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Study Suggests Prolonged Acetaminophen Use in Pregnancy Could Affect Boys' Fertility

May 27, 2015

New research from the University of Edinburgh suggests that long-term exposure to acetaminophen during pregnancy could lower a boy’s production of testosterone, possibly affecting his fertility.

The findings suggest that if a pregnant woman takes acetaminophen for several days it could affect her unborn boy, lowering his future sperm count, Medical News Today (MNT) reports. Acetaminophen is an over-the-counter pain-reliever and fever-reducing drug available under brand names including Tylenol.

The authors of the study explain that the risks of low testosterone in developing male fetuses include disorders seen at birth, such as an undescended testis (cryptorchidism) and hypospadias, a urethral malformation in which the urine outlet is not in the normal position at the end of the penis. Low sperm counts and testicular germ cell cancer can appear in young adulthood, according to MNT.

One of the study’s authors, pediatric endocrinologist Dr. Rod Mitchell, a Wellcome Trust clinical research fellow at the University of Edinburgh, says, "This study adds to existing evidence that prolonged use of acetaminophen in pregnancy may increase the risk of reproductive disorders in male babies." Mitchell’s advice to pregnant women is that if acetaminophen is needed, it should "be taken at the lowest effective dose for the shortest possible time."

Dr. Sander van den Driesche and colleagues at the MRC Centre for Reproductive Health at the University of Edinburgh conducted the study, which was published in Science Translational Medicine, a journal of the American Association for the Advancement of Science. To examine the effects of acetaminophen on testosterone production, the researchers grafted fragments of human fetal testes into castrated mice. This technique— xenograft—helped the researchers avoid the problems they would encounter in trying to measure testosterone production in unborn boys. The authors say their model "reflects physiological development and can be used to test the effects of chemical exposures on testosterone production," according to MNT.

Three times a day for seven days, the grafted mice received an acetaminophen dose equivalent to a human dose of 20 mg per kg of bodyweight. The researchers found that testosterone levels in the blood dropped by 45 percent and the weight of the seminal vesicle glands fell by 18 percent. Seminal vesicles secrete the large part of the semen fluid, and the researchers used the weight of the vesicles as a biomarker of exposure to testosterone. They compared these results with mice receiving no acetaminophen in a placebo. Exposure to acetaminophen for a single day did not affect the measures of testosterone production.

The researchers say that while it is too early to say exactly how these findings should affect pregnant women’s use of acetaminophen, they do advocate caution and they say further research is needed to understand how acetaminophen affects testosterone production in male fetuses. Dr. Martin Ward-Platt, of the Royal College of Paediatrics and Child Health, says pregnant women should avoid prolonged acetaminophen use and "should always consult with their health care professional before taking any prescription or over-the-counter medicine." But, Dr. Ward-Platt notes, fever during pregnancy can be harmful to the developing embryo so small doses of acetaminophen are sometimes necessary, MNT reports.

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