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Diethylstilbestrol syndrome (DES)

What is Diethylstilbestrol Syndrome?

Orphanet — The portal for rare diseases and orphan drugs — defines Diethylstilbestrol Syndrome (DES) as a malformative syndrome reported in the offspring (children and grandchildren) of women exposed to DES (diethylstilbestrol) during pregnancy.

DES is a non-steroidal synthetic estrogen that was widely prescribed to pregnant women between 1940 and 1977 to prevent miscarriage and premature birth.

DES was sold in France under the brand names Distilbène®, Stilbestrol-Borne® and Furostilboestrol® (delayed-release form).


  • DES embryofetopathy
  • DES syndrome
  • Diethylstilbestrol embryofetopathy
  • Distilbene embryofetopathy

ICD-11 (International Classification of Diseases 11th Revision) : LB44.6

Diethylstilbestrol Syndrome is (currently) characterized by:


In men exposed to DES

Reproductive malformations: hypospadias (birth defect in boys in which the opening of the urethra is not located at the tip of the penis), cryptorchidism (undescended testicle) or testicular hypoplasia (poor development of sperm-producing tissue and reduced size of testicles).

We also find epididymal (a narrow, tightly-coiled tube connecting rear of the testicles to the deferent duct) cysts, microphallus (or micropenis, is defined as a stretched penile length of less than 2.5 standard deviations (SDs) below the mean for age), subfertility (reduced fertility).

In women exposed to DES

There is an increased risk of developing clear cell carcinoma of the vagina and cervix (or ACC, a rare variant of adenocarcinoma), cervical or vaginal dysplasia (a precancerous condition in which abnormal cells grow on the surface of your cervix/vagina).

These women may also experience decreased fertility, reproductive malformations which include a vaginal septum, a hypoplastic (underdeveloped) T-shaped uterus or abnormalities of the fallopian tubes, which increase the risk of obstetric complications and miscarriages.


Updating the definition of Diethylstilbestrol Syndrome

Studies carried out at the same time as the definition of Diethylstilbestrol Syndrome have highlighted other disorders which would justify its updating.

Other health problems not listed in Diethylstilbestrol Syndrome are numerous. They include:

Known health effects of DES for both men and women exposed in utero (second generation)

  • There is an 11-fold increased risk of any pancreatic disorder and a 7-fold increased risk of pancreatitis1.
  • The data from the Hhorages association cohort show a link between prenatal exposure to DES and the appearance of psychological and psychiatric disorders such as: schizophrenia, depression, bipolar disorders, eating disorders, obsessive-compulsive disorder, anxiety, aggressiveness, and suicide attempts2,3,4.
  • Epigenetic anomalies: in French psychotic patients exposed to DES in utero, modifications in the expression of two genes were found. These are the ADAM TS9 gene, involved in controlling the shape of the sexual organs during development, and the ZFP57 gene, an alteration of which can impact neurodevelopment.5.

In women exposed to DES in utero

  • An increased risk of pancreatic cancer 1, endometriosis6,7, osteoporosis8.

In men exposed to DES in utero

  • Increased risk of testicular cancer9.
  • A possible increase in cases of transgenderism (male to female) — work is underway10.
Consequences of DES exposure in children suffering from Diethylstilbestrol Syndrome (DES)
People exposed in utero to diethylstilbestrol (DES) are called “DES Children”.
Thus, “DES Daughters” and “DES Sons” are children whose mothers received a drug containing diethylstilbestrol during pregnancy.
They represent the second generation of patients exposed to DES (in color on the tree above), the first generation being represented by the “DES Mothers”.
Consequences of DES exposure in grandchildren suffering from Diethylstilbestrol Syndrome (DE
People whose at least one parent was exposed to diethylstilbestrol in utero are called “DES Grandchildren”.
Thus, the “DES Granddaughters” and the “DES Grandsons” are the grandchildren of a woman who received a medication containing diethylstilbestrol during pregnancy.
They represent the third generation of patients affected by DES (in color on the tree above). Their children represent the fourth generation.

In DES Grandchildren, i.e. the third generation

  • An increased rate of Cerebral Palsy (CP), related to premature, even very premature births11.
  • A significant increase of attention deficit / hyperactivity disorder or ADHD — a neurodevelopmental disorder12.
  • An increased risk of cardiovascular malformations13.
  • An increased number of esophageal atresia, malformations of the oral cavity, and abnormalities of the musculoskeletal system13,14.

In DES Granddaugthers

  • Uterovaginal aplasia has been found, i.e. MRKH syndrome (Mayer-Rokitansky-Küster-Hauser syndrome), that is to say aplasia of the uterus and the upper two thirds of the vagina.15.
  • Precocious puberty: breast development in girls less than 8 years, pubic or underarm hair, start of menstruation before age 10...16.
  • Endometriosis7.
  • Irregular menstrual cycle, amenorrhea17.
  • Risk of ectopic pregnancy, premature deliveries17.
  • 3 cases of ovarian cancer have been reported by the NCI 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 women18.

Prevalence of Diethylstilbestrol Syndrome

In France, the number of women given diethylstilbestrol (Distilbène®, Stilbestrol-Borne® or Furostilboestrol®) is estimated at 200,000 and the number of children exposed in utero at 160,000.

As there is no patient register or national cohort, the prevalence of the disease is unknown.

This is why we have launched a national census of patients affected by diethylstilbestrol, below which you will find the resulting statistics.

The prevalence of Diethylstilbestrol Syndrome (DES) is unknown.

Diagnosis and management of Diethylstilbestrol Syndrome

It is currently impossible for a patient to be diagnosed.

Indeed, there is no Reference Center for this rare iatrogenic disease, and no French National Diagnostic and Care Protocol (PNDS).

The PNDS is a reference document for health professionals, written by the experts of the Reference Center using a methodology proposed by the High Authority of Health (HAS).

The objective of a PNDS is to explain to the professionals concerned the current optimal diagnostic and therapeutic care and the care path of a patient suffering from a rare disease given.

There is no diagnosis and no treatment for Diethylstilbestrol Syndrome (DES)

The D.E.S is it association has set itself the objective of filling all these gaps, starting by joining one or more Reference Centers, in order to constitute a group of experts and work, hand in hand, on the development of a PNDS for Diethylstilbestrol Syndrome (DES).

DES is it want to work on the development of a National Diagnostic and Care Protocol (PNDS) for Diethylstilbestrol Syndrome (DES)

Notes & references

  1. 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
  2. O'Reilly EJ, Mirzaei F, Forman MR, Ascherio A. Diethylstilbestrol exposure in utero and depression in women. Am J Epidemiol. 2010 Apr 15;171(8):876-82. doi: 10.1093/aje/kwq023. Epub 2010 Mar 23. PMID: 20332145; PMCID: PMC2877444.
  3. "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 ?".
  4. "Exposition in utero au diéthylstilbestrol (DES)  troubles psychiques confirmés" Revue Prescrire 2018 ; 38 (412).
  5. 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.
  6. Stillman RJ, Miller LC. Diethylstilbestrol exposure in utero and endometriosis in infertile females. Fertil Steril 1984 ;41:369–72.
  7. a b Gaspari, L., Soyer-Gobillard, MO., Paris, F. et al. Multigenerational endometriosis : consequence of fetal exposure to diethylstilbestrol ?. Environ Health 20, 96 (2021).
  8. Find a complete list of studies on Journal of a DES Daughter
  9. 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.
  10. « 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.
  11. 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.
  12. Kioumourtzoglou MA, Weisskopf MG. Grandmaternal Diethylstilbestrol and Attention-Deficit/Hyperactivity Disorder in Children-Reply. JAMA Pediatr. 2018 Dec 1;172(12):1204-1205. doi: 10.1001/jamapediatrics.2018.3743. PMID: 30383104.
  13. a b 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.
  14. 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.
  15. 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.
  16. Assemblée Nationale - Question N° : 109961
  17. a b 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.
  18. 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
  19. The images on this page are the creation of / Freepik