Ibuprofen triggers infertility-linked testosterone problems in young men

Taking high doses of the pain reliever ibuprofen is linked to a higher risk of male infertility, according to a small clinical trial on young men.

When consumers grab a bottle of ibuprofen off the shelf of a pharmacy, supermarket or even a gas station, they'll find a long list of possible uses, including "fast and effective relief" of headaches, dental pain, backache, sprains or strains, and fever. 

Health Canada says the majority of ibuprofen products in Canada are available over-the-counter. Sold as Advil, Motrin, and in a variety of other brand and generic forms, the painkiller is commonly taken at low doses with few if any side-effects.  

On its website, Health Canada recommends that these products have a maximum recommended dose of 1,200 milligrams per day, and are to be used for seven days or less. 

Now researchers in Europe have found a reason not to be so cavailier about the pain reliever.

Dr. Bernard Jégou is a senior researcher at the French Medical Research Council or INESRM in Rennes, France, where he led the fertility study published this week in the journal Proceedings of the National Academy of Sciences.

• Research Paper in PNAS

Hormone levels tracked

Previously, scientists found that young, elite male athletes have taken ibuprofen daily for long periods. For instance, researchers said more than half of FIFA soccer players at the 2014 World Cup took a class of painkillers that includes ibuprofen. After stepping down, FIFA's former chief medical officer told the BBC that it was an "alarming trend."  

That's one reason Jégou and his team were concerned about long-term use of ibuprofen.

To investigate, they conducted an experiment in three parts:

• A clinical trial — the highest quality of medical research — on 31 healthy, young men who were randomly assigned to take 600 milligrams of ibuprofen or a sugar pill as a control twice a day. Their hormone levels were tested after two weeks and and at the end of the six-week trial.
• A study on how testes from organ donors responded to ibuprofen.
• A test tube study on cells that produce testosterone.

The researchers found the participants showed evidence of "compensated hypogonadism," meaning their testes weren't producing testosterone normally. Instead, the brain sent signals to ramp up another hormone called lutenizing hormone or LH, which created a hormonal imbalance with testosterone.

"The pituitary [in the brain] pumps as much as it can to maintain the levels of testosterone," said Jégou.

Study co-author David M. Kristensen of Copenhagen University Hospital compared it to driving a car with the hand brake on, so the engine/brain has to work harder to maintain the same speed or testosterone level. 

'Pretty concerning'

Kristensen said the fear is a man's condition could worsen and lead to problems with fatigue and erectile issues if the brain can no longer compensate. This normally occurs in elderly men.

"It was pretty concerning to see that after only 14 days of ibuprofen, suddenly men have endocrine behaviour of the testes as if they were elderly men," Kristensen said. 

In France, Jégou's team looked in detail at the whole machinery of how ibuprofen suppressed the body's hormonal machinery. He found that in testes cells, as the dose of ibuprofen increased, testosterone levels dropped. (In cells alone, there was no way to produce lutenizing hormone to compensate the way a man's body does.)

Caution on dose and duration

"One important message of course is to say that men who don't need to take this compound at high doses and for long duration, they should simply stop," suggested Jégou, who is also dean for research at France's school of public health. "The preventive effect for injury in sports etc. for ibuprofen has never been proved."

There was no evidence that low, occasional doses of ibuprofen caused any problems.

For his part, Jégou noted that he keeps ibuprofen tablets on his desk. But he's concerned about long-term use, which he said needs careful follow-up by medical professionals.  

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