16 ms·

Ibuprofen alters human testicular physiology to produce compensated hypogonadism

300 points by wallace_f 8y ago

jey 8y ago
"Ibuprofen and hypogonadism — bench to bedside to misinterpreted hype?" at https://www.nature.com/articles/nrurol.2018.26 https://www.nature.com/articles/nrurol.2018.26 : > A recent study suggests modulation of luteinizing hormone signalling within the hypothalamic–pituitary–gonadal axis and downstream transcriptional effects caused by sustained ibuprofen use. However, this study cannot be used to draw any clinical conclusions regarding effects of ibuprofen on male androgenic or reproductive health. Thus, the andrological effects of its use remain unclear and would benefit from further investigation.
- michaco33 8y ago
  Sounds like the industry responding with "we cant really know guys, right?" I'm throwing away my Advil right now. Screw that.
  - gonyea 8y ago
    I get what you're saying, but ibuprofen and acetaminophen save lives. The problem is the western (American?) tendency to self-medicate and to over medicate with really potent stuff. That shouldn't be as normal as it is.
    - scjr 8y ago
      I am not aware of any common uses of Ibuprofen and Acetominophen that saves lives?
      - an_account_name 8y ago
        Fevers kill. Ibuprofen and acetaminophen reduce fevers.
        potiuper 8y ago
        Fevers do not kill. Fever is a symptom, which is subjective, not a cause of death.
        deleted 8y ago
        [deleted]
        sandworm101 8y ago
        Fever can indeed kill. Raise the body temp a few degrees, no matter the cause, and things start going wrong very quickly. Google hyperthermia. In fact, i cannot think of any disease that literally kills. Even with the big stuff like cancer or aids, it is always the symptoms that get you. They damage body systems and the decline of those systems (aka symptoms) eventually causes the cardiac arrest or internal bleeds that shut off nutrients to the brain. Those symptoms are just as lethal no matter thier cause. A massive fever that stops normal body chemistry, whether caused by flu or ebola, will kill you just the same.
        lgregg 8y ago
        I can confirm a fever can kill, saw and heard about it in SE Asia.
        potiuper 8y ago
        Hyperthermia differs from fever in that the body's temperature set point remains unchanged. https://en.wikipedia.org/wiki/Hyperthermia https://en.wikipedia.org/wiki/Hyperthermia
        sandworm101 8y ago
        Yes but the extra heat in the body causes the same cascade of chemical changes that will eventually kill. Initial treatment is different, to a point. If a fever is too high it will suddenly need the same treatment as hyperthermia: direct cooling.
        anyfoo 8y ago
      - bitL 8y ago
        Ibuprofen is anti-inflammatory medication.
        docbrown 8y ago
        >Ibuprofen is anti-inflammatory medication. And an acetaminophen tablet is a painkiller. While your statement is in fact true, ibuprofen is still a better choice for a fever. The latter is also generally considered a safer alternative, especially in long-term use — even though alternating the two would be ideal.
        jrowley 8y ago
        If you have a fever, why not both (as long as you’re hydrated)?
        donatj 8y ago
        Acetaminophen is actually a pretty dangerous drug that is pretty easy to overdose on. It’s been said if it were discovered today it would be a prescription drug. On top of that numerous recent studies have shown many potential problems. https://www.webmd.com/drug-medication/news/20150302/does-long-term-acetaminophen-use-raise-health-risks#1 https://www.webmd.com/drug-medication/news/20150302/does-lon... > Heavy use of acetaminophen is associated with kidney disease and bleeding in the digestive tract, the paper reports. The medication also has been linked to increased risk of heart attack, stroke and high blood pressure, the study authors noted. > One cited study even showed that overuse of acetaminophen can increase a person's risk of early death as much as 60 percent, the study authors found.
        diydsp 8y ago
        how true would rate wikipedia's current claim that "how it works is not entirely clear" ?
      - gamma-male 8y ago
        That was what I used (nothing else) when I got H1N1. I thought I was going to die but I made it.
    - acct1771 8y ago
      And acetaminophen reduces empathy, according to some convincing research. What's wrong with cannabis-derived solutions, again?
      - tejasmanohar 8y ago
        What about it reduces empathy? My uneducated guess would be that it's unrelated to _which_ pain medicine you choose. Also, FWIW, in the past, I tried both CBD and THC without any luck where Ibuprofen helped so it's certainly not 1:1
        acct1771 8y ago
        See other response. What forms did you try? What brands? Were they lab tested? Like any "new" drug - there's a lot of nonsense floating around. Please don't simply buy CBD capsules from Walmart, and say "this shit doesn't work for me".
      - SubiculumCode 8y ago
        For those downvoting parent please see https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5015806/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5015806/ And others. True or not, parent wasn't just making up the empathy-painkiller association.
        snibss 8y ago
        The point being: it's a psychological study, in relation to behavior and emotion, which cannot be measured with NEARLY the same degree of ease or precision as sex-related endocrine effects. It's behavior, and thus potentially non-replicable. It's soft science at best. Is someone being a jerk? Is it some strange long term NSAID side-effect? Why are they being so cold and callous? Is this just an artifact of social biases that have existed since time immemorial? Is it the drug? Good luck with that one. Have fun p-value hacking it. Meanwhile, is this person on the effeminate side for a male? Immediately apparent in many cases. Does there seem to be a lot more of this gender dysphoria business going around ever since the 80's when Ibuprofen went OTC? Why yes! Is it the drug? Well, we can introduce a protocol, and study it, and know conclusively in perhaps 10 years. But, between then and now...
    - rixrax 8y ago
      This. Just had friends visiting. Their teenage son had had his wisdom tooth pulled last week. Dentist had then given him (as a standard practice?) prescription for Ibuprofen (800mg tabs?) AND some opioid based pain killer! Needless to say, latter they said went directly to trash after they realized what it contained and for ibuprofen they halved the dosage. To me and his parents this was pain management gone way over dose! But we’re not medical experts and should not be doing clinical decisions since at one end of this rabbit hole you will find anti-vaccination and other nut jobs. So what to do?
      - adrianN 8y ago
        Move to Europe where we don't get as many drugs prescribed? I think the only time you get opioids is after major surgery. Personally I don't know anybody who had to take them.
        phil21 8y ago
        No opioids after my wisdom teeth extraction would have resulted in potentially suicide. The pain was unbearable, and 3-4 days of hydrocodone was absolutely proscribed. There is nothing wrong with opiates being used for acute pain relief. They are a modern miracle when put to such uses. The problem comes when you start using them for long-term pain relief - a use-case in which they are neither appropriate or effective. A typical 2-3 day prescription after major dental (or other) work is not remotely a problem, and I really have no idea why this is where the focus is. It's always been long-term abuse as the actual problem - the weird overreaction over a few days use for acute pain is utterly absurd and only hurts people in some bizzare way for folks to feel they are "helping" fix the abuse problem.
        mindcrime 8y ago
        Definitely varies by individual, and by the nature of the situation. My personal experience, as somebody who considers himself to have a pretty high threshold of pain tolerance, is that I never needed any of the Vicodin I was prescribed after wisdom tooth removal... but I can't imagine how I would have survived without Oxycodone in the first week after rotator cuff surgery.
  - sergiotapia 8y ago
    Same just did that. >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. Fuck that. I wonder what I should give my kids when they have fevers though
    - logicchains 8y ago
      >I wonder what I should give my kids when they have fevers though You don't have to give them anything. Ibuprofen doesn't make the underlying infection causing the fever go away any quicker, it just alleviates the symptoms. It's a trade off between reducing short-term suffering and risking long-term defects. Personally my parents never gave me painkillers for fever and I'm grateful for it: fever pain is just a temporary feeling, but some of the uncommon side effects of painkillers are much longer-lasting. *Edit: To whomever downvoted, I'm curious what part of what I said you disagree with.
      - frostburg 8y ago
        Your parents probably aren't doctors. The issue isn't cut and clean... To a point a moderate fever usually helps your immune system (the response exists for a reason), but anything other than a moderate fever can be a lot more dangerous than long term issues stemming from sporadic usage of antipyretics.
      - babuskov 8y ago
        I didn't downvote you, but you seem to lack experience/knowledge on the topic if you think it's only a painkiller. Ibuprofen's main use is to help to keep the body temperature in check. When your body temperature goes too high you can lose consciousness and even die. I had a very high fever once and didn't want to take any medicine until I started to lose consciousness and I almost fell while waiting in a line in pharmacy. I was able to go through it only because I was adult. Children are more fragile. Fever is the reason people died so much before discovery of antibiotics. You are right that it alleviates the symptoms, and it's actually better not to use it when the temperature is moderate because high temp kills some germs. But if it goes too high, you have to stop it before it's too late.
  - drb91 8y ago
    OTOH acetaminophen is known to be toxic; is there an alternative here for non narcotic inflammation, fever, and pain relief that is shown NOT to have tradeoffs for use?
    - tchaffee 8y ago
      No tradeoffs? I don't think such a thing exists. Aspirin kills people every year. The only pain reliever I know of that has never killed anyone is cannabis. I don't think it does much for fever though?
      - sureaboutthis 8y ago
        Inhaling smoke into your lungs is never a good thing. Your lungs (cough) are trying to tell you something.
        tchaffee 8y ago
        Where did I say anything about smoking? And I also didn't say cannabis has no tradeoffs either. But it won't kill you. That's a pretty strong pro in my book if you are looking for occasional pain relief.
        sureaboutthis 8y ago
        You didn't say anything about not smoking it either.
        deleted 8y ago
        [deleted]
    - arcticbull 8y ago
      Naproxen / Aleve?
      - sparn5 8y ago
        The naproxen molecule is very similar to ibuprofen, so I expect it would have similar effects.
  - tzjmetron 8y ago
    Ditto.
  - rsynnott 8y ago
    I doubt anyone is interested in protecting ibuprofen from a commercial point of view. Generic ibuprofen is extremely cheap; if anything the industry would probably like people to stop using it so that they could sell novel NSAIDs.
- lvs 8y ago
  Ironically, that title itself hypes the content of the perspective piece that follows. It does to not refute any finding in the PNAS paper. They simply question whether the observed effect on LH, which wasn't disputed, is clinically relevant or should result in modification of clinical recommendation, for which further work is needed. >Despite the excellent quality of the work, the main point to emphasize is the confusion that has arisen concerning the study conclusions versus the real-world relevance and application of its results.
- ricardobeat 8y ago
  In curious how can they make a statement such as “the study cannot be used to draw any conclusions” without providing any kind of reasoning, and get published in Nature?
  - raverbashing 8y ago
    Well, the reasons are probably explained in the text (which is not open), but I suppose Nature is peer-reviewed
  - Valmar 8y ago
    Whenever I see blanket statements like this in such studies ~ it's like they're trying to avoid pissing any powerful corporations that profit from whatever we're told to not draw any conclusions about. They don't want to potentially endanger their careers. Drug companies hate it when a cash-cow drug is threatened in any way. Anything that threatens those profits is a potential target in one way or another. Researchers studying these drugs know just how much power and influence these drug companies have, and so, are afraid of angering them. The reasoning is simple ~ make a vaguely disqualifying statement that hopefully keeps them in the good books.
    - skybrian 8y ago
      Well, except that it's also common that the people who did the study are often well aware of its limitations, and it's the media that's hyping it up to make a better story. Ignoring disclaimers is how the hype gets started. Understanding people's incentives will often result in reasons to be suspicious, but suspicions aren't evidence and it's not a shortcut for understanding the science.
    - pergadad 8y ago
      Ibuprofen is not really a cash cow though as it is now out of patent protection. So while you seem to desire maliciousness I'd venture to say.this is a rather prudent scientific approach. Should all men stop taking ibuprofen on the basis of this one study? No, obviously not.
  - appleflaxen 8y ago
- gameswithgo 8y ago
  >However, this study cannot be used to draw any clinical conclusions regarding effects of ibuprofen on male androgenic or reproductive health why not?
  - just_one_time_ 8y ago
    Because legal reasons.
  - zenexer 8y ago
    Their argument is that we have yet to determine the real-world consequences for the correlation observed in the experiment. In other words: yes, ibuprofen seems to affect something, but we don’t really know whether that effect is significant enough to warrant avoidance of ibuprofen. It might have no observable impact. (Not saying I agree—this is just their argument.)
azhenley 8y ago
This is terrifying. I used to take a lot of ibuprofen for frequent headaches (much better now). Military doctors were overzealous with the 800mg prescriptions (double the OTC dose). I suppose I should just use naproxen or acetaminophen? Ibuprofen always seemed the most effective to me.
- philliphaydon 8y ago
  I've been suffering from migraines since ~14yo, to the point that I can wake up and know if I'm going to get a migraine or not. I take naproxen, if I know I'll get a migraine I'll take 1x250mg, if I have a migraine I take 2-3x250mg depending on how severe it is. Cause of mine is generally lack of sleep when stressed so I make sure to sleep properly and don't let myself get stressed out, so I only get migraines ~once a month now, compared to several times a week when I was at school.
  - Escolte 8y ago
    As someone who's had a permanent migraine since months ago, second on naproxen. Ibuprofen does nothing to relieve my headache, and so far the only drug I've found that's effective against it at least mildly is naproxen. Don't take it every day though. Maybe once a month if I feel like the headache hurts me more than usual.
  - donjoe 8y ago
    Just as a side hint: did you ever get your vitamin levels checked? I had migraines with aura a couple of times a week until I got a full vitamine check up on B vitamines and Q10. I had a huge lack of B12 plus Q10. I managed to compensate with supplements (the expensive ones from the pharmacy) and didn't have migraine now in 3 months. Might be worth looking into :)
    - philliphaydon 8y ago
      I haven't. I have a stack of multi vitamins & B12 here so I'll take them and see how I go. Thanks for the info.
Alex3917 8y ago
600mg per day is an enormous dose, albeit not especially uncommon. I’d be more interested though in the effects of, say, 200 - 400mg per week.
- eigenvector 8y ago
  I recently went to the doctor with a shoulder strain and without even looking at it he prescribed 1000mg daily for 2 weeks then "come back if it still hurts".
  - wallace_f 8y ago
    It's so bizzare how in order to do this, that person had a barrier to entry of hundreds of thousands in private and public resources getting a license to help you. And they dont really help you. Compare to something like cops, who you have to interact with whether you like it or not, virtually have a license to kill, and are actually selected based on low IQ.
  - goldfeld 8y ago
    These people are only barely doctors.
- azhenley 8y ago
  It isn’t enormous at all. 400mg every 4 hours is the OTC dose (at least in the US). My prescription was 800mg.
  - Alex3917 8y ago
    > My prescription was 800mg. Sure, but it’s not like 800mg is 4x or even 2x more effective than 200mg. Ibuprofen is great, I just don’t really see the point of risking dying and whatever else for what’s at most a very marginal benefit. It’s not enormous in the sense that it’s uncommon per se, but rather in the sense that it’s way outside the efficient frontier on the risk/reward curve.
    - 8y ago
jimmyswimmy 8y ago
Having read half the paper, the treatment group took 600mg ibuprofen daily for 14 to 44 days to induce the reported effect of compensated hypogonadism, though the 12 and 24 hour effects on testosterone were apparently easily detectable on ex vivo testicle samples. So, maybe if you need your testosterone, keep off the OTC pain medications. And probably don't donate samples of your testicle either. Interesting paper though.
- azhenley 8y ago
  Did the effect go away when they stopped the treatment? I can’t read it at the moment due to slow WiFi.
  - benmarten 8y ago
    What was the effect in the first place?
    - chiph 8y ago
      Hypogonadism. Which is basically "Your testosterone levels drop"
- defertoreptar 8y ago
  > the treatment group took 600mg ibuprofen daily for 14 to 44 days to induce the reported effect of compensated hypogonadism That phrasing is misleading. We don't know if it takes 600 mg for 14 days "to induce" hypogonadism. The study didn't test for that. It only tested if there would be an effect, and as with most pilot experiments, it did so cheaply and quickly. That's the idea of small sample size experiments such as this. Try a big dose as see if you get an effect at all. If so, that's a jumping off point for more rigorous, expensive studies later on.
  - rjf72 8y ago
    600mg is not a large dose. Ibuprofen over the counter recommends 400mg (two tablets) every 4-6 hours with up to 6 tablets (1200mg) per day.
wmccullough 8y ago
As someone who is XXY, I can’t help but wonder what, if any issues would be caused by a pregnant mother taking a lot of this.
- usaphp 8y ago
  Pregnant women are advised to take Tylenol instead of Ibuprofen
- lelandgaunt 8y ago
  Long term acetaminophen usage is linked to a reduction in empathy.[0] [0]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5015806/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5015806/
  - sawhit 8y ago
    As far as I can tell, the article linked says that there was a reduction in empathy (for pain) directly after being administered acetaminophen. I'm not seeing anything about long term use.
- ojm 8y ago
  In Australia , pregnant women are told not to take ibuprofen unless told by doctor. Paracetamol Is the pain killer suggested, and only if really required.
- tbabb 8y ago
  This seems like an endocrine effect, rather than a chromosomal one. I'd expect XXY to cause endocrine effects because sex-linked cells are operating with bad genetic info. This paper suggests that Ibprofen might cause sex-linked cells to misbehave because of chemistry. It doesn't seem like there is evidence here that Ibprofen would have had an effect on chromosomes. These are two independent causes of sex-linked malformity/endocrine issues, not a case of one causing the other.
iandanforth 8y ago
Along with the high sustained dosage others have mentioned the small sample size (14 in the experimental group) should be noted.
- arikr 8y ago
  This is worth reading: The "Unreliable Small-Sample" Misconception https://www.dailykos.com/stories/2008/11/9/656465/- https://www.dailykos.com/stories/2008/11/9/656465/- > My point here is that arguing that the sample is inaccurate simply because of how large or small it is is not correct. The size of the sample actually makes very little difference in how applicable the results are to the population. It simply makes the range of possible results smaller as the size of the sample increases. I've noticed a trend on reddit and HN where commenters will point out small sample sizes, often with the direct or indirect implication that this makes the study mostly invalid. I believe that's false - studies with small sample sizes can be very valid. The smaller the sample size the larger the effect size needs to be for it to be a statistically significant result, but a small sample size by itself isn't bad. And I think that the internet would be able to better appreciate research if more people were aware of the small sample size misconception.
  - SamReidHughes 8y ago
    There's also temporal sample size: you can infer that A causes B if B happens very soon after A, and nothing else around that time might cause B. For example, if A is exposure to a chemical and B is an allergic reaction. Edit: A great example is that stomach ulcer guy.
  - stewbrew 8y ago
    Since the article doesn't mention test power (and should it be for the reason of rebuttal of that Pearson-Neyman concept) I don't think it's a worth read. Sorry. "studies with small sample sizes can be very valid." They could be with a certain probability but (unless you believe in a very strong prior) you can't know with sufficient certainty.
  - devwastaken 8y ago
eikenberry 8y ago
So back to good old aspirin? Acetaminophen slowly kills your liver and Ibuprofen messes with testosterone production.
- tejasmanohar 8y ago
  https://news.ycombinator.com/item?id=18787422 https://news.ycombinator.com/item?id=18787422
- tchaffee 8y ago
  Aspirin kills people too. Usually from stomach bleeding. If it's pain you're trying to reduce the only one I know of that has never killed anyone is cannabis.
- Geimfari 8y ago
  Please note that acetaminophen/paracetamol is incredibly safe at normal doses and does not kill your liver. It is only when you attempt to overdose (or if you have severely limited liver function) that you run out of the liver enzymes that break it down, causing liver damage.
  - sodosopa 8y ago
    At normal doses, Acetaminophen can trigger Stevens-Johnson Syndrome and toxic epidermal necrolysis. You're lucky if you wind up with rashes as opposed to skin falling off.
    - naasking 8y ago
      > At normal doses, Acetaminophen can trigger Stevens-Johnson Syndrome Probably not: https://www.ncbi.nlm.nih.gov/m/pubmed/28963996/ https://www.ncbi.nlm.nih.gov/m/pubmed/28963996/
      - sodosopa 8y ago
        In my case, it does.
ttflee 8y ago
I once had an extraordinarily low level of blood testosterone reading after I had taken Ibuprofen for a few days.
- tejasmanohar 8y ago
  Just curious-- Did your blood T levels recover? How much / what % lower than normal? Was it just by chance that the T reading was days after Ibuprofen?
deleted 8y ago
[deleted]
emersonrsantos 8y ago
Ibuprofen induced liver toxiticy: https://livertox.nih.gov/Ibuprofen.htm https://livertox.nih.gov/Ibuprofen.htm "Rates of serum aminotransferase elevations during low dose, chronic ibuprofen therapy are comparable to those that occur with placebo controls (0.4%). However, higher rates of ALT elevations occur with high, full doses of 2,400 to 3,200 mg daily (up to 16%)."
- tejasmanohar 8y ago
  This is news to me. The more common side effect I've heard of from regular or excess NSAIDs like Ibuprofen are stomach problems (eg ulcers, gastritis, etc.).
  - jjtheblunt 8y ago
    That's a side-effect of inhibiting cyclooxygenase-1, which correlates to mucus production, such as that which protects stomach linings. Ibuprofen is a non-selective "COX"=cyclooxygenase inhibitor so inhibits COX-2, correlated with inflammation, while undesirably also inhibiting COX-1. This gives rise to the selective COX-2 inhibitors, meant to reduce inflammation with minimal mucus inhibition, such as Celebrex and Firocoxib.
- gregw2 8y ago
  Speaking of liver toxicity, acetominophen/tylenol and alcohol can kill you. Not in the common case but if you are maxing out the acetaminophen for a prolonged period and drink and stop drinking, you should get educated on the dynamics and side effects. I was shocked to only find out about this midlife when my wife was on painkillers post surgery for an extended period and was using both painkillers and alcohol to self medicate. And her doc noticed some concerning liver results which later turned out fine. Be careful out there!
- sannee 8y ago
  > high, full doses of 2,400 to 3,200 mg daily Holy shit that's a lot of ibuprofen. If you are taking that much every day, you definitely have some more pressing concern than liver toxicity...
aejnsn 8y ago
Just had a kidney stone problem—first for me, quite painful experience. My ibuprofen dosage is 800mg every 8 hours, as needed. I had little choice. “Sustained” is the keyword of the study here. On another note, maybe this will drive alternative treatments such as CBD/marijuana for those who need to sustain their pain relief.
- aiyodev 8y ago
  I’ve suffered from kidney stones off and on for years. Here’s what helps. Make sure you’re drinking enough water. 2 gallons per day minimum. If your pee isn’t clear, you’re not drinking enough. I add flavor packets to mine to make it more palatable. I carry a water bottle with me all day. Went from an attack once a month to once a year. Mix pain meds. It’s perfectly healthy. Don’t take 800 mg of ibuprofen. Take a normal dose of ibuprofen (200 mg) and a normal dose of tylenol. Then tylenol and naproxen. Then naproxen and aspirin. Rotate them so you don’t get a megadose of any one. Each time take one that treats pain and one that treats pain and inflammation. A low dose of multiple drugs works way better than a large dose of just one. You’ll find yourself taking a lot less medicine overall and you won’t be in as much pain. Buy an electic heating pad and apply it to your lower back as soon as the symptoms start. Hope this helps.
  - aejnsn 8y ago
    Thank you so much! I’ve been trying to gather as many details as I can to make sure this happens less frequently. I have changed my entire diet, drastically cutting sugar consumption. I had an ER doctor tell me there’s no possibility of this being hereditary. However, kidney stones are a problem for my mother, one of her siblings, and both of my grandparents. Waiting on a urologist consultation, but it’s under control for now.
    - aiyodev 8y ago
      It’s hereditary in my family.
- Amezarak 8y ago
  There is no silver bullet for targeted pain relief, or really, pretty much anything in the body. The body is an enormously complicated biological organism. Trading ibuprofen for Cvs/marijuana doesn’t trade side effects for no side effects, it trades one known and some unknown side effects for mostly unknown side effects.
Escolte 8y ago
Ibuprofen, as far as I am given to understand, is one of the most common drugs all around the world. Why didn't anyone notice before now, I wonder?
- fuzzfactor 8y ago
  Maybe their wives are taking it too.
bitL 8y ago
So, if one wants to reduce sex drive in order to focus on much more interesting tasks without any interruption, ibuprofen is the way?
- ttflee 8y ago
  https://www.buzzfeed.com/caseygueren/feeling-happy-but-not-sexy https://www.buzzfeed.com/caseygueren/feeling-happy-but-not-s...
burke 8y ago
> Our data demonstrate that ibuprofen alters the endocrine system via selective transcriptional repression in the human testes, thereby inducing compensated hypogonadism. Interesting. I’m no doctor, but this sounds like a not-super-transient effect. Amazing and slightly horrifying that they were able to measure this after a relatively short period of high-moderate sustained use.
- Valmar 8y ago
  I have to wonder how long the drug industry knew about this, but just brushed it under the rug like they do with all of their drugs, just to get them approved. When there's money to be made, dangerous side effects don't matter to them.
  - Escolte 8y ago
    I also wonder why for example the Chinese or heck the Cubans didn't discover this before, who have less of a corporate interest. Ibuprofen (And Naproxen, etc...) is one of the most common drugs all around the world. I think most people I know have taken them at least once in their lifetimes. It's just all too weird. Is this all a malignant cover up by the industry? Don't know what to say, especially considering this was released 1 year ago and afaik no more research has been conducted on this.
    - zzzcpan 8y ago
      My perception is that in the US ibuprofen is used like candy, while it's not the same in other countries, where, for example, aspirin has that role.
      - Escolte 8y ago
        I was prescribed to take Naproxen, another NSAID with potentially the same harmful effects as Ibuprofen, for two weeks three times a day half a dose. I'm from Spain. But IDK. Let me reiterate that everyone all around the world uses Ibuprofen.
dilyevsky 8y ago
Really cool. I’ve been hearing for years now in the athletic community that ibuprofen “kills gains”. Thought it was just a fud. Turns out - likely not.
- skellera 8y ago
  I thought that’s based on the anti inflammatory effects of it. I don’t personally understand it but inflammation is supposed to help muscle growth.
tzjmetron 8y ago
Okay, that's enough ibuprofen for me. Ever. Fuck the whole pharma industry.
rbjorklin 8y ago
My understanding is that Hypogonadism can also affect women. Have a similar study been made on women? I’m under the impression that a lot of women eat painkillers to get through menstrual cramps so this could be a huge problem for women too I guess?
miguelrochefort 8y ago
I've had frequent migraines all my life (although it's much better now) and ibuprofen is the only thing that works. As a kid, I would take 200mg whenever I had a headache. To this day, I still haven't switched to the adult dose of 400mg. I think a lot of people will find ibuprofen to be effective even at lower doses. I'm sad to find that ibuorofen has so many negative side effects. For me, it's been a miracle drug. I rarely feel as good as I do after taking it. I generally feel happier, with clearer thoughts and less anxiety.
godelmachine 8y ago
Does ibuprofen have anything to do with finasteride?
mirimir 8y ago
From the paper:[0] > The so-called “over-the-counter” mild analgesics (hereafter simply called “analgesics”), such as acetaminophen/paracetamol, acetylsalicylic acid/aspirin, and ibuprofen, are among the most commonly used pharmaceutical compounds worldwide (6, 7). Increasing evidence from recent years shows that exposure to analgesics can generate negative endocrine and reproductive effects during fetal life (6). Nonetheless, no in-depth studies have analyzed the effect of mild analgesics on the human pituitary–gonadal axis. In this context, ibuprofen is especially interesting because of its increasing use in the general population and in particular by elite athletes (8⇓⇓⇓–12). So now I wonder about acetaminophen/paracetamol, and aspirin. And naproxen. Maybe that's why I need testosterone supplementation. In addition to the fact that I'm old. 0) https://www.pnas.org/content/115/4/E715.long https://www.pnas.org/content/115/4/E715.long
CapitalistCartr 8y ago
Prior discussion: https://news.ycombinator.com/item?id=16101072 https://news.ycombinator.com/item?id=16101072
Barjak 8y ago
Due to an autoinflammatory condition, I've taken ~1800mg daily for periods of 6 months several times. I don't like the idea of going on opioids for longer that a couple weeks, but maybe I need to switch.
cfmcdonald 8y ago
Ibuprofen has been taken regularly in substantial doses by millions of people for decades. The prior probability that it has some heretofore unknown serious side effect is very low, so it would take a lot of evidence to convince me that this is real.
TagAsDelusion 8y ago
quick, fill the conversation with doubt

300 points by wallace_f 8y ago

jey 8y ago

"Ibuprofen and hypogonadism — bench to bedside to misinterpreted hype?" at https://www.nature.com/articles/nrurol.2018.26 https://www.nature.com/articles/nrurol.2018.26 : > A recent study suggests modulation of luteinizing hormone signalling within the hypothalamic–pituitary–gonadal axis and downstream transcriptional effects caused by sustained ibuprofen use. However, this study cannot be used to draw any clinical conclusions regarding effects of ibuprofen on male androgenic or reproductive health. Thus, the andrological effects of its use remain unclear and would benefit from further investigation.

michaco33 8y ago
Sounds like the industry responding with "we cant really know guys, right?" I'm throwing away my Advil right now. Screw that.
- gonyea 8y ago
  I get what you're saying, but ibuprofen and acetaminophen save lives. The problem is the western (American?) tendency to self-medicate and to over medicate with really potent stuff. That shouldn't be as normal as it is.
  - scjr 8y ago
    I am not aware of any common uses of Ibuprofen and Acetominophen that saves lives?
    - an_account_name 8y ago
      Fevers kill. Ibuprofen and acetaminophen reduce fevers.
      - potiuper 8y ago
        Fevers do not kill. Fever is a symptom, which is subjective, not a cause of death.
        deleted 8y ago
        [deleted]
        sandworm101 8y ago
        Fever can indeed kill. Raise the body temp a few degrees, no matter the cause, and things start going wrong very quickly. Google hyperthermia. In fact, i cannot think of any disease that literally kills. Even with the big stuff like cancer or aids, it is always the symptoms that get you. They damage body systems and the decline of those systems (aka symptoms) eventually causes the cardiac arrest or internal bleeds that shut off nutrients to the brain. Those symptoms are just as lethal no matter thier cause. A massive fever that stops normal body chemistry, whether caused by flu or ebola, will kill you just the same.
        lgregg 8y ago
        I can confirm a fever can kill, saw and heard about it in SE Asia.
        potiuper 8y ago
        Hyperthermia differs from fever in that the body's temperature set point remains unchanged. https://en.wikipedia.org/wiki/Hyperthermia https://en.wikipedia.org/wiki/Hyperthermia
        sandworm101 8y ago
        Yes but the extra heat in the body causes the same cascade of chemical changes that will eventually kill. Initial treatment is different, to a point. If a fever is too high it will suddenly need the same treatment as hyperthermia: direct cooling.
        anyfoo 8y ago
    - bitL 8y ago
      Ibuprofen is anti-inflammatory medication.
      - docbrown 8y ago
        >Ibuprofen is anti-inflammatory medication. And an acetaminophen tablet is a painkiller. While your statement is in fact true, ibuprofen is still a better choice for a fever. The latter is also generally considered a safer alternative, especially in long-term use — even though alternating the two would be ideal.
        jrowley 8y ago
        If you have a fever, why not both (as long as you’re hydrated)?
        donatj 8y ago
        Acetaminophen is actually a pretty dangerous drug that is pretty easy to overdose on. It’s been said if it were discovered today it would be a prescription drug. On top of that numerous recent studies have shown many potential problems. https://www.webmd.com/drug-medication/news/20150302/does-long-term-acetaminophen-use-raise-health-risks#1 https://www.webmd.com/drug-medication/news/20150302/does-lon... > Heavy use of acetaminophen is associated with kidney disease and bleeding in the digestive tract, the paper reports. The medication also has been linked to increased risk of heart attack, stroke and high blood pressure, the study authors noted. > One cited study even showed that overuse of acetaminophen can increase a person's risk of early death as much as 60 percent, the study authors found.
        diydsp 8y ago
        how true would rate wikipedia's current claim that "how it works is not entirely clear" ?
    - gamma-male 8y ago
      That was what I used (nothing else) when I got H1N1. I thought I was going to die but I made it.
  - acct1771 8y ago
    And acetaminophen reduces empathy, according to some convincing research. What's wrong with cannabis-derived solutions, again?
    - tejasmanohar 8y ago
      What about it reduces empathy? My uneducated guess would be that it's unrelated to _which_ pain medicine you choose. Also, FWIW, in the past, I tried both CBD and THC without any luck where Ibuprofen helped so it's certainly not 1:1
      - acct1771 8y ago
        See other response. What forms did you try? What brands? Were they lab tested? Like any "new" drug - there's a lot of nonsense floating around. Please don't simply buy CBD capsules from Walmart, and say "this shit doesn't work for me".
    - SubiculumCode 8y ago
      For those downvoting parent please see https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5015806/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5015806/ And others. True or not, parent wasn't just making up the empathy-painkiller association.
      - snibss 8y ago
        The point being: it's a psychological study, in relation to behavior and emotion, which cannot be measured with NEARLY the same degree of ease or precision as sex-related endocrine effects. It's behavior, and thus potentially non-replicable. It's soft science at best. Is someone being a jerk? Is it some strange long term NSAID side-effect? Why are they being so cold and callous? Is this just an artifact of social biases that have existed since time immemorial? Is it the drug? Good luck with that one. Have fun p-value hacking it. Meanwhile, is this person on the effeminate side for a male? Immediately apparent in many cases. Does there seem to be a lot more of this gender dysphoria business going around ever since the 80's when Ibuprofen went OTC? Why yes! Is it the drug? Well, we can introduce a protocol, and study it, and know conclusively in perhaps 10 years. But, between then and now...
  - rixrax 8y ago
    This. Just had friends visiting. Their teenage son had had his wisdom tooth pulled last week. Dentist had then given him (as a standard practice?) prescription for Ibuprofen (800mg tabs?) AND some opioid based pain killer! Needless to say, latter they said went directly to trash after they realized what it contained and for ibuprofen they halved the dosage. To me and his parents this was pain management gone way over dose! But we’re not medical experts and should not be doing clinical decisions since at one end of this rabbit hole you will find anti-vaccination and other nut jobs. So what to do?
    - adrianN 8y ago
      Move to Europe where we don't get as many drugs prescribed? I think the only time you get opioids is after major surgery. Personally I don't know anybody who had to take them.
      - phil21 8y ago
        No opioids after my wisdom teeth extraction would have resulted in potentially suicide. The pain was unbearable, and 3-4 days of hydrocodone was absolutely proscribed. There is nothing wrong with opiates being used for acute pain relief. They are a modern miracle when put to such uses. The problem comes when you start using them for long-term pain relief - a use-case in which they are neither appropriate or effective. A typical 2-3 day prescription after major dental (or other) work is not remotely a problem, and I really have no idea why this is where the focus is. It's always been long-term abuse as the actual problem - the weird overreaction over a few days use for acute pain is utterly absurd and only hurts people in some bizzare way for folks to feel they are "helping" fix the abuse problem.
      - mindcrime 8y ago
        Definitely varies by individual, and by the nature of the situation. My personal experience, as somebody who considers himself to have a pretty high threshold of pain tolerance, is that I never needed any of the Vicodin I was prescribed after wisdom tooth removal... but I can't imagine how I would have survived without Oxycodone in the first week after rotator cuff surgery.
- sergiotapia 8y ago
  Same just did that. >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. Fuck that. I wonder what I should give my kids when they have fevers though
  - logicchains 8y ago
    >I wonder what I should give my kids when they have fevers though You don't have to give them anything. Ibuprofen doesn't make the underlying infection causing the fever go away any quicker, it just alleviates the symptoms. It's a trade off between reducing short-term suffering and risking long-term defects. Personally my parents never gave me painkillers for fever and I'm grateful for it: fever pain is just a temporary feeling, but some of the uncommon side effects of painkillers are much longer-lasting. *Edit: To whomever downvoted, I'm curious what part of what I said you disagree with.
    - frostburg 8y ago
      Your parents probably aren't doctors. The issue isn't cut and clean... To a point a moderate fever usually helps your immune system (the response exists for a reason), but anything other than a moderate fever can be a lot more dangerous than long term issues stemming from sporadic usage of antipyretics.
    - babuskov 8y ago
      I didn't downvote you, but you seem to lack experience/knowledge on the topic if you think it's only a painkiller. Ibuprofen's main use is to help to keep the body temperature in check. When your body temperature goes too high you can lose consciousness and even die. I had a very high fever once and didn't want to take any medicine until I started to lose consciousness and I almost fell while waiting in a line in pharmacy. I was able to go through it only because I was adult. Children are more fragile. Fever is the reason people died so much before discovery of antibiotics. You are right that it alleviates the symptoms, and it's actually better not to use it when the temperature is moderate because high temp kills some germs. But if it goes too high, you have to stop it before it's too late.
- drb91 8y ago
  OTOH acetaminophen is known to be toxic; is there an alternative here for non narcotic inflammation, fever, and pain relief that is shown NOT to have tradeoffs for use?
  - tchaffee 8y ago
    No tradeoffs? I don't think such a thing exists. Aspirin kills people every year. The only pain reliever I know of that has never killed anyone is cannabis. I don't think it does much for fever though?
    - sureaboutthis 8y ago
      Inhaling smoke into your lungs is never a good thing. Your lungs (cough) are trying to tell you something.
      - tchaffee 8y ago
        Where did I say anything about smoking? And I also didn't say cannabis has no tradeoffs either. But it won't kill you. That's a pretty strong pro in my book if you are looking for occasional pain relief.
        sureaboutthis 8y ago
        You didn't say anything about not smoking it either.
      - deleted 8y ago
        [deleted]
  - arcticbull 8y ago
    Naproxen / Aleve?
    - sparn5 8y ago
      The naproxen molecule is very similar to ibuprofen, so I expect it would have similar effects.
- tzjmetron 8y ago
  Ditto.
- rsynnott 8y ago
  I doubt anyone is interested in protecting ibuprofen from a commercial point of view. Generic ibuprofen is extremely cheap; if anything the industry would probably like people to stop using it so that they could sell novel NSAIDs.
lvs 8y ago
Ironically, that title itself hypes the content of the perspective piece that follows. It does to not refute any finding in the PNAS paper. They simply question whether the observed effect on LH, which wasn't disputed, is clinically relevant or should result in modification of clinical recommendation, for which further work is needed. >Despite the excellent quality of the work, the main point to emphasize is the confusion that has arisen concerning the study conclusions versus the real-world relevance and application of its results.
ricardobeat 8y ago
In curious how can they make a statement such as “the study cannot be used to draw any conclusions” without providing any kind of reasoning, and get published in Nature?
- raverbashing 8y ago
  Well, the reasons are probably explained in the text (which is not open), but I suppose Nature is peer-reviewed
- Valmar 8y ago
  Whenever I see blanket statements like this in such studies ~ it's like they're trying to avoid pissing any powerful corporations that profit from whatever we're told to not draw any conclusions about. They don't want to potentially endanger their careers. Drug companies hate it when a cash-cow drug is threatened in any way. Anything that threatens those profits is a potential target in one way or another. Researchers studying these drugs know just how much power and influence these drug companies have, and so, are afraid of angering them. The reasoning is simple ~ make a vaguely disqualifying statement that hopefully keeps them in the good books.
  - skybrian 8y ago
    Well, except that it's also common that the people who did the study are often well aware of its limitations, and it's the media that's hyping it up to make a better story. Ignoring disclaimers is how the hype gets started. Understanding people's incentives will often result in reasons to be suspicious, but suspicions aren't evidence and it's not a shortcut for understanding the science.
  - pergadad 8y ago
    Ibuprofen is not really a cash cow though as it is now out of patent protection. So while you seem to desire maliciousness I'd venture to say.this is a rather prudent scientific approach. Should all men stop taking ibuprofen on the basis of this one study? No, obviously not.
- appleflaxen 8y ago
gameswithgo 8y ago
>However, this study cannot be used to draw any clinical conclusions regarding effects of ibuprofen on male androgenic or reproductive health why not?
- just_one_time_ 8y ago
  Because legal reasons.
- zenexer 8y ago
  Their argument is that we have yet to determine the real-world consequences for the correlation observed in the experiment. In other words: yes, ibuprofen seems to affect something, but we don’t really know whether that effect is significant enough to warrant avoidance of ibuprofen. It might have no observable impact. (Not saying I agree—this is just their argument.)

azhenley 8y ago

This is terrifying. I used to take a lot of ibuprofen for frequent headaches (much better now). Military doctors were overzealous with the 800mg prescriptions (double the OTC dose). I suppose I should just use naproxen or acetaminophen? Ibuprofen always seemed the most effective to me.

philliphaydon 8y ago
I've been suffering from migraines since ~14yo, to the point that I can wake up and know if I'm going to get a migraine or not. I take naproxen, if I know I'll get a migraine I'll take 1x250mg, if I have a migraine I take 2-3x250mg depending on how severe it is. Cause of mine is generally lack of sleep when stressed so I make sure to sleep properly and don't let myself get stressed out, so I only get migraines ~once a month now, compared to several times a week when I was at school.
- Escolte 8y ago
  As someone who's had a permanent migraine since months ago, second on naproxen. Ibuprofen does nothing to relieve my headache, and so far the only drug I've found that's effective against it at least mildly is naproxen. Don't take it every day though. Maybe once a month if I feel like the headache hurts me more than usual.
- donjoe 8y ago
  Just as a side hint: did you ever get your vitamin levels checked? I had migraines with aura a couple of times a week until I got a full vitamine check up on B vitamines and Q10. I had a huge lack of B12 plus Q10. I managed to compensate with supplements (the expensive ones from the pharmacy) and didn't have migraine now in 3 months. Might be worth looking into :)
  - philliphaydon 8y ago
    I haven't. I have a stack of multi vitamins & B12 here so I'll take them and see how I go. Thanks for the info.

Alex3917 8y ago

600mg per day is an enormous dose, albeit not especially uncommon. I’d be more interested though in the effects of, say, 200 - 400mg per week.

eigenvector 8y ago
I recently went to the doctor with a shoulder strain and without even looking at it he prescribed 1000mg daily for 2 weeks then "come back if it still hurts".
- wallace_f 8y ago
  It's so bizzare how in order to do this, that person had a barrier to entry of hundreds of thousands in private and public resources getting a license to help you. And they dont really help you. Compare to something like cops, who you have to interact with whether you like it or not, virtually have a license to kill, and are actually selected based on low IQ.
- goldfeld 8y ago
  These people are only barely doctors.
azhenley 8y ago
It isn’t enormous at all. 400mg every 4 hours is the OTC dose (at least in the US). My prescription was 800mg.
- Alex3917 8y ago
  > My prescription was 800mg. Sure, but it’s not like 800mg is 4x or even 2x more effective than 200mg. Ibuprofen is great, I just don’t really see the point of risking dying and whatever else for what’s at most a very marginal benefit. It’s not enormous in the sense that it’s uncommon per se, but rather in the sense that it’s way outside the efficient frontier on the risk/reward curve.
  - 8y ago

jimmyswimmy 8y ago

Having read half the paper, the treatment group took 600mg ibuprofen daily for 14 to 44 days to induce the reported effect of compensated hypogonadism, though the 12 and 24 hour effects on testosterone were apparently easily detectable on ex vivo testicle samples. So, maybe if you need your testosterone, keep off the OTC pain medications. And probably don't donate samples of your testicle either. Interesting paper though.

azhenley 8y ago
Did the effect go away when they stopped the treatment? I can’t read it at the moment due to slow WiFi.
- benmarten 8y ago
  What was the effect in the first place?
  - chiph 8y ago
    Hypogonadism. Which is basically "Your testosterone levels drop"
defertoreptar 8y ago
> the treatment group took 600mg ibuprofen daily for 14 to 44 days to induce the reported effect of compensated hypogonadism That phrasing is misleading. We don't know if it takes 600 mg for 14 days "to induce" hypogonadism. The study didn't test for that. It only tested if there would be an effect, and as with most pilot experiments, it did so cheaply and quickly. That's the idea of small sample size experiments such as this. Try a big dose as see if you get an effect at all. If so, that's a jumping off point for more rigorous, expensive studies later on.
- rjf72 8y ago
  600mg is not a large dose. Ibuprofen over the counter recommends 400mg (two tablets) every 4-6 hours with up to 6 tablets (1200mg) per day.

wmccullough 8y ago

As someone who is XXY, I can’t help but wonder what, if any issues would be caused by a pregnant mother taking a lot of this.

usaphp 8y ago
Pregnant women are advised to take Tylenol instead of Ibuprofen
lelandgaunt 8y ago
Long term acetaminophen usage is linked to a reduction in empathy.[0] [0]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5015806/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5015806/
- sawhit 8y ago
  As far as I can tell, the article linked says that there was a reduction in empathy (for pain) directly after being administered acetaminophen. I'm not seeing anything about long term use.
ojm 8y ago
In Australia , pregnant women are told not to take ibuprofen unless told by doctor. Paracetamol Is the pain killer suggested, and only if really required.
tbabb 8y ago
This seems like an endocrine effect, rather than a chromosomal one. I'd expect XXY to cause endocrine effects because sex-linked cells are operating with bad genetic info. This paper suggests that Ibprofen might cause sex-linked cells to misbehave because of chemistry. It doesn't seem like there is evidence here that Ibprofen would have had an effect on chromosomes. These are two independent causes of sex-linked malformity/endocrine issues, not a case of one causing the other.

iandanforth 8y ago

Along with the high sustained dosage others have mentioned the small sample size (14 in the experimental group) should be noted.

arikr 8y ago
This is worth reading: The "Unreliable Small-Sample" Misconception https://www.dailykos.com/stories/2008/11/9/656465/- https://www.dailykos.com/stories/2008/11/9/656465/- > My point here is that arguing that the sample is inaccurate simply because of how large or small it is is not correct. The size of the sample actually makes very little difference in how applicable the results are to the population. It simply makes the range of possible results smaller as the size of the sample increases. I've noticed a trend on reddit and HN where commenters will point out small sample sizes, often with the direct or indirect implication that this makes the study mostly invalid. I believe that's false - studies with small sample sizes can be very valid. The smaller the sample size the larger the effect size needs to be for it to be a statistically significant result, but a small sample size by itself isn't bad. And I think that the internet would be able to better appreciate research if more people were aware of the small sample size misconception.
- SamReidHughes 8y ago
  There's also temporal sample size: you can infer that A causes B if B happens very soon after A, and nothing else around that time might cause B. For example, if A is exposure to a chemical and B is an allergic reaction. Edit: A great example is that stomach ulcer guy.
- stewbrew 8y ago
  Since the article doesn't mention test power (and should it be for the reason of rebuttal of that Pearson-Neyman concept) I don't think it's a worth read. Sorry. "studies with small sample sizes can be very valid." They could be with a certain probability but (unless you believe in a very strong prior) you can't know with sufficient certainty.
- devwastaken 8y ago

eikenberry 8y ago

So back to good old aspirin? Acetaminophen slowly kills your liver and Ibuprofen messes with testosterone production.

tejasmanohar 8y ago
https://news.ycombinator.com/item?id=18787422 https://news.ycombinator.com/item?id=18787422
tchaffee 8y ago
Aspirin kills people too. Usually from stomach bleeding. If it's pain you're trying to reduce the only one I know of that has never killed anyone is cannabis.
Geimfari 8y ago
Please note that acetaminophen/paracetamol is incredibly safe at normal doses and does not kill your liver. It is only when you attempt to overdose (or if you have severely limited liver function) that you run out of the liver enzymes that break it down, causing liver damage.
- sodosopa 8y ago
  At normal doses, Acetaminophen can trigger Stevens-Johnson Syndrome and toxic epidermal necrolysis. You're lucky if you wind up with rashes as opposed to skin falling off.
  - naasking 8y ago
    > At normal doses, Acetaminophen can trigger Stevens-Johnson Syndrome Probably not: https://www.ncbi.nlm.nih.gov/m/pubmed/28963996/ https://www.ncbi.nlm.nih.gov/m/pubmed/28963996/
    - sodosopa 8y ago
      In my case, it does.

ttflee 8y ago

I once had an extraordinarily low level of blood testosterone reading after I had taken Ibuprofen for a few days.

tejasmanohar 8y ago
Just curious-- Did your blood T levels recover? How much / what % lower than normal? Was it just by chance that the T reading was days after Ibuprofen?

deleted 8y ago

[deleted]

emersonrsantos 8y ago

Ibuprofen induced liver toxiticy: https://livertox.nih.gov/Ibuprofen.htm https://livertox.nih.gov/Ibuprofen.htm "Rates of serum aminotransferase elevations during low dose, chronic ibuprofen therapy are comparable to those that occur with placebo controls (0.4%). However, higher rates of ALT elevations occur with high, full doses of 2,400 to 3,200 mg daily (up to 16%)."

tejasmanohar 8y ago
This is news to me. The more common side effect I've heard of from regular or excess NSAIDs like Ibuprofen are stomach problems (eg ulcers, gastritis, etc.).
- jjtheblunt 8y ago
  That's a side-effect of inhibiting cyclooxygenase-1, which correlates to mucus production, such as that which protects stomach linings. Ibuprofen is a non-selective "COX"=cyclooxygenase inhibitor so inhibits COX-2, correlated with inflammation, while undesirably also inhibiting COX-1. This gives rise to the selective COX-2 inhibitors, meant to reduce inflammation with minimal mucus inhibition, such as Celebrex and Firocoxib.
gregw2 8y ago
Speaking of liver toxicity, acetominophen/tylenol and alcohol can kill you. Not in the common case but if you are maxing out the acetaminophen for a prolonged period and drink and stop drinking, you should get educated on the dynamics and side effects. I was shocked to only find out about this midlife when my wife was on painkillers post surgery for an extended period and was using both painkillers and alcohol to self medicate. And her doc noticed some concerning liver results which later turned out fine. Be careful out there!
sannee 8y ago
> high, full doses of 2,400 to 3,200 mg daily Holy shit that's a lot of ibuprofen. If you are taking that much every day, you definitely have some more pressing concern than liver toxicity...

aejnsn 8y ago

Just had a kidney stone problem—first for me, quite painful experience. My ibuprofen dosage is 800mg every 8 hours, as needed. I had little choice. “Sustained” is the keyword of the study here. On another note, maybe this will drive alternative treatments such as CBD/marijuana for those who need to sustain their pain relief.

aiyodev 8y ago
I’ve suffered from kidney stones off and on for years. Here’s what helps. Make sure you’re drinking enough water. 2 gallons per day minimum. If your pee isn’t clear, you’re not drinking enough. I add flavor packets to mine to make it more palatable. I carry a water bottle with me all day. Went from an attack once a month to once a year. Mix pain meds. It’s perfectly healthy. Don’t take 800 mg of ibuprofen. Take a normal dose of ibuprofen (200 mg) and a normal dose of tylenol. Then tylenol and naproxen. Then naproxen and aspirin. Rotate them so you don’t get a megadose of any one. Each time take one that treats pain and one that treats pain and inflammation. A low dose of multiple drugs works way better than a large dose of just one. You’ll find yourself taking a lot less medicine overall and you won’t be in as much pain. Buy an electic heating pad and apply it to your lower back as soon as the symptoms start. Hope this helps.
- aejnsn 8y ago
  Thank you so much! I’ve been trying to gather as many details as I can to make sure this happens less frequently. I have changed my entire diet, drastically cutting sugar consumption. I had an ER doctor tell me there’s no possibility of this being hereditary. However, kidney stones are a problem for my mother, one of her siblings, and both of my grandparents. Waiting on a urologist consultation, but it’s under control for now.
  - aiyodev 8y ago
    It’s hereditary in my family.
Amezarak 8y ago
There is no silver bullet for targeted pain relief, or really, pretty much anything in the body. The body is an enormously complicated biological organism. Trading ibuprofen for Cvs/marijuana doesn’t trade side effects for no side effects, it trades one known and some unknown side effects for mostly unknown side effects.

Escolte 8y ago

Ibuprofen, as far as I am given to understand, is one of the most common drugs all around the world. Why didn't anyone notice before now, I wonder?

fuzzfactor 8y ago
Maybe their wives are taking it too.

bitL 8y ago

So, if one wants to reduce sex drive in order to focus on much more interesting tasks without any interruption, ibuprofen is the way?

ttflee 8y ago
https://www.buzzfeed.com/caseygueren/feeling-happy-but-not-sexy https://www.buzzfeed.com/caseygueren/feeling-happy-but-not-s...

burke 8y ago

> Our data demonstrate that ibuprofen alters the endocrine system via selective transcriptional repression in the human testes, thereby inducing compensated hypogonadism. Interesting. I’m no doctor, but this sounds like a not-super-transient effect. Amazing and slightly horrifying that they were able to measure this after a relatively short period of high-moderate sustained use.

Valmar 8y ago
I have to wonder how long the drug industry knew about this, but just brushed it under the rug like they do with all of their drugs, just to get them approved. When there's money to be made, dangerous side effects don't matter to them.
- Escolte 8y ago
  I also wonder why for example the Chinese or heck the Cubans didn't discover this before, who have less of a corporate interest. Ibuprofen (And Naproxen, etc...) is one of the most common drugs all around the world. I think most people I know have taken them at least once in their lifetimes. It's just all too weird. Is this all a malignant cover up by the industry? Don't know what to say, especially considering this was released 1 year ago and afaik no more research has been conducted on this.
  - zzzcpan 8y ago
    My perception is that in the US ibuprofen is used like candy, while it's not the same in other countries, where, for example, aspirin has that role.
    - Escolte 8y ago
      I was prescribed to take Naproxen, another NSAID with potentially the same harmful effects as Ibuprofen, for two weeks three times a day half a dose. I'm from Spain. But IDK. Let me reiterate that everyone all around the world uses Ibuprofen.

dilyevsky 8y ago

Really cool. I’ve been hearing for years now in the athletic community that ibuprofen “kills gains”. Thought it was just a fud. Turns out - likely not.

skellera 8y ago
I thought that’s based on the anti inflammatory effects of it. I don’t personally understand it but inflammation is supposed to help muscle growth.

tzjmetron 8y ago

Okay, that's enough ibuprofen for me. Ever. Fuck the whole pharma industry.

rbjorklin 8y ago

My understanding is that Hypogonadism can also affect women. Have a similar study been made on women? I’m under the impression that a lot of women eat painkillers to get through menstrual cramps so this could be a huge problem for women too I guess?

miguelrochefort 8y ago

I've had frequent migraines all my life (although it's much better now) and ibuprofen is the only thing that works. As a kid, I would take 200mg whenever I had a headache. To this day, I still haven't switched to the adult dose of 400mg. I think a lot of people will find ibuprofen to be effective even at lower doses. I'm sad to find that ibuorofen has so many negative side effects. For me, it's been a miracle drug. I rarely feel as good as I do after taking it. I generally feel happier, with clearer thoughts and less anxiety.

godelmachine 8y ago

Does ibuprofen have anything to do with finasteride?

mirimir 8y ago

From the paper:[0] > The so-called “over-the-counter” mild analgesics (hereafter simply called “analgesics”), such as acetaminophen/paracetamol, acetylsalicylic acid/aspirin, and ibuprofen, are among the most commonly used pharmaceutical compounds worldwide (6, 7). Increasing evidence from recent years shows that exposure to analgesics can generate negative endocrine and reproductive effects during fetal life (6). Nonetheless, no in-depth studies have analyzed the effect of mild analgesics on the human pituitary–gonadal axis. In this context, ibuprofen is especially interesting because of its increasing use in the general population and in particular by elite athletes (8⇓⇓⇓–12). So now I wonder about acetaminophen/paracetamol, and aspirin. And naproxen. Maybe that's why I need testosterone supplementation. In addition to the fact that I'm old. 0) https://www.pnas.org/content/115/4/E715.long https://www.pnas.org/content/115/4/E715.long

CapitalistCartr 8y ago

Prior discussion: https://news.ycombinator.com/item?id=16101072 https://news.ycombinator.com/item?id=16101072

Barjak 8y ago

Due to an autoinflammatory condition, I've taken ~1800mg daily for periods of 6 months several times. I don't like the idea of going on opioids for longer that a couple weeks, but maybe I need to switch.

cfmcdonald 8y ago

Ibuprofen has been taken regularly in substantial doses by millions of people for decades. The prior probability that it has some heretofore unknown serious side effect is very low, so it would take a lot of evidence to convince me that this is real.

TagAsDelusion 8y ago

quick, fill the conversation with doubt