Are the negative effects of antibiotics on male fertility permanent?

[Alfred001]

I was shocked to find recently that there is apparently a lot of animal and some human data showing that antibiotics have a negative effect on male fertility. Given how serious this is, I couldn't believe this isn't more widely known and I was even more shocked at how little human data there is, again, given the seriousness.

Does anyone know whether these effects are permanent?

From the review I'm currently reading, it seems the effects usually last a long time post-treatment (weeks or months) and whether they are permanent or not is usually not answered due to how short the followup is. But certainly, the effects will usually still be present many weeks post-treatment.

[StringJunky]

Aw shucks, recently did a week on Co-Amoxiclav 500. That's my baby making prowess down the the toilet for a while. No drugs are risk-free and is always subject to risk-benefit analysis. I'm sure we've been here before.

Edited March 19 by StringJunky

[Alfred001]

3 hours ago, StringJunky said:

Aw shucks, recently did a week on Co-Amoxiclav 500. That's my baby making prowess down the the toilet for a while. No drugs are risk-free and is always subject to risk-benefit analysis. I'm sure we've been here before.

But the point is we don't know whether it's for a while or permanently. Were it just for a while, who cares.

[StringJunky]

22 minutes ago, Alfred001 said:

But the point is we don't know whether it's for a while or permanently. Were it just for a while, who cares.

That is probably specific to an individual and how low their fertility is in the first place.

[swansont]

23 hours ago, Alfred001 said:

But the point is we don't know whether it's for a while or permanently. Were it just for a while, who cares.

If it were permanent we’d probably notice the correlation.

[exchemist]

14 minutes ago, swansont said:

If it were permanent we’d probably notice the correlation.

There have, I believe, been reports of reduced sperm count in industrialised societies and some discussion about what might be responsible. Things like endocrine disruptors get mentioned but so far as I know nobody has fingered the widespread prescribing of antibiotics. 

Edited March 20 by exchemist

[StringJunky]

14 minutes ago, exchemist said:

There have, I believe, been reports of reduced sperm count in industrialised societies and some discussion about what might be responsible. Things like endocrine disruptors get mentioned but so far as I know nobody has fingered the widespread prescribing of antibiotics. 

Pthaalates probably, that softens plastics. Apparently, they migrate out over time.

[TheVat]

On 3/18/2024 at 12:33 PM, Alfred001 said:

I was shocked to find recently that there is apparently a lot of animal and some human data showing that antibiotics have a negative effect on male fertility. 

Got citation?  Would like to see the data.

[Alfred001]

2 hours ago, swansont said:

If it were permanent we’d probably notice the correlation.

If everyone who took an antibiotic became infertile and this was true of every antibiotic, maybe, but if the effect is not that strong, not necessarily.

https://www.nature.com/articles/nrurol.2015.145

Quote

Some of the effects of medications are difficult to study
and are only identified after drug approval and market-
ing. The difficulty in determining the influence of medi-
cations on male fertility arises from several factors. Some
of the early research did not investigate effects on male
reproduction at all; for example, sulphasalazine was used
in clinical therapy for ulcerative colitis and rheumatoid
arthritis in young men for nearly 40 years before its
gonadotoxic effects were identified.

Now, sulphasalazine actually has a temporary effect, but it goes to the point that effects of medications can be difficult to notice.

43 minutes ago, TheVat said:

Got citation?  Would like to see the data.

Here's a review

https://www.researchgate.net/profile/Tosin-Titus-Olaniran/publication/373776557_Research_Advances_on_the_Adverse_Effects_of_Antibiotics_on_Male_Fertility/links/64fc46fa90dfd95af620eb67/Research-Advances-on-the-Adverse-Effects-of-Antibiotics-on-Male-Fertility.pdf

[John Cuthber]

I checked the data.
It turns out that every man who died from an infection is infertile.

[TheVat]

To whoever neg repped John C, I think he was joking.  And his jest reminds us that male fertility drop is, as the paper notes, quite "multifactorial" in its causation.

Indeed, I find it really hard to pinpoint much beyond fuzzy correlations there.  For instance, the cohort of young men in one of the studies could likely include many men who are temporarily unemployed (i.e. they have free time to volunteer for such a medical study, especially if they were compensated).  Unemployment might present other causal factors towards reduced sperm count, e.g. certain leisure time activities that reduce sperm count, or psychological factors that correlate with a drop in fertility.  My sense is that sample randomization is extremely challenging in such studies.  

 

@Alfred001  Thanks for the citations!

 

 

Edited March 20 by TheVat
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[Alfred001]

20 minutes ago, TheVat said:

To whoever neg repped John C, I think he was joking.  And his jest reminds us that male fertility drop is, as the paper notes, quite "multifactorial" in its causation.

Indeed, I find it really hard to pinpoint much beyond fuzzy correlations there.  For instance, the cohort of young men in one of the studies could likely include many men who are temporarily unemployed (i.e. they have free time to volunteer for such a medical study, especially if they were compensated).  Unemployment might present other causal factors towards reduced sperm count, e.g. certain leisure time activities that reduce sperm count, or psychological factors that correlate with a drop in fertility.  My sense is that sample randomization is extremely challenging in such studies.  

 

@Alfred001  Thanks for the citations!

 

 

I don't think there can be any doubt that the relationship is causal. I've read quite a bit of literature at this point. They take lab animals, give them antibiotics, and you see negative effects on all kinds of parameters of fertility, as well as outcomes (implantations and births). As clearly causal as it gets.

Take this study as an example. Four groups of rats, three given imipenem/cilastatin, one control group. The treatment groups see negative effects on sperm parameters and sexual organs relative to control. There are endless studies like that.

Edited March 20 by Alfred001

[swansont]

2 hours ago, Alfred001 said:

If everyone who took an antibiotic became infertile and this was true of every antibiotic, maybe, but if the effect is not that strong, not necessarily.

You characterized this as a possible serious issue, which suggests a strong effect. If it’s hard to notice, it can’t be. You can’t have it both ways.

[TheVat]

 

 

14 minutes ago, Alfred001 said:

I don't think there can be any doubt that the relationship is causal. I've read quite a bit of literature at this point. They take lab animals, give them antibiotics, and you see negative effects on all kinds of parameters of fertility, as well as outcomes (implantations and births). As clearly causal as it gets.

Take this study as an example. Four groups of rats, three given imipenem/cilastatin, one control group. The treatment groups see negative effects on sperm parameters and sexual organs relative to control. There are endless studies like that.

But this still only establishes a correlation, i.e. it could be an indirect causation.  For example, antibiotics temporarily alter our colonies of gut microflora (and do so in other mammalian species).  This can change nutritional absorption, which in turn can affect fertility markers.  So it is possible that humans, if they combined antibiotic treatment with probiotic treatments in the gut to counteract shifts in population of microflora, would not see the same decline in fertility.  So "clearly causal" can have many hidden assumptions that need to brought to light and studied.  Humans are incredibly complex ecosystems. 

 

[Alfred001]

19 minutes ago, TheVat said:

 

 

But this still only establishes a correlation, i.e. it could be an indirect causation.  For example, antibiotics temporarily alter our colonies of gut microflora (and do so in other mammalian species).  This can change nutritional absorption, which in turn can affect fertility markers.  So it is possible that humans, if they combined antibiotic treatment with probiotic treatments in the gut to counteract shifts in population of microflora, would not see the same decline in fertility.  So "clearly causal" can have many hidden assumptions that need to brought to light and studied.  Humans are incredibly complex ecosystems. 

 

But the exact mechanism is not relevant for the purpose of discovering whether there's a permanent effect. The point is it establishes that there is a clear causal effect. The question I'm wondering about is, is there data that shows a permanent effect.

23 minutes ago, swansont said:

You characterized this as a possible serious issue, which suggests a strong effect. If it’s hard to notice, it can’t be. You can’t have it both ways.

If half of antibiotics make half of people half as likely to conceive (substantial effect), would we make the connection that someone failing to conceive now is failing because he took a course of antibiotics 10 years ago?

Quote

Some of the effects of medications are difficult to study
and are only identified after drug approval and market-
ing. The difficulty in determining the influence of medi-
cations on male fertility arises from several factors. Some
of the early research did not investigate effects on male
reproduction at all; for example, sulphasalazine was used
in clinical therapy for ulcerative colitis and rheumatoid
arthritis in young men for nearly 40 years before its
gonadotoxic effects were identified.

They are not talking about a permanent effect there, but it makes the point. (source)

Edited March 20 by Alfred001

[swansont]

1 hour ago, Alfred001 said:

If half of antibiotics make half of people half as likely to conceive (substantial effect), would we make the connection that someone failing to conceive now is failing because he took a course of antibiotics 10 years ago?

Given how many people are prescribed antibiotics, I’d say yes.

270 million prescriptions a year in the US. 805 per 1,000 people.

https://www.michiganmedicine.org/health-lab/nearly-quarter-antibiotic-prescriptions-may-be-unnecessary#

 

Fertility clinics would be flooded. Not the ~8% rate we see from men.

https://www.yalemedicine.org/conditions/male-infertility/

[Alfred001]

34 minutes ago, swansont said:

Given how many people are prescribed antibiotics, I’d say yes.

270 million prescriptions a year in the US. 805 per 1,000 people.

https://www.michiganmedicine.org/health-lab/nearly-quarter-antibiotic-prescriptions-may-be-unnecessary#

 

Fertility clinics would be flooded. Not the ~8% rate we see from men.

https://www.yalemedicine.org/conditions/male-infertility/

Ok, fair point. But, if you assume 10% of antibiotics reduce fertility in 50% of men who take them and you take into account that antibiotics are probably more often prescribed to older people not trying for children... I'm not sure.

[swansont]

3 hours ago, Alfred001 said:

Ok, fair point. But, if you assume 10% of antibiotics reduce fertility in 50% of men who take them and you take into account that antibiotics are probably more often prescribed to older people not trying for children... I'm not sure.

That would still account for a large fraction - about half - of the cases of infertility. It would mean other factors are not in play.

[Alfred001]

13 hours ago, swansont said:

That would still account for a large fraction - about half - of the cases of infertility. It would mean other factors are not in play.

How do you get to half cases of infertility?

[swansont]

19 minutes ago, Alfred001 said:

How do you get to half cases of infertility?

10% of antibiotics is about 8% of prescriptions in a given year. I’m assuming a similar fraction of the population gets a prescription at some point. 50% of that is 4%. That would account for half of the infertility rate.

Even with a shift from “antibiotics have a negative effect on male fertility” to “a small fraction of antibiotics have a negative effect on male fertility”

[Alfred001]

But this is an argument in my favor.

[Luc Turpin]

It is clear from data that sperm count is down from previous decades (-50% in some studies)

It is also clear that multiple causes are involved in lowering sperm count (pollution, endocrine disruptors, etc.)

There is evidence that antibiotics reduce fertility.

But, I don't think that considerable permanent infertility can be extrapolated from any of the available data.

And as mentioned, we see no evidence of this in the real world (fertility clinics for example)

Also, notwithstanding the reason, use antibiotics only when needed or when other treatments have failed.

We should be more worried about antibiotic resistance then infertility.

....than infertility.....sorry

[John Cuthber]

Though I made it humorously, the point  I was making is very simple.
They don't give you antibiotics unless you are sick.
So the question is, which is likely to have a greater effect on fertility; the drugs or the infection?

It's perfectly plausible that not taking the pills will leave you dead.
And that's going to reduce our fertility much more than the drugs will.
(An infection may also reduce it)

Doctors and health insurance systems (private or nationalised)  are fairly good at doing risk/ benefit analyses.
Only focussing on the risks of antibiotics is just as  foolish as ignoring them.

[swansont]

1 hour ago, Alfred001 said:

But this is an argument in my favor.

When you have to move the goalposts, I wouldn’t say so.

[Alfred001]

3 hours ago, swansont said:

When you have to move the goalposts, I wouldn’t say so.

Moving the goal posts is valid when we're talking about an unknown effect. We don't know whether 100% or 10% of antibiotics have this effect. Both are possible given the data we have, so there's nothing invalid in discussing the first scenario and then moving to the second.