Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jun;40(6):659-668.
doi: 10.1007/s10654-025-01234-9. Epub 2025 May 28.

Cancer risk after in utero exposure to diethylstilbestrol

Naomi B Boekel  1 , Janneke Verloop  2 , Hester H van Boven  3 , Elisabeth J M van Erp  4 , Lieske Schrijver  1 , Matti A Rookus #  1 , Flora E van Leeuwen #  5
Affiliations

Cancer risk after in utero exposure to diethylstilbestrol

Naomi B Boekel et al. Eur J Epidemiol. 2025 Jun.

Abstract

In utero exposure to diethylstilbestrol (DES) is associated with increased risk of clear cell adenocarcinoma (CCAC) of the vagina or cervix. It is not clear whether these risks remain increased at older ages, and if the risks of other cancer sites, including breast cancer, are increased. This nationwide cohort study included 12,249 DES-exposed women and 2,070 unexposed sisters. Hormone-related risk factors and medical history were assessed through questionnaires, and cancer incidence through linkages with nationwide registries. Comparison with general population rates showed no difference in overall cancer risk (SIR = 0.98, 95%CI 0.93-1.04) or breast cancer risk (SIR = 1.03, 95%CI 0.96-1.11) for DES-exposed women. The rate of vaginal cancer was strongly increased for DES-exposed women (SIR = 10.5, 95%CI 5.72-17.6) and was increased in all age categories, including age 60-69 years (SIR = 8.3, 95%CI 1.00-29.9). Risks of both CCAC (SIR = 49.1, 95%CI 21.2-96.8) and squamous cell carcinoma (SCC; SIR = 5.86, 95%CI 2.15-12.8) of the vagina were significantly elevated. When comparing DES-exposed women with DES-unexposed sisters, overall cancer risk and risk of breast cancer were similar (HR = 0.93, 95%CI 0.78-1.11 and HR = 0.97, 95%CI 0.76-1.23, respectively). Apart from the established increased risk of vaginal cancer, women exposed to DES in utero do not seem to be at increased risk of cancer, including breast cancer. The risk of vaginal cancer remains increased also for women in their fifties/sixties. Moreover, the increased risk of vaginal cancer was seen for both subtypes CCAC and SCC. Screening for vaginal cancer up to higher ages than currently recommended (< 60 years) should be considered.

Keywords: Breast cancer; Cancer of the vagina; Cervical cancer; Clear cell adenocarcinoma; DES; DES daughters; Diethylstilbestrol; Screening; Squamous cell carcinoma.

PubMed Disclaimer

Conflict of interest statement

Declarations. Ethical approval: This is an observational study. The study was approved by the Institutional Review Board of the Netherlands Cancer Institute and the Surveillance Committees of PALGA, the nationwide Dutch Pathology Registry, and the Netherlands Cancer Registry (NCR). Competing interests: None of the authors have conflicts of interest.

References

    1. Heinonen OP. Diethylstilbestrol in pregnancy. Frequency of exposure and usage patterns, Cancer, vol. 31, no. 3, pp. 573-7, Mar 1973.
    1. Noller KL, Fish CR. Diethylstilbestrol usage: its interesting past, important present, and questionable future. Med Clin North Am. Jul 1974;58(4):793–810. https://doi.org/10.1016/s0025-7125(16)32122-8 .
    1. Giusti RM, Iwamoto K, Hatch EE. Diethylstilbestrol revisited: a review of the long-term health effects. Ann Intern Med, 122, 10, pp. 778– 88, May 15 1995, https://doi.org/10.7326/0003-4819-122-10-199505150-00008
    1. 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, vol. 284, no. 15, pp. 878– 81, Apr 22 1971, https://doi.org/10.1056/NEJM197104222841604
    1. Palmer JR et al. Infertility among women exposed prenatally to diethylstilbestrol. Am J Epidemiol, 154, 4, pp. 316– 21, Aug 15 2001, https://doi.org/10.1093/aje/154.4.316

MeSH terms

Substances