I have not posted here in a while for this exact reason – I paused rapamycin while trying to conceive with my wife. Previously I was taking 5-6mg//wk with an absorption enhancer. It took us approximately 8 months, and I also had my sperm tested around month 6 (all normal).
So at least another datapoint suggesting that fertility is not impaired long term, at least not with intermittent dosing.
38M.
Thanks
The point about fertility is that apart from the issues of sperm getting to the egg, the mitochondria in the sperm don’t make their way through to the zygote. Hence the effect of Rapamycin on males is reducing spermatogenisis. For females it could be particularly helpful in improving mitochondrial quality, but I am unaware of any research into autophagy in oocytes.
Why are people of reproductive age taking Rapamycin?
Why not I guess? My take is that aging is already happening at 30+ and thus I will have a longer lifespan/healthspan if I start this early. This seems reasonable considering that mice seem to live longer when started on rapamycin earlier (citation needed). I use 10mg/week and get zero side effects. The only downside is the $$$. Open to hearing counter viewpoints.
I’m not trying to be “anti”Rapamycin here, and I take it myself. But from a risk/benefit standpoint, I would question a young person (<40) taking a medication with unproven benefits and unknown risk factors.
I take it because at my age (65) the risk is small and the possible benefit is moderate. I don’t know if that applies to someone 30 years younger.
From a mechanistic standpoint, why would we want to inhibit mtor and thus inhibit the growth/reproduction side of a young person?
I vaguely recall Matt K. In a recent video questioning the use of Rapamycin in someone <40. Correct me if I’m wrong.
If I were a lot younger (I am 64) I would probably take a reasonably large dose of Rapamycin, but very infrequently.
As I see it it stimulates a spring clean of mitochondria. That is probably not warranted every week for younger people.
This is very interesting, In my previous marriage me and my wife tried to have children without luck (ended up adopting the most wonderful girl in existence at birth, she is now 19 years old). During this time I tested my sperm and got very negative results back, very low quality and sperm count. I divorced about 12 years ago. I got a younger girlfriend in October last year, she is in her thirties and I am 54 now. She got pregnant in March this year. I was most surprised as I was convinced that I could never have kids. I have been on Rapamycin for 2 years (6mg every 2 weeks)
The mitochondria come from the mother. It only takes 1 sperm cell.
There are studies showing that rapamycin protects the ovarian reserve in women, that is, it increases the age of menopause. This feature may be due to its ability to protect stem cells. That’s why I think intermittent and low dosage will have a positive effect on sperm parameters rather than harm.
Probably overly cautious but I think those wanting to have kids would do well to play it safe and abstain for 3 months (a bit longer than full sperm regeneration time) prior to conception.
And for the mother obviously to abstain during pregnancy and breastfeeding.
Hard to find good data, stopping for 3 months seems necessary. But are we sure the potential negative effects are fully reversible?
While a clear negative effect on sperm quality was evident for sulfasalazine and cyclophosphamide, a dubious effect was identified for colchicine, methotrexate and sirolimus.
In addition, reversible infertility associated with sirolimus was reported in three studies. One prospective study reported that testosterone levels increased from baseline levels (pre-transplant) in an undefined number of patients using everolimus (Kramer et al., 2005). Despite the lack of reproductive safety information for tacrolimus in humans, in these studies, patients were switched from sirolimus to tacrolimus and their sperm quality improved.
Immunosuppressive drugs and fertility 2015
Anti-TNF-alpha and mTOR-inhibitors are to be used cautiously if pregnancy is desired, since experience using these drugs is still relatively scarce.
Sirolimus qualitatively and quantitatively alters spermatogenesis in men, as observed in 132 heart transplant patients. This adverse effect is purportedly reversible upon stopping the treatment, although this reversibility is controversial. A testicular histological study done in a patient treated with sirolimus who needed surgical intervention for leydigioma showed testicular atrophy and vacuolation of the seminiferous epithelium, in agreement with the animal studies.
Young women treated with sirolimus and tacrolimus have an increased risk of oligospanio- or amenorrhoea) and ovarian cysts (50 to 62 % of cases) in the first year of the transplant [45–47]. These cysts diminish in 80 % of cases when sirolimus is stopped or with the use of combined oestrogen plus progestin contraceptive pills.
In animals, sirolimus does not have an in vitro or in vivo mutagenic effect, but it is embryo- and foetotoxic.
Currently, experience with the use of this treatment during pregnancy is insufficient. Even though the published data seem to be reassuring, it is recommended that another drug be used as a substitute for mTOR inhibitors, and that contraception be continued for 12 weeks after stopping treatment due to the clearance time.
I would use embryo selection if I chose to have kids: https://www.orchidhealth.com/, no way I am leaving it to chance, I would also possibly download all of the genomes for the embryos and select for health, wellbeing, then afterwards I could be an eunuch from rapamycin or whatever.
If someone and their partner or surrogate has the best genes and family history possible then I guess it doesn’t matter as much, but I don’t.
As I have five children I have not really considered fertility issues that much.
However, it strikes me that although Rapamycin may reduce sperm count (by inhibiting cell division) otherwise for males it would not be that much of an issue.
On the other hand once a woman becomes pregnant I think Rapamycin would be potentially harmful for child development.