Is Delaying Menopause the Key to Longevity? (NY Times)

Its good to see The NY Times finally catching up on the news around this development. And of course they cover rapamycin in this new story!

Scientists are studying how to keep the ovaries working longer — and potentially, prevent age-related diseases in the process.

In March, the first lady, Jill Biden, announced a new White House women’s health initiative that highlighted a seemingly obscure research question: What if you could delay menopause and all the health risks associated with it?

The question comes from a field of research that has started to draw attention over the last few years, as scientists who study longevity and women’s health have come to realize that the female reproductive system is far more than just a baby-maker. The ovaries, in particular, appear to be connected to virtually every aspect of a woman’s health.

They also abruptly stop performing their primary role in midlife. Once that happens, a woman enters menopause, which accelerates her aging and the decline of other organ systems, like the heart and the brain. While women, on average, live longer than men, they spend more time living with diseases or disabilities.

How Delaying Menopause Could Extend Life Span

There is some evidence, mostly in animals, that suggests prolonging ovarian function can improve health and increase longevity. In mice, for example, transplanting an ovary from a younger animal into an older one lengthens the older mouse’s life.

Scientists are now experimenting with different ways to prolong ovarian function and delay the onset of menopause in humans.

A clinical trial currently running at Columbia University is also trying to slow the rate at which women lose their eggs. The study is testing the use of an immunosuppressive drug called rapamycin — which is used to prevent organ transplant rejection and has become a darling of the longevity movement — in women between the ages of 35 and 45 to see how it affects their ovarian reserve. Rapamycin influences the number of eggs that mature each month, and the drug has been shown in mice to extend ovarian function.

The study is still ongoing, and the researchers don’t know which participants received the medication or a placebo, but the lead scientist on the trial, Dr. S. Zev Williams, said that two patterns had already emerged: Some women appear to have a normal decline of ovarian reserve, which can be measured via ultrasounds and AMH levels, but in others, “it seems to have been altered,” he said. “So, you know, that’s promising.” Dr. Williams, an associate professor of women’s health at Columbia, is also applying for the health agency funding.
The experts were explicit that the goal of this type of research was not to prolong women’s periods indefinitely, nor to make pregnancy possible at age 70 — though the treatments could potentially extend fertility.

Read the full story: Is Delaying Menopause the Key to Longevity? (NY Times)

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Seeing that this is in the news today, at the risk of TMI, I’ll share that my 58 year old self got her period today.

According to Oura, my last period was 6/18/23… so, by all definitions, I was officially in menopause last week.

I thought it was worth sharing incase it winds up helping anyone.

If I have a baby, I’ll call him RapAdmin… and if it’s advanced cancer, I’ll miss you all!!! :slight_smile:

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This is great news. It sounds a lot like what @Dwidrick reported the other week:

If anyone else has similar results, please post here.

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I hadn’t seen that! Interesting!

I stopped taking NMN once I learned Sinclair was FOS, but I will say, when it was not regular anymore, I took it and immediately got my period. I read that could happen.

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Did I understand you correctly? You got your periods back from NMN (no rapamycin then) and now from Rapamycin (no NMN anymore)?

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I wasn’t in menopause yet but NMN appeared to bring one partial cycle back. Hard to know for sure because I was no longer regular at the time. It definitely did not continue to make me regular.

I have not been on NMN in well over a year, so IF this was due to a drug/supplement, it would be rapa. For clarity, this is day one, no idea if this will continue.

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I had the same experience : when I took NMN after a pause, it seemed to bring back my period ( before I started taking rapa) especially when I start a new batch (I started ordering smaller quantities for this reason)

Rapa sometimes brings it back but not consistently ( for the moment ). Am still on 4 mg dose at present.

FWIW : Emsculpt on my abdomen also seems to stimulate ( or speed up?) the start of my period.

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Im 48, been on rapa 14 mg/week for 11 years, so much higher than the studied 5 mg/wk. Family hx wise, should’ve had meno signals already, but no. My little sis 6 years younger has already been through natural meno. Havent had, and am not trying for a baby, but still have a super regular cycle. No surgeries, but put on rapa in 2013 due to LAM. Now i sorta want an amh check.

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Wow, thanks for sharing. Please tell me more about how you started… I am assuming you are not an organ transplant recipient, what is LAM?. Did you just go ahead based on the early research, do you take breaks, any side effects, do you do blood testing?

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LAM is lymphangioleiomyomatosis, with me its a genetic non-hereditary condion that grows non cancerous cysts in my lungs. RAPA was trialed to inhibit disease progression due to mtor inhibition, and in 2013, there were no fda approved treatments, So I gave it a try, and its held my lungs steady in function for 11 years.

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Women on rapamycin - it would be really interesting to know if (if you ever do this testing) how your AMH levels compare to the typical trendiness for females (see following graph). If we see significant outliers in the rapamycin group (higher than expected) it would be a very good sign that rapamycin is doing what we think it should be doing.

| AMH levels according to age for women 24-50 years of age. Median values are shown with standard deviations. Reproduced with permission from Seifer et al. Age-specific serum anti-Mullerian hormone values for 17,120 women presenting to fertility centers within the United States. Fertil Steril. 2011; 95 (2): 747-50.

Mean-values-of-AMH-of-three-different-tests-as-a-function-of-age-We-can-see-the-decrease

Mean values of AMH of three different tests as a function of age. We can see the decrease in the mean values of each consecutive test placed on the market.
Source: https://www.researchgate.net/figure/Mean-values-of-AMH-of-three-different-tests-as-a-function-of-age-We-can-see-the-decrease_fig2_261746114

I think the menopause is caused by the same processes as aging more generally. Interestingly other things that may resist the aging process such as Melatonin are thought (by some) to delay the menopause

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10045124/

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I’ve never tested AMH and I don’t even regularly test my hormones (should I?). I was told that hormones change so much throughout the month that a test isn’t going to reveal anything very useful ?? This was relating to if I should be on low dose HRT (I’m on the lowest dose)

Also, @John_Hemming, I’ll note I just started melatonin for the first time this week.

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Good news on AMH, you can test anytime during the month and its representative of the levels at all times. I hope you and other women here who are taking rapamycin will consider getting this test and reporting on the results to help us all understand better if rapamycin is working (so we don’t have to wait a few years for the Columbia University study to be complete and results published).

From the Cleveland Clinic:

You can have an AMH test at any point during your menstrual cycle. Unlike other reproductive hormones, AMH doesn’t fluctuate much throughout the month

Source: Anti-Mullerian Hormone (AMH) Test: Purpose, Levels & Results

How to get an AMH Test

Just order it online (if its available in your area) then go to the LabCorp or Quest facilities to get the test done. Its quite inexpensive. (check to see if which lab the online service uses to fulfill the blood draw, make sure there is one in your area).

Marek: $65

UltaLabs: $87 at current listing

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Note that AMH is also influenced by your vitamin D levels, stress level, diet & exercise (e.g. overdoing sports & dietary restriction) and smoking.
Also, supplements like DHEA and CoQ10 might have an influence (at least if you suffer from PCOS or hormonal difficulties).

For young women, AMH seems to be quite constant from one cycle to another, older women have larger fluctuations.

To sum this up, we have to test often and maybe add other parameters.

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Hi, do you have any references / sources for this? I’m not doubting you, but I’d like to read the original sources for this information (regarding older women having larger fluctuations)… what is the standard deviation?, etc. It seems that above 50 the levels are so low that the fluctuations may be high from a percentage standpoint but very small in an absolute sense.

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I’ve never tested it but I’ll add it to my next set of labs. Fwiw My estradiol did increase a modest amount for the first time since 2015 after starting rapa to just above the menopausal range. I’ve been on the patch for 7 years but my levels had always remained below the menopausal cutoff even with the patch.

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Sure, I’m happy to answer!
If you approache a lab for testing AMH, they will tell you about the deviations in the results from cycle to cycle. The AMH value can change up to 20% between cycles. My Gyn told me about AMH being quite constant in younger women and having high fluctuations in the older ages.

Anti-Müller-Hormon - Was der Wert aussagt | Bioscientia | Labordiagnostik.

Note: the lab result of AMH reflects the number of recruited eggs in the ovary, as they are producing the AMH. So if you use an ultrasound, you can count eggs and estimate AMH.

My influence list above wasn’t even complete: a high BMI also causes AMH to drop faster. So there seems to be an ideal range of BMI for fertility.
With low BMIs and with a lot of sports, AMH seems to drop, too. Would be interesting, to see a regenerative potential for both cases (high BMI loses weight, low BMI gains it).
Several animal species can stop their fertility if there is insufficient nutrient supply or too much environmental stress and re-start it when times are easier. Is this the same mechanism with rapamycin? Is there a threshold, where stress gets too high for a certain period of time and fertility stops altogether? Or does the stress induced delay give you just a few more years and after that you become infertile anyway?

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Actually bad news, also CR can be overdone and could cause early menopause. Especially CR in young girls:

CR, but not undernutrition:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780671/

I don’t think delaying menopause is the key to longevity - I think healthy aging, or delaying aging results in delaying menopause. I’d also put forth that hormone normalization at a point that estrogens and progesterone are dropping is a sensible longevity step for most females.

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