Scientists Link Paracetamol Use In Early Pregnancy To Smaller Ovaries And Testes

Taking the painkiller paracetamol (acetaminophen) during pregnancy has been linked to smaller ovaries and testes in baby girls and boys.

Despite the discovery, the experts still explained that the such intake does not, however, directly affect fertility.

According to the finding, girls whose mothers took paracetamol (acetaminophen) during pregnancy had smaller ovaries at three months old, on average, than those whose mothers didn’t take the drug, according to a study of about 300 infant girls in Denmark. Infant boys whose mothers took paracetamol had smaller testes on average too, the study found.

That doesn’t prove paracetamol caused the reduction in the average size of ovaries and testes, though – this association could be a result of the conditions that led to the women taking paracetamol during pregnancy, or even due to chance alone, according to experts.

They also observed that it is neither clear whether having smaller ovaries or testes as an infant affects fertility in adulthood. However, the findings are in line with separate studies done in rats and mice, in isolated human ovaries and in human embryonic cells.

“We still recommend that pregnant women should use paracetamol with high fever or strong pain,” said Margit Bistrup Fischer at Copenhagen University Hospital–Rigshospitalet, who also pointed out that not doing so could be risky.

But most of the women in the study used paracetamol for headaches or musculoskeletal pain, rather than fevers, and could have managed their pain or discomfort in other ways, such as via rest, heat treatment or physiotherapy, says Fischer.

“We should have a dialogue about when paracetamol is actually necessary. It is still a drug and it does have side effects. Maybe it shouldn’t be the first thing that we grab when we have discomfort,” she said.

The issue is that there are almost no safe drug-based alternatives to paracetamol for pregnant women. Most other painkillers aren’t recommended because they can cause congenital conditions.

Fischer’s team recruited 685 pregnant women during their first trimester, who were asked about their use of medicines every two weeks. They had an fetal ultrasound during their third trimester, and 302 daughters were examined around three months after birth.

Those exposed to paracetamol as a fetus had, on average, 40 percent smaller ovaries by volume, 13 percent smaller uteruses by volume and 23 percent fewer ovarian follicles – the sacs that nurture immature eggs – compared with those who weren’t exposed.

Higher doses were associated with a bigger effect, says Fischer, but no women took more than the recommended daily maximum of 4000 milligrams.

The researchers also analysed data from another study on 1210 girls born in Copenhagen between 1997 and 2002, and found a link between fetal exposure to paracetamol and smaller ovaries during adolescence.

In animal studies, such effects led to reduced fertility and earlier reproductive ageing, but it isn’t clear whether this applies to people.

“We cannot say anything about the reproductive consequences for these girls,” said Fischer, adding that the effects would require long-term follow-up, which is hard to do.

The team also examined the boys who were born to the 685 women.

“We do see a difference, on average, in the boys as well. (They have a reduced testicular volume,” Fischer said.

Animal studies suggest this could affect fertility in adulthood, but again it is still unclear if this will be the case for the boys. “We can’t say anything about that because our cohort does not follow them that long,” she said.

A paper describing the findings in girls was published today. A separate paper describing the findings in boys has been accepted by the same journal, but not yet published, says Fischer.

“It is still too early to sound the alarm, and to remove this tool from the therapeutic arsenal for treating pain and fever,” said Séverine Mazaud-Guittot at the National Institute of Health and Medical Research in France, who in 2022 co-authored research showing that paracetamol impairs the development of isolated human ovaries.

But this latest study, along with one from last year showing that paracetamol affects the proliferation of human embryonic cells, suggest that the precautionary principle should be applied, especially during the first trimester, says Mazaud-Guittot.

“Raising awareness of alternative, non-pharmacological methods should help to encourage a reduction in the use of medication for the treatment of various mild pains.

“This paper would not change my practice or advice,” says Dimitrios Siassakos at University College London. The team carried out a number of different statical analyses, he says, and the more of these you do, the greater the odds of getting a statistically significant association by chance.