November 8, 2010

expert reaction to research linking use of painkillers with male reproductive disorders

The research suggested that use of painkillers such as paracetamol, aspirin and ibuprofen during pregnancy may be linked to male reproductive disorders such as undescended testicles.

Neal Patel MRPharmS, spokesperson for the Royal Pharmaceutical Society, said:

“This study adds to the body of evidence about the effect of medicines on foetal development. However, due to study limitations, further research is needed to draw firm conclusions about the effect of painkillers on male fertility. Women are already advised to avoid using medicines unless necessary during pregnancy and should get advice from their pharmacist if they have any questions about taking them. Women who are pregnant and have taken paracetamol should not panic as it is still safe for occasional use for the relief of minor symptoms such as headache.”

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

“In a study to be published in Human Reproduction, researchers suggest that the use of mild painkillers in pregnancy is associated with an increased incidence of either partly or completely undescended testes (cryptorchidism) in male babies. The authors further suggest that there is a dose-dependent effect with the use of multiple analgesics having a stronger association, as did use in the second trimester of pregnancy.

“Although this association is noteworthy given the increase in male reproductive tract disorders seen in the last few decades, 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. Undoubtedly, larger prospective data will eventually resolve the issue of whether mild analgesics in pregnancy are associated with significant male reproductive tract anomalies.”

Prof Richard Sharpe, Principle Investigator at the Medical Research Council Human Reproductive Sciences Unit, Edinburgh, and co-convenor of the Society for Endocrinology’s Endocrine Disruptors Special Interest Group, said:

“The study shows that prolonged use of common painkillers, including paracetamol, at around weeks 10-20 of pregnancy is associated with increased risk of incomplete testicular descent into the scrotum (termed cryptorchidism) if the baby is a boy. This likely results from suppression of testosterone (androgen) production by the fetal testis, as androgens play a key role in testis descent into the scrotum and, in experimental studies in rats by the authors, they showed that such suppression occurs.

“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:

a.,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).
b.,Most women in this study who used paracetamol did not have a baby boy with cryptorchidism.
c.,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!).
d.,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.”

Dr Allan Pacey, Senior Lecturer in Andrology, University of Sheffield, said:

“Scientists have been concerned for some time about chemicals that the mother may be exposed to during pregnancy having the potential to cause reproductive problems in male babies. However, there are relatively few concrete examples and much of the work to date has been theoretical. That makes these studies somewhat alarming as I doubt that anyone would have suspected that common painkillers would have these effects. It is worth noting the researchers found a significant difference when women had used painkillers for 2 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.”

Intrauterine exposure to mild analgesics is a risk factor for development of male reproductive disorders in human and rat, Møbjerg et al., published Monday 08 November 2010, in the journal Human Reproduction.