Paracetamol Harms Unborn Babies

Using paracetamol during pregnancy might affect the development of male babies, researchers in Edinburgh have shown.

Paracetamol is the world's most widely-used analgesic, and over two-thirds of women in western countries report using the drug at some point during pregnancy.

There is evidence, however, that the agent might be linked to male birth defects, including the conditions hypospadias, where the urethra opens in the wrong place, and cryptorchidism, when the testes do not descend correctly into the scrotum.

Critically, the incidence of both conditions, which are also linked to lower-than-normal levels of testosterone during foetal development, is increasing. The role that paracetamol might play in the process, however, wasn't understood, and there was previously no evidence linking paracetamol use and low testosterone.

Writing in Science Translational Medicine, University of Edinburgh scientist Rod Mitchell and his colleagues grafted small fragments of human foetal testis tissue into 64 castrated male rats that were then dosed with different regimens of paracetamol.

Alongside measures of testosterone concentration in the animals' bloodstreams, the team also measured the weights of the rats' seminal vesicles, which are structures that depend upon signals from testosterone to grow and remain active.

This allowed them to establish whether paracetamol exposure was affecting both testosterone levels, and the effects of testosterone on tissues that are sensitive to the hormone's actions.

After a week, rats given a large daily dose of paracetamol had seminal vesicles weighing nearly a third less than un-medicated controls. Some rats were given three smaller doses a day in order to mimic more closely the dosing regimen a person would use. These animals showed a 45% drop in testosterone and a 20% drop in the mass of their seminal vesicles.

The Edinburgh researchers also measured the levels of activity in the genes used to make testosterone in the paracetamol-exposed rats. Two genes, Cyp11a1 and Cyp17a1, were much less active than normal, accounting for the drop in testosterone, although they do not know yet how paracetamol might be producing this effect.

The findings suggest that longer-term paracetamol use in pregnancy might have implications for male babies, including an increased risk of birth defects in tissues that depend upon testosterone for their development. The Edinburgh team emphasise that the findings need to be interpreted cautiously, because they are based on a model system rather than direct measurements of human foetuses.

They also point out, reassuringly, that exposure to a single dose of paracetamol in their study, analogous to someone popping a pill for an incidental headache, did not produce any changes in the animals they tested.

According to Rod Mitchell, the results do nonetheless "support current recommendations that paracetamol should be taken for the shortest possible time and at the lowest possible dose."