In the 1950s and ’60s, a synthetic oestrogen called diethylstilbestrol (DES) was used extensively to prevent pregnancy disorders, starting off in Europe. There was a belief in the decades prior to this that oestrogen deficiency may be causing or contributing to a high foetal death rate amongst diabetic women. Diabetic women were therefore the first to be given the drug, followed quickly by anyone thought to have a high risk of miscarriage or stillbirths.
In 1970, research was published that reported young women with vaginal cancers, with the type of tumour (clear-cell carcinoma) very rare in anyone young. Clear- cell carcinomas are almost exclusively found in elderly women. The cause was drawn back to those young women whose mothers had been given DES during their pregnancy.
Over five million women are thought to have been treated with DES during their pregnancies, and only occurs with DES derivatives, not natural oestrogens. There was initially a great fear of the malignant outcomes, but this largely has not come to fruition, with the chances of vaginal malignancy small, and with frequent checks, treatable.
Vaginal adenosis is now thought to be a benign condition, not a precancerous condition. There have only been hundreds of cases of vaginal cancers in offspring, despite the millions of pregnant women treated.
The effect of DES on a foetus
It became clear over time that DES was causing structural changes in girls born to mothers who took the drug, particularly in the cervix and vagina. Most of these changes seem to be benign, but there is an increased cancer risk.
- Vaginal adenosis (cervical and endometrial cells found in the vaginal wall, where they are not normally found)
- Cockscomb cervix
- Uterine malformations
- Cervix malformations
How these abnormalities occur (theory)
The exact mechanism is not fully understood, but a working theory exists. In the womb, the cervix and most of the vagina are lined with a specific cell, columnar epithelium. At birth, most of these cells have converted to squamous epithelium. Further changes occur at puberty and onwards.
DES administration may stop this conversion of cells, and allow columnar epithelium to remain in the vagina and outer portion of the cervix (the ectocervix). As the delayed conversion occurs at puberty, these glandular structures are still present. This results in small ‘glands’ in the vaginal mucosa being covered by squamous epithelium, replacing the glandular tissue completely, eventually.
The presence of these glands, either covered or uncovered, is called adenosis.
When the change in cells from columnar epithelium to malignant cells occurs is unknown, as is the delay of 10-30 years. The effect seems to be dose-dependent: mothers whose daughters have adenosis or clear-cell cancer had greater exposure earlier in the pregnancy.
Fertility outcomes of those with in utero DES exposure
Structural abnormalities in the uterus or an underdeveloped cervix may impede pregnancy and/or cause miscarriage. However, many women with DES exposure remain fertile and able to carry a healthy baby to term.
- Gerbie, M. V., M.D. (1981). Management of the adolescent girl exposed in utero to DES. Pediatric Annals, 10(12), 23-26.
- Michel Tournaire, Jacques Lepercq, Sylvie Epelboin. The daughters of diethylstilbestrol Lessons from an error. European Journal of Obstetrics & Gynecology and Reproductive Biology 75 (1997) 25–27