#1

Rapamycin aged my ovaries rapidly! Very upsetting ! AMH results show it too!

I have no time right now to study the mechanisms of rapa in details, but the time overlap is pretty disturbing .

At 35,6 months, 2023 - I went on to freeze my eggs and had AMH very high for that age 29-30 pmol/L.
This is excellent for my age, on a level of 25-30 yr olds.
So I went through 3 hormonal cycles and froze many eggs from May 2023 to December 2023.
I measured AMH couple of times always was 28.8-29.9 pmol range, ā€¦
The last time I measured it was June 2024 - when it was again 28.9, unchanged.
According to studies it drops by 0.3-0.5 mg/mL per year for women in 30s, which is 2.1-3.5 pmol/L.
My cycle has been precise 33 days, for 10-15 yrs, without any changes. Very precise. According to data long cycle is very good, shows more ovarian reserve.
So to prolong my ovarian healthspan I started rapamycin 6 mg a week. Summer July 2024.
Immediately after it i got my period earlier and that was very very strange because it never happens.
I wrote a thread about it here:

I freaked out and sid a pause, and later I tried lower doses, 2-3 mg per week.
The same repeated in November and my cycle started to be 29-30 days.
I knew the shortening of cycle canā€™t be good.
Measured my AMH now and got shocked by 16.6 pmol/L (2.25 mg/mL).
So it dropped in 10 months (probably less because i didnt measure in August-November/December 2024) by 40%
Projected drop should gave been 3-4 pmol/L tops. Not to mention the purpose of rapamycin was to SLOW it down.

I dig in studies and found this;
Now Iā€™m more convinced it caused me ovarian toxicity and even these studies mentioned lowered number of primordial follicles in young rats. I am not very young but my ovarian age was 25-28 as mentioned based on AMH, and I look extremely younger (it is probably linked to hormones and less aging in face?)
Currently my ovarian age speeded up and is like average 35.
Iā€™m very very bummed and concerned about this. The significance was that the first time ever shortened sudden period cycle was after first rapa.
And, yeah, the drop seems not usual, seems 3.5 x faster than expected. As my AMH shoule be now 26-27 pmol/L with the usual rate of aging.

The studies I found saying it causes aging.
Couples with what Bryan Johnson is claiming about epigenetic clocks, i am so discouraged now. this aged me over 5++ yrs over night, maybe thanks to this I wont have kids even and hit menopause earlier.
Very upset that i took this risk

The study below even mentions LOW dose.

https://www.fertstert.org/article/S0015-0282(24)01694-7/fulltext

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#2

My humble opinion.

What we measured may not be exactly what happened, if my memory serve me right, one rapamycin expert said, rapamycin preserve pancreas so less insulin secreted, consequently higher blood sugar will be measured. Itā€™s not the same to morbid hyperglycemia which caused by the body failed to adjust blood sugar.

Itā€™s the same to GLP-2 medicine to preserve kidney, but at first the kidney filteration rate may drop, made many people shocked and feared the medicine may instead hurt kidney.

Anyway just stay calm, the measured value may just be a temporary phenomenon caused by positive action.

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#3

I understand what you mean but this is completely uninformed guess because AMH is EXTREMELY reliable marker of ovarian age /reserve and the value approaches zero when heading to menopause
Also, my cycle SHORTENED which another sign of reproductive aging

Have you looked at the research I provided? It finds exactly what Iā€™ve experienced, that low dose rapamycin causes ovarian aging

#4

Both researches said menstrual disorder or disturbance, not aging faster, and most important of all is itā€™s reversible after stop using sirolimus.

Just stop using sirolimus and see if the AMH value bounce back.

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#5

Thanks for sharing your story. I think the AMH change may or may not be related, and thereā€™s obviously no way to know for sure, but itā€™s certainly possible IMO. The paper you shared is interesting, but obviously many limitation to the interpretation - tiny sample size and a massive range of confidence limits. I can say anecdotally that when my wife started Rapamycin, she also had some bleeding, though not really an early cycle.

Presumably you will stop taking Rapa, and youā€™ll take another AMH test a few months down the line? If you could share your updated experience and result, that would be really useful for others.

I honestly wouldnā€™t put such huge faith in a single marker, and I definitely wouldnā€™t be convinced by epigenetic clocks. But IMO, I would categorise taking Rapamycin when youā€™re a young woman hoping to have a baby as far beyond my own risk tolerance. Thereā€™s a huge amount to lose, Rapamycin during a pregnancy itself would be a terrible idea, and the potential benefits for ovarian aging are not well established at all. I hope everything works out for you.

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#6

@Forever29 , its been a while since I have done a deep dive into the fertility-improvement results of rapamycin done by the many labs studying this issue. I know that the Dr. Aimee, who is prescribing rapamycin for fertility improvement is having good results, and sheā€™s a Harvard, and UCLA-trained doctor who is in communication with the Columbia University group that is also doing studies on this.

Do you know I they have been using AMH as the primary way to measure the improvements in fertility that they have seen? Rapamycin for Fertility and Menopause; Clinical Results

Obviously, while the researchers and the clinicians seem to be having generally very good results with rapamycin it doesnā€™t mean that everyone is having great results; perhaps a small percent have less success, but Iā€™d be very cautious about interpreting any results until you know for certain if:

  1. AMH is the measure that the researchers are using to estimate the 20% fertility improvement they are seeing with rapamycin. And how/when they measure (i.e. after pausing treatment for a while, or during treatment)
  2. Are there other measures that are relevant, that these researchers are measuring? Exactly when and how do they measure their variables? And how do your measures compare to those other measures, if there are other measures?

Given all the positive research around rapamycin for slowing aging, and improving fertility in mammals, (dozens and dozens of studies), I would be careful about jumping to negative conclusions without a full understanding of all the relevant measures and testing protocols.

We have people here in our forums who have participated in the Columbia University Medical School fertility research; perhaps they have some insights that they can share on the measurement protocols.

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#7

Well Iā€™d like you to comment my results which are extremely bad, and also, the studies I have attached saying that the number of primordial follicles dropped drastically from rapamycin in young rats etc. and even AMH immunohistocological staining was lowered.

Iā€™m not taking rapamycin for those who said itā€™s reversible, I stopped in January when it triggered this faster aging

#8

You have not read the studies it seems. It clearly says the Number Of primordial follicles (eggs!) dropped drastically in young mice.

#9

@LilyD was in the Columbia University study on this topic (the VIBRANT study), and perhaps she can comment on the measures, etc. that they did and her results over the period of the study (if she knows them).

See her statements here: Women Taking Rapamycin for Enhanced Fertility / Menopause Prevention? - #218 by LilyD

and its important to note this:

I notice in the writeup on the VIBRANT study they mention:

Early results from the VIBRANT study suggest that it is possible for rapamycin to decrease ovarian aging by 20%. While a woman typically loses around 50 eggs each month, weekly doses of rapamycin can slow this rate, leading the ovaries to release only 15 eggs a month. Furthermore, study participants have reported improvements in their overall health, memory, hair and nails, findings which are consistent with other studies on rapamycin. By decreasing the number of mature eggs, scientists at Columbia Fertility hope that rapamycin can be utilized to delay menopause.

and Iā€™m wondering how exactly they measure the rate of loss of eggs. Does anyone know?

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#10

Hi, yes, so for the Columbia study. I had to go in for testing between the 2nd and 5th day of my cycle. They took blood and measured estradiol, progesterone, AMH, FSH, and LH, and did an ultrasound of both ovaries to count follicles.

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#11

I have all my data, but I still donā€™t know whether I had placebo, and also Iā€™m a little unsure whether at least some of the changes were due to my coming off hormonal birth control, which can depress some of these measures.
My numbers went up during the period where I was taking whatever it was - then I had a 3-week cycle for some reason, and the numbers were down at that appointment. Again, that was probably 4-6 weeks AFTER my last dose of either placebo/rapa. So while I was taking whatever pill it was, the numbers were all up. But again, lots of confounding variables, so hard to draw any conclusions.
I do know the researchers were feeling positive, i.e., that the rapa was seeming to do what they hoped it would, but again, itā€™s a double-blind study that hasnā€™t been unblinded yet, so grain of salt with everything.

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#12

How did your AMH change over the period of tracking / testing? Did you see any changes?

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#13

Yes so AMH bounced around a little but overall went up, even at the last appointment where it was lower (and I was back on my hormonal bc). Iā€™ll just tell you all the numbers:
Initial (1 month off BC, pre-treatment): 0.24
Month 1 of treatment: 0.98
Month 2 of treatment: 0.31
Month 3 of treatment: 1.36
Month 4 (post-treatment): 0.99
Final assessment (6 months after last treatment, 2-3 months back on hormonal bc): 0.33

Unfortunately I missed some planned assessments in between, when I was still off bc, because there is only a narrow window for assessment (certain days of your period), and a couple of times that happened while the research facility was closed for a holiday. So this is what I have. I will be sure to update when I know what experimental condition I was in.

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#14

Thanks for the detailed information. Iā€™m just trying to understand @Forever29 's test results. So it sounds like the exact timing of the measurement (i.e. day of the cycle) matters a lot in terms of the results you get. So Iā€™m wondering if we donā€™t know the exact timing of Forever29ā€™s testing then Iā€™m wonder how we need to (or can) interpret her results. Do you have any insights on this, given your conversations with the researchers, etc.?

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#15

So yes, my understanding is that the day of the cycle matters a lot because those numbers move around quite a bit but are pretty stable in cycle day 2 or 3 especially.

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#16

@Forever29 I donā€™t know if this matters, but the measure I see on my chart is different from what youā€™re quoting. My AMH was measured as ng/mL, and the numbers youā€™re saying, 28-29, are double the top of the range for 18-25 y/o (median 3.6, range 1.02-14.63), so Iā€™m wondering if itā€™s possible you could be comparing different measuring methods? Iā€™m sorry youā€™re having this worry! It would freak me out too. But I hope thereā€™s a reassuring explanation to be found.

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#17

@Forever29 Just want to point out that in the top study you linked, the participants were taking low-dose Sirolimus daily, not intermittently. I believe itā€™s known that daily dosing has very different effects from intermittent (e.g., once a week) doses, in case that gives you any comfort.
Update: I also looked up the dosing abbreviations used in this study you linked (https://www.fertstert.org/article/S0015-0282(24)01694-7/fulltext), and I believe the macaques were receiving rapa twice a day and intramuscularly, which is not how itā€™s typically used for anti-aging purposes. So I donā€™t think that these studies are necessarily relevant to what youā€™re experiencing, just so you donā€™t use them against yourself as evidence youā€™ve done something harmful to your fertility!

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#18

These studies are relevant in the lack of better ones. In fact, every single argument FOR rapamycin used in these circles is based on studies where the dose is never the one that we wanna use intermittentlyā€¦but theyā€™re still making claims based on those arguments.
And now you pick the only difference in these studies and dismissing it instead of explaining why daily low dose could cause so severe ovarian aging observed in th se studies.
Why it does it? If itā€™s ā€œdifferentā€ effects, how different?
Its all too blant to me

I clearly did harm myself, actually i dont blame myself I blame health influencers who make rash claims without any backup arguments.

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#19

It might be possible if I was 6 year old child,ā€¦ But itā€™s also evident you havenā€™t read my post at all where i speak that 28-29 is 4 ng/mL approx.
Sorry but youā€™re questioning if Iā€™m a complete retard to compare values with different measures. LOL.
so th answer is: who would have guessed but Iā€™m not a retard

#20

AMH doesnā€™t move much.
Why are you in this forum, You donā€™t sound like you read studies?