
Ibuprofen alters human testicular physiology to produce compensated hypogonadism - wallace_f
https://www.ncbi.nlm.nih.gov/m/pubmed/29311296/
======
jey
"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
Sounds like the industry responding with "we cant really know guys, right?"
I'm throwing away my Advil right now. Screw that.

~~~
drb91
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?

~~~
conanthe
Kratom / Cannabis oh wait these are illegal so big pharma can milk their
poisons.

~~~
braythwayt
Here in Canada, Big Pharma are falling over themselves to get into the
Cannabis business.

I honestly think the obstacle to Cannabis legalization in the US is social
conservatism, not industrial lobbying.

~~~
code_duck
The social conservatism about cannabis was created and stoked by propaganda
and laws created in large part due to industrial lobbying, if you look back a
generation or two.

------
jimmyswimmy
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.

~~~
defertoreptar
> 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
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.

~~~
gameswithgo
and doctors will commonly suggest taking 4 tablets 4 times a day

------
azhenley
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
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.

~~~
donjoe
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
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.

~~~
donjoe
Better check with the doc first. Otherwise you'll produce expensive piss with
no effect. All vitamins I bought outside the pharmacy didn't work for me so
better try to go with the 'real' but more expensive stuff prescribed by a doc.

Edit: I got Sanomit q10 and Ankermann B12 (1000ug).

------
burke
_> 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
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
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
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
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.

~~~
zzzcpan
I'm curious, did you have naproxen/ibuprofen at home before they prescribed it
to you? Probably not, but I bet you have aspirin at home.

~~~
Escolte
Nope, but Aspirin, Ibuprofen and Paracetamol yes, since they are considered
"staple" medicine.

------
aejnsn
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
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
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
It’s hereditary in my family.

------
wmccullough
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.

~~~
lelandgaunt
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
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.

------
miguelrochefort
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.

------
emersonrsantos
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
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
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.

------
mirimir
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)

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

~~~
Geimfari
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
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
> 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
In my case, it does.

~~~
naasking
So you took acetaminophen in a controlled setting and definitively established
a causation? Or was it uncontrolled and could have been caused by any number
of uncontrolled variables? Because a definitive causation is publication
worthy.

------
rbjorklin
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?

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

~~~
arikr
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.

~~~
devwastaken
Sample size is related to the conclusions you can draw. If their goal is that
ibuprofen has this effect, then 15 can be enough given the specific effects
they are getting. If their goal is more complex, say that ibuprofen reduces
fertility, that's be a lot harder if the effect wasn't massive and well
reproduceable.

~~~
yomly
I find this topic hard to comment on specifically, but I think you are
probably on the right lines about specificity of the observed phenomenon being
of key here.

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

------
Escolte
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
Maybe their wives are taking it too.

------
cfmcdonald
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.

------
Barjak
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.

------
CapitalistCartr
Prior discussion:
[https://news.ycombinator.com/item?id=16101072](https://news.ycombinator.com/item?id=16101072)

------
godelmachine
Does ibuprofen have anything to do with finasteride?

------
dilyevsky
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
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.

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

~~~
tejasmanohar
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?

------
Alex3917
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.

~~~
eaandkw
Clearly you have never been in the USMC. In hind sight it was pretty stupid
but I have taken up to 1600mg per day for several days/ weeks in a row.

We pretty much call the 800mg tablets grunt candy.

~~~
whatshisface
What is happening that gets everyone so inflamed? If you take a painkiller and
go right back to the activity that damaged you you are begging for permanent
injury.

~~~
gaius
Wear and tear on the knees generally. And yes, many infantrymen do have
permanent problems by their 30's.

~~~
eaandkw
We usually have an expression that infantrymen age in dog years.

------
bitL
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
[https://www.buzzfeed.com/caseygueren/feeling-happy-but-
not-s...](https://www.buzzfeed.com/caseygueren/feeling-happy-but-not-sexy)

