DES for preventing miscarriage
01
What institutions accepted
Diethylstilbestrol (DES) was treated as an effective preventive treatment for miscarriage, premature labor and related adverse pregnancy outcomes.
02
What the evidence supports now
Controlled trials found no benefit from DES for preventing miscarriage or other adverse pregnancy outcomes, and prenatal exposure can cause serious long-term harms in offspring, including an increased risk of clear-cell adenocarcinoma and reproductive abnormalities. DES should not be used during pregnancy.
03
Evidence for the overall belief
Open sources, locators and notes
- DocumentsHistorical beliefDES Case Study — Women and Health ResearchNational Academies Press / NCBI Bookshelf
Where in the source: History of Development and Testing of DES, paragraphs 1–2 (uncontrolled studies, 1947 FDA approvals and subsequent controlled trials).
Authoritative historical case study stating that the FDA approved NDAs in 1947 to market DES for miscarriage prevention, that controlled 1950s studies found no benefit, and that DES nevertheless continued to be administered to pregnant women for years afterward.
- SupportsPresent correctionDiethylstilbestrol (DES) Exposure and CancerU.S. National Cancer Institute
Where in the source: What is DES?; What is the cancer risk of people who were exposed to DES in utero?; Do the children of women who took DES have problems with fertility and pregnancy?
Current evidence summary stating that DES was prescribed in pregnancy to prevent miscarriage and premature labor, that 1950s studies showed it was ineffective, and that prenatal exposure is associated with cancer and other long-term health risks.
- DocumentsHistorical beliefDrug Therapeutics & Regulation in the U.S. — DiethylstilbestrolU.S. Food and Drug Administration
Where in the source: Diethylstilbestrol Lilly approved 1941, first paragraph, describing prophylactic indications and prescribing during pregnancy.
The FDA's historical exhibit records the use of DES to prevent preterm labor, miscarriage and other pregnancy complications, including its spread from high-risk into routine pregnancies.
Institutional episode 01
United States
North America
In 1947 the FDA approved DES for marketing as a miscarriage preventive, institutionalizing a treatment rationale that had been built largely on uncontrolled evidence. Better trials in the 1950s showed that the treatment did not prevent the pregnancy complications for which it was being prescribed, but use persisted. The decisive regulatory reversal came in 1971, when evidence linked prenatal DES exposure to a rare cancer in young women and the FDA warned clinicians not to prescribe DES during pregnancy.
Institutions involved
- U.S. Food and Drug Administration
Institutional context
DES had already been approved for other indications when the FDA approved new drug applications in 1947 allowing it to be marketed to prevent miscarriage. Controlled studies in the 1950s found that DES did not improve pregnancy outcomes, yet the drug continued to be prescribed during pregnancy for roughly two more decades. In 1971, after researchers linked in-utero DES exposure to a rare clear-cell adenocarcinoma in young women, the FDA notified physicians and required pregnancy to be listed as a contraindication.
Why this persisted
Administrative adoptionFDA approval of new drug applications in 1947 allowed DES to be marketed for miscarriage prevention, giving the treatment rationale a formal regulatory pathway into obstetric use even though later controlled trials found no benefit.
How correction happened
Corrected1971
Action: Required pregnancy to be listed as a contraindication and warned physicians not to prescribe DES during pregnancy.
In 1971, after prenatal DES exposure was linked to clear-cell adenocarcinoma, the FDA warned physicians against prescribing DES during pregnancy and required pregnancy to be listed as a contraindication.
Consequences
- Continued exposure of pregnant women and fetuses after controlled trials had failed to show the intended benefit
- Increased risk of clear-cell adenocarcinoma of the vagina and cervix among women exposed in utero
- Long-term reproductive and other health abnormalities among DES-exposed offspring
- Decades of follow-up of exposed mothers and offspring, with research into possible health effects in subsequent generations
Evidence for this episode
9 evidence linksOpen sources, locators and notes
- DocumentsInstitutional carrierDES Case Study — Women and Health ResearchNational Academies Press / NCBI Bookshelf
Where in the source: History of Development and Testing of DES, paragraphs 1–2, particularly the 1947 new drug applications in paragraph 1.
Authoritative historical case study stating that the FDA approved NDAs in 1947 to market DES for miscarriage prevention, that controlled 1950s studies found no benefit, and that DES nevertheless continued to be administered to pregnant women for years afterward.
- DocumentsMechanismDES Case Study — Women and Health ResearchNational Academies Press / NCBI Bookshelf
Where in the source: History of Development and Testing of DES, paragraphs 1–2 (marketing approval and later controlled studies).
The recorded 1947 approvals permitted marketing for miscarriage prevention; subsequent controlled studies did not validate the intended benefit. This documents the regulatory route into obstetric use rather than proof of efficacy.
- DocumentsConsequencesDES Case Study — Women and Health ResearchNational Academies Press / NCBI Bookshelf
Where in the source: History of Development and Testing of DES, paragraph 2, describing continued administration for the next 20 years despite evidence of ineffectiveness.
The case study records continued prescribing to pregnant women for roughly two decades after controlled studies had failed to show benefit, documenting the continued exposure of women and fetuses.
- DocumentsInstitutional correctionSelected Item from the FDA Drug Bulletin — November 1971 — Diethylstilbestrol Contraindicated in PregnancyU.S. Food and Drug Administration, reproduced in California Medicine via PubMed Central
Where in the source: November 1971 FDA Drug Bulletin, reprinted in California Medicine 116(2), February 1972, p. 85, introductory notice and numbered precautions 1–2.
Reproduction of the 1971 FDA Drug Bulletin announcing pregnancy as a contraindication after the association between maternal DES use and clear-cell adenocarcinoma in exposed offspring.
- ContextualizesContextDrug Therapeutics & Regulation in the U.S. — DiethylstilbestrolU.S. Food and Drug Administration
Where in the source: Diethylstilbestrol Lilly approved 1941, first paragraph (indications and prescribing) and final sentence (FDA's 1971 drug alert).
FDA history describing DES use as prophylaxis against preterm labor, miscarriage and other pregnancy complications, its spread into routine pregnancy use, and the agency's 1971 warning against treating pregnant women with DES.
- DocumentsContextDES Case Study — Women and Health ResearchNational Academies Press / NCBI Bookshelf
Where in the source: History of Development and Testing of DES, paragraphs 1–2.
The case study connects the early uncontrolled treatment rationale, the FDA's 1947 marketing approvals, the negative controlled studies of the 1950s and continued prescribing despite those findings.
- SupportsConsequencesDiethylstilbestrol (DES) Exposure and CancerU.S. National Cancer Institute
Where in the source: What is DES?; What is the cancer risk of people who were exposed to DES in utero?, clear-cell adenocarcinoma item.
Current evidence summary stating that DES was prescribed in pregnancy to prevent miscarriage and premature labor, that 1950s studies showed it was ineffective, and that prenatal exposure is associated with cancer and other long-term health risks. Its cancer-risk section identifies the increased risk of clear-cell adenocarcinoma in prenatally exposed women while noting that this cancer remains rare.
- SupportsConsequencesDiethylstilbestrol (DES) Exposure and CancerU.S. National Cancer Institute
Where in the source: Do the children of women who took DES have problems with fertility and pregnancy?; What other health issues or characteristics might DES daughters and DES sons have?
NCI describes reproductive and pregnancy risks in women exposed before birth and testicular abnormalities in exposed men, without finding an increased risk of male infertility. Its other-health-issues section describes additional risks and the limits of the evidence.
- DocumentsConsequencesDiethylstilbestrol (DES) Exposure and CancerU.S. National Cancer Institute
Where in the source: What is the focus of current research on DES exposure?; Where can DES-exposed people get additional information?, DES Follow-up Study; What health issues might DES grandchildren have?
NCI describes long-term follow-up of exposed mothers and offspring since 1992, with third-generation women added in 2000. It treats health effects in grandchildren as a continuing research question, with several reported associations based on small numbers of events.
Source registryEach source is registered once and can carry several precise evidence relationships.4 sources
- 01DES Case Study — Women and Health ResearchNational Academies Press / NCBI Bookshelf5 evidence links
- 02Drug Therapeutics & Regulation in the U.S. — DiethylstilbestrolU.S. Food and Drug Administration2 evidence links
- 03Selected Item from the FDA Drug Bulletin — November 1971 — Diethylstilbestrol Contraindicated in PregnancyU.S. Food and Drug Administration, reproduced in California Medicine via PubMed Central1 evidence link
- 044 evidence links