The use of mild painkillers, such as paracetamol, in pregnancy — previously considered harmless to the baby in the womb — could be a major factor in the rise of male reproductive disorders, according to a study.
Scientists in Denmark, Finland and France found that women who took mild painkillers during pregnancy — such as paracetamol, ibuprofen or aspirin — ran seven times the risk of having a son with undescended testicles (cryptorchidism), a condition that can affect their fertility in later life.
The effect in the second trimester of pregnancy was most marked. The use of any painkiller during the second trimester more than doubled the risk of the condition in a boy baby. The use of ibuprofen or aspirin appeared to quadruple the risk. Taking more than one type of painkiller increased the risk 16-fold.
The work sheds new light on a condition previously blamed on environmental pollution. A general decline in male fertility has been linked to chemicals called endocrine disruptors in the environment, including phthalates, which are used in the manufacture of plastics.
Research in rats by the same scientists showed that painkillers such as paracetamol, ibuprofen and aspirin are also endocrine disruptors. They limit male hormone production, leading to insufficient supplies of the male hormone testosterone during the crucial early period of gestation when the male organs are forming.
The risks of simple painkillers
The research, published in the journal Human Reproduction, is likely to lead to calls for women to be warned about the potential risks of simple painkillers in pregnancy.
“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 it could be a major reason for the problems,” said Dr Henrik Leffers, a senior scientist at Rigshospitalet in Copenhagen, who led the research.
“A single paracetamol tablet [500mg] contains more endocrine disruptor potency than combined exposure to the 10 most prevalent of the currently known environmental endocrine disruptors during the entire pregnancy.
“In fact, a single tablet will, for most women, be at least a doubling of the exposure to the known endocrine disruptors during the pregnancy and that dose comes on a single day, not spread out over nine months as with the environmental endocrine disruptors. Thus, for women using mild analgesics during the pregnancy, the mild analgesics will be by far the largest exposure to endocrine disruptors.”
Information gathering
The researchers investigated the use of painkillers among two groups of pregnant women: 834 in Denmark and 1 463 in Finland. Boys were examined after birth for any signs of cryptorchidism.
Telephonic interviews found that women significantly under-reported their use of painkillers in written questionnaires. Among 298 Danish mothers, 30.9% said they used painkillers when they filled in a questionnaire, but 57.2% reported using them when asked in a telephone interview.
They explained that they had not considered the tablets to be “medication”.
The adverse effects of the painkillers showed up in the Danish women, but not in a statistically significant way among the Finnish group. The scientists said they did not understand the disparity.
“However, the use of mild analgesics in the Finnish cohort was examined only by questionnaire, not by telephone interview and the telephone interviews gave the most reliable information in the Danish cohort, which may explain some of the differences,” said Leffers.
“Moreover, the prevalence of cryptorchidism is much lower in Finland (2.4%) compared with Denmark (9.3%) and, therefore, this would require a larger cohort to find the same number of cases.”
Dr Allan Pacey, a senior lecturer in andrology at the University of Sheffield, said scientists had been concerned for some time that chemicals mothers may be exposed to during pregnancy could cause reproductive problems in male babies.
“That makes these studies somewhat alarming as I doubt that anyone would have suspected that common painkillers would have these effects,” he said.
“It is worth noting the researchers found a significant difference when women had used painkillers for two weeks or more and that the impact was greatest when taking them during their second trimester. Clearly further research is needed as a matter of priority.”–