Health Risks Associated with Diethylstilbestrol (DES) Exposure
Diethylstilbestrol (DES) exposure is associated with significant long-term health risks including increased risk of clear cell adenocarcinoma of the vagina and cervix, reproductive tract abnormalities, infertility, poor pregnancy outcomes, and breast cancer in those exposed in utero or who took the medication during pregnancy.
Background
Diethylstilbestrol is a synthetic nonsteroidal estrogen that was prescribed to pregnant women between 1938 and 1971 in the United States (and into the 1980s in other countries) to prevent miscarriage and pregnancy complications. The FDA issued a warning against its use in 1971 after discovering its association with clear cell adenocarcinoma.
Health Risks for Women Exposed In Utero
Cancer Risks
- Clear Cell Adenocarcinoma (CCAC): Women exposed to DES in utero have a significantly increased risk of vaginal and cervical CCAC (SIR = 49.1,95% CI 21.2-96.8) 1
- Vaginal Cancer: Overall risk is 10.5 times higher than the general population (95% CI 5.72-17.6) 1
- Risk remains elevated even at ages 60-69 (SIR = 8.3,95% CI 1.00-29.9)
- Includes both CCAC and squamous cell carcinoma (SCC) subtypes
- Cervical Intraepithelial Neoplasia: 6.9% risk vs. 3.4% in unexposed women (hazard ratio 2.28; 95% CI 1.59-3.27) 2
- Breast Cancer: Evidence is mixed
Reproductive Health Risks
- Structural Abnormalities: Alterations in development of the müllerian ducts leading to reproductive tract anomalies 3
- Infertility: 33.3% vs. 15.5% in unexposed women (hazard ratio 2.37; 95% CI 2.05-2.75) 2
- Pregnancy Complications:
- Spontaneous abortion: 50.3% vs. 38.6% (hazard ratio 1.64; 95% CI 1.42-1.88) 2
- Preterm delivery: 53.3% vs. 17.8% (hazard ratio 4.68; 95% CI 3.74-5.86) 2
- Second-trimester pregnancy loss: 16.4% vs. 1.7% (hazard ratio 3.77; 95% CI 2.56-5.54) 2
- Ectopic pregnancy: 14.6% vs. 2.9% (hazard ratio 3.72; 95% CI 2.58-5.38) 2
- Preeclampsia: 26.4% vs. 13.7% (hazard ratio 1.42; 95% CI 1.07-1.89) 2
- Stillbirth: 8.9% vs. 2.6% (hazard ratio 2.45; 95% CI 1.33-4.54) 2
- Early Menopause: 5.1% vs. 1.7% (hazard ratio 2.35; 95% CI 1.67-3.31) 2
Health Risks for Women Who Took DES During Pregnancy
- Breast Cancer: Slightly higher risk compared to general population 4
- Cardiovascular Toxicity: Significant cardiovascular complications including myocardial infarction, stroke, and pulmonary embolism, especially at higher doses 5
- 5 mg daily dose associated with 58% 5-year cardiovascular mortality vs. 32% with 1 mg dose 5
- Other Side Effects: Edema, cramps, dyspnea, and gynecomastia 5
Health Risks for Male Offspring
- Genital Abnormalities: Increased incidence 4
- Cancer Risk: Possibly increased risk of prostate and testicular cancer (though definitive evidence is lacking) 4, 3
Screening Recommendations
For Women Exposed In Utero
- Cervical/Vaginal Screening:
- Obstetric Care: Consultation recommended during pregnancy due to higher risk of complications 4
For Women Who Took DES During Pregnancy
- Regular Mammography: Due to slightly increased breast cancer risk 4
For Male Offspring
Clinical Pitfalls and Caveats
- Many DES-exposed individuals may be unaware of their exposure status
- The risk of vaginal cancer persists into older age (60s), beyond current screening recommendations
- Both CCAC and SCC subtypes of vaginal cancer show increased risk
- DES is contraindicated in individuals who have not completed growth and sexual maturation due to interference with epiphyseal plate closure 5
- DES has been used in the treatment of prostate cancer and stuttering priapism but carries significant cardiovascular risks compared to other options 5
The health impacts of DES exposure represent one of the most significant examples of iatrogenic harm in medical history, with effects spanning multiple generations and continuing to be observed decades after exposure.