Could mild painkillers, taken by women during pregnancy, be linked to male fertility problems?
The question is raised by a new study which suggests that these over-the-counter analgesics may be a greater risk than hormone-disrupting chemicals and plastics that are most blamed for causing reproductive problems in later life.
Researchers pored over data from 834 women in Denmark and 1,463 in Finland who were questioned during their pregnancy about their health and use of medication.
They found nothing that was statistically interesting in the Finnish group, but in the Danish group, two startling phenomena emerged.
Women who took a combination of one or more painkiller - such as aspirin and paracetamol together - during pregnancy had a seven-fold increased risk of giving birth to sons with undescended testicles.
This condition, known as cryptorchidism, is a risk factor in poor semen quality and a form of testicular cancer in later life.
In addition, those who took any analgesic during the second trimester of pregnancy more than doubled the risk of cryptorchidism for their child.
"We do not quite understand why the Finnish cohort (group) does not show the same associations as the Danish cohort," said Henrik Leffers, senior scientist at Rigshospitalet in Copenhagen, who led the research.
"However, the use of mild analgesics in the Finnish cohort was only examined by questionnaires, not by telephone interviews, and the telephone interviews gave the most reliable information in the Danish cohort, which may explain some of the differences."
Incidence of cryptorchidism in Denmark is nearly four times higher than in Finland, having surged almost fivefold between 1960 and 2001.
"The magnitude of this difference is too large to be accounted for by random fluctuations and differences in ascertainment," according to the paper, published in the European journal Human Reproduction late Monday.
"Moreover, this finding is in accordance with the reported decline in reproductive health in the adult male population over the past five decades."
Furthering the research, investigators in France carried out tests on lab rats.
They found that exposure to paracetamol reduced levels of testosterone in the uterus and reduced the distance between the offspring's anus and genitals - a key marker of reproductive flaws in the adult.
Leffers cautioned that further investigation was needed.
But, he said, the evidence was that a painkiller exposed the foetus to a bigger one-shot of endocrine disruptors than phthalates and other environmental sources of these hormone-interfering compounds.
"A single, 500mg paracetamol tablet contains more endocrine disruptor potency than the combined exposure to the 10 most prevalent of the currently known environmental endocrine disruptors during the whole pregnancy," Leffers said.
"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."
He urged women to restrict their use of painkillers as far as possible during pregnancy and seek advice from their doctor.