What if you could delay menopause? How scientists are working to slow down ovarian aging

“We don’t have to accept menopause as destiny,” says Kutluk Oktay, an ovarian biologist and director of the Yale School of Medicine and Director of Laboratory of Molecular Reproduction and Fertility Preservation. Oktay, a leading researcher in fertility preservation, is one of the many scientists in the race to end menopause as we currently understand it. 

For most women, menopause means a gradual decline of progesterone and estrogen beginning in their mid-40s. The menopausal transition, or perimenopause, can last between two and eight years, and even up to a decade, before menopause, the point at which a woman’s menstrual period has stopped for a year. During perimenopause, women can experience a range of associated symptoms, including hot flashes to night sweats, pain during sex, joint pain, and mood and cognitive effects. Though hormone replacement therapy (HRT) can mitigate some of the effects, many of the physical impacts of menopause are lifelong health risks that can’t be treated with HRT, including bone density loss and a significantly higher risk of cardiovascular disease.   

But what if that timeline wasn’t inevitable? What if women were able to delay the onset of menopause or, more provocatively, end it all together? Medical researchers are tackling those questions, exploring drug therapy and other treatments that will, if successful, result in significantly delaying the onset of menopause.  

“I think it’s long overdue,” says Zev Williams, director of the Columbia University Fertility Center, who is currently studying how to delay ovarian aging. “For too long, menopause [has been] treated as an inevitability rather than a modifiable health event.” 

Oktay agrees, comparing menopause to other natural aging processes that can be corrected, like getting eyeglasses for vision loss. “Up until now everybody said, ‘Well, menopause is a given, it’s a natural process’,” Oktay says. “We have a lot of natural [processes for which] we are intervening.”  

​​​​Williams’ and Oktay’s teams aren’t the only researchers examining the possibility of extending​ ovarian longevity. Researchers​ at the startup Gameto are currently animal testing engineered​ young ovarian support cells from stem cells with the hopes of slowing menopause. And biotech firm Celmatix is working on a drug that they hope will slow ovarian reserve depletion. Other projects involve senolytics, a class of medicines designed to selectively remove old, damaged cells that contribute to inflammation and disease; and there are additional studies on ​compounds that boost cellular energy production​​​​​, and some researchers are investigating stem cell therapy to regenerate ovarian tissue. ​​​​​​  

Though much of this research is still in the development phase, ​new clinical trials are accelerating,​​​​​ finally giving menopause the scientific attention it deserves. “This field is still in its early stages, but with continued scientific investment, we may soon reach a point where delaying menopause is a real, accessible option,” Williams says. This, he says, could have profound implications: “By rethinking ovarian aging, we have an opportunity to reshape how we approach aging in general.” 

As researchers race towards finding medical interventions to delay or, eventually, end menopause, their work demands a reassessment of our current perception of women’s bodies and the inescapable, and rapid, march of ovarian aging. What does it mean to potentially expand women’s fertile years? And, perhaps most intriguingly: Do women need to go through menopause at all?      

The science of menopause—and why it might be beneficial to delay it  

Menopause is a bit of a scientific black box. Scientists aren’t exactly sure why women even go through menopause or the purpose it serves. “Humans are one of only a few species, along with some whales, that experience menopause,” Williams says. While many female mammals remain fertile for most of their lifespan, humans lose fertility decades before other systems show signs of aging.  

“In many species, fertility gradually declines but doesn’t cease entirely until very late in life, if at all,” Williams points out. In addition, women lose eggs each month through a natural selection process called atresia, where multiple follicles are recruited but only one matures. That inefficiency is present in many other mammals, but because humans have such a long lifespan relative to our reproductive window, the consequences of ovarian aging are especially pronounced in our species. 

There are a few theories as to why women experience menopause. One, Williams points out, is the grandmother hypothesis, which theorizes that menopause evolved so that women would stop reproducing and instead invest their energy in supporting their grandchildren, increasing the​ir​ survival​​​​. Others think that menopause protects women from the risks of late-age pregnancy, a threat to both the longevity of women and their offspring.  

It’s possible, however, that menopause isn’t an evolutionary feature at all: “The onset of menopause may just be a reflection of our longer lifespan​,” Williams says​. ​​When the average lifespan was under 50 years, the ​end​ of ovulation and ovarian function would not have been a factor​, he adds.​​ ​The average American woman now lives until she’s 80 years old, meaning she will spend roughly 25 years postmenopausal, significantly longer than, for example, her great-grandmother. A woman born in 1900 had an average lifespan of 48 years. 

Scientists do know one thing: menopause is the direct consequence of ovarian aging—which is also the key to delaying it. “Unlike other organs, the ovaries experience accelerated aging, with a dramatic decline in function beginning in a woman’s 30s,” Williams explains. It follows then, that if medical advancements can slow ovarian aging, it may be the key to extending the reproductive and hormonal lifespan of the ovaries, delaying ​​menopause while potentially reducing the health risks associated with it. Researchers point to women who naturally start menopause later, after the age of 55—which occurs in about 10 percent of women—who have better health outcomes, including a longer life span. ​     ​​​     ​​ 

“Late onset menopause has been shown in some studies to be associated with decreased bone loss, vascular disease, and dementia,” says Cheryl Cox Kinney, physician and President-Elect of the Menopause Society, in addition to increased longevity. Plus, as Williams points out, menopause can change body composition and insulin resistance, as well as raising a woman’s risk for several health conditions from vascular disease to dementia.  

Oktay adds to the list of potential benefits a reduced risk of diabetes and depression, not to mention more youthful skin, hair, and teeth. And those aesthetic effects aren’t just surface level; they can have a real and measurable impact on women’s body image and self-esteem. A review of 18 studies published in the journal Women’s Health in 2023 found that menopausal symptoms were consistently associated with a more negative body image, and the more intense and/or frequent a woman’s symptoms, the higher the negative impact. This research might have implications beyond women. According to Williams, the ovary is a “model of accelerated aging” and can “serve as a model for testing other treatments designed to slow aging.”  

​​​The scientific interest in delaying menopause emerges from the intersection of fertility and anti-aging research. If ovarian aging holds the key to longevity, including expanded fertile years, then delaying menopause could be an answer to both. ​​But one important question remains unanswered: ​​Would artificially delaying menopause lead to the same outcomes as when it’s naturally delayed? Researchers are optimistic that the answer is yes.  

An outpatient procedure that could hit the pause button on menopause​     ​ 

Oktay is currently offering an experimental procedure he’s been performing for​ about​ ​the last four years​ to delay menopause. Developed to help preserve fertility for women undergoing cancer treatments, he and his team began to think about other indications for the procedure, realizing it could be applied to ovarian aging. “Basic science and clinical experience merged. We got to a point [of] ‘Why not this?’”  

Oktay says that the key is to this procedure is to do it before the rapid acceleration of egg loss—around 37 or 38 years old for most women. Patients undergo an outpatient ​​laparoscopic procedure to retrieve the cortex, or the outer layer of the ovary, which contains tens of thousands of reserve eggs, also called primordial follicles. “We do this through three-quarter-inch incisions,” Oktay says. Patients return home that same day, and their tissue is frozen in a lab for about a decade.  

When their AMH (antimullerian hormone) levels, ​which forewarns​ that menopause is near, fall below a critical threshold, patients return to the lab and have the tissue transplanted back into their body.  “After the transplant, we expect about 60 percent of the reserve eggs in the tissue to survive,” he says. In the future, he says this survival rate may increase to 80 percent “making the grafts last even longer.”  The greater the number of younger eggs that survive, the greater the potential they have to delay or reverse menopause.  Oktay says that they are also able to transplant smaller amounts of tissue at three-year intervals (rather all in one shot) which could stretch out the delay even longer.  

Oktay doesn’t know yet if this procedure will delay or even stop menopause—it’s still in experimental phases. So far, his clinical trial has only collected ovarian tissue. It will take another decade for the study’s participants to age into their perimenopausal years, and for the re-transplantations to begin. “The future of this area of research is bright,” Oktay says. “It’s like we’ve planted the first seeds and we’re waiting, letting it grow.” 

​​Rapamycin could be the key to slowing ovarian aging​​ 

As Oktay works on developing a surgical procedure, Williams and his team at Columbia University Fertility Center are currently examining whether low doses of the immunosuppressant drug rapamycin could produce similar effects as the surgery. 

​​​Rapamycin is already FDA-approved for a range of use-cases unrelated to ovarian aging, including post-renal transplantation, and is widely available, intensively studied, and has an excellent safety profile according to Williams. ​If rapamycin sounds familiar it’s also because the drug has become popular among “anti-agers” after being touted by author and doctor Peter Attia for its purported longevity and health benefits, but more research is needed to definitively prove this link. 

Rapamycin works by inhibiting a protein called mTOR, a key component of the cellular pathway involved in aging and metabolic regulation. ​​​​In preclinical mouse and cell systems models, inhibiting ​this​ activity extends ovarian lifespan, ​which ​preserv​es​ egg quantity and quality, Williams explains. To go a layer deeper, Williams ​theorizes that the drug will slow down the rate at which a woman’s eggs turn over every month. Instead of losing dozens every month, a woman might only lose 10, for example, while keeping the other eggs in her reserve. Like the surgery, the trick is to start taking the drug before menopause, as it cannot bring eggs back. It most likely wouldn’t work for postmenopausal women.  

“It could very quickly be translated into an intervention that could have a meaningful impact for human health,” he says.  

Proving this out in a randomized, placebo-controlled, double-blind trial is the next step. Fifty women agreed to be part of a study called VIBRANT which is ongoing. ​​​​One thing that surprised Williams was how many women were interested in joining the study. He notes that one of the challenges of completing a clinical study is finding people who want to participate. But, with VIBRANT, that wasn’t the case. “The day the study went live, we had over 100 people,” Williams says. That, he argues, “speaks to just how much interest there is” in delaying menopause. The women will take either low-dose rapamycin or placebo once a week for three months. Williams and his team will then follow them for nine additional months, tracking how rapamycin is (or isn’t) working.  ​​​     ​ 

Williams is hopeful but stresses that the team can’t draw definitive conclusions until the study is complete, but he noted that “one group is reporting benefits such as better mood, better memory, and feeling that their skin looks better, and another group is reporting that they feel the same.” 

He reiterates that this research could also lead to ways to slow aging in general and prevent aging-related diseases. But the timeline for public availability depends on the clinical trial outcomes and regulatory approval, which could take several years. 

(Can this ‘anti-aging’ drug live up to the hype? Here’s what we know)

A new age of motherhood? 

If this new research raises hard-to-answer questions about the purpose of menopause, it could also mandate a reassessment of motherhood and fertility. We understand the ability to become pregnant as an event limited by time and age, even with medical interventions like in vitro fertilization. Currently, women who become pregnant at 35 years old and older are considered “geriatric” pregnancies, monitored for complications ranging from increased risk of miscarriage to low birth weight, and preterm birth. For most women, fertility and egg quality rapidly declines at 35, with a substantial drop-off by 40 years old. But delaying menopause could change the timeline significantly: Women could be fertile well into their 50s and beyond. 

Oktay believes that the rapid acceleration of medical research to delay or pause menopause might make society rethink the age at which it’s “expected” for women to have children. “A big change is due to the way we perceive menopausal age, ​​just like it happened to the perceptions on life expectancy,” he says.​ Now, with modern medicine, it might be possible to live to over 100 years old. But menopause still happens around the same age, meaning as longevity increases, some women might spend more of their lives postmenopausal. “If​ we are going to let women live that long, I think we also need to stretch significantly the reproductive lifespan and reproductive hormone lifespan, at least somewhat to improve quality of life,” Oktay says.​ 

​​​But, having a baby later in life raises ethical questions. Deborah Gomez Kwolek, founding lead of the Mass General Women’s Health and Sex and Gender Medicine Program argues that the rapid speed of ovarian aging—twice that of regular aging—may have a real biological imperative. Having children earlier increases the likelihood that women will be alive long enough to raise their biological children. “Until you can really slow regular aging, you might not want to delay menopause too far,” she says, pointing to the age limits placed on parents who are interested in adopting.  

For Williams’ part, he sees the implications of his and other work in this space more broadly: “What this work really invites is a broader rethinking of how we view ovarian aging—not necessarily to redefine when women should have children, but to reframe ovarian aging in the context of overall health and longevity,” he says. “There’s no stigma around efforts to maintain brain health or prevent memory loss. Why should ovarian aging be viewed any differently?” 

For many women, however, prolonging their reproductive years might not be a compelling argument to delay menopause. One of the primary benefits of menopause is the end of menstruation and the potential for unwanted pregnancy. There may be other risks as well. 

The fact that​ ovaries will produce​ estrogen ​​​​for longer could be a double-edged sword. It may slightly increase the risk of breast or endometrial cancer, Kwolek says, noting that it’s not a “major risk” while still emphasizing that women should be “careful.” Oktay acknowledges this risk as well, although he says that “there are studies that take into account these risks in terms of women having late menopause and their life expectancy [and] they still live longer.” 

Kwolek also points out that there are other options that are more researched and have more of a track record, like IVF and HRT: “It may be better to just bank some eggs. The research [on delaying menopause] is really cutting edge, but it’s also really niche at this point and there’s some catching up to do.” 

Shifting perspectives on what’s natural  

As medical researchers race to find treatments to delay menopause and slow ovarian aging, we’ll soon have to answer the questions that their work raises. Oktay believes ovarian longevity is inevitable—that the scientific inquiry itself is the result of expanded lifespans. “Medical advances are making women and men live longer, and women live even longer. [Women] end up spending close to half of their life in menopause, which did not [happen] 50 years ago,” Oktay points out.  

It’s a provocative rethinking of the way in which women age, particularly the rapid progression from perimenopause to postmenopause that’s currently perceived as both natural and inevitable. The assumption that women must spend decades of their life postmenopausal is a uniquely modern one—and, historically, we’ve made many assumptions about women’s bodies that have proven wrong. Maybe we’re due for another shift.