Acetaminophen May Harm Male Fetuses

By Pat Anson, Editor

The pain reliever acetaminophen may inhibit the sexual development of male babies whose mothers take the over-the-counter drug while pregnant, according to a new study by Danish researchers. The study only involved laboratory rodents, but one researcher called the findings “very worrying” and said pregnant women should think carefully before using the painkiller.

Acetaminophen – which is more commonly known as paracetamol outside the U.S. -- is used by over half the pregnant women in the United States and European Union. It is the active ingredient in Tylenol, Excedrin, and hundreds of pain medications.

Previous research has already indicated that acetaminophen can suppress the development testosterone in male fetuses. It has also been linked to autism and attention deficit problems in young children.

The new study, published in the journal Reproduction, involved mouse fetuses that were exposed to acetaminophen at varying doses. The dose that produced the most effect was three times higher than the maximum recommended daily dose in humans.

Researchers evaluated the male rodents' behavior after their birth, studying their aggressiveness toward other male mice, their ability to mark their territory, and their ability to mate. They were found wanting in all three areas.

The abnormal behavior was apparently caused by lower levels of testosterone, the male sex hormone that fuels the development and programming of the male body and brain. Testosterone also controls sex drive and the production of sperm.

"We have demonstrated that a reduced level of testosterone means that male characteristics do not develop as they should. This also affects sex drive," said Dr. David Møbjerg Kristensen of the Department of Biomedical Sciences at the University of Copenhagen. "Mice exposed to paracetamol at the fetal stage were simply unable to copulate in the same way as our control animals. Male programming had not been properly established during their fetal development, and this could be seen long afterwards in their adult life. It is very worrying."

When the brains of the mice exposed to acetaminophen were analyzed, researchers found significantly fewer neurons in the brain region that controls sex drive.

“These findings add to the growing body of evidence suggesting the need to limit the widespread exposure and use of APAP (acetaminophen) by pregnant women,” said Kristensen.

A study published last year in JAMA Pediatrics  linked prenatal use of acetaminophen to a higher risk of behavior problems, hyperactivity and emotional problems in children. The pain reliever has also long been associated with liver injury and allergic reactions such as skin rash.

The FDA label for products containing acetaminophen warns about the risk of liver damage and other side effects, but does not specifically warn pregnant women about using the pain reliever. The agency said in 2015 that the evidence was “too limited” to justify such a warning.  

In its 2016 opioid prescribing guidelines, the CDC recommends acetaminophen as an alternative to opioid pain medication. The guideline only briefly mentions that acetaminophen was involved in nearly 900 overdose deaths in 2010 and can cause liver problems. The guideline does warn pregnant women -- at length -- that opioids can cause birth defects, poor fetal growth, still births and neonatal opioid withdrawal syndrome.