6 ms·

Ibuprofen alters human testicular physiology including testosterone production

185 points by inglondon 9y ago

deftnerd 9y ago
I've been paying attention to the lowering fertility rate across the world. My instinct, until now, was that it was because of fire retardant chemicals found in furniture that act as an endocrine disruptor. It didn't totally fit though so I felt like there was something else that was a major contributor. Ibuprofen being a cause of lower sperm counts could be the missing piece of the puzzle. It's also a big deal because Tylenol has been pushed aside for the last 20 years as being more unsafe for children than Ibuprofen.
- bonzini 9y ago
  At least in Italy, children are almost exclusively given paracetamol (Tylenol) to lower temperature. Ibuprofen is only used as an anti-inflammatory drug, for example if they have faryngitis
  - Tharkun 9y ago
    Paracetamol comes with its own set of problems. It's somewhat dangerous to people with a variety of liver conditions.
    - pilsetnieks 9y ago
      In large enough doses it is dangerous to everyone. The problem is that the large enough dose is much smaller than other OTC drugs.
- kalleboo 9y ago
  Are there any good numbers on the fertility among people who actually WANT to conceive, rather than the raw total population rates (which is affected by people who don't want kids - prevented through birth control and abortions)
  - deftnerd 9y ago
    "One 2012 report, which presented the results of the study of over 26,000 French men, showed that the sperm count had fallen by a third between 1989 and 2005. A 2007 report in the UK presented the results of a study done on one city in the country. It showed that sperm counts had declined by over 29 percent between 1989 and 2002. And more recently, in the summer of 2017, a study by scientists at the Hebrew University of Jerusalem analyzed data from over 43,000 North American, European, Australian, and New Zealand men concluded that the average sperm count had fallen by almost 60 percent in the past 40 years. " From an article at https://www.inquisitr.com/4757173/the-human-race-could-be-infertile-in-50-years-researcher-claims/ https://www.inquisitr.com/4757173/the-human-race-could-be-in... dated just a few days ago
    - scott_karana 9y ago
      Not what GP was asking. Desire might not even correlate with sperm count! Maybe decreased desire even leads to count and motility decreases?
- farnsworthy 9y ago
  Funny to see this now, as I was thinking a little while ago of the break-in period for a new mattress I owned, where I dealt with a sore throat or asthma-like condition for a week before realizing the probable cause, after doing some reading about many with similar problems. (I closed off the bedroom with the windows open during that winter period and slept elsewhere for a little while after that.) To me it's emblematic of the Safety State: a (relative) few die from mattress fires, so now everybody is gassed with possible or probable toxins in hyper-response. PSA: Careful of those new mattresses…
- pilsetnieks 9y ago
  My money would be on increasing levels of education and healthcare instead of fire retardant chemicals and ibuprofen.
  - fiblye 9y ago
    How exactly would education affect the testicles?
    - pilsetnieks 9y ago
      He started by talking about global fertility rates. He then mentions lower sperm counts but it's not a given that one is solely or mostly because of the other. Fertility rates are expressed in children per woman, not sperm count. A large drop in global fertility rates is attributable to lower infant mortality, better access to healthcare, contraception, and education about using it. Also, as levels of education in general rise, people tend to have fewer children.
- snarfy 9y ago
  I doubt there is one smoking gun. It's a basket of causes. Too much exposure to weird chemicals, ibuprofen, not enough zinc, obesity, lack of exercise, etc are all causes.
  - zamber 9y ago
    Death by 1000 papercuts. My point here is that it's possible that there are many circumstances accumulating but that doesn't discredit efforts for finding the biggest contributors. You can easily smuggle a couple of razors between the paper sheets.
- gaius 9y ago
  My instinct, until now, was that it was because of fire retardant chemicals found in furniture that act as an endocrine disrupto What are your thoughts on synthetic hormones, e.g. used in farming or in contraception? Those enter the water supply and are not broken down.
raverbashing 9y ago
While the results do matter, this is probably being blown out of proportion > One group of subjects received ibuprofen, 2 × 600 mg/d, (Ibumetin; Nycomed Denmark Aps) for a period of 6 wk Yeah, that's a lot of Ibuprofen for a long time
- TheSpiceIsLife 9y ago
  Have you seen how some people gobble this stuff? I've felt compelled to say to more than one person: probably shouldn't take that much ...
  - SwellJoe 9y ago
    Sometimes pain management is a balancing act between dangerous side effects and misery that makes it hard to want to keep living. Chronic pain isn't really something a third party can make decisions about; it may be that ibuprofen isn't the right choice, but lots of other choices (opiates, for instance) may have even more negative effects (like addiction and risk of deadly overdose). Of course, there are folks who take over-the-counter meds as though it is safe at any dose and frequency. That might warrant a nudge toward reading the label about safe dosage, or a mention of a recent study on the subject.
    - tinbucket 9y ago
      Exactly this. I have a chronic wrist injury from a previous job. Physiotherapy hasn't really helped, and the only thing that does help when I have a bad day is naproxen (another NSAID in the same class as ibuprofen). I feel guilty taking it in the dose I do (1000mg/day) but it's the only thing that makes life bearable and makes me functional.
- rdl 9y ago
  I've known plenty of people who do 400mg 2-3x/day for weeks/months.
  - gadders 9y ago
reallymental 9y ago
I read the paper, I saw the plots accompanying the paper, and I tried following the rabbit hole in search of some raw data that I can get my hands on, just to see if I can. Perhaps the data is the result of the experiments that have been paid for by a third party, fine, but please mention that! People might be willing to pay for it, for example, me! What's wrong with "Here's the raw data, here's how we measured it, Here's how we've shown the data, and look you can see for yourself that we are right! oh and the data costs $$$ much." ? I understand experiment reproducibility is not incentivised in academia, but then why make it hard for an external party to reproduce it/study it? Do we have to go through the usual "Contact the academic, maybe they answer, and maybe you'll get the same (version of) data that they used in that experiment, maybe you'll have to go through Elsevier, oh and you must have .edu/.ac.uk address to be taken seriously through all those requests." What a chore. Just adds to the hate towards 'experts' and their opinions.
- Gatsky 9y ago
  Blame the journal. Scientists are generally pretty busy. Writing a (life sciences) paper is an incredible amount of work usually done in a short period of time. Preparing raw data and explaining what everything means is quite involved. If they don't have to do something they won't. The journal should mandate data access, then it will get done. This is crucial for human experiments, if only because the authors can lose the data and it will be gone forever.
  - stinos 9y ago
    As far as I know this is slowly changing. According to scientists I've met (life science fields) there is an ongoing trend towards demanding raw data and even the code used to analyze it. Not every journal everywhere yet of course, but the consensus seemed to be that in 5 to 10 years it would become the new norm. Which might cause quite the disruption. Having seen quite the amounts of code written by PHD students I'm 100% sure tere are many, many bugs out there. Possibly leading to faulty results.
    - c12 9y ago
tejasmanohar 9y ago
This was discussed ~3 weeks ago. Here's the thread-- https://news.ycombinator.com/item?id=16101072 https://news.ycombinator.com/item?id=16101072
- no_identd 9y ago
  A note about one of the comments there related to Aspirin, namely, this one: https://news.ycombinator.com/item?id=16102328 https://news.ycombinator.com/item?id=16102328 There's an alternative solution for the stomach lining issue: https://en.wikipedia.org/wiki/Carbasalate_calcium https://en.wikipedia.org/wiki/Carbasalate_calcium Which reminds me, this testicle study seems to fail to distinguish Dex(tro)ibuprofen from Levoibuprofen. That seems rather disappointing, as we've known about the difference between the two for quite a while. This continued ignorance of medical science when it comes to (stereo)isomers never ceases to amaze me. I mean... You'd think they'd have learned their lessons by now. (Then again, we also still fail to employ multi-compartment models of pharmacology in the vast majority of studies. And... ugh. I'll avoid ranting on how shitty medical science seems to me and just leave it at this.) [btw., if you wonder why you can't get your hands on Dexibuprofen in the US: "Open committee discussion. The committees will discuss new drug application (NDA) 20–373, S+ Ibuprofen (dexibuprofen, Sterling Winthrop/ Bayer) 200-milligram caplet, indicated for the temporary relief of minor aches and pains associated with the common cold, headache, toothache, muscular aches, back ache, menstrual cramps, minor pain of arthritis, and for the temporary reduction of fever for OTC status." From the Federal Register, from 1996. It never got approved, and one can't even find the application on the FDA page, thus one can't find out more about why it never made it to market!]
amelius 9y ago
Is this a permanent effect, or does T production return to normal after stopping the drug?
- erokar 9y ago
  > For the small group of young study participants who used ibuprofen for only a short time, “it is sure that these effects are reversible,” Jégou said. However, it’s unknown whether the health effects of long-term ibuprofen use are reversible, he said. http://wgntv.com/2018/01/08/ibuprofen-linked-to-male-infertility-study-says/ http://wgntv.com/2018/01/08/ibuprofen-linked-to-male-inferti...
  - amelius 9y ago
    > For the small group of young study participants who used ibuprofen for only a short time, “it is sure that these effects are reversible,” Jégou said. That could be true, but of course, there's some self-interest in that statement. Bringing long-term harm to your study participants is not exactly a good move for a medical researcher.
mdomans 9y ago
This isn't really huge news, technically speaking. Any anti-inflammatory drug will have negative net impact on your body function. For a while we know now that NSAIDs alter ROS levels in response to injury and in fact any normal process. NSAIDs also have negative impact on training adaptation or cell death due to overexpression of ROS. So no - taking overabundant levels of oral NSAIDs isn't going to be good for you and that's why topical NSAIDs make sense in cases of joint pain, tough they're not as convenient. Note: I remember taurine had protective effect on testicular function in men treated in 19-nor derivatives. Maybe worth checking out if it does so also for ibuprofen :)
- joezydeco 9y ago
  The energy drink makers have been trying to defend the use of taurine in their ingredients for a long time. This looks like a golden opportunity for them....
  - mdomans 9y ago
    Probably, not so much. The amounts of ingredients and composition of ingredients in energy drinks are just stupid. I see now a trend of "health" drinks that actually seem sensible, though a bit more pricey. Like magnesium, ginseng and vitamins. The problem with energy drinks is that they're alike to a bottle of all things that may be fuel, combined. I've seen recently a tin of Monster that had 0.5g of caffeine. That's insane. And caffeine pills are even more insane. You can drop 1g of caffeine like it's M&Ms. At this rate we're going to have coke and amphetamine in those next year. And, you know, you can go on a limb and say that some of the modified amphetamines or phenidatess or what not maybe should be on the market. In Canada they have effedrine in OTC supplements and people don't die from overdose. But the thing is, we either demonise or just assume something is safe. How many people knows that acetaminophen (APAP, paracetamol) is liver toxic? And how many people knows that NAC is the antidote (N-acetylo-cysteine, popular OTC expectorant)?

185 points by inglondon 9y ago

I've been paying attention to the lowering fertility rate across the world. My instinct, until now, was that it was because of fire retardant chemicals found in furniture that act as an endocrine disruptor. It didn't totally fit though so I felt like there was something else that was a major contributor. Ibuprofen being a cause of lower sperm counts could be the missing piece of the puzzle. It's also a big deal because Tylenol has been pushed aside for the last 20 years as being more unsafe for children than Ibuprofen.

bonzini 9y ago
At least in Italy, children are almost exclusively given paracetamol (Tylenol) to lower temperature. Ibuprofen is only used as an anti-inflammatory drug, for example if they have faryngitis
- Tharkun 9y ago
  Paracetamol comes with its own set of problems. It's somewhat dangerous to people with a variety of liver conditions.
  - pilsetnieks 9y ago
    In large enough doses it is dangerous to everyone. The problem is that the large enough dose is much smaller than other OTC drugs.
kalleboo 9y ago
Are there any good numbers on the fertility among people who actually WANT to conceive, rather than the raw total population rates (which is affected by people who don't want kids - prevented through birth control and abortions)
- deftnerd 9y ago
  "One 2012 report, which presented the results of the study of over 26,000 French men, showed that the sperm count had fallen by a third between 1989 and 2005. A 2007 report in the UK presented the results of a study done on one city in the country. It showed that sperm counts had declined by over 29 percent between 1989 and 2002. And more recently, in the summer of 2017, a study by scientists at the Hebrew University of Jerusalem analyzed data from over 43,000 North American, European, Australian, and New Zealand men concluded that the average sperm count had fallen by almost 60 percent in the past 40 years. " From an article at https://www.inquisitr.com/4757173/the-human-race-could-be-infertile-in-50-years-researcher-claims/ https://www.inquisitr.com/4757173/the-human-race-could-be-in... dated just a few days ago
  - scott_karana 9y ago
    Not what GP was asking. Desire might not even correlate with sperm count! Maybe decreased desire even leads to count and motility decreases?
farnsworthy 9y ago
Funny to see this now, as I was thinking a little while ago of the break-in period for a new mattress I owned, where I dealt with a sore throat or asthma-like condition for a week before realizing the probable cause, after doing some reading about many with similar problems. (I closed off the bedroom with the windows open during that winter period and slept elsewhere for a little while after that.) To me it's emblematic of the Safety State: a (relative) few die from mattress fires, so now everybody is gassed with possible or probable toxins in hyper-response. PSA: Careful of those new mattresses…
pilsetnieks 9y ago
My money would be on increasing levels of education and healthcare instead of fire retardant chemicals and ibuprofen.
- fiblye 9y ago
  How exactly would education affect the testicles?
  - pilsetnieks 9y ago
    He started by talking about global fertility rates. He then mentions lower sperm counts but it's not a given that one is solely or mostly because of the other. Fertility rates are expressed in children per woman, not sperm count. A large drop in global fertility rates is attributable to lower infant mortality, better access to healthcare, contraception, and education about using it. Also, as levels of education in general rise, people tend to have fewer children.
snarfy 9y ago
I doubt there is one smoking gun. It's a basket of causes. Too much exposure to weird chemicals, ibuprofen, not enough zinc, obesity, lack of exercise, etc are all causes.
- zamber 9y ago
  Death by 1000 papercuts. My point here is that it's possible that there are many circumstances accumulating but that doesn't discredit efforts for finding the biggest contributors. You can easily smuggle a couple of razors between the paper sheets.
gaius 9y ago
My instinct, until now, was that it was because of fire retardant chemicals found in furniture that act as an endocrine disrupto What are your thoughts on synthetic hormones, e.g. used in farming or in contraception? Those enter the water supply and are not broken down.

raverbashing 9y ago

While the results do matter, this is probably being blown out of proportion > One group of subjects received ibuprofen, 2 × 600 mg/d, (Ibumetin; Nycomed Denmark Aps) for a period of 6 wk Yeah, that's a lot of Ibuprofen for a long time

TheSpiceIsLife 9y ago
Have you seen how some people gobble this stuff? I've felt compelled to say to more than one person: probably shouldn't take that much ...
- SwellJoe 9y ago
  Sometimes pain management is a balancing act between dangerous side effects and misery that makes it hard to want to keep living. Chronic pain isn't really something a third party can make decisions about; it may be that ibuprofen isn't the right choice, but lots of other choices (opiates, for instance) may have even more negative effects (like addiction and risk of deadly overdose). Of course, there are folks who take over-the-counter meds as though it is safe at any dose and frequency. That might warrant a nudge toward reading the label about safe dosage, or a mention of a recent study on the subject.
  - tinbucket 9y ago
    Exactly this. I have a chronic wrist injury from a previous job. Physiotherapy hasn't really helped, and the only thing that does help when I have a bad day is naproxen (another NSAID in the same class as ibuprofen). I feel guilty taking it in the dose I do (1000mg/day) but it's the only thing that makes life bearable and makes me functional.
rdl 9y ago
I've known plenty of people who do 400mg 2-3x/day for weeks/months.
- gadders 9y ago

reallymental 9y ago

I read the paper, I saw the plots accompanying the paper, and I tried following the rabbit hole in search of some raw data that I can get my hands on, just to see if I can. Perhaps the data is the result of the experiments that have been paid for by a third party, fine, but please mention that! People might be willing to pay for it, for example, me! What's wrong with "Here's the raw data, here's how we measured it, Here's how we've shown the data, and look you can see for yourself that we are right! oh and the data costs $$$ much." ? I understand experiment reproducibility is not incentivised in academia, but then why make it hard for an external party to reproduce it/study it? Do we have to go through the usual "Contact the academic, maybe they answer, and maybe you'll get the same (version of) data that they used in that experiment, maybe you'll have to go through Elsevier, oh and you must have .edu/.ac.uk address to be taken seriously through all those requests." What a chore. Just adds to the hate towards 'experts' and their opinions.

Gatsky 9y ago
Blame the journal. Scientists are generally pretty busy. Writing a (life sciences) paper is an incredible amount of work usually done in a short period of time. Preparing raw data and explaining what everything means is quite involved. If they don't have to do something they won't. The journal should mandate data access, then it will get done. This is crucial for human experiments, if only because the authors can lose the data and it will be gone forever.
- stinos 9y ago
  As far as I know this is slowly changing. According to scientists I've met (life science fields) there is an ongoing trend towards demanding raw data and even the code used to analyze it. Not every journal everywhere yet of course, but the consensus seemed to be that in 5 to 10 years it would become the new norm. Which might cause quite the disruption. Having seen quite the amounts of code written by PHD students I'm 100% sure tere are many, many bugs out there. Possibly leading to faulty results.
  - c12 9y ago

tejasmanohar 9y ago

This was discussed ~3 weeks ago. Here's the thread-- https://news.ycombinator.com/item?id=16101072 https://news.ycombinator.com/item?id=16101072

no_identd 9y ago
A note about one of the comments there related to Aspirin, namely, this one: https://news.ycombinator.com/item?id=16102328 https://news.ycombinator.com/item?id=16102328 There's an alternative solution for the stomach lining issue: https://en.wikipedia.org/wiki/Carbasalate_calcium https://en.wikipedia.org/wiki/Carbasalate_calcium Which reminds me, this testicle study seems to fail to distinguish Dex(tro)ibuprofen from Levoibuprofen. That seems rather disappointing, as we've known about the difference between the two for quite a while. This continued ignorance of medical science when it comes to (stereo)isomers never ceases to amaze me. I mean... You'd think they'd have learned their lessons by now. (Then again, we also still fail to employ multi-compartment models of pharmacology in the vast majority of studies. And... ugh. I'll avoid ranting on how shitty medical science seems to me and just leave it at this.) [btw., if you wonder why you can't get your hands on Dexibuprofen in the US: "Open committee discussion. The committees will discuss new drug application (NDA) 20–373, S+ Ibuprofen (dexibuprofen, Sterling Winthrop/ Bayer) 200-milligram caplet, indicated for the temporary relief of minor aches and pains associated with the common cold, headache, toothache, muscular aches, back ache, menstrual cramps, minor pain of arthritis, and for the temporary reduction of fever for OTC status." From the Federal Register, from 1996. It never got approved, and one can't even find the application on the FDA page, thus one can't find out more about why it never made it to market!]

amelius 9y ago

Is this a permanent effect, or does T production return to normal after stopping the drug?

erokar 9y ago
> For the small group of young study participants who used ibuprofen for only a short time, “it is sure that these effects are reversible,” Jégou said. However, it’s unknown whether the health effects of long-term ibuprofen use are reversible, he said. http://wgntv.com/2018/01/08/ibuprofen-linked-to-male-infertility-study-says/ http://wgntv.com/2018/01/08/ibuprofen-linked-to-male-inferti...
- amelius 9y ago
  > For the small group of young study participants who used ibuprofen for only a short time, “it is sure that these effects are reversible,” Jégou said. That could be true, but of course, there's some self-interest in that statement. Bringing long-term harm to your study participants is not exactly a good move for a medical researcher.

mdomans 9y ago

This isn't really huge news, technically speaking. Any anti-inflammatory drug will have negative net impact on your body function. For a while we know now that NSAIDs alter ROS levels in response to injury and in fact any normal process. NSAIDs also have negative impact on training adaptation or cell death due to overexpression of ROS. So no - taking overabundant levels of oral NSAIDs isn't going to be good for you and that's why topical NSAIDs make sense in cases of joint pain, tough they're not as convenient. Note: I remember taurine had protective effect on testicular function in men treated in 19-nor derivatives. Maybe worth checking out if it does so also for ibuprofen :)

joezydeco 9y ago
The energy drink makers have been trying to defend the use of taurine in their ingredients for a long time. This looks like a golden opportunity for them....
- mdomans 9y ago
  Probably, not so much. The amounts of ingredients and composition of ingredients in energy drinks are just stupid. I see now a trend of "health" drinks that actually seem sensible, though a bit more pricey. Like magnesium, ginseng and vitamins. The problem with energy drinks is that they're alike to a bottle of all things that may be fuel, combined. I've seen recently a tin of Monster that had 0.5g of caffeine. That's insane. And caffeine pills are even more insane. You can drop 1g of caffeine like it's M&Ms. At this rate we're going to have coke and amphetamine in those next year. And, you know, you can go on a limb and say that some of the modified amphetamines or phenidatess or what not maybe should be on the market. In Canada they have effedrine in OTC supplements and people don't die from overdose. But the thing is, we either demonise or just assume something is safe. How many people knows that acetaminophen (APAP, paracetamol) is liver toxic? And how many people knows that NAC is the antidote (N-acetylo-cysteine, popular OTC expectorant)?