Male: stop rapamycin to have kids? How long?

Hi all,

I’m a 37 year old male who started dating a 28F wonderful woman recently and we’re looking to start trying for kids in possibly a year or so (4 kids is the goal). I’ve been taking around 10mg/week of rapamycin for the past 3-4 years with no ill effects, but am aware of detrimental effects on sperm and male fertility. I want to ensure we have the best chance of a quick pregnancy and healthy children, so am looking to get a sperm/fertility test now (as baseline), and stop taking rapamycin sometime.

I’m concerned about sperm amounts (which has been seen in rat studies), but even more so about potential teratogenic effects (i.e. increased chance of birth defects, not seen in rat studies?).

Do you guys have any ideas/studies on how long I should be off rapamycin for trying to have children? Any relevant studies or guidelines?

Thanks!

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Hi, I’ve done a little research into this but I’m not sure what I’ve posted in the past. I’m not a doctor - so the best thing to do is talk with your doctor who you’ve been working with on the rapamycin prescription. If you’ve been taking the biohacker approach then here is some information I’ve found that may be of help.

The half life of rapamycin is around 60 to 70 hours typically - so in a week or 2 weeks it should be completely out of your system. So thats one consideration.

Another consideration is the growth and development cycle of sperm. I’ve read here that its about 64 days, and I suspect that given rapamycin’s impact on cell growth and development that it likely has an impact on early sperm development and growth - so if it were me, I’d want at least one, and perhaps two of these cycles to have passed before trying for a pregnancy. How Long Does It Take for Sperm to Regenerate? Tips for Production.

If you review the research literature on transplant patients I seem to remember that their doctors have the patients move off of rapamycin and stay on other immosupressant drugs typically at least 12 to 16 weeks prior to pregnancy. I don’t have that info in front of me but will look for it. There are of course many examples of this now - transplant patients going off rapamycin for pregnancy purposes - so a fair amount has been written about it.

Of course the situation with transplant patients is very different from a healthy person pausing rapamycin, as most longevity enthusiasts have not not had the health problems / complexities and long period of multiple immune suppressant medications (e.g. cyclosporin), for years prior to pregnancy. Most organ transplant patients (males) have been overweight and in poor health for many years - so they likely have many health and reproductive issues irrespective of the rapamycin use. But its the best Information we have available.

So, if I were in this situation I would plan at least 4 months of being off rapamycin prior to pregnancy to be on the safe side.

Please post your sperm count information pre and post - as that would be interesting information for others in your situation.

Some reading you may want to do:

The rapamycin analog Everolimus reversibly impairs male germ cell differentiation and fertility in the mouse.

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I finally submitted the sample and got the results. Overall it was simple and inexpensive: $190 for the test, take a sample in the morning and mail it in the provided container/box.

Good news! All the results came back great - my semen quality is all ok. So it seems that the pulsed dosing doesn’t affect sperm production too much. But who knows: I’m overall very healthy so maybe the stats would be even better without rapamycin.

In any case - this is a positive indicator that the dosing frequency really does matter and creates different results. I’ve attached my anonymized results in case you all are curious.

I think I’ll just stay on rapa for now…

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Those studies are helpful, thanks! I am in my mid 40s and my wife is in her early 30s and we have been having similar discussions. I had been on rapamycin for a few years (stopping prior to any attempt to conceive) and she is considering doing the same after pregnancy and breast feeding have concluded.

We have an additional question:

Are there any risks to the baby or mother if the father resumes taking rapamycin during pregnancy or breastfeeding?

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Are there risks to the baby or mother if the father is taking rapamycin?

I can’t see how there could be, unless you’re doing blood transfusions from the father to the mother or baby? Its not going to transfer in any meaningful quantity from bodily fluids (i.e. kissing or sex)…

How are you thinking it might get from the father to the other bodies?

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Good question. Although the amounts would be minuscule I was worried about rapamycin being present in semen and transported to the already pregnant mother that way.

Of course I would be happy to learn that is not a risk

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I really can’t imaging that the amount of rapamycin in any discharge of semen is going to be anything meaningful in terms of a medical effect on a woman. The average dose that people are taking of rapamycin is in the 6mg to 10mg per week (once per week). Most of that gets degraded in the stomach, and about 14% gets into the blood stream I think (going off memory). so, a few mg of rapamycin in total in 5 liters of blood (for average person). A tiny, tiny percent of that might get into the testes, and ultimately into sperm, but I believe it would be a negligible amount.

Perhaps someone here with a medical background or biology background can confirm (or counter) this hypothesis. (people like @McAlister , @rivasp12 , @John_Hemming …)

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That is exactly the answer I was hoping for as I hope to resume rapamycin soon.

It sounds like my wife also has an interest in taking rapamycin in the next few years (after childbirth and breastfeeding).

If we eventually have a dog I am sure our dog will go on rapamycin as well.

Thanks for creating and moderating this forum. It is a great place to learn about rapamycin and related healthspan topics.

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The risk would not be from delivery of rapamycin to the motther or the baby (that amount would be insignificant) but from the potential of rapamycin to change the sperm. Note that the sperm doesn’t just carry the DNA of the father, it also carries epigenetic information. That’s why the lifestyle of the father before conception can influence that of the child.

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He was talking about post pregnancy… whether the rapamycin would be transported to the already pregnant mother…

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Oh I see. My mistake. In that case, I agree, there is no concern.

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FYI my husband was on low dose pulsed Rapa on / off when I got pregnant. So clearly didn’t hurt his fertility.

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Fertility isn’t the only concern here. Transfer of epigenetic information is also a potential factor.

So my baby’s epigenome might resemble that of children of Auschwitz survivors

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Yes, to some degree it actually could.

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Well I’m actually intrigued by the prospect, being a first gen immigrant raised on food rations in Eastern Europe with the prospect of ethnic cleansing and genocide looming large over my people’s conscience, not to mention the shadow of WWII. My children by contrast are complacent lazy Americans. Maybe baby #5 will be a neurotic hustler like mamma who doesn’t take the next meal for granted and I’ll finally have someone who “gets” me :wink:

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