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Acetaminophen is the name adopted in the U.S. and Japan for Paracetamol. Widely used as an over-the-counter pain reliever and fever reducer, it is approved in a variety of countries under the common trade names of Tylenol and Panadol.

Acetaminophen can lower testosterone in fetal boys

Use of acetaminophen — or paracetamol — by pregnant women reduces testosterone in unborn boys. These findings help explain links between acetaminophen use in pregnancy and testicular problems in boys.

Acetaminophen/paracetamol is the primary medicine used for managing pain and fever during pregnancy. It is a widely used over-the-counter analgesic (pain reliever) and antipyretic (fever reducer). Acetaminophen is the name adopted for paracetamol in the U.S. and Japan and is approved in a variety of international countries and in English-speaking markets under the common trade names of Tylenol and Panadol.

Acetaminophen is classified as a mild analgesic. It is commonly used for the relief of headaches and other minor aches and pains and is a major ingredient in numerous cold and flu remedies. In combination with opioid analgesics, acetaminophen can also be used in the management of more severe pain such as post-surgical pain and providing palliative care in advanced cancer patients. Though acetaminophen is used to treat inflammatory pain, it is not generally classified as an NSAID because it exhibits only weak anti-inflammatory activity.

Researchers recommend that expectant mothers follow existing guidelines that the painkiller be taken at the lowest effective dose for the shortest possible time.

Testosterone, produced in the testicles, is crucial for life-long male health. Reduced exposure to testosterone in the womb has been linked to an increased risk of infertility, testicular cancer and undescended testicles.

The University of Edinburgh study tested the effect of acetaminophen on testosterone production in mice that carried grafts of human testicular tissue. These grafts have been shown to mimic how the developing human testes grow and function during pregnancy.

Scientists gave the mice a typical daily dose of acetaminophen over a period of either 24 hours or seven days. They measured the amount of testosterone produced by the human tissue graft an hour after the final dose of acetaminophen.

They found no effect on testosterone production following 24 hours of acetaminophen treatment.

But after seven days of exposure, the amount of testosterone was reduced by 45%.

The team - from the University's MRC Centre for Reproductive Health - say further research is required to establish the mechanism by which acetaminophen might have this effect.

The study is published in the journal Science Translational Medicine. It was funded by the Wellcome Trust, the British Society of Paediatric Endocrinology and Diabetes and the Medical Research Council.

From Dr Rod Mitchell, a Wellcome Trust Intermediate Clinical Research Fellow at the University of Edinburgh: "This study adds to existing evidence that prolonged use of acetaminophen in pregnancy may increase the risk of reproductive disorders in male babies.

"We would advise that pregnant women should follow current guidance that the painkiller be taken at the lowest effective dose for the shortest possible time."

Abstract
Most common male reproductive disorders are linked to lower testosterone exposure in fetal life, although the factors responsible for suppressing fetal testosterone remain largely unknown. Protracted use of acetaminophen during pregnancy is associated with increased risk of cryptorchidism in sons, but effects on fetal testosterone production have not been demonstrated. We used a validated xenograft model to expose human fetal testes to clinically relevant doses and regimens of acetaminophen. Exposure to a therapeutic dose of acetaminophen for 7 days significantly reduced plasma testosterone (45% reduction; P = 0.025) and seminal vesicle weight (a biomarker of androgen exposure; 18% reduction; P = 0.005) in castrate host mice bearing human fetal testis xenografts, whereas acetaminophen exposure for just 1 day did not alter either parameter. Plasma acetaminophen concentrations (at 1 hour after the final dose) in exposed host mice were substantially below those reported in humans after a therapeutic oral dose. Subsequent in utero exposure studies in rats indicated that the acetaminophen-induced reduction in testosterone likely results from reduced expression of key steroidogenic enzymes (Cyp11a1, Cyp17a1). Our results suggest that protracted use of acetaminophen (1 week) may suppress fetal testosterone production, which could have adverse consequences. Further studies are required to establish the dose-response and treatment-duration relationships to delineate the maximum dose and treatment period without this adverse effect.

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