Women Taking Rapamycin for Enhanced Fertility / Menopause Prevention?

[RapAdmin]

Last week I spoke with a woman who I think is in her early 40s who is starting rapamycin to maintain her fertility (slow, or prevent ovarian aging) and prevent / delay menopause. She will be writing about the process, and the results over the coming months and I’ll provide a link to her articles when they come out.

But this got me thinking and I’m wondering if there are other women here who might be taking rapamycin to either enhance their fertility (maintain their fertility as they age past 30) or for menopause prevention. Please post your experience if you are.

Following is some research on how rapamycin has proven to help in fertility:

Fertility

In terms of female fertility, there is already strong evidence in mice and rats that rapamycin delays (reverses?) reproductive aging in females.

Note: Matt Kaeberlein touches upon rapamycin / mtor pathway and ovarian aging in this new presentation on the current state of the science around Rapamycin. An interesting comment Matt makes related to ovarian aging was he was at a recent conference on reproductive aging and there were 3 or 4 presentations on how mTOR was involved in ovarian aging. He notes that he saw a presentation where:

“they had remarkable pictures with old mice and atrophied ovaries, and then you look at an old mouse that had been treated with rapamycin and the ovaries look like young ovaries from a young mouse.”

I’ve positioned the video to the exact spot where reversing ovarian aging / function is discussed, below: Targeting aging with rapamycin: On the path toward 21st Century Medicine - YouTube

Here are some research studies that report this benefit:

• Short‐term rapamycin treatment increases ovarian lifespan in young and middle‐aged.
• Rapamycin can preserve the developmental potential of eggs.
• Rapamycin can maintain the developmental potential of eggs (full paper, PDF)
• Rapamycin keeps the reproductive clock ticking.
• Rapamycin prolongs female reproductive lifespan.
• Effect of caloric restriction and rapamycin on ovarian aging in mice

The inhibition of mTOR signaling can also prolong ovarian lifespan. Compared to that in control rats, rapamycin-treated rats have a 2-fold increase in the number of primordial follicles after 10 weeks of treatment with rapamycin (5 mg/kg every other day, i.p.) (17, 111). These results indicate that rapamycin can protect the ovarian reserve and extend ovarian lifespan. An interesting experiment also showed that a transient 2-weeks regimen of rapamycin facilitates the sufficient extension of ovarian lifespan in mice regardless of the age at treatment initiation.

Role of mTOR Signaling in Female Reproduction

[Note: other compounds like Ca-AKG and NMN seem to also help with preservation of fertility (sources: 1, and 2). So perhaps an ideal approach would be to combine these three approaches.]

There are researchers who argue that rapamycin effectively “slows down time” from a biological growth and development perspective - while maintaining that potential for growth in the future. I’ve spoken to some academics at major US universities that are planning more studies focused on rapamycin and human fertility so its an area ripe for more research, but the preliminary evidence is very encouraging. It seems to me that preservation of fertility is easier and more likely than reversal of fertility loss, but of course, I could be wrong.

Menopause

If rapamycin is slowing fertility declines, then it suggests that it might also delay or prevent menopause. Delayed menopause has many benefits and is associated with a longer life overall for women.

Source: The time is now: Regular exercise maintains vascular health in aging women

And while there is no research on this published that I can find, there are anecdotal reports that people are seeing positive results and delay of menopause with rapamycin:

I have been taking rapamycin for 6 months on and off. It has improved my hdl and ldl ratio to the point where my hdl is now higher than my ldl. I have also been giving it to my mother who is 63 years of age. She rather unwillingly told me that she has been having her period again for the first time in 14 years. Now that is a turn up for the books and can hardly be seen as placebo or coincidence

Tammi Kaeberlein

Tammi Kaeberlein

I just wanted to inform the group of an interesting ongoing small pilot study I’ve been doing at home. I’ve been feeding my chickens that I purchased in 2017 as chicks, rapamycin for the past two years on a periodic (weekly) basis. One of the chickens died last year due to a plugged duct, which is a common problem. But prior to that, and with the one remaining chicken that is now on year 4 of egg production, the daily egg product is still up at the 90% to 95% daily laying schedule that is typical only of much younger chickens - 1 year olds, for example (see below). So my 4 year old chicken is laying eggs like a 1 year old chicken. Obviously, N=1 doesn’t mean too much, but the indication seems quite positive and supports all the research mentioned above.

What the Typical Egg Laying Ability Trend Line is for Chickens (No Rapamycin)

[RapAdmin]

It seems that women to try rapamycin out for this purpose - and track results relatively easily using these techniques. It would be great if any women interested in trying this, to please report back on results…

Assessment of ovarian reserve

• This is a very important assessment of a woman’s remaining egg supply
• It is done with blood testing and ultrasound:
  • Blood – day 3 FSH, LH and estradiol hormone testing and AMH hormone levels
  • Ultrasound – assessment of ovarian volume and antral follicle counts

Blood tests

Depending on the individual couple’s situation, various blood tests on either the female or the male may be needed. Blood tests that might be needed include day 3 follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), AMH, prolactin, testosterone (T), progesterone (P4), 17-hydroxyprogesterone (17-OHP), thyroxin (T4), thyroid stimulating hormone (TSH).

If there is a history of recurrent miscarriages (2 or more) a lupus anticoagulant (LAC) and anti-cardiolipin antibody (ACL) are often done, as well as other tests.

Source: Basic Infertility Evaluation – Fertility Tests – Advanced Fertility Center of Chicago

Another site (reproductive facts.org ) suggests:

Ovarian Reserve Testing: When attempting to test for a woman’s ovarian reserve, the clinician is trying to predict whether she can produce an egg or eggs of good quality and how well her ovaries are responding to the hormonal signals from her brain. The most common test to evaluate ovarian reserve is a blood test for folliclestimulating hormone (FSH) drawn on cycle day 3. In addition to the FSH level, your physician may recommend other blood tests, such as estradiol, antimüllerian hormone (AMH), and/or inhibin-B, as well as a transvaginal ultrasound to do an antral follicle count (the number of follicles or egg sacs seen during the early part of a menstrual cycle).

Ovarian reserve testing is more important for women who have a higher risk of reduced ovarian reserve, such as women who:

1. are over age 35 years;
2. have a family history of early menopause;
3. have a single ovary;
4. have a history of previous ovarian surgery, chemotherapy, or pelvic radiation therapy;
5. have unexplained infertility; or
6. have shown poor response to gonadotropin ovarian stimulation.

Other Blood Tests: Thyroid-stimulating hormone (TSH) and prolactin levels are useful to identify thyroid disorders and hyperprolactinemia, which may cause problems with fertility, menstrual irregularities, and repeated miscarriages. In women who are thought to have an increase in hirsutism (including hair on the face and/or down the middle of the chest or abdomen), blood tests for dehydroepiandrosterone sulfate (DHEAS), 17-α hydroxyprogesterone, and total testosterone should be considered. A blood progesterone level drawn in the second half of the menstrual cycle can help document whether ovulation has occurred.

[ekf17]

Hi - I am interested in starting Rapamycin for extending fertility. The above linked articles were very interesting. Do you know what protocol dosage and duration would be recommended? Or a good place to start? Thanks!

[RapAdmin]

So - a human clinical study is just being started on this at Columbia University focused on this use. I will be talking with a woman who is somewhat involved with this study in the next week and I’ll post details on what they are doing.

Right now there is no evidence-based protocol because this is all very new. Fundamentally what I’m seeing is people are following the general anti-aging protocol / dosing for rapamycin as outlined here: What is the Rapamycin Dosing / Dosage for Anti-Aging or Longevity, and Life Extension?

Some women are posting on twitter about their rapamycin use:

Andreea Nitescu

[RapAdmin]

And read this post: The Case for Rapamycin, and Female Fertility

[ekf17]

Great, thanks that will be very interesting to hear about the human clinical trial. Also good to know about people mostly doing the longevity dozing for extending fertility. I was curious about that because of the cited mice trials where follicle growth/ovarian function was impaired during the Rapa dosage of 2 weeks and then for 2 months following, but after that the follicular growth and ovarian reserve were better than ever. So curious how that translates to humans. Like if ovarian function is impaired during the Rapa dosage, and how long it takes to come back for someone still interested in fertility, not just delaying menopause.

[RapAdmin]

Well, rapamyin (sirolimus) has been in use by women for over 20 years, in transplant patients - and of course, many of those women have had children. They even seem to keep these patients on the drug during pregnancy (which I found somewhat surprising), but I suspect they lower the dose as much as possible.

Generally the recommendation seems to be at least 6 weeks gap between taking sirolimus and getting pregnant, from the following paper:

Sirolimus and mycophenolate mofetil should be stopped 6 weeks prior to conception. The optimal time to conception continues to remain an area of contention.

Overview of Pregnancy in Renal Transplant Patients

But organ transplant patients are different than healthy people - they have to take sirolimus (or drugs like it) as part of their treatment program to keep a transplanted organ in their body functioning without problems. So - they are much more about balancing the risks of loss of a key organ, vs. potential damage to the fetus. Healthy people will want to focus more purely on minimizing risk to the fetus, so more time is probably a very good thing. Talking with an OBGYN would be a good thing for this type of thing.

As to how quickly full fertility returns… I’m not sure of the specifics. Rapamycin has some significant similarities to calorie restriction. Rapamycin in part seems to trick your body into thinking that it is nutrient deprived. Just as if a woman is eating a very low calorie diet - they will lose their menstruation cycle and ability to become pregnant until they begin eating more. The same applies to rapamycin. I have not done research on the exact speed of return to full return to fertility - you can look for research on “caloric restriction and return to ovulation” or some such terms I suspect.

[RapAdmin]

From one woman using rapamycin. 4mg/week seems like a reasonable and conservative dose for a woman age 30. I would just note that while she comments on the fact that in the mouse studies, the female mice were much more dose-responsive to rapamycin (for a given dose, much higher levels of circulating rapamycin), I don’t believe this has been found to be true in humans (i.e. women). There is also great individual variability in terms of dose responses of rapamycin - so best to do a blood /sirolimus test: How to get a Rapamycin (sirolimus) Blood Level Test

Andreea Nitescu

Andreea Nitescu

Andreea Nitescu

[ekf17]

Very interesting, thanks. Good to think about it that way - in terms of being similar to the affects of caloric restriction.

[ekf17]

Makes sense about getting the blood test to get better insight. Is Rapamycin dosage often based on age then? Does body weight play a part?

[RapAdmin]

@ekf17

Is Rapamycin dosage often based on age then? Does body weight play a part?

When talking about dosing and rapamycin there are two areas to consider. Historically its been dosed for organ transplant patients and cancer patients. In those application the dosing is focused on getting the blood/sirolimus levels to a specific therapeutic range (I seem to recall something like 5 to 15 ng/mL). I’m not sure if body weight has much to do with how sirolimus dosing translates to blood levels.

Of course we are talking about rapamycin (sirolimus) for anti-aging, and we have much less data here. We really don’t know what the optimal dosing is yet. So there are no hard and fast rules.

That said, I have seen people of very low weight (e.g. 100lbs to 125lbs, 45 to 55kg), sometimes getting more side effects at a specific dose, so probably better to be cautious rather than aggressive when testing the typical dosing ranges (e.g. 3 to 10mg/week) that are common in anti-aging applications. Details see: What is the Rapamycin Dosing / Dosage for Anti-Aging or Longevity, and Life Extension?

[RapAdmin]

Related to this general topic:

Advancing the Frontiers of Reproductive Longevity: Frontier Stage Day 2

and

Everything You Didn't Know About Reproductive Longevity

相关阅读：

Global Consortium for Reproductive Longevity and Equality - BUCK

Webinar Series:
https://www.buckinstitute.org/events/webinars/

Other News:

Don’t count on having kids if you freeze your eggs

What If Fertility Didn't Have a Shelf Life?

Whitepaper: The Unspoken Truth - Reproductive Longevity and Equality Affects Us All

[Stazio]

My wife, with early menopause, tried with 3mg every day for 10 days for 2 months in a row. The first round she got a wicked tongue ulcer. 20 days later she did the protocol again and got swollen glands in her armpits - that stayed painful and swollen even after stopping. She also had a very light but discernable period, each month at the 30 day mark. She has stopped given how uncomfortable and swollen the underarms were…

[RapAdmin]

@Stazio

3mg every day for 10 days for 2 months in a row.

Wow - thats an extremely high dose level. I would expect significant side effects at that level.

I’ve found the most side-effect free approach is to start slowly, and still dose only once per week. I started at 1mg/once per week, then slowly increased by 1mg/week up to the 5mg/6mg per week. Only had one mouth sore once. I think slower, lower dosing is the best strategy, though some people have jumped right to higher dosing without problems.

Details on dosing here: What is the Rapamycin Dosing / Dosage for Anti-Aging or Longevity, and Life Extension?

[Stazio]

She had been on 3mg weekly for a year. The dosing was based on an anecdotal report that had worked for another woman with a similar case. Also, it should be noted, that the menses did return - at least for now - though it’s very light. I’m certainly not reporting here as a recommendation but for information to the community.

[RapAdmin]

@Stazio

The dosing was based on an anecdotal report that had worked for another woman with a similar case.

Interesting - I’d not heard of that.

Do you have any more information on that anecdotal report? How long she took rapamycin, what the dosing was, for how long, and what the results were? Is there anything ever posted on any public forums or twitter, etc. that you can refer us to? The more datapoints we all can have here, the better we are all informed. Thanks in advance for any additional information you can share.

[MAC]

@Stazio

My wife, with early menopause, tried with 3mg every day for 10 days for 2 months in a row. The first round she got a wicked tongue ulcer. 20 days later she did the protocol again and got swollen glands in her armpits - that stayed painful and swollen even after stopping.

As @RapAdmin stated, this is a massive dose outside of a cancer/transplant clinical setting. Although at 10 days, and barely 5 half lives, and without a loading dose, the full tissue effects hadn’t fully reached steady state. The side effects at a longer duration would probably amplify. The 2nd round definitely had stronger effects. At 20 days later post 1st round, most all of the Rapamycin would have been excreted and not measurable in blood, but perhaps some lingered in some fatty/high lipophilic tissue levels such as lymphocytes, ergo the swollen armpits side effects with re-dosing.

What data point someone would have to follow this protocol would be interesting to understand if some science based therapeutic rationale we’ve not seen before.

[Arhu]

@RapAdmin

I’m not sure if body weight has much to do with how sirolimus dosing translates to blood level

Oncologists usually use body surface area for dosing chemotherapy, my gf uses the one below for dosing …

Body Surface Area Calculator

(Even for obese with water soluble chemo this apparently works well)

[ekf17]

Ah okay thanks that is good to know about lower weight people potentially having more side affects at a specific dose. I am 5’4" and about 125 pounds, and while that is about my ideal weight perhaps that is lower on the general scale. I will see how it goes in terms of dosage and any ramping up.

[ekf17]

Interesting, okay thanks