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Logo of D.E.S is it, DES Action group in France (Diethylstilbestrol)

Health effects of DES exposure

In the early 1970s, an American study revealed a increased risk of developing rare types of vaginal and cervical cancers in DES daughters (exposed in utero to diethylstilbestrol). The United States then sounded the alarm. In 1971, the United States, but also Canada, recommended to stop prescribing DES to pregnant women. France was alerted by the United States, however, DES continued to be prescribed until 1977.

In France, around 200,000 pregnant women received Distilbène® or Stilbestrol® (french brand names of DES), and 160,000 children, including 80,000 daugthers and 80,000 sons, were born to these pregnancies. We call them "DES children".

Effects in DES Mothers (First Generation)

  • Mothers who took D.E.S. while pregnant have an increased risk of developing breast cancer1. DES injections have caused a proliferation of the endometrium (uterine lining)2,3.
  • An increased risk of endometrial cancer has also been observed in women treated with DES for gonadal dysgenesis as well as menopausal symptoms.
  • Relations between exposure to DES and ovarian and cervical cancers have been highlighted, although the current data do not allow firm conclusions4.

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Interview with a DES mother, worried about her child's potential sterility, Antenne 2 Midi (french TV channel). INA Archives. 1983.

Effects in DES Daughters and Sons (Second Generation)

Known health effects for DES Daughters (women exposed in utero to diethylstilbestrol):

  • Breast cancer risk is greatly increased5.
  • There is an increased risk of developing vaginal and cervical cancers (clear-cell adenocarcinoma or CCA)6.
  • About 45% have vaginal adenosis (which can disappear with time)7;
  • DES daughters are at increased risk for having of structural abnormalities of the uterus and birth defects of the genitals: narrowing of the uterine cavity, abnormalities of the fallopian tubes, deformation of the uterus, T-shaped uterus, hood, cervix or ridge - which may also disappear over time - uterine septum8;
  • These malformations can lead to impaired fertility and a number of obstetric complications such as difficulties in carrying a pregnancy to term: early and late miscarriages, ectopic pregnancy, or premature delivery9. They also can suffer from postpartum hemorrhage;
  • Women exposed in utero to DES who have undergone assisted reproductive technology (ART) have reported embryo implantation defects, uterine vascularization abnormalities, in vitro fertilization (IVF) specific problems, as well as ovarian and oocyte function abnormalities in IVF resulting in fewer live births10.
  • Menstrual irregularities7;
  • Endometriosis11,12;
  • A study reports that women who have been exposed to DES in utero undergo menopause 1.45 times earlier than unexposed women, about a year earlier than unexposed women13;
  • They have an increased risk of developing pancreatic cancer14.

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'Endocrine disruptors in women' (« Les perturbateurs endocriniens chez les femmes »), Extract from the documentary 'Our Daily Poison' (« Notre poison quotidien »). INA Archives. 2011.

Known health effects for DES Sons (men exposed in utero to diethylstilbestrol):

  • No difference in overall cancer risk, but there is an increased risk of testicular cancer15;
  • An increased risk of epididymal non-cancerous cysts has been documented consistently in DES Sons in several studies. Epididymal cysts are known to have a deleterious effect on seminal quality, decrease sperm count and, therefore, decline fertility16;
  • Urinary tract infection, kidney and bladder pain, urethral stenosis, discharge, difficulty urinating7;
  • Varicocele17.
  • Abnormalities of sex differentiation: prenatal DES exposure also induces malformations of the external genitalia such as testicular atrophy, cryptorchidism (undescended testicle) and micropenis18. Anomalies of the position of the urinary meatus (hypospadias, epispadias) are more frequent in men exposed to DES in the womb than in the general population. Indeed, the external urethral orifice can be located on the underside of the penis or even at the level of the scrotum19;
  • These anomalies do not seem to affect the ability of DES Sons to father children17.
  • Possible increase in left-handedness17
  • They are more likely to have same sex partner in adulthood17.
  • A preliminary work, still in progress, carried out from the cohort of the Hhorages association, has highlighted cases of transgenderism (male to female)20.

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Biography Interview with Guillaume Depardieu (French actor & musician), a DES Son, 'Tout le monde en parle'. INA Archives. 2004.

Kristen's testimony questionning the link between DES and transgenderism.

Known health effects for both DES Daughters and Sons:

French study report on DES psychiatric side effects, by the association Hhorages, 2011, Mar. (Subscribe to Ben Distile's Youtube Channel)

DES-exposed Grandchildren

DES Third Generation (the DES Grandchildren, i.e. women and men whose grandmother took DES) also suffer medical issues.

In DES Granddaughters, adverse health effects have been observed:

1. from women exposed in utero to diethylstilbestrol

  • Precocious puberty< (breast development in girls less than 8 years, pubic or underarm hair, start of menstruation before age 10...)25.
  • Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, characterized by congenital aplasia of the uterus and the upper part (2/3) of the vagina26.
  • Endometriosis12;
  • Irregular menstrual cycle, amenorrhea27.
  • Risk of ectopic pregnancy27.
  • Premature deliveries27.
  • Increased risk of delivering a low birth weight baby28 ;
  • Several cases of vaginal or cervical cancers (clear-cell adenocarcinoma or CCA) have been reported29,30.
  • 3 cases of ovarian cancer have been reported by the NCI (National Cancer Institute) in: two women aged 20 and 22 years included in the cohort, and one girl too young to be included. These are really rare cancers in young women10.

Urbania - Le Distilbène | Entre moi et moi, Stephy, a DES Granddaughter, shares her story.

 

It has been observed in DES Grandsons:

1. from women exposed in utero to diethylstilbestrol

  • Disorders of sex development: an increased risk of hypospadias (when mothers were exposed to DES in utero) and cryptorchidia31, 32.
  • Risk of genital malformations 2 times higher33.

2. from men exposed in utero to diethylstilbestrol

  • Genital abnormalities: cryptorchidism, penile hypoplasia (micropenis), but no hypospadias10.

It has been observed in DES Grandchildren:

  • An increased number of esophageal atresia, as well as an increase in the number of malformations of the oral cavity and abnormalities of the musculoskeletal system34
  • An increased rate of Cerebral Palsy (BMI), related to premature, even very premature births35.
  • An increased risk of cardiovascular malformations (including the tetralogy of Fallot) has also been reported36.
  • A study found a significant increase in the number of Attention Deficit Disorders with or without Hyperactivity (ADHD)37.
  • There appears to be an increased risk of developing Autism Spectrum Disorders (ASD)38, but no scientific study has yet shown this.

Hypospadias in grandsons of women who took diethylstilbestrol (DES). (Subscribe to Ben Distile's Youtube channel)

Potential Health Effects from DES (diethylstilbestrol) for the Fourth Generation

For the moment, scientific data are not available for the Fourth Generation, but the possibility that they will also be affected by the adverse effects of DES (diethylstilbestrol) cannot be excluded.

Indeed, transmission to the Third Generation is notably due to a phenomenon of epigenetic alteration: DES induces changes in gene expression that are transmitted from one generation to the next.

Therefore, we can imagine that the DES will not only affect the Fourth Generation, but also future generations...

 

Obstetrician-gynecologist Dr. Anne Wautier explains very clearly (using examples helping to understand) complex notions such as: epigenetics, endocrine disruptors, transgenerational effects of DES (diethylstilbestrol). (Subscribe to Distilbene DES's Youtube channel)

Psychological consequences

Beyond the psychological disorders induced by exposure to DES (diethylstilbestrol), we can easily imagine the lasting psychological repercussions.

Because of the mothers' guilt, DES remains a sensitive, even taboo, subject in some families. This guilt, induced or not, can alter the mother-child bond. And we know today how much the weighs of the unspoken within a family...

Victims of diethylstilbestrol faced with difficulties conceiving a child must embark on a process of assisted reproduction or adoption, which can be a long, complicated and emotional ride, when they do not have to give up the idea of having a child, a painful mourning… This situation can also generate conflicts within the couple.

Malformations of the urogenital sphere, both in men and in women, can lead to self-esteem issues and relationship difficulties.

Also, it is obvious that the health problems caused by DES significantly alter the quality of life, impacting morale.

Finally, what can we say about all the people who still don't dare to talk to their doctor about their difficulties, for fear of not being taken seriously or taken into consideration when talking about DES?

References

  1. Hilakivi-Clarke L1, de Assis S, Warri A. Exposures to synthetic estrogens at different times during the life, and their effect on breast cancer risk. J Mammary Gland Biol Neoplasia. 2013 Mar;18(1):25-42. doi: 10.1007/s10911-013-9274-8. Epub 2013 Feb 8.
  2. Ehrhardt, K., Kramann, H. und Schaefer, H., Vorläufige klinische Ergebnisse mit oestrogenen stilbenpräparaten. Münch. Med. Woch.; 86, 261-262, 1939; Tietze, K., Zur Einführung der Cyrens in die Therapie hormonalen Strörungen der weiblichen Genitalfunktion. Geburtshilfe und Frauenheilkunde, 1, 486-490, 1939.
  3. Schockaert, J. A. et Ferin, J., Acta Brevia Neerlandica, 1941, XII, 1-3.
  4. Cancer environnement. Diethylstilbestrol (DES), Mise à jour le 24 juil. 2019.
  5. Palmer JR, Boggs DA, Hatch EE, Troisi R, Titus-Ernstoff L, Strohsnitter WC, Adam E, Hoover RN. Prenatal DES exposure in relation to breast size. 2013.
  6. Herbst AL, Scully RE. Adenocarcinoma of th evagina in adolescence. A report of 7 cases including 6 clear-cell carcinomas (so-called mesonephromas) Cancer. 1970;25:745–757.
  7. a b c Diethylstilbestrol – Informations à l’usage des spécialistes de la santé, DES ACTION CANADA
  8. Kaufman RH, Adam E, Noller K, Irwin JF, Gray M. Upper genital tract changes and infertility in diethylstilbestrol-exposed women. Am J Obstet Gynecol 1986 ;154:1312–8
  9. Afssaps, 2011. Complications liées à l’exposition in utero au diéthylstilbestrol (DES), 2011.
  10. a b c Sylvie Epelboin, Michel Tournaire, Emmanuel Devouche. Exposition au Distilbène® in utero : effets transgénérationnels. Médecine de la Reproduction. 2022;24(1):37-48. doi:10.1684/mte.2022.0875
  11. Stillman RJ, Miller LC. Diethylstilbestrol exposure in utero and endometriosis in infertile females. Fertil Steril 1984 ;41:369–72.
  12. a b Gaspari, L., Soyer-Gobillard, MO., Paris, F. et al. Multigenerational endometriosis : consequence of fetal exposure to diethylstilbestrol ?. Environ Health 20, 96 (2021). https://doi.org/10.1186/s12940-021-00780-5
  13. Casey E. Reeda and Suzanne E. Fentona. Exposure to Diethylstilbestrol during Sensitive Life Stages: A legacy of heritable health effects. 2013.
  14. a b Troisi, R., Hyer, M., Titus, L., Palmer, J., Hatch, E., Huo, D., Hoover, R. (2020). Prenatal diethylstilbestrol exposure and risk of diabetes, gallbladder disease, and pancreatic disorders and malignancies. Journal of Developmental Origins of Health and Disease, 1-8. doi:10.1017/S2040174420000872
  15. Hom M, Sriprasert I, Ihenacho U, Castelao JE, Siegmund K, Bernstein L, Cortessis VK. Systematic Review and Meta-analysis of Testicular Germ Cell Tumors Following In Utero Exposure to Diethylstilbestrol. 2019.
  16. Gill WB, Schumacher GF, Bibbo M, Straus FH 2nd, Schoenberg HW. Association of diethylstilbestrol exposure in utero with cryptorchidism, testicular hypoplasia and semen abnormalities. J Urol. 1979 Jul;122(1):36-9. doi: 10.1016/s0022-5347(17)56240-0. PMID: 37351.
  17. a b c d Heritable impacts of diethylstilbestrol (DES) – Health outcomes in prenatally DES-exposed men, Linda Titus phD, 12/04/2020.
  18. Sultan C1, Balaguer P, Terouanne B, Georget V, Paris F, Jeandel C, Lumbroso S, Nicolas J. Environmental xenoestrogens, antiandrogens and disorders of male sexual differentiation. 2001.
  19. Contracept Fertil Sex 1993 Sep ;21(9):658-72; Eur J Cancer 1992;28A(6-7) :1182-9; Int J Epidemiol 1989 Jun;18(2) : 462-3; IARC Sci Publ 1989;(96) : 335-48; Lancet 2002; 359: 1102-07.
  20. « Trans-sexualisme M-F à l’adolescence : conséquence d’une contamination fœtale par le DES ? », par Charles Sultan, Laura Gaspari, Françoise Paris et M-O Soyer-Gobillard. Colloque de Gynécologie et Obstétrique Pratique, Paris,17 Mars 2016.
  21. VERDOUX, H., ROPERS, J., COSTAGLIOLA, D., CLAVEL-CHAPELON, F., & PAOLETTI, X. (2007). Serious psychiatric outcome of subjects prenatally exposed to diethylstilboestrol in the E3N cohort study. Psychological Medicine, 37(9), 1315-1322. doi:10.1017/S0033291707000438
  22. Distilbène et Troubles du Comportement : Hasard ou Evidence ?, présentation du Dr Marie-Odile Soyer-Gobillard, directeur de recherche émérite honoraire au CNRS et présidente de Hhorages-France (Halte aux HORmones Artificielles pour les GrossessES) lors du colloque du 18 juin 2011 à l'Assemblée Nationale "Distilbène/Médiator, 1977 - 2009, 2 époques, 2 scandales... Et demain ?", organisé par l'association Les filles DES; Revue Prescrire. Diéthylstilbestrol (DES) : troubles psychiques confirmés.2018 ; O'Reilly EJ et coll., American Journal of Epidemiology, Diethylstilbestrol Exposure in Utero and Depression in Women. 2010.
  23. Verdoux H, Devouche E, Tournaire M, L e v a d o u A. Impact of prenatal exposure to diethylstilbestrol (DES) on psychological outcome: a national survey of DES daughters and unexposed controls. Arch Womens Ment Health. 2017;20:389-395 https://www.ncbi.nlm.nih.gov/pubmed/28064340
  24. Find a complete list of studies on Journal of a DES Daughter
  25. Assemblée Nationale - Question N° : 109961 http://questions.assemblee-nationale.fr/q13/13-109961QE.htm
  26. Wautier A, Tournaire M, Devouche E, Epelboin S, Pouly JL, Levadou A. Genital tract and reproductive characteristics in daughters of women and men prenatally exposed to diethylstilbestrol (DES). Therapie. 2020 Sep-Oct;75(5):439-448. doi: 10.1016/j.therap.2019.10.004. Epub 2019 Nov 1. PMID: 31806244.
  27. a b c Titus L, Hatch EE, Drake KM, Parker SE, Hyer M, Palmer JR, Strohsnitter WC, Adam E, Herbst AL, Huo D, Hoover RN, Troisi R. Reproductive and hormone-related outcomes in women whose mothers were exposed in utero to diethylstilbestrol (DES): A report from the US National Cancer Institute DES Third Generation Study. Reprod Toxicol. 2019 Mar;84:32-38. doi: 10.1016/j.reprotox.2018.12.008. Epub 2018 Dec 27. PMID: 30594671; PMCID: PMC6382553.
  28. Yim G, Roberts A, Wypij D, Kioumourtzoglou M-A, Weisskopf MG. Grandmothers’ endocrine disruption during pregnancy, low birth weight, and preterm birth in third generation. Int J Epidemiol 2022 ;50:1886–96.
  29. Laura Gaspari, Françoise Paris, Nathalie Cassel-Knipping, Julia Villeret, Arnauld Verschuur, Marie-Odile Soyer-Gobillard, Xavier Carcopino-Tusoli, Samir Hamamah, Nicolas Kalfa, Charles Sultan, Diethylstilbestrol exposure during pregnancy with primary clear cell carcinoma of the cervix in an 8-year-old granddaughter: a multigenerational effect of endocrine disruptors?, Human Reproduction, deaa267, https://doi.org/10.1093/humrep/deaa267
  30. DES Info a rapporté deux cas d'Adénocarcinome à cellules claires du vagin chez des petites-filles DES en 2018.
  31. Pons JC, Hypospadias in sons of women exposed to diethylstilbestrol in utero. 2005
  32. Brouwers MM, Feitz WF, Roelofs LA, Kiemeney LA, de Gier RP, Roeleveld N. Hypospadias: a transgenerational effect of diethylstilbestrol?.2006
  33. Kalfa N, Paris F, Soyer-Gobillard MO, Daures JP, Sultan C. Prevalence of hypospadias in grandsons of women exposed to diethylstilbestrol during pregnancy: a multigenerational national cohort study. Fertil Steril. 2011 Jun 30;95(8):2574-7. doi: 10.1016/j.fertnstert.2011.02.047. Epub 2011 Apr 2. PMID: 21458804.
  34. Michel Tournaire , Sylvie Epelboin, Emmanuel Devouche, Géraldine Viot, Jérôme Le Bidoi, Anne Cabau, Annabel Dunbavand, Anne Levadou. Adverse health effects in children of women exposed in utero to diethylstilbestrol (DES). 2016.
  35. Hatch EE, Troisi R, Wise LA, Titus-Ernstoff L, Hyer M, Palmer JR, Strohsnitter WC, Robboy SJ, Anderson D, Kaufman R, Adam E, Hoover RN. Preterm birth, fetal growth, and age at menarche among women exposed prenatally to diethylstilbestrol (DES). 2011.
  36. Titus-Ernstoff L, Troisi R, Hatch EE, Palmer JR, Hyer M, Kaufman R, Adam E, Noller K, Hoover RN. Birth defects in the sons and daughters of women who were exposed in utero to diethylstilbestrol (DES). 2010.
  37. Kioumourtzoglou MA, Weisskopf MG. Grandmaternal Diethylstilbestrol and Attention-Deficit/Hyperactivity Disorder in Children-Reply. 2018.
  38. Rise in Autism Travels Through Generations, By Jane Kay, from Environmental Health News. 2014.