Tamoxifen is a selective oestrogen receptor modulator that acts as an oestrogen antagonist in some tissues, including breast, and as an agonist in others, including endometrium. Tamoxifen is used for prevention and treatment of breast cancer and may be used to treat infertility (ovulation induction). It is also used for a number of off-licence indications such as mastalgia.
There are limited data on the use of tamoxifen in human pregnancy. No large studies have been carried out to assess its pregnancy safety profile. Human pregnancy data consist of only a small number of retrospective case reports, and a small prospective cohort study which included two infants exposed to tamoxifen in the second trimester.
It is therefore not currently possible to undertake an evidence-based risk assessment of whether gestational exposure to tamoxifen increases the risk of congenital malformations in the infant. Animal studies have suggested that tamoxifen exposure in utero and in the early neonatal period is associated with structural and histological changes of the female genital tract. Genital tract malformation as a consequence of altered oestrogenic signalling during embryogenesis is plausible, and in humans a small number of case reports have described abnormalities of female external genitalia following exposure in utero. There are also a number of case reports of infants with craniofacial malformations following tamoxifen exposure (although there is no discernible malformation pattern); however, there are also reports documenting numerous non-malformed
infants. The retrospective nature of these data, as well as lack of details in the reports, co-exposure to other drugs in most cases, and a likely publication bias towards adverse outcomes, means that the available information cannot be used to assign causality or assess the overall risk of malformation following gestational exposure to tamoxifen.
There are no data on which to assess risk of other outcomes, such as fetal loss, low or high birth weight, preterm delivery, neonatal complications, or neurodevelopmental impairment.
A theoretical risk of transplacental carcinogenesis (increased risk of cancer in the offspring, specifically in this case of cancers of the reproductive tract) following in utero tamoxifen exposure has been proposed but remains unproven.
The Royal College of Obstetricians and Gynaecologists (RCOG) guidelines state that tamoxifen should not be used in pregnancy. Women are advised to stop treatment three months before trying to conceive because of the long half-life of the drug. Where pregnancy has occurred in a woman with an underlying potentially life-threatening illness, maternal treatment with tamoxifen during pregnancy may occasionally be indicated. The fact that there are limited human pregnancy data for tamoxifen, together with an explanation of the risks and benefits of continuing treatment, should be explained.
Exposure to tamoxifen in pregnancy may warrant additional fetal monitoring, the need for which should be assessed on a case-by-case basis. However, other risk factors may be present in individual cases which may independently increase the risk of adverse pregnancy outcome. Clinicians are reminded of the importance of consideration of such factors when performing case-specific risk assessments.
This is a summary of the full UKTIS monograph for health care professionals and should not be used in isolation. The full UKTIS monograph and access to any hyperlinked related documents is available to NHS health care professionals who are logged in.
If you have a patient with exposure to a drug or chemical and require assistance in making a patient-specific risk assessment, please telephone UKTIS on 0344 892 0909 to discuss the case with a teratology specialist.
If you would like to report a pregnancy to UKTIS please click here to download our pregnancy reporting form. Please encourage all women to complete an online reporting form.