May 20, 2015

expert reaction to paper on effects of paracetamol use in pregnancy on foetal testosterone

In a study published in the journal Science Translational Medicine, scientists have used a mouse model to look at possible effects of paracetamol on levels of testosterone in foetuses. Testosterone is important for male foetus development, and the researchers report that in the mouse model, exposure to paracetamol for seven days could lower testosterone production by 45%.

Dr Christoph Lees, Clinical Reader in Obstetrics, Imperial College London, and Head of Fetal Medicine, Imperial College NHS Trust said:

“This is an important and carefully conducted study performed in mice with grafted human second trimester fetal testicular tissue. It examines a potential mechanistic link between acetaminophen (known in the UK as paracetamol) and inhibited fetal testicular development. The blood levels of paracetamol in the experiments were not higher than those expected in normal human use’

“The results suggest that prolonged paracetamol exposure in pregnancy could affect testicular development. Short term exposure to paracetamol had no effect. This is not new in itself, as the authors point out. Several recent human epidemiological studies have suggested a link between the use of analgesics and particularly paracetamol and abnormalities of testicular development. But what we see here is the possible link between paracetamol levels and a reduced production of androgen hormones which are responsible for testicular development’.

“This study by itself should not lead to an immediate change in prescribing practice. It is quite unusual for women to require protracted paracetamol in pregnancy and the evidence is that it is quite safe in short term usage. However, it will be for regulatory authorities to consider the evidence from this study and others in relation to longer duration paracetamol use especially after the first trimester of pregnancy. It raises the interesting question, as the possible adverse effects are as far as we know limited to testicular development, as to whether advice on prescribing should differentiate between mothers carrying boys and girls”

Prof. Adam Balen, Chair of The British Fertility Society & Professor of Reproductive Medicine and Surgery, Leeds Teaching Hospitals, said:

“This is a robust piece of research but it is always difficult to extrapolate exactly from an animal model to pregnant women, as the authors state themselves.

“The mechanism by which paracetamol lowers testosterone levels may be by affecting steroidogenic enzymes in the testis, thereby increasing the risk for  congenital abnormalities (cryptorchidism and hypospadias) which then may have long term implications for fertility. In recent times there have been a number of reports suggesting that male infertility is on the increase as a result of falling sperm counts.  This study is therefore highly relevant, however we have to be cautious when interpreting these findings and it is probably too early to say whether advice to pregnant women on paracetamol should be changed. Nonetheless pregnant women should only take medication during pregnancy if absolutely necessary and should always check with their doctor if they have any concerns.”

Dr Sadaf Ghaem-Maghami, Chair of the Royal College of Obstetricians and Gynaecologists (RCOG) Scientific Advisory Committee, said:

“Paracetamol is one of the most common medicines used to reduce a high temperature and ease pain and is used routinely during all stages of pregnancy.

“This is a robust piece of research, however, it is important to note that the study was carried out in animal models and it is not possible to translate the findings into a recommendation regarding what would be safe or unsafe in pregnant women. Additionally, the mice were not pregnant but in a ‘pregnancy state’ which was induced by a hormone and human fetal testicular tissue which was grafted onto them.

“Further research needs to be conducted into how paracetamol may affect testosterone levels as well as examining the long term developmental effects on testosterone production.

“We recommend that pregnant women continue to follow current guidance and take the lowest effective dose for the shortest possible time when necessary. If the recommended dose of paracetamol doesn’t control your symptoms or pain, please seek advice from your midwife, GP or obstetrician.”

‘Prolonged exposure to acetaminophen reduces testosterone production by the human fetal testis in a xenograft model’ by Driesche et al. published in Science Translational Medicine on Wednesday 20th May. 

Declared interests

Dr Christoph Lees, Prof. Adam Balen and Dr Sadaf Ghaem-Maghami have no interests to declare.