Rapamycin’s Promise Could It Delay Menopause

Menopause, that long-overlooked life transition once brushed aside as a foregone conclusion of aging, has quietly become a focal point of cutting-edge research and therapy. For decades, individuals experiencing menopausal symptoms were routinely told to accept certain degrees of discomfort and health fluctuations as an unavoidable stage of life. As new discoveries unfold, however, a different story emerges—one of renewed energy in the scientific community to better understand and treat this complex biological shift. From the potential of restoring ovarian function for longer, to rethinking the safety and timing of hormonal replacement therapies, the future of menopause care looks poised for a significant revolution. And behind this momentum is both a wave of scientific inquiry and a cultural insistence that it is high time to address a domain of health that affects half the global population.

The story begins, rather simply, with individuals such as Seattle-based physician Naomi Busch. As the only doctor in her book club, she found herself bombarded by questions about the so-called “hallmark” menopause experiences—hot flushes, unpredictable mood swings, stubborn insomnia. Although these are well-documented changes, Busch realized she was ill-prepared to provide answers that extended beyond what a quick Internet search might yield. Menopause, it turned out, was not part of the typical medical-school syllabus, at least not in any robust manner. When she tried referring her acquaintances to local experts, she found such specialists were often booked up for months, leaving these women in limbo, forced to soldier through hot flushes, irregular cycles, and unsettled mental states with little more than a shrug from their regular providers.

Motivated to fill this knowledge gap, Busch immersed herself in continuing education, ultimately passing a competency exam to become a certified practitioner through The Menopause Society, which is based in Pepper Pike, Ohio. In 2024, more than 1,300 practitioners followed a similar path—an astonishing rise from prior years, underscoring a mounting curiosity to revisit menopause in fresh, evidence-based ways. The UK-based International Menopause Society has also seen a surge, with more than 2,600 people completing its free online training program in 2024 compared to fewer than 2,000 the prior year. This phenomenon suggests that medical education might soon catch up with the reality that an ever-growing percentage of the population, both in high-income and developing nations, need specialized care for the menopausal transition.

In parallel with this surge in professional interest, the cultural conversation around menopause is evolving. Beyond the classic symptoms that prompt day-to-day discomfort—hot flushes, night sweats, brain fog—there are heightened risks of chronic health conditions such as cardiovascular disease, osteoporosis, and type 2 diabetes. Additionally, researchers note potential risks to neurological health and cognitive functioning. These are not minor side concerns: a woman (or transgender, non-binary, or intersex person who undergoes a similar transition) might be at the height of a career or still raising children, yet finds themselves coping with unpredictable episodes of insomnia, confusion, or palpitations. If health-care providers are poorly prepared to help, this stage of life can become deeply isolating.

Typical advice to those in midlife—perhaps an oral contraceptive if still perimenopausal and seeking to avoid a surprise pregnancy—might help modulate hormones to a certain extent, but can also bring risks of blood clots or insufficiently address the full slate of symptoms. Some might attempt a patchwork approach: non-hormonal medication for hot flushes, antidepressants, behavioral therapies, or acupuncture for mood. But many remain dissatisfied, feeling these methods barely dent the life-altering realities of menopause.

For a long time, hormone replacement therapy (HRT)—or, increasingly, “menopausal hormone therapy”—was the gold standard for easing symptoms. In the eyes of many older physicians, it was once so routine as to be unremarkable. Then, in 2002, the large Women’s Health Initiative (WHI) study published an alarming early report (1) linking combined oral oestrogen and progestin therapy to a heightened risk of breast cancer, stroke, and heart attacks. Immediately, prescriptions for hormone therapy plummeted around the globe. Women in the United States, for example, who had previously been on or considering hormone therapy reacted to the headline that “HRT is unsafe,” and usage dropped from roughly 40% to below 5%. Countries worldwide witnessed similarly precipitous declines.

In subsequent years, however, deeper data analysis from that same WHI study and more modern investigations has revealed a more nuanced picture. Timing seems crucial. When hormone therapy is initiated years after menopause has already ended, it might indeed exacerbate heart disease and bring certain risks. Yet for those who begin therapy earlier—close to the onset of menopause—evidence now points to potential benefits, such as reduced risk for fractures, possible cardioprotection, and less cognitive decline. Additionally, the formulations of hormones have changed drastically since 2002: lower doses, different routes of delivery (especially transdermal patches), and “body-identical” hormones have gained prominence, minimizing some of the risks that were associated with older methods. A major re-analysis (2) published in May 2024 reaffirmed that the original study did not reflect current best-practices, yet a swirl of misconceptions has lingered in the public mind and even in some scientific communities.

Meanwhile, the conversation has grown more sophisticated. Modern hormone therapy does not consist solely of adjusting oestrogen and progesterone levels; contemporary researchers are investigating whether testosterone might protect against bone density loss in the menopausal population. Others are examining how to best mitigate vascular risks in women who may already be predisposed to conditions such as hypertension or atherosclerosis. Some data even point to a possibility that well-timed hormone therapy could reduce the incidence of dementia or memory decline, though these findings remain preliminary. Skeptics, however, caution that it is easy to over-interpret observational data. To truly confirm these hypotheses, randomized controlled trials must be carefully designed and implemented.

While refining hormone therapy is one path, there is an altogether different line of research attempting to forestall menopause itself. The reasoning goes like this: ovaries do more than produce the well-known reproductive hormones. They coordinate a complex network of signaling molecules, beneficial compounds, and cyclical processes throughout the body. If the ovaries age prematurely or fail, that can trigger a cascade of chronic health conditions. By delaying or slowing ovarian aging, some scientists hope to prolong the period when these hormonal benefits naturally persist.

Among the researchers tackling this idea is Zev Williams at Columbia University in New York. One method involves drugs such as rapamycin, already used for immunosuppression in organ transplant recipients but found in animal models to prolong ovarian function in mice (4). In principle, if rapamycin can slow the depletion of egg-containing follicles in humans, it might postpone the menopausal transition by up to seven years or more. That is a remarkable idea, but also one that must be tested rigorously. Williams and his colleagues are in the midst of a prospective, randomized, double-blind trial with about 50 healthy women between the ages of 35 and 45, who will either take rapamycin or a placebo for 12 weeks. The research community remains cautious, as rapamycin is already popular in anti-aging circles, and premature use without strong data can lead to unforeseen complications.

Another intriguing technique involves surgically removing small sections of ovarian tissue in a woman’s younger years, freezing that tissue, and reimplanting it later, perhaps well into midlife. This approach has already been used successfully for younger cancer patients who must undergo chemotherapy; reintroducing ovarian tissue years later can restore fertility. Could the same concept help healthy women to “pause” their ovarian clock, effectively forestalling menopause? Simulations by reproductive specialists, including Kutluk Oktay at Yale University, suggest this tissue reimplantation might yield a delay of several years or more (5). If started early enough, repeated transplants might even stave off menopause indefinitely. That possibility is both alluring and fraught with ethical and practical implications. Indeed, no guidelines exist for reimplanting cryopreserved tissue in completely healthy individuals. Many clinicians point out that there could be uncharted risks to removing slices of a functioning ovary, including potential to trigger earlier menopause if something goes awry.

However it ultimately plays out, the possibility that researchers might one day “control” menopause is not science fiction. The US National Institutes of Health, for instance, held a round table on menopause research in May 2024 to chart priorities. Meanwhile, the White House Initiative—established during the administration of Joe Biden—directed $113 million specifically for women’s health research. Moreover, ARPA-H (Advanced Research Projects Agency for Health) is orchestrating some of these new investigatory thrusts, with the aspiration to accelerate game-changing biotech solutions. Menopause is increasingly viewed as a domain ripe for breakthroughs, simply because it affects so many people at a time of life when they often hold major responsibilities—professional and personal alike.

Of course, any sophisticated therapy for menopause, be it hormone-based or reliant on preserving ovarian function, is only as good as the clinicians delivering it. Yet today’s doctors, especially in general medicine, are often undertrained in menopause management. A 2023 survey (6) indicates that roughly 31% of obstetrics and gynecology residency programs in the United States admit they dedicate insufficient formal time to the subject. That leaves many front-line physicians either inadvertently reinforcing the outdated notion that “this is just something you must bear,” or resorting to incomplete solutions for patients. Busch’s anecdote in Seattle resonates: there is a wide gap between evidence-based best practices and what average patients hear in clinical settings.

One reason for that gap is the lingering fear from 2002—some older physicians are still reluctant to mention hormone therapy because they themselves internalized the message that it was harmful. Younger physicians, on the other hand, might have grown up in a climate where menopause care is rarely discussed. A few experts, including Mayo Clinic’s Stephanie Faubion and Harvard’s JoAnn Manson, are tirelessly trying to correct the public record on hormone therapy. They emphasize that the “window of initiation” matters: it is probably safer and more beneficial to start hormone therapy within a decade of menopause or before age 60, so long as no contraindications exist. Doing so, they say, may reduce the risk of osteoporosis, help with heart health, and mitigate the symptoms that can compromise quality of life. Over time, the medical field might see a return to routine hormone therapy as a meaningful intervention for many. But they also caution that it is not for everyone; risk factors, lifestyle, personal preferences, and comorbid conditions all shape whether hormone therapy is advisable.

Meanwhile, other intriguing fronts are opening up in the realm of gut microbiome research. Observations linking gut flora to shifting levels of female sex hormones suggest that targeted interventions—probiotics, carefully tuned diets, or other ways to nudge the microbiome—could help manage weight gain, mood, or bone health. And because female hormones are tightly tied to circadian rhythms, researchers including Julie Pendergast at the University of Kentucky are exploring whether restricting food intake to certain times of day or optimizing one’s light exposure might buffer some of menopause’s metabolic challenges. By pulling these levers, scientists may find new ways to ease transitions for people who are highly symptomatic.

Yet all these breakthroughs, from hormone reformulations to extended ovarian life, will mean little if only a small fraction of the population can access or trust them. Socioeconomic disparities already plague women’s health. Surveys show that non-white women tend to have more severe menopausal symptoms yet are less likely to receive hormones, for reasons that include systemic barriers and historical distrust. This disparity intensifies the urgency of forging policy changes that ensure equitable access to the next generation of menopause treatments. Similarly, cost remains a looming factor. Although rapamycin, for instance, is relatively inexpensive, repeated cryopreservation surgeries or real-time hormone monitoring devices might not be. If the objective is to improve public health on a large scale, the success of any solution will hinge on whether it can be delivered affordably and ethically.

Then there is the matter of who is included in the conversation: the push to mainstream menopause care must also take into account transgender, non-binary, and intersex people, who can undergo a menopause-like transition if they have ovaries. Studies seldom address these groups in detail, compounding their struggle to find specialized care. If a wave of education for providers does come to fruition, it must incorporate these diverse experiences, ensuring that everyone can reap the benefits of new scientific insights.

Naomi Busch, for her part, exemplifies a new breed of physician taking up the banner for menopause care. She left her old model of primary-care practice to open Seattle Menopause Medicine. About 400 patients now rely on her for deeper, more individualized discussions of hormone therapy, symptom management, and overall well-being. She mentions that most are middle-class and a majority are white, reflecting broader access inequities. Busch hopes to counter that by offering group classes, working with family-practice residents, and participating in local programs that expand access. Nonetheless, it is a constant struggle to ensure that all who need these resources can receive them in a timely manner. Some activists call for government policy that directly invests in menopause education for medical students and general practitioners, so that no future patient is told “Well, that’s just menopause,” with a dismissive shrug.

Bubbling beneath all of this is a sense of real excitement among researchers. Many see menopause as a puzzle that stands at the crossroads of reproductive biology, endocrinology, neurology, and aging. If the puzzle is cracked—if we can safely modulate or even delay the onset of menopause, or tailor hormone regimens perfectly—then the broader payoffs could be enormous. Fewer fractures mean a significant reduction in medical costs and improved quality of life. Better cardiovascular outcomes imply fewer hospitalizations for heart disease, a leading cause of death in postmenopausal women. And if cognition and mood remain more stable, that supports workplace productivity, personal relationships, and mental health.

Perhaps that is why advocates ranging from Hollywood celebrities such as Halle Berry to local activism groups have become so vocal. Berry’s support of US legislation that would bolster menopause research and the formation of various grassroots campaigns in the UK and other regions underscore that it is not just a “hot flash” in the scientific literature; it is a cultural shift. Women (and others who experience menopause) are increasingly speaking openly about symptoms that were once private hush-hush matters, thereby validating the experiences of half the population. In some sense, society is rejecting the old norm that menopause is merely an invisible endpoint of reproductive life that must be endured in silence.

Still, many complexities await resolution. For instance, the exact interplay between hormone therapy and cancer risk demands more careful scrutiny. Even with lower-dose formulations, certain populations might face slightly elevated risks. Meanwhile, more data on diversity—variations in genetics, ethnicity, comorbidities—are essential to develop truly personalized recommendations. Studying the best possible interventions for bones, hearts, brains, and emotional stability will require extensive, long-term cohort studies. The White House Initiative’s $113 million infusion is just an initial step. Critics note that it is dwarfed by the overall health-research budget and that more targeted funds must be allocated to see real transformation. Yet, for the first time in decades, one sees genuine alignment among government agencies, private foundations, and the public.

Busch, having confronted these uncertainties head-on, often tells her patients that menopause management is still more of an art than a perfect science. Hormone therapy itself “is not one-size-fits-all,” she says, adding that her role is to explain the potential risks and benefits to each person, factoring in family history, personal predispositions, and tolerance for side effects. She encourages early conversation: do not wait until years of suffering have gone by. If a woman in her late 40s starts to notice disruptive cycles or dramatic hot flushes, it might be exactly the right time to explore treatment that fits her lifestyle. Conversely, some want to avoid exogenous hormones altogether, either out of caution or personal preference, and might find partial relief through lifestyle adjustments, mindfulness, or non-hormonal interventions such as fezolinetant or elinzanetant.

The broader transformation, though, is not merely about a menu of pharmaceutical choices. It is also about reframing the conversation so menopause feels less like a dreaded breakdown and more like a natural, though complicated, transition—one that can be navigated with science on one’s side. Let it be said: there is a distinct mood among experts that we are entering a “new science of menopause” era, where old prejudices against hormone therapy are countered by fresh, data-driven arguments for targeted usage. Meanwhile, radical lines of inquiry—extending ovarian longevity, developing real-time hormone sensors, or even regenerating functional tissue—promise to continue capturing headlines.

The scale and impact could be enormous: at the population level, lessening the burdens of menopause could potentially help keep more people in the workforce, reduce healthcare expenditures on advanced osteoporosis or heart disease, and enhance family dynamics by ensuring a more stable midlife. Specialists emphasize that extended ovarian function is not about pandering to a youth-obsessed culture, but rather about healthy aging and giving individuals the fullest possible quality of life. If, one day, someone can choose to preserve their reproductive system and hormones far into their fifties or sixties without unacceptable risk, that might be as revolutionary as the introduction of the birth-control pill was for earlier generations.

For now, we remain in a transitional phase. Doctors such as Busch are bridging the knowledge chasm by getting certified in menopause management, but there remain countless regions where no specialized providers exist, leaving people to search online for answers or rely on guesswork. Medical schools are slowly recognizing that training in menopause should be fundamental, not optional. From a research standpoint, newly established training programs, collaborations, and dedicated NIH or ARPA-H grants could rapidly expand the ranks of investigators delving into ovarian biology, endocrine function, and the intricacies of menopause. Ultimately, the measure of success will be how well this emerging science translates into tangible help—whether that means developing sophisticated hormone patches that adapt to daily fluctuations, or launching powerful public-health campaigns that remove the stigma of what is, in effect, a universal life transition.

The potential payoff is as vast as it is overdue. At a time in history when we can decode genomes, regenerate tissues, and create advanced vaccines in record time, it is perhaps remarkable that half the population’s fundamental biological transition has remained, for so long, an afterthought in mainstream science. Now, the tide is turning, driven by a potent mix of patient advocacy, scientific breakthroughs, and political support. It is not hyperbole to suggest that if we get menopause research right—if we can offer real relief and improved health outcomes to millions around the world—the result might be one of the most transformative developments in women’s health in a generation.

Subject of Research: The evolving science of menopause and emerging therapies
Article Title : The New Science of Menopause: These Emerging Therapies Could Change Women’s Health
News Publication Date : 22 January 2025
Article Doi References : https://doi.org/10.1038/d41586-025-00069-4
Image Credits : Illustration by Maria Corte
Keywords : Menopause, Hormone Therapy, Ovarian Function, Women’s Health, Bone Density, Rapamycin

Tags: ARPA-H initiativesBone DensityClinical TrialsCultural Shift in MedicineDelayed menopauseEmerging medical therapieshealth equityhealthcare disparitiesHormone Replacement TherapyMedical education reformMenopauseMenopause DelayMenopause researchMenopause treatment innovationNIH fundingOvarian AgingOvarian function preservationPersonalized MedicineRapamycin ResearchRapamycin therapyWomen’s healthWomen’s Health Initiative