Taking mild painkilllers such as aspirin, acetaminophen and ibuprofen during pregnancy, especially during the second trimester, can cause a sharp increase in reproductive problems in male offspring, researchers from Denmark, Finland and France reported Monday. The team found that women who used two of the drugs simultaneously during the second trimester were as much as 16 times as likely to bear a son with undescended testicles, a condition known as cryptorchidism. Cryptorchidism is known to be a risk factor for poor semen quality and testicular germ cell cancer in later life. The researchers demonstrated in rats that the drugs block the production of testosterone, which is necessary for the formation of male sex organs.

Reproductive biologist Henrik Lefferts of the University of Copenhagen and his colleagues questioned 834 pregnant women in Denmark and 1,463 in Finland about their medication use, then examined their sons at birth. The Danish women received only a written questionnaire, while the Finnish women received both a written questionnaire and a phone interview. The women were more likely to say they had taken the painkillers in the phone interview, apparently not considering them to really be “medications.”

The team found that women who used more than one painkiller simultaneously had a seven-fold increase in risk of having a son with cryporchidism compared with women who took nothing. The second trimester appeared to be particularly sensitive. Any painkiller use during this period doubled the risk of cryptorchidism. Ibuprofen or aspirin quadrupled the risk, while acetaminophen doubled the risk. Using more than one painkiller simultaneously led to a 16-fold increase in risk. Overall, the researchers said, the incidence of cryptorchidism in Denmark during the study was 8.5%, compared with 1.8% in a similar study in 1959 to 1961. “Moreover, this finding is in accordance with the reported decline in reproductive health in the adult male population in the last five decades,” they wrote in their report in the journal Human Reproduction.

As part of the same study, biologist Ulla Hass of the Technical University of Denmark in Soborg and Bernard Jegou of the University of Rennes in France found that the analgesics disrupted the production of androgenic hormones in rats, leading to an insufficient supply of the male hormone testosterone during the crucial early period of gestation when the male organs were forming. The effects were comparable to that caused by similar doses of known endocrine disruptors such as phthalates, whch are used in the manufacture of plastics like PVCs.


In a statement, Lefferts said that, “Women may want to try to reduce their analgesic use during pregnancy. However, as biologists, this is not something we can advise women about. So we recommend that pregnant women seek advice from their physician before using mild analgesics and in general follow the advice to use as little medicine during pregnancy as possible.”