Ibuprofen could increase risk of fertility issues in men

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Men who take high doses of ibuprofen for months at a time may be at greater risk of fertility issues and also other health problems, such as muscle wastage, erectile dysfunction and fatigue. Research on healthy young men who took the common painkiller for up to six weeks showed that the drug disrupted the production of male sex hormones and led to a condition normally seen in older men and smokers.

The 18 to 35-year-olds who took part in the study developed a disorder called “compensated hypogonadism” within two weeks of having 600mg of ibuprofen twice a day. The condition arises when the body has to boost levels of testosterone because normal production in the testes has fallen.

Doctors in Copenhagen who led the study said that while the disorder was mild and temporary in the volunteers, they feared it could become permanent in long-term ibuprofen users. This would lead to continuously low levels of testosterone, because the body could no longer compensate for the fall.

“Our immediate concern is for the fertility of men who use these drugs for a long time,” said David Møbjerg Kristensen at the University of Copenhagen in the report. “These compounds are good painkillers, but a certain amount of people in society use them without thinking of them as proper medicines.”

In March this year Jiři Dvořák, Fifa’s former chief medical officer, warned of an “alarming trend” among elite football players to “abuse” legal painkillers such as ibuprofen. Before he stepped down in November 2016 he asked players about their use of over-the-counter painkillers and found that nearly half of those who played in the past three World Cups took anti-inflammatory drugs, such as ibuprofen, every day.

Bernard Jégou, a senior author on the study at the French National Institute of Health and Medical Research, said he saw no problem in people taking ibuprofen to alleviate pain in the short term – for toothache, for example – but warned against taking the drug for months on end if it was not strictly necessary. “We normally see this condition in elderly men, so it raises an alarm,” Jégou said. “We are concerned about it, particularly for healthy people who don’t need to take these drugs. The risk is greater than the benefit.”

The report says the finding comes after repeated warnings from other researchers that ibuprofen can raise the risk of heart attacks in the general population and cause medical problems for pregnant women and their babies, including a more than doubling of the risk of miscarriage.

In the latest research, scientists looked at the impact of ibuprofen on 31 healthy young men over six weeks and performed further tests on cells and pieces of human testes in the lab. Ibuprofen lowered testosterone production in the tissues, but levels of the hormone remained the same in the men. This is because the pituitary gland at the base of the brain had ramped up levels of another hormone that drives the production of extra testosterone.

“In the living body the pituitary gland kicks in to compensate for this, but the brain is pushing more to get the same amount of testosterone,” Kristensen said. “If you go on and stress the pituitary gland over the long term, this state could become permanent and you develop a more serious condition.”

William Colledge, professor of reproductive physiology at the University of Cambridge, who was not involved in the research, is quoted in the report as saying: “It’s a fascinating study that suggests that men should be cautious about using high doses of ibuprofen for extended periods.” While the findings needed to be replicated in further studies, he said, a precautionary approach made sense. “Based on these data, I personally would be very reluctant to take ibuprofen for longer than the 10 days normally indicated on the packet.”

Abstract
Concern has been raised over increased male reproductive disorders in the Western world, and the disruption of male endocrinology has been suggested to play a central role. Several studies have shown that mild analgesics exposure during fetal life is associated with antiandrogenic effects and congenital malformations, but the effects on the adult man remain largely unknown. Through a clinical trial with young men exposed to ibuprofen, we show that the analgesic resulted in the clinical condition named “compensated hypogonadism,” a condition prevalent among elderly men and associated with reproductive and physical disorders. In the men, luteinizing hormone (LH) and ibuprofen plasma levels were positively correlated, and the testosterone/LH ratio decreased. Using adult testis explants exposed or not exposed to ibuprofen, we demonstrate that the endocrine capabilities from testicular Leydig and Sertoli cells, including testosterone production, were suppressed through transcriptional repression. This effect was also observed in a human steroidogenic cell line. Our data demonstrate that ibuprofen alters the endocrine system via selective transcriptional repression in the human testes, thereby inducing compensated hypogonadism.

Authors
David Møbjerg Kristensen, Christèle Desdoits-Lethimonier, Abigail L Mackey, Marlene Danner Dalgaard, Federico De Masi, Cecilie Hurup Munkbøl, Bjarne Styrishave, Jean-Philippe Antignac, Bruno Le Bizec, Christian Platel, Anders Hay-Schmidt, Tina Kold Jensen, Laurianne Lesné, Séverine Mazaud-Guittot, Karsten Kristiansen, Søren Brunak, Michael Kjaer, Anders Juul, Bernard Jégou

The Guardian report
Proceedings of the National Academy of Sciences abstract


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