal and international regulatory agencies and professional associations have provided varying terminology and classifications; however, in general, exposure to endocrine disruptors, or endocrine‐disrupting chemicals (EDCs), at environmentally relevant doses results in adverse effects consequent to interfering with endocrine function. Apart from minor nomenclature disagreements, there are challenges and limitations to this field, as EDC classification criteria can vary substantially in considering evidence for a biologically plausible causal relationship between the endocrine activity and the induced adverse effect. Accordingly, international consensus for unambiguous designation of EDCs is lacking. Therefore, this chapter will not attempt to resoundingly identify all known or suspected EDCs; rather, the objective of this chapter is to first provide historical context to chemical regulation, including on endocrine disruption and its development as a field, and then follow with a review of the health implications, which highlights some fundamental concepts of endocrine disruption and incorporates a tale of the infamous public health disaster resulting from prescribing pregnant women diethylstilbestrol (DES), a potent synthetic estrogen. The current testing guidelines and standards for EDCs are also reviewed, demonstrating the restricted focus on canonical endocrine disruption that is characterized by nuclear hormone receptor‐based activity and the estrogenic, androgenic, thyroidal, and steroidogenic (EATS) modalities. To end, some of the more recently regulated EDCs, particularly bisphenol A and phthalates, as well as other ubiquitous EDCs, like phytoestrogens and flame retardants, are reviewed.

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Adverse Health Outcomes in Women Exposed In Utero to Diethylstilbestrol

Abstract: In utero exposure of women to DES is associated with a high lifetime risk of a broad spectrum of adverse health outcomes. (Funded by the National Cancer Institute.).

Cited by 383 publications

References 33 publications

Bisphénol A et cancers hormono-dépendants

Bisphénol A et cancers hormono-dépendants

Diethylstilbestrol (DES) Pregnancy Treatment: A Promising Widely Used Therapy with Unintended Adverse Consequences

Endocrine Disruptors

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