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Painkillers, pregnancy and male reproductive problems

Fergus Walsh | 15:35 UK time, Monday, 8 November 2010

The use of painkillers such as ibuprofen, aspirin and paracetamol during pregnancy could be linked to male reproductive disorders according to new research. A study in the journal Human Reproduction (opens pdf) found that women who took more than one painkiller at the same time during pregnancy, or who took the drugs during the second trimester, were at increased risk of giving birth to boys with undescended testicles.

The condition, known as cryptorchidism, affects about one in 20 boys in the UK. It is known to be a risk factor for male fertility problems later in life and an increased risk of testicular cancer.

1,463 pregnant women in Finland completed written questionnaires and 834 women in Denmark did the same or took part in a telephone interview. The researchers found that women significantly under-reported the use of painkillers in the written questionnaire because they did not consider mild painkillers to be "medication".

The study showed that women who used more than one painkiller simultaneously (such as paracetamol and ibuprofen) had a seven-fold increased risk of giving birth to sons with some form of undescended testes compared to women who did not take the drugs.

The second trimester appeared to be a particularly sensitive time. Any analgesic use at this point more than doubled the risk of the condition. Simultaneous use of more than one painkiller during this time appeared to increase the risk 16-fold.

The scientists behind the research believe painkillers may be part of the reason for the increase in male reproductive disorders in recent decades, possible by interfering with the role of the male hormone testosterone. Research carried out on rats in Denmark and France found that painkillers disrupted androgen production, leading to insufficient supplies of testosterone during the crucial early period of gestation when the male organs were forming. The effects of the painkillers on the rats was comparable to that caused by similar doses of known endocrine (hormone) disrupters such as phthalates - a family of chemical compounds used in the manufacture of plastics such as PVC.

Dr Henrik Leffers, senior scientist at Righospitalet in Copenhagen, who led the research, said: "If exposure to endocrine disruptors is the mechanisms 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".

But the study is not without limitations. The researchers could not find a statistically significant effect among the Finnish women, which was the larger group, but did find significant effects among the Danish women.

Dr Leffers said: "We do not quite understand why the Finnish cohort does not show the same associations as the Danish cohort." However, he said the telephone interviews used in Denmark gave the "most reliable information" and this may explain some of the differences. He added: "The prevalence of cryptorchidism is much lower in Finland (2.4%) compared to Denmark (9.3%) and, therefore, this would require a larger cohort to find the same number of cases."

Pregnant women in the UK are already advised to avoid taking ibuprofen or aspirin, unless they are advised to do so by their doctor.

Instead they are told they can take paracetamol. The NHS Choices website puts it like this:

Paracetamol has been used routinely through all stages of pregnancy to reduce a high temperature (fever) and relieve pain. There is no clear evidence that paracetamol has any harmful effects on the baby.

As with any medicine that is used during pregnancy, paracetamol should be taken at the lowest effective dose for the shortest possible time.

This raises a further concern with the research. Of the individual painkillers, ibuprofen and aspirin approximately quadrupled the risk of cryptorchidism. Paracetamol doubled the risk, but this was not statistically significant. This suggests that a link between paracetamol use alone in pregnancy and male fertility problems is not clear-cut.

Dr Leffers said: "Although we should be cautious about any over-extrapolation or over-statement, the use of mild analgesics constitutes by far the largest exposure to endocrine disruptors among pregnant women."

Prof Richard Sharpe of the Medical Research Council's Human Reproductive Sciences Unit at the University of Edinburgh, said:

"The studies are top quality from groups with considerable expertise. The association between painkiller (paracetamol) use in early pregnancy and increased risk of cryptorchidism in sons has been independently confirmed in another study from Denmark (MS Jensen et al. November 2010, Epidemiology). Painkillers/paracetamol are likely to be one of several factors that cause cryptorchidism - some environmental chemicals are also implicated - it is probably the sum of all such exposures that determines the outcome.

Pregnant women who are alarmed by these studies should note the following:

It is only prolonged use that has an effect - taking occasional painkiller for a headache will have no adverse effect (and the stress, worry and sickness from not taking something for a bad headache may be worse for the mother and baby).

Most women in this study who used paracetamol did not have a baby boy with cryptorchidism.

Prolonged use of painkillers in pregnancy should not be contemplated without medical approval. For certain, taking paracetamol as a 'feel good' factor should be avoided (by all of us!).

It is sound common sense to minimize your exposure (and therefore your baby's exposure) to all drugs, environmental (pesticides, paints, household chemical exposures) and lifestyle (smoking, alcohol, cosmetics usage) chemicals during pregnancy wherever possible."

Update at 17:00

Basky Thilaganathan, Spokesperson for the Royal College of Obstetricians and Gynaecologists, said:

"The findings need to be interpreted with caution. Firstly, the study shows an association rather than causation; it is entirely possible that mothers took these analgesics for an ailment (for example, a viral infection) in pregnancy that may have been the real cause for the noted problems. Secondly, the dose-dependent effect was seen in one study cohort but not another, raising the possibility that this preliminary study may be prone to inadvertent bias of patient recruitment and ascertainment. Furthermore, the definition of cryptorchidism is broad and clinical, rather than specific and the overall number of cases is so small that a small change in affected numbers would have nullified the findings.

"Given these limitations, the findings of the study should be interpreted with caution and it would be inappropriate to spread alarm to pregnant women on this basis."


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