Ibuprofen alters human testicular physiology to produce compensated hypogonadism
ncbi.nlm.nih.gov
ncbi.nlm.nih.gov
> 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.
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.
For those talking about hyperthermia killing, yes but in almost all those cases the cause is not an infection.
In fact, I would say that paracetamol kills a hell of a lot more patients than it actually ‘saves’.
A study I have taken to heart is that permissive hyperthermia (up to 40 deg c) in ICU patients has a greater survival than those where fever is treated aggressively.
Physiologically, this resonates because high temperatures activate the immune system and raised temperatures are non-optimal for bacterial proliferation; so the immune system is primed by fever; suppressing it can dull immune system response.
In fact, malaria was used as a treatment for syphillis in the early parts of the 20th century because high temperatures kill spirochetes. There are also a decent number of case reports of cancers going into remission following fever.
However in my quick mobile google then I could only see the following study that demonstrated no advantage for either control of permissive hyperthermia group in ICU patients; so perhaps I was relying on a study that has been superceeded.
You don't want to stop a fever ~ just keep it within the safe zone where it's healing, but not dangerous.
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.
On top of that numerous recent studies have shown many potential problems.
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.
What's wrong with cannabis-derived solutions, again?
Also, FWIW, in the past, I tried both CBD and THC without any luck where Ibuprofen helped so it's certainly not 1:1
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".
And others.
True or not, parent wasn't just making up the empathy-painkiller association.
(Even though it's clearly not net-helpful due to the serious physiological side-effects.)
That's amazing!
... why isn't there more research on isolating this particular side-effect?
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?
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.
I had Oramorph for abdominal pain (in hospital, no surgery thankfully). The condition may have been caused by medium term use of Ibuprofen (in my non-medical opinion).
One thing is not to put medicines, OTC or not, into the trash. They are nasty stuff to have in the dump.
As for the drugs: don’t take analegics if you don’t need to; do if you can’t tolerate the pain. Everybody has a different level of pain and tolerance and I bet the prescription said something along the lines of “...as needed”
As for other prescriptions, do your research; odds are you do need it but not always.
My recommendation is to go and talk to your doctor and confront him or her with this "finding".
Also, most importantly, this "finding" has been out for almost a year now. I wonder what's the more recent development on it.
These doctors don’t just give pills out randomly, they do it for a reason based on evidence and science. A side note is that my pharmacist made it very clear to only use the painkillers as necessary. You should always consult the doctor and pharmacist after major surgery to clarify these things if needed.
IMHO the doctors should prescribe less at first and see if it would be enough, but I also get that they are overcrowded and the same patient coming back for just more painkillers might be a little too much.
Regarding opioid based pain-killers... for all the negative attention they get, they're also usually fine for most people - when used as directed and, again, for a short-period of time.
Not everybody who takes a few Oxycodone tablets winds up addicted and then reduced to using heroin to get their fix.
I finally caved and then took a half dose right after the extraction because I was fearing terrible pain, especially since the surgeon said mine was a fairly difficult job that would probably end up causing more pain than is typical.
The half dose of painkiller made me extremely nauseous, and so I decided to just try the 800mg of ibuprofen, and it did the job perfectly. I did feel a little sore and stiff, but never in pain unless I waited too long for another ibuprofen dose. It was the same for my girlfriend, who was also prescribed the pain killer but didn't take it because she didn't feel she needed it either.
The pain killer being prescribed didn't bother me per se, and neither did the recommendation, and I don't think anything nefarious was going on. Also, everyone's body is different. But given the side effects, and potential side effects, I just felt that even a simple "we recommend you get this prescription filled, but please see how the ibuprofen works first, and only take the pain killer if you can't handle the pain on ibuprofen alone" would have been a better way to handle it.
>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
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.
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.
I thought bacterial infections were the response were the reason people died before antibiotics. Fever is the body's response to infection, a primitive means of fighting it. If somebody has a serious infection and you give them anti-fever medication but no antibiotics, they're still at serious risk of death even if their fever goes away.
According to the first article I found while Googling: https://www.google.com/amp/s/www.nytimes.com/2018/05/11/well... :
"The best evidence suggests that there is neither harm nor benefit to treating a fever with fever-reducing medications like acetaminophen or ibuprofen."
"In 1997, these data led to a large, randomized, placebo-controlled trial of ibuprofen in 455 patients with sepsis, a life-threatening infectious condition. In this study, ibuprofen failed to prevent the worsening of sepsis and failed to decrease the risk of death."
So there's no evidence that such drugs actually stop fever "before it gets too late" in adults, as they don't reduce risk of death. I had wrongly assumed the same applies to children.
As often as you need when they have a fever. Modern thermometers can give you the temperature in a minute or so.
There should be no major variation then. On the other hand, if the child reaches 38+ or so, you need to be on the lookout...
"The best evidence suggests that there is neither harm nor benefit to treating a fever with fever-reducing medications like acetaminophen or ibuprofen."
"In 1997, these data led to a large, randomized, placebo-controlled trial of ibuprofen in 455 patients with sepsis, a life-threatening infectious condition. In this study, ibuprofen failed to prevent the worsening of sepsis and failed to decrease the risk of death."
The science doesn't seem to support the notion that reducing fever will reduce the risk of fatality in the general case. I had assumed the same thing also applied to children, as before this thread I'd never heard of children getting seizures from fever (at least not from any of the children/parents I knew growing up in rural Australia).
Seems like teaching kids to meditate would have all sorts of benefits, including drug free pain management.
https://www.psychologytoday.com/us/blog/mindfulness-in-frant...
Do you give your children general anesthesia when they are in pain? E.g. they've fallen and bummed their knee or something?
Why not, since it would be the ultimate pain-killer? Because it's both dangerous and unnecessary.
The parent has the same reasoning for other unneeded and dangerous drugs.
Why can discuss whether they're really as unneeded and dangerous as the author implies, but that's another question, not loaded with "why don't you love your children" implications...
Thought effect: if you had the option to eliminate a kid's pain with an 0.01% chance of causing a lasting defect, would you do it? Not everybody would; different people have different time preferences.
That’s the more shocking belief from my perspective.
Or are you OK with hurting your kids, as long as they don't feel the pain?
(I'm putting the questions in the same tone you put yours)
Would you also give your kid anti-diarrhea and let the disease spread in order to stop the immediate unpleasantness?
[1]https://www.health.harvard.edu/diseases-and-conditions/fever...
Strong fevers should be controlled usually
Also don't forget about patient comfort (if it gets too high it feels awful)
You can use any drug containing Paracetamol (Tylenol, Panadol). It isn't that effective, but it works and as far as we know it's perfectly safe if you adhere to dosage recommendations.
My sons hated taking medication. I gave them non drug options on a routine basis for minor ailments because they didn't want to take drugs if they didn't have to.
How much/often were those people taking ibuprofen to have those effects? And how worse were they than the baseline? From what I see, they took 3 times a day for 2-3 weeks (not just to pass a small fever), and they were older men to begin with (e.g. already on a downfall for testosterone).
https://www.mayoclinic.org/diseases-conditions/reyes-syndrom...
https://www.mdmag.com/medical-news/is-there-a-link-between-l...
I honestly think the obstacle to Cannabis legalization in the US is social conservatism, not industrial lobbying.
I’m taking 5Mg capsules 2x a day.
This is news to me. What exactly does "toxic" mean? Do you have a citation I can read?
Acetaminophen is not for inflammation anyway.
In fact, paracetamol poisoning is the primary cause of death in overdoses (in the US, UK, Australia and New Zealand)[2]. And in 2006, [3] found it was the most commonly used compound for intentional overdosing (i.e. suicide by overdose).
But of course, this depends on taking a very high dose -- paracetamol isn't dangerous in moderate doses.
[1]: https://en.wikipedia.org/wiki/Paracetamol_poisoning [2]: https://www.ncbi.nlm.nih.gov/pubmed/18312195 [3]: https://www.ncbi.nlm.nih.gov/pubmed/16805658
Sure, and drinking too much water causes hypernutremia that can also kill you. Toxicity is always dose dependent, so the initial unqualified claim seemed to imply toxicity at normal dosages.
Paracetamol poisoning is fairly common, hypernutremia isn't. Don't get me wrong, I disagree with the original statement that paracetamol is toxic (with the implication that this is a reason not to use it in normal dosages). But it's definitely not harmless.
Probably the closest to harmless you can get are the inert gasses, and even then they can cause harm by displacing oxygen to deadly levels.
This doesn't really undercut anything you say, but if I was given accurate information I assume a subset of those acetaminophen OD deaths are from people abusing painkillers it's combined with. I haven't looked into it, but I assume this is also a partial explanation of why OTC cold medications with Dextromethorphan in them tend to be combined with a relatively high dose of acetaminophen. I would guess there are other good examples of abusable pharmaceuticals combined with acetaminophen.
However, there's a more important medical reason: acetaminophen accentuates the analgesic affects of opioids, although the mechanism for this is not clearly understood. This makes acetaminophen-enhanced opioids more effective drugs.
Opioid abuse has become so rampant, though, that we're moving away from prescribing acetaminophen-enhanced opioids like Vicodin and Percocet to try to stop them entering the recreational drug market. As opioid use has increased, so has the number of liver toxicity deaths due to the acetamiophen in some prescription opioid drugs.
But the original point was about whether paracetamol is toxic, not how often people overdose on Panadol (though that does happen in suicides). And the answer is "yes, but not in the dosages you'd normally see".
No, it isn't, and for the people who die from paracetamol it's an intentional overdose, it's very rarely an accidental overdose.
In the US about 500 people die each year from acetaminophen overdose per year, compared to over 70,000 from opioids.
Your link number 3 is talking about compounds containing paracetamol. For example, this includes coproxamol. Anyone overdosing on coproxamol was dying from the opioid (dextropropoxyphene), not from the paracetamol.
In the UK we have the ONS deaths related to drugs poisoning. Figure six shows deaths compared by drug type, and paracetamol clear isn't the highest: https://www.ons.gov.uk/peoplepopulationandcommunity/birthsde...
We also have the NCISH data. Item 120 here: https://documents.manchester.ac.uk/display.aspx?DocID=38469
3095 deaths by self-poisoning.
Substance Number
Opiates/opioids 947 33%
- opiates only 746 26%
- paracetamol/opiate compound 201 7%
Non-opiate analgesics 205 7%
Antipsychotics 302 11%
Antidepressants 587 21%
- tricyclics 271 9%
- SSRI/SNRIs 260 9%
- other antidepressants 56 2%
>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.
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.
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.
The rebuttal was also not published in Nature, but it was closer, published in Nature Reviews Urology.
I think the main basis for the criticism is that they didn't look at clinical outcomes like infertility or ability to conceive. As a result, we only have a (very robust) report of a relationship between ibuprofen and hormone levels, not between ibuprofen and x, where x is some directly important/meaningful clinical outcome.
why not?
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.)
Interesting paper though.
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.
Doctors can also recommend an even higher dosage of 600mg 4 times a day to about 2400mg a day if needed.
Source: Https://www.nhs.uk/medicines/ibuprofen-for-adults/
I suppose I should just use naproxen or acetaminophen? Ibuprofen always seemed the most effective to me.
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.
Don't take it every day though. Maybe once a month if I feel like the headache hurts me more than usual.
Edit: I got Sanomit q10 and Ankermann B12 (1000ug).
That sounds strikingly familiar. Is it my eyes? My sinuses? Allergies? My pillow? For 15 years and countless doctors nobody could figure it out. Then I went to the dentist and had my bite corrected and have not had a migraine since. I believe my bad bite was causing me to clench my jaw in my sleep.
In NZ / Singapore I have to visit a doctor to get synflex, so I usually just visit the pharmacy while I'm in Taiwan and pick up ~50 or so Naposin pills (generic naproxen) while I'm there. Costs ~$10 usd.
Never needed to go any stronger.
That said, like the OP, I used to also take lots of Ibuprofen for headaches, and unfortunately, Acetaminophen never seemed to work for more than an hour or two max (tested in "isolation" for 7+ days), while Ibuprofen could stop the headache cycle for a day+.
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.
When there's money to be made, dangerous side effects don't matter to them.
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.
But IDK. Let me reiterate that everyone all around the world uses Ibuprofen.
On another note, maybe this will drive alternative treatments such as CBD/marijuana for those who need to sustain their pain relief.
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.
A friend used to pop ibuprofen casually after gym sometimes to relieve sore muscles. That's messed up.
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.
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.
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%)."
This gives rise to the selective COX-2 inhibitors, meant to reduce inflammation with minimal mucus inhibition, such as Celebrex and Firocoxib.
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...
> 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.
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.
Probably not:
The "Unreliable Small-Sample" Misconception
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.
Edit: A great example is that stomach ulcer guy.
"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.
Using a ridiculous example "for a sample set of 10, the author found that exposure to fire causes burns" would hopefully not draw similar sampling concerns but as I don't know this subject matter deeply, I can't comment whether it is true for this case
In seriousness, this is a lazy claim when you could have actually addressed the study in question. Since you did not, I assume you have no supporting observations.
Or, if you want to some it all up in a single graph: https://andrewgelman.com/2014/11/17/power-06-looks-like-get-... (although your experiments hopefully have power much greater than 0.06)
The gist of the point: If your sample size is small, significant results are likely to (sometimes vastly) overestimate the true effect size, and there is a non-negligible chance that the effect size is actually estimated in the wrong direction.
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.
Ibuprofen is not the painkiller where taking 2x the recommended limit has an enormous risk of death.
Mostly because of renal damage and gastrointestinal issues, if I remember correctly.
600mg a day is barely above a single dose.
600mg is over half a gram of pure active ingredient.
Namely isobutylphenylpropionic acid, a cheap commodity product.
This material is not non-toxic and different people will succumb at different levels of lethality to different doses over different periods of time.
Not long ago I lost a friend to liver and kidney failure attributed by her final doctor as due to the 800mg daily recommended by her previous physician over a few year period.
We pretty much call the 800mg tablets grunt candy.
In my 20 years I beat my body up pretty bad and I am paying for it now. I have had a couple of surgeries on my shoulders. I have bad knees, lower back, and some neck issues that I am trying to rehab and make better but I will never be 100%. I'm just shooting for less pain and more mobility.
Oh, and for going right back into the same activity after you injured yourself. That is just the job. The training keeps going. In a wartime situation you would not be able to quit if you get hurt. You just have to keep moving.