Hey. Yes! I’ve not tested specifically for 17-a estradiol but have definitely tested for regular estradiol as well as testosterone, FSH, LH, DHT, DHEA, etc. It might be helpful to check inflammatory markers like CRP in someone taking 17a Estradiol since there’s some animal evidence that inflammation goes down.
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I started rapa over a year ago…. I started at 1 mg once per week, but have worked my way up to 5mg once per week now.
Before rapa, I was experiencing periomenopause symptoms…. Lighter periods that came once every 2 - 3 months or so… I think… I wasn’t really keeping track….
Now I didn’t start taking rapa for fertility…. I never even read anything about rapa having an impact on extending fertility…. I just wanted it for longevity….
I have started noticing when I got to my higher dose (5mg) that my periods have returned once a month…. And they are no longer light as well…. Btw- I’m 48 now….
I’m glad to see this post, because to be honest, I was getting worried…
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@AmyK nice to see you here also 
!
Do you follow a certain stack and timing with supplements and medications? Dr. Mindi Pelz recommends to fast only in the 1st half of a cycle. Now this would translate into taking rapamycin and certain polyphenols only in the 1st half.
My personal stack looks as follows: The day I take rapamycin, I’ll fast and I’ll take fisetin, resveratrol, spermidine and quercetin. Sometimes I use this day as a starting point for a longer fast of 4 days in a row. If I don’t fast, I’ll at least keep my protein and sugar intake low.
After 4 days of taking rapamycin I ramp up my protein intake, supplement with collagen and once a month do a microneedling session during refeeding.
Now, do I have to pay attention to my cycle and not take rapa in the 2nd half?
Many thanks to all of you, this forum really helps!
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I think your plan makes sense. I don’t fast (I’m already thin and don’t want to lose muscle) but I do plan my more difficult/heavier weight training on the second half of the week if possible (furthest from my Sunday Rapa dose).
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Why do you start your fast when you take Rapa? Rapa mimics starvation. If you fast in addition to taking Rapa, it’s like double fast.
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Lara, there does seem to be some overlap in what rapamycin and fasting does, but there also seems to be significant differences. For example in muscle:
Distinct and additive effects of calorie restriction and rapamycin in aging skeletal muscle
https://www.nature.com/articles/s41467-022-29714-6
So, its not unreasonable to do both.
More of a discussion here: How Rapamycin Extends Lifespan (mechanism and implications) Discussion
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I try to deactivate mTor with rapamycin. If I eat high protein at the same time, I fear that mTor gets turned back on.
I’m just guessing, so could also be too much.
Same with additional supplements in the fields senolytic, mitophagy, autophagie, energy,… There is just not much data and we kind of have to guess how to stack or combine.
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We are all guessing alot when it comes to issues around rapamycin use in longevity. We still have a lot to learn.
We try things that seem to go with the science, we see how our bodies react, ideally we do blood testing to confirm (if possible) that things are going in the right direction, and then we adjust if we need to.
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Do you fellow women take rapamycin according to your cycle? If so, do you choose 1st or 2nd half?
According to Mindy Pelz, 1st half would be reasonable and 2nd half could even be bad. I personally am not sure if this is true…
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Is Mindy Pelz your doctor? I just looked her up, she’s based in the San Francisco Bay Area (San Jose) - but I had not heard of her before. Where did you hear her recommendations related to this - does she podcast etc. or did you get this from her directly?
Mindy Pelz: About - Dr. Mindy Pelz
She does podcasts about fasting and the female cycle/ hormones. She strongly recommends to stop fasting in the 2nd half of the cycle. As rapamycin mimics some effects of fasting, I wonder if it should be restricted to 1st half.
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Does fasting in the 2nd half of your menstrual cycle influence progesterone?
There is some evidence to suggest that fasting during the luteal phase of the menstrual cycle may have an impact on progesterone levels. The luteal phase is the time period between ovulation and the start of the next menstrual period and typically lasts for about 14 days. During this time, the hormone progesterone is produced in high levels to prepare the endometrial lining for a potential pregnancy.
However, studies have shown that fasting and caloric restriction can lower progesterone levels and disrupt the normal hormonal balance of the menstrual cycle. This can lead to changes in the luteal phase and potentially interfere with ovulation and conception. In addition, changes in progesterone levels can also affect menstrual cycle regularity, leading to changes in the length of the luteal phase.
It is important to note that more research is needed to fully understand the relationship between fasting and progesterone levels during the menstrual cycle. Additionally, it is always best to talk to your doctor before starting any new dietary or fasting practices, especially if you are trying to conceive.
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Estrogene dominance bc of low progesterone is not anti aging… So we should be careful.
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I got a few labs from my family doctor-LH, FSH and estradiol and will have to order the rest on my own. I’ve been post menopausal since @2015-2016 and unfortunately I don’t have prior labs because my old doctor left his practice and I was never able to track down my medical records. I currently get copies of everything so that doesn’t happen again! All I know from memory is that my estradiol was in the 50 range in 2015 and it’s currently 11.5 pg/ml. I’ve been using bio identical topical Estradiol in patch or gel form since 2016. My LH is 33.1 and FSH 120 which are all post menopausal numbers. I have no idea if I should be doing anything different to try to change these numbers tbh. So far I have been planning to stay on estrogen because it’s been helpful. These numbers will have to serve as my baseline to see if there are any changes from taking rapamycin moving forward. These labs were taken after a month of dosing at 1mg, 2mg, 2mg and 3mg. Another thing I take that could possibly have an impact is melatonin and I plan on staying on that as well due to sleep/circadian rhythm issues. I should also mention I only have one ovary and the rest was removed in 2006.
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Perhaps someone in this thread has had this experience, and can comment: Tender breast similar to premenstrual
@AmyK do you know Stacy Sims? I’ve now bought her book about women body hacking, optimization, hormones, fasting…
Does anyone here know her book? What do you think?
There is a breed of egyptian mice, which cycle. So maybe I should get some as pets and try rapamycin as I think would make sense for a cycling woman.
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I don’t know Stacy Sims. Sorrry
Insider: Doctors want to know if rapamycin can prolong fertility.
The study, called VIBRANT (Validating Benefits of Rapamycin for Reproductive Aging Treatment), is designed to measure whether the drug rapamycin can slow down aging in ovaries — but it’s not just about reproductive health. If successful, this very first controlled study of the drug rapamycin for human aging could have wide-ranging implications for helping reduce the pains of menopause, and extending the lives of people of all genders, with a cheap, once-weekly drug that’s already widely used by some cancer patients and transplant recipients.
Full Article:
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Another news story on this research:
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The Secrets of Aging Are Hidden in Your Ovaries
By Emily Mullin
WIRED
May 2, 2023
The ovary is a time machine. It travels to the future, reaching old age ahead of the rest of the body. At birth, each ovary contains around a million follicles—tiny, fluid-filled sacs that hold immature eggs. But the decline of these follicles is immediate and unceasing. By puberty, only about 300,000 remain. By age 40, the vast majority are gone. And by 51, the average age of menopause in the United States, virtually none are left.
Humans are an oddity in this regard. Most mammals remain fertile up to the end of their lives; the only species known to experience menopause naturally are humans and some whales. In humans, the loss of hormones during menopause sets off a cascade of negative health effects: Bones get brittle; metabolism slows; and the risk of cardiovascular disease, diabetes, stroke, and dementia increases. Paradoxically, women live longer than men on average but spend more of their older years in poor health.
Jennifer Garrison has a hunch that the ovaries are the culprit. “That cocktail, that orchestra of chemicals that the ovaries make, is really important to overall health,” says Garrison, an assistant professor at the Buck Institute for Research on Aging in Novato, California. “When it goes away at menopause, it has a dramatic effect.” On the other hand, having working ovaries for longer seems to carry longevity benefits. One study of 16,000 women found that later menopause made it more likely someone would live to age 90.
Despite the fact that half the world’s population experiences ovarian aging—including cisgender women and trans and nonbinary people—longstanding gender bias in science means it has remained an understudied field. But that’s starting to change.
Garrison leads the Buck Institute’s Center for Reproductive Longevity and Equality, a first-of-its-kind facility established in 2018 with a $6 million gift from attorney and philanthropist Nicole Shanahan. In 2019, the institute launched a related effort, the Global Consortium for Reproductive Longevity and Equality, to fund outside researchers. An initial 22 researchers received inaugural grants totaling $7.4 million. Their goal is to understand why the ovaries seem intricately connected to health and longevity. Unraveling these mysteries could mean extending a person’s reproductive years—and potentially lifespan—by delaying menopause.
In 2018, the field of reproductive longevity was so nascent that Garrison had a hard time finding faculty to interview, let alone hire, to staff the center. Few people were actively researching it, partly because the only other mammals that experience it are whales—which can’t exactly be studied in a lab. It’s also hard to study ovarian aging in such long-lived species—killer whales, for example, can live up to 90 years in the wild. Instead, researchers have often tried to crack menopause and its link to aging by proxy: by observing chemotherapy’s effects on fertility, by studying a common menopause treatment that mimics female hormones, or by experimenting on mice, which are imperfect stand-ins for humans.
Five years later, the Buck Institute’s efforts are starting to deliver results. Researchers might not have figured out how to slow reproductive aging yet, but they’ve spurred interest in a long-overlooked organ and opened a new avenue of inquiry that could have implications for how everyone ages—not just people with ovaries. “If we can understand what’s happening in the ovary,” Garrison says, “that will probably tell us something about aging in the rest of the body, and could also give us a handle on how to intervene.”
To work out how fast ovaries age, you need to look at a lot of cells. At Columbia University in New York, geneticist Yousin Suh and her colleagues have been collecting and analyzing cells taken from the ovaries of women in their twenties and those in their late forties and early fifties who haven’t yet gone through menopause. What they found shocked them. Cells from the ovaries of middle-aged women often resembled cells in other tissues from people in their seventies and older.
In cell type after cell type, Suh’s team found unmistakable signatures of aging. They saw damaged DNA and dysfunctional mitochondria—the energy powerhouses within cells. Communication between cells broke down. They stopped dividing. A key regulator of cell growth and metabolism, called mTOR, was also overactive. Too much mTOR is associated with cancer and aging, and drugs that suppress it are used to slow tumor growth. For Suh, it was “crystal clear” evidence that the ovary is aging faster than the rest of the body at the molecular and cellular levels. Suh and her team posted their findings online last year, and the paper is currently undergoing peer review.
The mTOR discovery was particularly intriguing. Blocking the protein has already been shown to increase lifespan in flies, worms, and mice. Now Suh wonders if the same benefits could extend to human ovaries.
Over at Northwestern University in Illinois, Kara Goldman, an associate professor of obstetrics and gynecology, has also been exploring the link between mTOR and ovarian aging. She was interested in whether mTOR inhibitors could protect the ovaries against fertility loss caused by chemotherapy.
In a 2017 study, she gave the drugs to otherwise healthy female mice that were also treated with chemotherapy. The hope was that the mTOR mice would be better protected against ovarian damage compared to mice that only received chemotherapy. And it worked. Both groups lost follicles because of the chemo, but the mice that received mTOR inhibitors had more of them left. Those mice went on to have more than twice as many offspring. In other words, the drugs seemed to preserve the ovaries, says Goldman, who serves as director of the clinical advisory board for the Buck’s consortium.
Then Goldman took the research a step further. She wanted to see if these drugs could boost fertility in healthy mice. She gave daily oral doses of mTOR inhibitors to female mice for four weeks, beginning in young adulthood. When these mice mated, they produced twice as many pups over a seven-month period as a control group that didn’t receive the drugs, suggesting they were better at reproducing than untreated mice.
Goldman and her team also wanted to make sure the drugs didn’t have negative side effects—a drug to be used in otherwise healthy people to extend the lifespan of their ovaries would need to be extremely safe, she says. Her team monitored the health and fertility of the treated mice, as well as their first- and second-generation offspring, and thus far have found no ill effects. The researchers presented preliminary findings in 2021 and are still analyzing their data.
But will the same be true for humans? To find that out, Suh and her collaborator Zev Williams launched a trial to test whether the drug rapamycin, an mTOR inhibitor, can slow aging in the ovaries. They plan to enroll 50 women in their mid-thirties to early forties who don’t plan on having any more children. For a year, half will take daily rapamycin pills and the other a placebo. Researchers will then test the number of healthy eggs the participants have left.
Their hope is that the group taking rapamycin will have more eggs. That would mean their ovaries are aging less rapidly than normal. “What we’re trying to do is slow down the rate at which eggs get lost,” says Williams, director of the Columbia University Fertility Center.
The fact that the ovaries age so much faster than other body tissues also makes them a valuable way to test anti-aging drugs. Studies like these could yield insights on a much shorter timescale than than those done on other tissues in the body—which could have implications for aging in both women and men.
Ultimately, Goldman sees a future in which women would take these drugs at an even younger age. “The moonshot idea is to not only protect fertility but prolong ovarian health span,” she says.
No one knows for sure if it’s possible to keep the ovaries functioning longer, or whether that will lead to a longer, healthier life. Mice, at least, seem to benefit when their ovaries stay healthy for longer. When researchers at Utah State University transplanted the ovaries of young mice into older ones, the recipients lived about 40 percent longer than their peers and also had healthier-looking hearts. But there’s one problem with relying on mice as a stand-in for people: Like most other animals, mice don’t go through menopause.
Bérénice Benayoun, an assistant professor of gerontology at the University of Southern California, is trying to genetically engineer menopause into mice so scientists can study the biological mechanisms behind it and figure out how to offset it. “Menopause is basically the single most consequential event in a woman’s life in terms of health,” says Benayoun, who’s funded by the Buck Institute.
Researchers elsewhere have tried inducing a menopause-like state in two- to three-month-old mice by removing their ovaries or injecting them with a chemical to stop the ovaries from working. But Benayoun says that’s like trying to suddenly make young adults menopausal. The animals don’t show a gradual loss of ovarian function over time like humans do.
Benayoun and her team have knocked out a gene in mice that, in humans, leads to early menopause. In mice, it led to a more gradual loss of hormones. The research has not been published yet, but Benayoun thinks it may offer a closer approximation of what happens in humans: “We can get hormonal states that are very similar to what’s described in human women,” she says.
Even if researchers figure out how to delay a fake menopause in mice, that doesn’t mean it would be safe to do so with people. “That’s the big question,” says Stephanie Faubion, medical director of the North American Menopause Society and the director of the Mayo Clinic Center for Women’s Health. “Would there be any harms associated with it? We have no idea.”
A common treatment for menopause may offer some clues. Hormone replacement therapy, or HRT, provides the body with estrogen and progesterone that stop getting made during menopause. While generally considered safe for most women, it can slightly increase the risk of blood clots and stroke, as well as some types of breast and ovarian cancers.
But the ovaries produce many more chemicals and signaling molecules than these two hormones. To Garrison, the issue with HRT is that it doesn’t fully replicate the work of the ovary. While she calls HRT “the best Band-Aid treatment we have,” she considers it “deeply imperfect” because it doesn’t mimic every chemical the ovary makes. “We don’t even know what they are, much less how to replace them,” she says.
Perhaps the biggest mystery about menopause is why humans experience it at all. The “grandmother hypothesis,” a concept proposed in the 1960s, suggests an evolutionary benefit. It argues that menopause allows older women to care for their grandchildren, thus boosting their kin’s chances of survival and ensuring the continuation of their own lineage. By studying killer whales—which also experience menopause—researchers have found that the presence of a living grandmother increases the chances of survival for a calf.
If the theory is right, this evolutionary mechanism could still be helpful to human families—but less so to the individual. Humans are living longer and starting families later than ever before. People born today may live as much of their lives after menopause as they do before it. Why shouldn’t those postmenopausal years start later and be healthier? “The reality is, the age of menopause is at odds with modern life,” Goldman says.
Menopause may be inevitable, but Garrison thinks it’s possible to at least stall it to help people remain healthier in older age. With her initiative at the Buck Institute, she’s trying to fill in the huge gaps created by sexism in science and chronic underfunding of women’s health research. Historically, investigators have relied too much on male lab animals and often excluded women from medical and toxicology studies, generalizing to women from data collected from men.
Today, clinical trials are more gender-balanced, and in 2014 the US National Institutes of Health announced an initiative to balance sex in cell and animal studies. Still, there’s catching up to do. “We don’t have a lot of basic knowledge because this area has been ignored by the biomedical research community for a very long time,” Garrison says. Now, the field of female reproductive aging is finally getting the attention it deserves. “These are solvable problems,” she adds. “We just need to do the work.”
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