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Diethylstilboestrol (DES) is a synthetic form of the female hormone oestrogen.1 DES was prescribed to pregnant women from the 1940s to the early 1970s to prevent miscarriage and other pregnancy-related complications.[1]

DES has since been shown to be ineffective in preventing miscarriage, and research identified that DES exposure increased risk for certain cancers and other health conditions.1,2,3  DES is no longer registered for use in Australia.

While the number of women in Australia who took DES is not known, it is estimated that approximately 15,000 women used DES during pregnancy. Over 10 million people were exposed to DES worldwide, with over 4 million women exposed in utero (“DES daughters”).[1] 

DES mothers 

Women given DES while pregnant are known as DES mothers. 

  • DES mothers may have an increased risk of breast cancer compared with women who have not been exposed to DES.4,5,6
  • There is no increased risk of developing other types of hormone-dependent cancers for DES mothers compared with women who did not take DES.1,7  

It is recommended that: 

  • DES mothers participate in the national BreastScreen screening program.1,8  BreastScreen Australia actively invites women aged 50-74 to undergo free screening mammograms every two years. Women aged 40-49 and 75 years of age and over are also eligible for free screening mammograms.1,8
  • GPs encourage DES mothers to inform their children who had in utero exposure to DES.1 

 

DES daughters 

Women whose mothers took DES during their pregnancy are known as DES daughters. 

  • DES daughters have an increased risk of developing a rare type of cancer of the vagina and cervix called clear cell adenocarcinoma (CCA).2,5,9,10,11 The risk of DES daughters developing CCA is about 1.5 cases for every 1000 women.1
  • Abnormal changes to cells of the vagina and cervix (high grade cervical and vaginal intraepithelial neoplasia) are more common in DES daughters compared with women not exposed to DES. However, this has not been found to be associated with a significant increased risk of cervical cancer.1,3,7,10,11 
  • Women who were exposed to DES in utero may have an increased risk of breast cancer. 6,7,12,13,14
  • DES daughters may also have a higher risk of developing other conditions associated with reproduction. Studies have found an increased risk of premature birth, miscarriage, ectopic pregnancy and early menopause in DES daughters.1,7

It is recommended that:

  • DES daughters participate in the national BreastScreen mammographic screening program.14  BreastScreen Australia8  actively invites women aged 50-74 to undergo free screening mammograms every two years. Women 40-49 years of age and 75 years of age and over are also eligible for free screening mammograms.8 
  • DES daughters have an annual gynaecological examination consisting of a general examination, colposcopic inspection of the lower genital tract, cervical co-test (HPV and LBC test) and bimanual examination to detect any vaginal induration. 1,15 
  • DES daughters who have a screen-detected abnormality should be managed by an experienced colposcopist.15

 

DES sons 

Men whose mothers took DES during their pregnancy are known as DES sons. 

  • DES sons have an increased risk of epididymal cysts, hypogonadism and undescended testes.
  • There is no specific cancer risk in DES sons, apart from the risk of testicular cancer associated with undescended testes.1,12,16

DES grandchildren 

The children of DES daughters or sons are known as DES grandchildren. They have had no direct exposure to DES. 

  • To date, no association has been shown between DES exposure and cancer in DES grandchildren.1,9,12,17,18

It is recommended that:

  • DES granddaughters be screened with a 5-yearly Cervical Screening Test in accordance with National Cervical Screening Program policy. However, if these women have concerns, testing similar to that recommended for DES daughters could be considered on an individual basis. Self-collection for HPV testing is not recommended. 1,15

References

  1. Royal Australian and New Zealand College of Obstetricians and Gynaecologists.  Diethylstilboestrol (DES) in utero (C-Obs 56). https://ranzcog.edu.au/wp-content/uploads/2022/05/Diethylstilboestrol-DES-exposure-in-utero.pdf. Accessed: August 2023 
  2. Herbst AL, Ulfelder H, Poskanzer DC. Adenocarcinoma of the vagina: association of maternal stilbestrol therapy with tumor appearance in young women. N Engl J Med 1971;284:878-81. 
  3. National Cancer Institute.  Diethylstilboestrol (DES) and Cancer  http://www.cancer.gov/cancertopics/factsheet/Risk/DES  Accessed: August 2023
  4. Titus-Ernstoff L, Hatch EE, Hoover RN, et al. Long-term cancer risk in women given diethylstilboestrol (DES) during pregnancy. British Journal of Cancer 2001; 84(1):126–133. 
  5. Colton T, Greenberg ER, Noller K, et al. Breast cancer in mothers prescribed diethylstilboestrol in pregnancy. Further follow-up. JAMA 1993; 269(16):2096–2100. 
  6. Cancer Australia, 2018. Risk factors for breast cancer: A review of the evidence, Cancer Australia. https://www.canceraustralia.gov.au/sites/default/files/publications/risk-factors-breast-cancer-review-evidence-2018/pdf/rfbcr_risk_factors_for_breast_cancer_a_review_of_the_evidence_2018_report.pdf. Accessed: August 2023. 
  7. Hoover RN, Hyer M, Pfeiffer RM, et al. Adverse health outcomes in women exposed in utero to diethylstilboestrol. N Engl J Med. 2011 Oct 6;365(14):1304-14. 
  8. BreastScreen Australia. About the Program.  http://www.cancerscreening.gov.au/internet/screening/publishing.nsf/Content/breast-screening-1. Accessed: August 2023
  9. Giusti RM, Iwamoto K, Hatch EE. Diethylstilboestrol revisited: a review of the long-term health effects. Annals of Internal Medicine 1995; 122(10):778–788. 
  10. Troisi R, Hatch EE, Palmer JR, Titus L, Robboy SJ, Strohsnitter WC, et al. Prenatal diethylstilbestrol exposure and high-grade squamous cell neoplasia of the lower genital tract. American Journal of Obstetrics and Gynecology. 2016;215(3):e1-322.
  11. Verloop J, van Leeuwen FE, Helmerhorst TJM, de Kok IMCM, van Erp EJM, van Boven HH, et al. Risk of cervical intra-epithelial neoplasia and invasive cancer of the cervix in DES daughters. Gynecologic Oncology. 2017;144(2):305-11.
  12. International Agency for Research on Cancer. Diethylstilboestrol. In: Monographs on the Evaluation of Carcinogenic Risks to Humans: Pharmaceuticals Volume 100A: A Review of Human Carcinogens. Lyon, France. World Health Organisation. 2012. 
  13. Palmer JR, Wise LA, Hatch EE, et al. Prenatal diethylstilboestrol exposure and risk of breast cancer. Cancer Epidemiology, Biomarkers & Prevention 2006; 15(8):1509–1514. 
  14. Verloop J, van Leeuwen FE, Helmerhorst TJ et al. Cancer risk in DES daughters.Cancer Causes Control. 2010 Jul;21(7):999-1007. 
  15. Cancer Council Australia. National cervical screening program: Summary of recommendations. https://www.cancer.org.au/clinical-guidelines/cervical-cancer/cervical-cancer-screening/summary-of-recommendations. Accessed: August 2023
  16. Strohsnitter WC, Noller KL, Hoover RN, et al. Cancer risk in men exposed in utero to diethylstilboestrol. J Natl Cancer Inst. 2001 Apr 4;93(7):545-51. 
  17. Titus-Ernstoff L, Troisi R, Hatch EE, et al. Offspring of women exposed to diethylstilboestrol (DES): a preliminary report of benign and malignant pathology in the third generation. Epidemiology 2008; 19(2):251–257. 
  18. Reed CE, Fenton SE. Exposure to diethylstilboestrol during sensitive life stages: a legacy of heritable health effects. Birth Defects Res C Embryo Today. 2013 Jun;99(2):134-46.