Paracetamol use linked to asthma and male infertility

New evidence has emerged that the use of paracetamol and other painkillers during pregnancy may be part of the reason for the increase in male reproductive disorders in recent decades, while another study has strengthened the link between maternal paracetamol use and infant asthma.

The first study, in the journal Human Reproduction, shows that women who took a combination of more than one mild analgesic during pregnancy, or who took the painkillers during the second trimester of pregnancy, had an increased risk of giving birth to sons with undescended testicles (cryptorchidism), a condition that is known to be a risk factor for poor semen quality and testicular germ cell cancer in later life.

The European researchers who discovered the link say that women who used more than one painkiller simultaneously (e.g. paracetamol and ibuprofen) had a seven-fold increased risk of giving birth to sons with some form of cryptorchidism compared to women who took nothing. Worryingly, they add that the risk from the analgesics is markedly higher than that seen for known endocrine disrupters such as phthalates (a family of chemical compounds used in the manufacture of plastics).

The study notes that the second trimester of pregnancy appears to be a particularly sensitive time. Any analgesic use at this point in the pregnancy more than doubled the risk of cryptorchidism. Of the individual painkillers, ibuprofen and aspirin approximately quadrupled the risk of cryptorchidism, while a doubling of the risk was found for paracetamol. Simultaneous use of more than one painkiller during this period increased the risk 16-fold.

Researcher Henrik Leffers, from the Rigshospitalet in Copenhagen, explained that analgesics disrupted androgen production, leading to insufficient supplies of the male hormone testosterone during the crucial early period of gestation when the male organs were forming.

Interestingly, the researchers found that women significantly under-reported the use of painkillers because they did not consider mild painkillers to be “medication”.

“The use of mild analgesics constitutes by far the largest exposure to endocrine disruptors among pregnant women… If exposure to endocrine disruptors is the mechanism behind the increasing reproductive problems among young men in the Western World, this research suggests that particular attention should be paid to the use of mild analgesics during pregnancy, as this could be a major reason for the problems,” concluded Leffers.

The second study, which strengthens the argument for a causal link between paracetamol exposure in early life and later childhood asthma, appears in the Journal of Allergy and Clinical Immunology. The study looked for evidence of interaction between paracetamol use during pregnancy or infancy and antioxidant genes in the mother or child. Variants in such genes may influence the toxicity of paracetamol.

Participating mothers reported on their use of paracetamol during pregnancy, as well as their child’s exposure to the drug during infancy. Histories of wheezing and any asthma and allergy symptoms and diagnoses in the children were recorded, along with details of environmental exposures and family lifestyles. Between ages 7 and 8 the children had allergy skin and blood tests and lung function tests. Both mothers and children had genetic testing performed.

The researchers found evidence suggesting that the risk of childhood asthma associated with prenatal paracetamol exposure depended on which variants of various antioxidant genes were present in the mother.

In contrast, interactions between infant paracetamol use and similar gene variants in the child were not seen. “Our latest findings add further weight to the evidence implicating prenatal paracetamol exposure in the development of childhood asthma. However, ultimately a cause and effect relationship can only be confirmed through randomized clinical trials,” concluded researcher Seif Shaheen, Professor of Respiratory Epidemiology at Barts and The London School of Medicine and Dentistry.

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Sources: Journal of Allergy and Clinical Immunology, European Society of Human Reproduction and Embryology

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