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. 2003;2003(3):CD004353.
doi: 10.1002/14651858.CD004353.

Oestrogen supplementation, mainly diethylstilbestrol, for preventing miscarriages and other adverse pregnancy outcomes

A A Bamigboye  1 , J Morris
Affiliations

Oestrogen supplementation, mainly diethylstilbestrol, for preventing miscarriages and other adverse pregnancy outcomes

A A Bamigboye et al. Cochrane Database Syst Rev. 2003.

Abstract

Background: Laboratory evidence in the 1940s demonstrated a positive role of placental hormones in the continuation of pregnancy. It was suggested that diethylstilbestrol was the oestrogen of choice for prevention of miscarriages. Observational studies were carried out with apparently positive results, on which clinical practice was based. This led to a worldwide usage of diethylstilbestrol despite controlled studies with contrary findings.

Objectives: To determine the effects of antenatal administration of oestrogens, mainly diethylstilbestrol, on high risk and unselected pregnancy as regards miscarriages and other outcomes.

Search strategy: We searched the Pregnancy and Childbirth Group Specialised Register of controlled trials in November 2002.

Selection criteria: Randomised and quasi-randomised trials were included.

Data collection and analysis: Both reviewers extracted data from the studies identified that met the selection criteria, and the data were analysed using the RevMan software.

Main results: Miscarriage, preterm labour, low birthweight and stillbirth or neonatal death were not positively influenced by the intervention (diethylstilbestrol) as compared to the control group. Diethylstilbestrol in utero exposure led to increased rate of miscarriage and preterm birth. There was also an increase in the numbers of babies weighing less than 2500 grams. The maternal outcome in terms of pre-eclampsia was not influenced. Exposed female offsprings have a non-significant trend towards more cancer of the genital tract and cancer other than of the genital tract. Primary infertility, adenosis of the vagina/cervix in female offsprings, and testicular abnormality in male offsprings were significantly higher in those exposed to diethylstilbestrol before birth.

Reviewer's conclusions: There was no benefit with the use of diethylstilbestrol in preventing miscarriages. Both short and long-term adverse outcomes in exposed offsprings were demonstration of the harm that this intervention caused women and their offspring during its usage.

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Conflict of interest statement

None known.

Figures

1.1
1.1. Analysis
Comparison 1 Diethylstilbestrol versus control, Outcome 1 Miscarriage.
1.2
1.2. Analysis
Comparison 1 Diethylstilbestrol versus control, Outcome 2 Preterm birth (gestational age < 38 weeks).
1.3
1.3. Analysis
Comparison 1 Diethylstilbestrol versus control, Outcome 3 Birthweight < 2500 g.
1.4
1.4. Analysis
Comparison 1 Diethylstilbestrol versus control, Outcome 4 Stillbirth.
1.5
1.5. Analysis
Comparison 1 Diethylstilbestrol versus control, Outcome 5 Neonatal death.
1.6
1.6. Analysis
Comparison 1 Diethylstilbestrol versus control, Outcome 6 Pre‐eclampsia.
1.7
1.7. Analysis
Comparison 1 Diethylstilbestrol versus control, Outcome 7 Cancer of genital tract (female offsprings).
1.8
1.8. Analysis
Comparison 1 Diethylstilbestrol versus control, Outcome 8 Cancer other than genital tract.
1.9
1.9. Analysis
Comparison 1 Diethylstilbestrol versus control, Outcome 9 Adenosis of vaginal and/or cervix and uterine polyps.
1.10
1.10. Analysis
Comparison 1 Diethylstilbestrol versus control, Outcome 10 Congenital anomaly.
1.11
1.11. Analysis
Comparison 1 Diethylstilbestrol versus control, Outcome 11 Unmarried (female offsprings).
1.12
1.12. Analysis
Comparison 1 Diethylstilbestrol versus control, Outcome 12 Psychiatric disorders (female offsprings).
1.13
1.13. Analysis
Comparison 1 Diethylstilbestrol versus control, Outcome 13 Primary infertility (female offsprings).
1.14
1.14. Analysis
Comparison 1 Diethylstilbestrol versus control, Outcome 14 Testicular abnormality (male offsprings).
1.15
1.15. Analysis
Comparison 1 Diethylstilbestrol versus control, Outcome 15 Infertility (male offsprings).
1.16
1.16. Analysis
Comparison 1 Diethylstilbestrol versus control, Outcome 16 Psychiatric disorders (male offsprings).
See this image and copyright information in PMC

References

References to studies included in this review

Bender 1988 {unpublished data only}
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Crowder 1950 {published data only}
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References to studies excluded from this review

Baird 1996 {published data only}
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Berle 1980 {published data only}
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Additional references

Bibbo 1975
    1. Bibbo M, Al‐Naqeeb M, Baccarini I, Gill W, Newton M, Sleeper KM, et al. Follow‐up study of male and female offspring of DES‐treated mothers. A preliminary report. Journal of Reproductive Medicine 1975;15:29‐32. - PubMed
Bibbo 1977
    1. Bibbo M, Gill WB, Azizi P, Blough R, Fang VS, Rosenfield RL, et al. Follow‐up study of male and female offspring of DES‐exposed mothers. Obstetrics and Gynecology 1977;49:1‐8. - PubMed
Everett 1997
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FDA 1971
    1. FDA Drug Bulletin. Diethylstilboestrol contraindicated in pregnancy. US Dept of Health, Education and Welfare 1971.
Herbst 1971
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Herbst 1975
    1. Herbst AL, Poskanzer DC, Robboy SJ, Friedlander L, Scully RE, et al. Prenatal exposure to stilboestrol. A prospective comparison of exposed female offspring with unexposed controls. New England Journal of Medicine 1975;292:334‐9. - PubMed
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Smith 1944
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Smith 1948
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References to other published versions of this review

Beral 1995
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