Exposure to Diethylstilbestrol: mental illness and neurodevelopmental disorders in descendants
In France, diethylstilbestrol (DES) was prescribed to approximately 200,000 pregnant women between 1948 (sometimes before) and its ban in 1977 (sometimes after), under the brand names Distilbène®, Stilboestrol-Borne® and Furostilboestrol®, to prevent miscarriages and premature births.
We don't hear much about it but it has also been prescribed for other indications (to see the full list, please visit our page “What is DES?”), such as to increase breast milk supply during breastfeeding (hypogalactia) and to artificially suppress lactation after childbirth (Inhibition of lactation).
It is estimated that 160,000 to 300,000 french peoples were exposed in utero to the molecule (diethylstilbestrol). DES grandchildren could be just as numerous.
This endocrine disruptor has caused numerous health problems in children exposed in utero, as well as in their children (the third generation): heightened risk of certain cancer, abnormalities of the reproductive tract, bone abnormalities (find out more about DES side effects at "Health effects of DES exposure").
The drug has caused as serious but less visible damages: mental disorders and neurodevelopmental disorders.
We already mentioned, in a previous article, the increase risk of ADHD (Attention Deficit Disorder with or without Hyperactivity) among the third generation generation of victims of diethylstilbestrol.
Psychological and neurodevelopmental disorders in DES descendants
Hhorages-France (Halte aux HORmones Artificielles pour les GrossessES), is a French association created in 2002 whose aim is to establish the cause and effect relationship between the intake of synthetic sex hormones during pregnancy and disorders generated in the exposed children, with priority given to psychological disorders.
n its 2006 report1, the Hhorages association, which collected many testimonies from French families, observed an increased rate of psychiatric disorders in children exposed in utero to the molecule: schizophrenia, eating disorders often associated with bipolar disorders, severe depression and even suicide…
In its 20172 activity report, Hhorages reveals:
among families adhering to the association exposed to synthetic sex hormones, including DES: anencephalies, pyloric stenosis, agenesis of the arms and the hand, vertebral dynesys, malformations of the foot, hand and hip, kidneys, absence of auditory canal, an increased rate of grandchildren (third generation) with Asperger's syndrome.
Results were published in the International Journal of Gynecological Endocrinology.
- following a study3, differential DNA methylation in major genes: the ADAM TS9 gene and the ZFP 57 gene.
DES and changes in genes expression
ADAM TS9 gene
This gene is involved in the control of the shape of the sexual organs during development, and therefore of sexual differentiation.
It also plays a role in the development of certain cancers and in the control the development of the central nervous system.
ZFP 57 gene
The 2017 study shows a higher rate of psychosis (schizophrenia) in people exposed to diethylstilbestrol.
In addition, compared to DES-exposed individuals without psychosis, exposed individuals with psychosis had differential methylation in the region encompassing the gene encoding the zinc finger protein ZFP57, located on chromosome 6 (6p21). Which means a change in the expression of the ZFP57 gene.
This change can affect neurodevelopment (the development of the nervous system during embryonic development) and neuroplasticity (the ability of neurons to change and remodel throughout life).
Thus, in addition to psychological and neurodevelopmental disorders, this study highlights a link between prenatal exposure to diethylstilbestrol and changes in the expression of certain genes.
DES taken between pregnancies has also had an impact on the children of subsequent pregnancies.
In its 2018 activity report4, Hhorages reports:
- a collection of new testimonials, carried out among the families, members of the association, which confirms a significant number of somatic and psychic disorders in DES Children and DES Grandchildren (3rd generation), in particular autistic spectrum disorders (Asperger Syndrome).
- a testimonial from a DES Daughter, Ruth, whose mother was prescribed an antigalactogenic drug, Stilboestrol®, after each of her 11 deliveries: her mother did not take diethylstilbestrol during her pregnancies, however, 10 of her 11 children suffered the consequences of DES exposure.The longest gap between stopping DES and the next pregnancy is 27 months. This testimony suggests that DES is so potent that it is not eliminated from the body between the time it is stopped and the next pregnancy.
"All the more so because, lodged in its adipose tissue, the residues of this molecule, escaping elimination, endlessly accumulated, under the assault of repeated doses, during the fifteen years separating the births" of the first and last child.
Dangerousness of synthetic progestins during pregnancy
Now, Hhorages draws attention to the dangers of taking progestin (not to be confused with progesterone, a hormone that the body produces naturally) during pregnancy for preventing miscarriage.
Indeed, Hhorages, with Professor Charles Sultan's team, demonstrated in 20185 the link between "the in utero administration of synthetic progesterone (or progestins) and somatic and/or psychiatric disorders" in children, which was confirmed by a Chinese study.
Thus, progestins cause the same psychiatric disorders as diethylstilbestrol.
1 ASSEMBLEE GENERALE HHORAGES-France du 15 Décembre 2006. Rapport sur la Recherche par Marie-Odile Soyer-Gobillard. https://www.hhorages.com/Rapport-recherche-M-O-SOYER-GOBILLARD.pdf [en ligne]
2 HHORAGES - INFOS numéro 14 - octobre 2018 - https://www.hhorages.com/documents/2018/hhorages-infos-14.pdf [en ligne]
3 Rivollier F, Chaumette B, Bendjemaa N, Chayet M, Millet B, Jaafari N, Barhdadi A, Lemieux Perreault LP, Provost S, Dubé MP, Gaillard R, Krebs MO, Kebir O. Methylomic changes in individuals with psychosis, prenatally exposed to endocrine disrupting compounds: Lessons from diethylstilbestrol. PLoS One. 2017 Apr 13;12(4):e0174783. doi: 10.1371/journal.pone.0174783. ECollection 2017.
4 HHORAGES - INFOS numéro 15 - septembre 2019 - https://www.hhorages.com/hhorages-infos-15.pdf [en ligne]
5 Soyer-Gobillard MO, Gaspari L, Courtet P, Puillandre M, Paris F, Sultan C. Neurodevelopmental disorders in children exposed in utero to progestin treatment : Study of a cohort of 115 children from the HHORAGES Association. Gynecological Endocrinology. 2019, 35, 247-250.