Ovarian research aims to extend fertility and lengthen lives by delaying menopause—but the ultimate moonshot would be ending it altogether.
Sometime when a woman is in her 40s or 50s, the supply of eggs she was born with gradually degrades and runs out. Hormones like estrogen, produced within her egg follicles as they ready for release each month, dwindle. And that shift ushers in an onslaught of often-brutal changes: the end of her fertility, menopausal symptoms that can undermine everyday functioning for years, and heightened risk of age-related illness, from heart disease to bone loss to dementia.
That’s just the way it’s always been and the way we’ve always assumed it had to be.
But what if it didn’t have to be that way?
A small but growing number of scientists are asserting that it’s time to cancel menopause—or at least substantially delay it. And their hypothesis is that if we do, we’ll not only extend women’s fertility but also postpone the onset of a cascade of potential health problems. proto.life has examined this effort over the last nine months, speaking to some of the leading experts in the field and surveying several of the companies driving the effort.
To cancel menopause, experts say, we will have to overcome the longstanding underfunding of women’s health research and the obscurity of the fledgling field of female reproductive longevity. Even then, the underlying question remains: Should we overcome our own evolutionary programming? And if it’s possible, can we make it safe? No one knows for sure what will happen if we re-score the symphony of biochemical signals that orchestrate and flow from a woman’s menstrual cycle, because no one’s ever done it before. Yet the scientists who are pursuing this goal (many of them pre-menopausal women) believe so fiercely in their pursuit that they’re willing to take on any challenges—be they from Mother Nature or their fellow man.
The age of menopause
One of the researchers leading the charge is Jennifer Garrison, an assistant professor at the Buck Institute for Research on Aging in California. Situated on an oak-studded hillside in upscale Marin County, just north of San Francisco, her lab overlooks grassy slopes where deer and mountain lions sometimes roam. She sits at her desk and speaks about menopause with a soft voice and gentle manner that downplays her ferocity. A mug on the desk bears a quote from Justice Ruth Bader Ginsburg: “Women belong in all places where decisions are being made.” When asked, she says she likes to bring the mug to meetings. Her Twitter bio declares, “Hear me roar.”
Garrison has emerged as a ringleader in research on female reproductive longevity—a realm she only stumbled into a few years ago. Her lab was studying neuropeptides, fragments of proteins in the brain that act as long-range biochemical signals, traveling across the body in what she likens to “the brain’s wifi.” They were examining how neuropeptides influence systemic aging in C. elegans worms, trying to figure out the workings of one specific neuropeptide that plays a profound role. When they discovered that it was functioning through the reproductive system, Garrison started asking more questions. Now a significant focus of her research is trying to understand these signals and how they change with the menstrual cycle and with aging.
“I did not consent to this thing called menopause, and I do not want to go through it.”
“This conversation between the brain and the reproductive organs, brain-ovaries-uterus, we know some of the words in that conversation,” she says—estrogen, testosterone, neuropeptides. “But in general, I would say that the full lexicon is completely undefined. There’s probably so many other things going back and forth that we don’t know about.” What we do know, she adds, is that the conversation is a dialogue. The brain exerts influence on the reproductive organs—and vice versa. Small as ovaries may be, they wield outsized power in the body.
“I have a personal interest because I own a pair of ovaries,” says Garrison, who is in her mid-40s and grew up as the oldest of four sisters. “I did not consent to this thing called menopause, and I do not want to go through it.”
Garrison joined the Buck Institute’s Center for Reproductive Longevity and Equality in 2019 as a founding member. The center launched that year with a $6 million grant from attorney Nicole Shanahan, who is married to Google co-founder Sergey Brin, via the Sergey Brin Family Foundation. (Shanahan was drawn to the subject when she struggled to get pregnant with Brin in her late twenties.) The next year, Garrison and Shanahan co-founded the Global Consortium for Reproductive Longevity and Equality to supercharge the tiny, obscure field of research on female reproductive aging, with $10 million in seed money from Shanahan’s Bia-Echo Foundation. Garrison directs the consortium, which hosts events and makes grants in an effort to, as she puts it, “basically build a scientific research field from almost nothing.”
The field is so new that as recently as 2013, when Garrison’s collaborator Francesca Duncan was at a training course on the biology of aging at the Marine Biological Laboratory in Woods Hole, Massachusetts, she was the only person focused on reproductive longevity. In a room full of longevity researchers, when Duncan said she was studying ovarian aging, “They looked at me like I had five heads: This is not a system that is aging in a 30-year-old; that’s not aging.” That awareness is changing now, as more researchers begin to ask why women’s age at menopause has barely budged over the past century even as our lifespans grew decades longer.
“The things that I learned about my own body the last five to seven years—horrifying that I didn’t know before—this should be on the cover of TIME magazine, and people should be talking about it at their dinner tables,” Garrison says.
Among the questions Garrison and her colleagues aim to answer is why the ovaries age so much earlier than the rest of the body, becoming basically geriatric when a woman is in her thirties. They also want to understand the biological reasons why we need menopause—or if we even do at all, considering the fact that only a handful of other species, including orcas and narwhals, are known to undergo it. Our close cousins the chimpanzees don’t stop their female cycles until near the age of death.
To the eyes of Garrison and her fellow innovators, this looks not only unfortunate but unfair—hence her inclusion of the term “equality” in the names of the center and consortium she runs. “We’re worsening the root causes of inequality in our society” if we don’t change this, says Dina Radenkovic, a physician and co-founder of Gameto, a New York-based startup developing treatments for infertility and menopause. There are already so many barriers to women’s professional advancement, Radenkovic reasons—and just when women hit peak career growth, they have to sit out a spell to become mothers or risk losing their chance to ever to give birth. When they finally attain leadership roles by their forties or fifties, menopause hits.
“This is an important battle for humanity and productivity and women,” Radenkovic says. “If it works out, it could change the way we think about gender and aging in society.”
Menopause, to be clear, is not just a hot-flash joke. A 2018 research review found that menopause substantially impedes women’s quality of life and work performance and disproportionately affects women of lower socioeconomic status. The NIH reports that 75 percent of women experience some of the most common symptoms, including hot flashes, night sweats, palpitations, and migraines, and these last an average of more than seven years. Sixty percent suffer urogenital symptoms such as vaginal dryness, painful sex, incontinence, and decreased libido, and 45 percent contend with mental health symptoms such as anxiety, depression, sleep disturbance, and difficulty concentrating. A study in the journal Menopause found that the most common symptoms, left untreated, cost more than $2,100 in health care and lost work productivity per woman per year.
“The suffering is real,” Radenkovic says. “This is not like cosmetics, this is real medicine.”
Only 1% of health care research dollars go to women’s health.
After menopause, women’s risk of disease and death increases. A U.K. government study in 2017 found that, while women in the United Kingdom live longer than men, they spend more years in poor health. It’s known that women who go through menopause later tend to live longer (as do their brothers, though we don’t know why). Radenkovic’s own great-grandmother died from breaking a hip (potentially a result of the bone fragility that menopause accelerates) and then developing pneumonia through her ensuing bed rest. Young women who lose their ovarian function early through chemotherapy for cancer face similar health risks, says Alicia Jackson, founder and CEO of the menopause-care company Evernow. With normal menopause, Jackson says, “We just don’t call it a health crisis, we call it getting older and aging.”
Meanwhile, a 2022 McKinsey & Company report estimates that only 1 percent of health care research dollars go to women’s health. Radenkovic says when she tells people what her company does, the response she sometimes gets is, “You’re in this field, you have this potential, why aren’t you curing something else?”
If this effort succeeds at illuminating how and why ovaries age, researchers predict those discoveries could be a key to unlocking insights about bodily aging more broadly. Think of the scientists laboring in the frothy field of longevity research to identify and reverse the causes of aging and disease, trying to gain quick insights on a biological process that unfolds over decades. Now imagine they have a canary they can drop into that coal mine to gauge the factors that slow or accelerate our demise. Garrison would say they already have one. It’s called the ovary, and it naturally ages two to three times faster than other tissues in the body—meaning the results of any experiments can be seen that much faster, as well.
“You basically need a time machine if you’re going to study aging interventions,” says Garrison. “The ovary is the time machine.”
There are lots of areas of research on female reproductive aging that Garrison considers promising. These include:
- Seeing how biochemical interventions that broadly affect aging work specifically in the ovary.
For example, the mTOR inhibitor drug rapamycin and NAD+ enzyme boosters, both known for their promising anti-aging effects, may also slow aging of the ovaries. Kara Goldman, associate professor at Northwestern Medicine in Chicago, says she and colleagues have compelling, not-yet-published data that mTOR inhibitors extend fertility in reproductively young mice. A grantee of Garrison’s consortium is now starting a study to test rapamycin for ovarian effects in humans.
- Understanding environmental influences on developing eggs—from food contaminants to the micro-environment of the ovary.
Researchers are increasingly discovering how chemicals in our everyday lives, such as pesticides or plastic residues in food and cosmetics, can affect the ovaries’ development and function. At a smaller scale, Garrison’s collaborator Francesca Duncan, who has been studying ovarian aging since 2007, is working to understand what she considers “the soil” that eggs grow in—the environment inside the ovaries themselves. Duncan, an assistant professor at Northwestern Medicine and assistant professor in residence at the Buck Institute, has found that ovarian tissue becomes stiff and inflamed with age, affecting egg quality and quantity. Her hunch is that the cause is the buildup of old egg follicles, hundreds of which go unused and die in every menstrual cycle. “Women are born with millions of eggs,” she reasons, “and if we could keep them happier longer [by fixing their environment], we could solve this problem of infertility and menopause.”
- Finding cellular targets for treatment, such as inflammation, mitochondrial function, senescence, and DNA damage.
For example, Duncan and collaborators at the Buck Institute are starting to map the senescent cells—long-lived cells that effectively retire from replicating themselves and then trigger inflammation in surrounding cells—inside ovarian, breast, and muscle tissues. Garrison believes such work has a good chance of yielding targets for drugs, but it’s hard to predict the timeline.
- Building better tools to illuminate individual women’s fertility status.
Including reproductive aging clocks, biomarkers for fertility span, and diagnostics for fertility problems. Considering that the normal range of age at menopause spans 14 years, “You should be able to have a way, an easy way, a noninvasive way, to know where you are in your fertility trajectory,” Garrison says. While much of the other research on reproductive longevity is likely to take a decade or more to produce practical applications, Garrison estimates we might have better clocks and diagnostics in half that time.
Meanwhile, a small handful of women scientist-entrepreneurs are forging ahead with startups aimed at marketing therapies for ovarian aging. Daisy Robinton’s Oviva Therapeutics is testing a lab-grown version of Anti-Müllerian hormone (AMH) to stop eggs from maturing and effectively hold them in reserve. Piraye Yurttas Beim’s Celmatix is developing a drug to dial up the gene that encodes for AMH. And Dina Radenkovic’s Gameto is using cell engineering and reprogramming to create a cell line and derive biologic drugs that replace some ovarian function. Gameto aims to develop one drug to help women undergoing IVF grow more mature eggs—and another to carry on the chemical conversation between the brain and the ovaries that after menopause sends the ovaries’ signals into silence.
Anyone who succeeds will potentially strike a massive untapped market, with an estimated 1.3 million women in the United States reaching menopause each year. Globally, it’s estimated that 1 billion women will be in menopause by 2025. If that prospect draws investors and scientists into the space, Garrison is happy to have them. But she still wants something more than a therapeutic Band-Aid. She wants to identify the fundamental, original cause of ovarian aging—the signal or combination of signals in the body that starts the ovaries aging to begin with—and correct it. “Until we understand what that causative factor is,” she says, “everything else is just window dressing.”
Is there a downside?
So who’s ready to sign up for extended fertility and a healthier later life? Actually, not everyone.
“The knee-jerk reaction to something like this is: It sounds very sci-fi, menopause happens for a reason, and we should respect biology,” says Northwestern’s Kara Goldman.
In fact, menopause doctor Lauren Streicher, founder and medical director of the Northwestern Medicine Center for Menopause and the Northwestern Medicine Center for Sexual Health (who does not work with Goldman or Duncan at Northwestern), is not sold. “There’s no question that we should mitigate the impacts of menopause,” she says. “But do we need to use a [new] drug to do that? No.”
Streicher contends that we already have a treatment that could go a long way to reducing the symptoms of menopause and the health risks that follow it: hormone therapy. Doctors tend to be skittish about prescribing estrogen because of a large study in 2002 that showed it increased the risk of breast cancer. But Streicher and a number of other experts argue that those results have been misinterpreted to grossly exaggerate the risks and undersell the benefits. “The issue is we have not enough women taking it and they’re not taking it long enough,” says Streicher. If more women started hormone therapy earlier, before the bodily damage done by dwindling estrogen, and sustained it longer, she says, we wouldn’t need Garrison’s hoped-for drug to slow the ovaries’ clock.
As for extending fertility, Streicher would rather invest in making egg freezing cheaper and easier from an early age, rather than pouring millions of dollars into a new drug with the hopes we might delay menopause by a few years. “I can think of a lot better uses of that money,” she says. (Freezing eggs earlier in life makes them more likely to be viable, but does still require IVF for conception and does not guarantee pregnancy or healthy birth.) Streicher also points out that having more hormonal cycles correlates to a higher risk of ovarian cancer, and that menopause brings relief from conditions such as endometriosis and anemia. “You bet there’s a downside” to extending the menstruating years, she says.
Garrison knows all these critiques. The objections she frequently hears run along the lines of: “You’re going to let women have babies when they’re 70?” or “Who wants to have a period forever?”
“And my answer to that is, well, it takes more than functioning ovaries to have a baby,” Garrison says, “and also, what business of mine is it to tell someone they can’t have a baby?”
She adds that, at least in theory, it could be possible to sustain ovarian signaling without having a period (the building up and shedding of the uterine lining). “We want women to be healthy,” she says. “We want their bones to be strong and their brains to be clear and their hearts to function properly.”
Yet Goldman strikes a note of caution about canceling menopause altogether. In addition to researching ovarian aging, she serves as medical director of fertility preservation at Northwestern Medicine and provides fertility treatment including IVF. “I would never want to give the impression that by expanding reproductive longevity we are endorsing pregnancy at advanced reproductive ages, because of the risks to mom and baby,” she says. But having just a few more years of ovarian function, so that a 43-year-old woman has a better chance at conceiving with her own eggs? And giving women just a few more years before menopause, which would lead to decreased illness and an overall lower risk of death? “In my mind,” she says, “that’s the ideal.”
A dream within reach
Multiple forces are converging to support this work now. There’s keen interest in aging research among government funders and private investors. There’s the new engine of the Buck Institute’s center and global consortium, backed by the contributing ideas and wallet of Nicole Shanahan. Plus there’s the increasingly interdisciplinary nature of science itself. “All of these things are coming together at the fulcrum,” says Duncan, who also runs the Buck Institute’s new Reproductive Biology Hub, a fee-for-service lab serving researchers anywhere who want to do specialized studies of the ovary. “It’s sort of the perfect time for this to happen.”
“I want to have traditional biotech investors pouring money into women’s health.”
Radenkovic wants to capitalize on that. “I really, really want to have a very big success story in this field and reframe the narrative,” she says. “I want to have traditional biotech investors pouring money into women’s health.”
In the interim, Garrison (like Streicher) wants better treatment options for women using the tools we have now. Alicia Jackson’s Evernow, where Garrison serves as a scientific advisor, is trying to provide this. The telehealth service pairs patients with clinicians who send them hormone therapy prescriptions by mail, customizing and adjusting their doses as symptoms evolve over time. Evernow takes an approach closer to what Lauren Streicher urges (starting medication early and sustaining it), rather than the more conservative approach taken in many ob-gyn offices. The company is also tracking tons of data on patients’ symptoms and treatments, seeking to deepen knowledge as they go.
Already, Jackson says, they’ve found that menopause symptoms often start much earlier than the hot flashes and night sweats that are considered the hallmark—and that symptoms are significantly more severe for Black and Latina women than for white women, though they don’t yet know why. Next, she wants to put women with different health profiles on different treatment regimens, watch how their symptoms change over time, and gauge their long-term outcomes. She envisions pairing this information with data from wearable devices, such as weight or daily steps walked, to come up with much better treatment protocols based on who you are. That said, if Garrison’s campaign ultimately makes hormone therapy, and by extension Evernow, unnecessary, Jackson says she will be “totally happy” with that outcome. “I’m committed to the dream,” she says.
Paradoxically, one challenge to realizing that dream could be the field’s rate of acceleration itself. “Because this is so societally charged, there’s a lot of pressure to come up with the magic formula that’s going to tell a woman her reproductive longevity, or the magic solution to extend longevity and fertility without really truly understanding the mechanisms underlying aging,” says Duncan. “I’m concerned things are moving too quickly without science behind it. We have to be very careful before we push things clinically that we’ve really evaluated that. It’s a double-edged sword.”
Garrison, for her part, feels encouraged by the quickening pace of this work. “There’s studies coming out from the first-round grants that [the consortium] funded that are going to be transformative of the field,” she says. She’s working to build the consortium into a global network of not only scientists but clinicians, funders, and experts from early-stage biotech, pharma, and technology—aiming to accelerate discoveries through shared expertise. She’s preparing to announce the consortium’s second round of grants and organizing the first international reproductive aging conference, in June 2022.
“If we could just push the age at which you go through menopause by five years, that would be a game changer,” she says. Many researchers would be satisfied with that. But for Garrison, that goal is just one step along the way to her ultimate menopause moonshot: to end it.
Author’s note: While this article refers broadly to cis women experiencing menopause, we recognize that trans men and other people who have ovaries but do not identify as women also experience menopause.
Editor’s note: The story was updated on 6/3/22 to correct the name of the Buck Institute’s Center for Reproductive Longevity and Equality and to reflect the fact that Nicole Shanahan is a co-founder of the Global Consortium for Reproductive Longevity and Equality and contributes ideas as well as financial support to it.