Diethylstilbestrol: Side Effects

Diethylstilbestrol (DES), also referred to as stilbestrol/stilboestrol, is an oestrogenic hormone formerly used in the treatment of threatened miscarriage and suppression of lactation. DES may still be prescribed in the United Kingdom for the treatment of certain types of cancer, however, it is no longer indicated in the treatment of threatened miscarriage or suppression of lactation.

There are safety concerns with DES related to historical usage. There are different safety concerns relating to:

• women exposed to DES in utero, DES daughters, when their mothers were pregnant and taking the drug for threatened miscarriage; and

• women who were exposed to DES whilst pregnant to prevent miscarriage or following pregnancy in order to supress lactation, DES mothers.
  

In 1971, a study from the United States reported that DES may cause a distinct type of vaginal cancer in the daughters of women who took DES in early pregnancy. These women are also referred to as ‘DES daughters’.

The risk of cervical and vaginal cancers was reviewed by the Committee on Medicines Safety (CSM), the predecessor to the Commission on Human Medicines, throughout the 1970’s. The CSM considered usage of DES in the UK to be low for the indication of threatened miscarriage from the 1970’s onwards. The CSM, working with clinicians and academics, followed up cases of these cancers identified in the Cancer Register to determine whether individuals had been exposed to DES, and no UK cases were identified.

In 1973, CSM wrote to all doctors to inform them of the results of the US study and the absence of identified cases in the UK. The earliest time a contraindication in pregnancy is formally recorded in the UK is in the 1981/82 data sheet compendium for medicines. We know that use in pre-menopausal women was advised against from at least 1984.

Separate to the risk of cervical and vaginal cancers in women exposed in utero, a potential risk of breast cancer in women who were given DES whilst pregnant was identified in the 1980’s and confirmed in further studies in the 1990s, when longer follow up of women who had taken DES was available. These women are also referred to as ‘DES mothers’.

DES may still be prescribed in the UK for certain types of cancer, including cancer of the prostate and metastatic post-menopausal cancer of the breast. The current product information for DES clearly describes the risk of harms related to its use in pregnancy and for this reason its use is contra-indicated in pregnant women, and it is not suitable for pre-menopausal women, and should not be prescribed to children or young people due to its carcinogenic potential. The product information notes that due to its carcinogenic potential DES use is only justified in the management of malignant disease.

Daughters of individuals exposed to DES in utero are at increased risk of clear cell cancer of the cervix and vagina. The current advice from UK Health Security Agency is that routine cervical screening is appropriate for those who were exposed to DES in utero. Participation in the National Breast Screening Programme is also recommended for those women exposed to DES. The UK Health Security Agency’s advice is available at the following link:

https://www.gov.uk/government/publications/cervical-screening-programme-and-colposcopy-management/5-screening-and-management-of-immunosuppressed-individuals

The Medicines and Healthcare products Regulatory Agency (MHRA) regulates medicines supplied in the UK. Our activity spans the whole of a medicine’s lifecycle. The MHRA continuously assesses the benefit risk balance of all medicines at the time of initial licensing and throughout their use in clinical practice, carefully evaluating any emerging evidence on their benefits and risks. It is important to note that the regulatory legislation and frameworks are significantly different now compared to the 1970’s and post-authorisation monitoring of safety is much stricter, allowing for earlier identification and action on emerging safety issues.