Pregnant women are advised to seek medical advice if they need paracetamol for more than one day

Pregnant women are being advised to see their doctor if they need to take paracetamol for more than a day, after researchers found in an animal study that prolonged use of the analgesic reduced the production of testosterone.1

Four previous studies have linked the use of paracetamol in pregnancy with an increased risk of cryptorchidism in male babies, but a causal effect has not been shown because it is not possible to test the association in women. To overcome this, researchers from the University of Edinburgh developed an animal model using castrated mice, into which they grafted human testicular tissue. These grafts have been shown to mimic how the developing testes grow and function in pregnancy.

The researchers gave the mice a typical dose of paracetamol that a woman would take (20 mg/kg orally three times a day) for one day or seven days. In Science Translational Medicine they reported that seven days of paracetamol led to a 45% reduction in plasma testosterone (2.49 ng/ml v 1.37 ng/ml; P=0.025) and an 18% reduction in the weight of seminal vesicles (7.83 mg v 6.42 mg; P=0.005) when compared with controls.1 However, one day’s worth of paracetamol had no such effects.

Cryptorchidism affects 2-4% of baby boys, although some recent studies have put the prevalence at 6%, said Richard Sharpe, a study author and group leader of the Male Reproductive Health Research Team at the MRC Centre for Reproductive Health, University of Edinburgh. Other male reproductive disorders that are believed to be caused by low testosterone in the womb include hypospadias and, in young adulthood, low sperm counts and testicular germ cell cancer—and their incidence may be rising, he told a press briefing at the Science Media Centre in London.

A US study found that 65% of women used paracetamol at some point in their pregnancy, but the data on how long women tend to take it are unreliable. Women in the United Kingdom are currently advised to take paracetamol if they need an analgesic during pregnancy but to take it at the lowest effective dose for the shortest possible time.

Rod Mitchell, lead researcher and an honorary consultant paediatric endocrinologist and Wellcome Trust clinical fellow at the MRC Centre for Reproductive Health at Edinburgh, also spoke at the press briefing. He said, “Paracetamol is an effective analgesic, and we don’t want women to be suffering. But we also have to recognise that, in situations where paracetamol is taken without a second thought for side effects, we have to bear in mind that there are side effects.

“First, women should decide if [paracetamol] is actually necessary, and then they should follow NHS recommendations.”

Sharpe said that there was probably a critical time during pregnancy when the testes are developing and when paracetamol should be especially avoided, noting that this is probably early during they pregnancy, although he could not be certain. If a woman thought that she might need paracetamol for more than a day her GP would be able to advise on whether she should continue to take it, he said.

Commenting on the study Martin Ward Platt, of the Royal College of Paediatrics and Child Health, said, “The findings of this study send a clear message—expectant mothers should not prolong paracetamol use during pregnancy, only taking it when necessary and as per current NICE [National Institute for Health and Care Excellence] guidelines.

“However, the study specifically relates to paracetamol use over at least several days. There are times where one or two doses is needed to treat one-off episodes of fever, for example. Fever during pregnancy can be harmful to the developing embryo, with links to a significant increase in the rates of spina bifida and heart malformations, so small doses of paracetamol are sometimes necessary.

“My message to expectant mothers is clear—avoid overuse of paracetamol, but if you do have a fever, or any other sort of pain where you would normally use paracetamol, seek medical advice.”

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