New efforts to boost women’s health and extend fertility depend on developing tools to slow the aging of ovaries
THE SATURDAY ESSAY
What if We Could Get Rid of Menopause?
New efforts to boost women’s health and extend fertility depend on developing tools to slow the aging of ovaries
Imagine if women never reached menopause, that dreaded middle-age milestone—or could delay it, or decide when to have it.
Women could remain fertile longer and would have more choice about when to start a family. They wouldn’t struggle with symptoms like hot flashes, mood swings and brain fog in the prime of their careers and family lives.
Even more significantly, women might live longer and healthier lives. Though menopause—a full year without a menstrual cycle—is associated with the end of fertility, it also marks another profound but less recognized change. When the ovaries stop functioning and releasing important hormones, biological aging in women speeds up, increasing the risk of numerous health problems.
“Menopause is the single biggest accelerant of the diseases of aging for women across the board, whether it’s heart disease and stroke, autoimmune disorders, osteoporosis or cognitive decline,” says Piraye Yurttas Beim, founder and CEO of a biotech startup called Celmatix focused on improving ovarian health. “It’s the end of the function of a key organ in our body, and we should not normalize it any more than we would normalize tooth decay, osteoarthritis or cognitive decline.”
Beim is part of a small but growing group of scientists—most, but not all, women—challenging the idea that menopause is an essential part of aging. They point to research showing that women who go through menopause later in life have reduced health risks and live longer compared with those who go through it at younger ages. Research also shows that women have fewer chronic diseases compared with men—until the women hit middle age and menopause.
“We are so ingrained in thinking that menopause is inevitable. That it’s just sort of something that has to happen,” says Dr. Zev Williams, an associate professor of women’s health and fertility expert at Columbia University who is leading an ovarian aging study. Yousin Suh, a professor of reproductive sciences at Columbia, says her own experience with menopausal symptoms such as brain fog and sleep issues helped motivate her to work with Williams on the study. “I was stimulated by my own misery,” she says.
All of the efforts to delay or end menopause focus on improving women’s long-term health. Some also aim to improve fertility. They hope to make it easier for women to get pregnant naturally at somewhat later ages. Women hoping to preserve their fertility past their mid-30s wouldn’t have to worry about freezing their eggs for later use. Women in their mid to late 40s might have a real chance to conceive a healthy child without fertility treatments, which can be emotionally brutal while costing tens of thousands of dollars and often not working.
With the slowdown or elimination of a ticking fertility clock, women could experience their 30s more like men can—able to pursue their careers and hobbies full force, without the pressure to find a partner and have a baby before the biological deadline.
Beyond fertility, the health consequences for midlife women could be profound: No more hot flashes that you struggle to hide during a work meeting. No more hormone-related mood swings or brain fog. Fewer women lying awake night after night, battling years of hormone-linked insomnia. Most important, debilitating diseases like heart disease and dementia could hit women later in life or less often.
Of course, not having to deal with a monthly period or worry about unwanted pregnancies are aspects of menopause that many women welcome. And some doctors remain unconvinced that delaying menopause is a worthy goal, saying that more research needs to be done.
“It’s quite a leap to say that we should be preventing menopause and that doing so would cure all our ills,” says Dr. Stephanie Faubion, director of Mayo Clinic Women’s Health and medical director of the North American Menopause Society. She cautions against overstating the evidence that it would improve health. The fact that having natural menopause at a later age is associated with a lower risk of heart disease, for instance, doesn’t necessarily mean that artificially delaying it would lower the risk.
Most women reach menopause in their 40s or 50s; the average age is 51. It is preceded by perimenopause, which can last from three to 10 years and is marked by irregular periods and fluctuating hormones that can trigger many symptoms.
Menopause happens when a woman’s ovaries run out of follicles—small sacs of fluid, each containing one egg surrounded by ovarian support cells. Most girls are born with an average of one million eggs at birth; that declines to around 300,000 at puberty. After that, eggs die at a rate of roughly 1,000 a month. Typically one mature egg every month gets released for potential fertilization. Hundreds of others are released from the ovarian reserve, but they eventually break down and die before they mature and have the chance to ovulate.
Most of the efforts to delay or end menopause focus on slowing down the rate at which a woman’s follicles and eggs are lost. In men, aging in the reproductive system is relatively in sync with aging in the rest of their body, so there is no sudden and dramatic change in hormones. But in women, ovaries age faster than other organs.
Ovaries also produce hormones though their support cells that are essential for maintaining a woman’s overall health. The best known of these are estrogen and progesterone, but ovaries also produce many other hormones that send chemical messages over long distances in the body. Estrogen and progesterone not only regulate the menstrual cycle and play an important role in pregnancy; they also help regulate other health systems, including brain and heart function.
“ There are dozens, if not hundreds of things that ovaries make and release that signal to different parts of the body,” says Jennifer Garrison, an assistant professor at the Buck Institute for Research on Aging in Marin County, Calif. When that stops, she says, “Essentially, this is what leads to those negative health cascades.”
Research has repeatedly found a correlation between women who reach menopause later and longer, healthier lifespans. In 2005, a study in the journal Epidemiology concluded that mortality was reduced by 2% with each increasing year of age at menopause. Women who reached menopause after age 55 lived two years longer on average than those who reached it before age 40. A 2016 meta-analysis in JAMA Cardiology found that early-onset menopause in women under 45 was associated with an increased risk of heart disease and mortality. A 2021 study in the journal BMC Cardiovascular Disorders found that women who experienced menopause before age 50 had a higher risk of stroke and death. And last year, a meta-analysis that reviewed 22 studies concluded that later menopause was associated with a lower risk of dementia.
Humans are one of the few mammals that experience menopause in midlife. Other long-lived mammals evolved either to make a larger supply of eggs or to slow down the rate at which they lose eggs, so they can continue to have babies almost to the end of their lifespan.
The best-known theory for how midlife menopause in humans evolved is the “grandmother hypothesis,” which posits that some of the burdens on mothers were shifted to grandmothers, who would gather food to help their grandchildren survive. This, in turn, increased human lifespans in general. Another hypothesis is that menopause removes conflict between potential older mothers and younger ones over resources for their children. A third theory is that midlife menopause evolved to prevent risky later-in-life childbirth and to improve the chance that mothers will live long enough to raise their existing children.
“Not being able to reproduce anymore and then living a significant portion of your life, that is really unusual,” says Deena Emera, an evolutionary biologist with the Buck Institute. “There probably are good reasons why our ancestors were going through menopause and not continuing to reproduce back when menopause and longevity were evolving. But the benefits certainly don’t carry over to now.”
Researchers hoping to push back menopause are mostly trying to slow the rate at which women lose their eggs. Some are looking at whether existing drugs used to treat other conditions might also slow down ovarian aging. At Columbia, researchers Williams and Suh recently launched a pilot clinical trial testing low-dose rapamycin—a kidney transplant drug also being studied more broadly as an antiaging treatment—on 50 premenopausal women to see whether it could slow down ovarian aging. The study was prompted by mounting evidence that rapamycin delays aging in the ovaries of mice.
At Northwestern University, Francesca Duncan, co-director of the Center for Reproductive Science, discovered several years ago that the tissue around the ovarian follicles stiffens with age, threatening the health of the eggs. She is now trying to see whether a drug approved to treat pulmonary disease might help to prevent this development. “You would maintain hormone function for a longer period of time,” she says. “So we’re both preserving the endocrine function and fertility.”
Others are looking to develop new therapies to reverse ovarian decline. Gameto, a New York-based biotech company, is using cell engineering. Their goal is to improve women’s health without extending fertility, says Dr. Dina Radenkovic, co-founder and CEO. Gameto researchers are making ovarian support cells from stem cells and hope to administer the chemicals they produce using a subcutaneous device that is currently being tested in mice. The device would lessen the profound disruption of signals between the ovaries and other organs that often occurs during menopause. Biotech startups are also working with the hormone AMH, which controls the rate of attrition of a woman’s ovarian reserve; slightly elevated levels of the hormone could reduce the depletion of eggs. Oviva Therapeutics, based in New York City, is developing a recombinant form of AMH to elevate those signals. “The idea would be you can push out the timing of menopause by delaying when you hit that low threshold” of eggs, says CEO and co-founder Daisy Robinton.
Robinton’s goal is to give women agency over menopause much in the way contraception has given them more control over reproduction. “I’d love for women to have a choice around how and when they experience menopause,” she says. Oviva has tested its recombinant AMH on animals and is conducting advanced preclinical studies in order to apply to the U.S. Food and Drug Administration to start human clinical trials. The hormone could be delivered as a daily injection, but the company is also trying to develop a pill.
At Celmatix, the startup founded by Beim, researchers are seeking to develop what’s called an activator of the AMH hormone. A woman could take a drug to reduce the loss of follicles and eggs in her reserve and thus maintain optimal ovarian health and then go off the drug when she wants more eggs to be released to try to get pregnant.
Beim started out with the goal of developing a treatment to prevent women undergoing chemotherapy from going into premature menopause. But then one night a few years ago she was out with her husband and joked about how he could look forward to her going through perimenopause. She described it as a “second puberty” because of the hormone effects and possible mood swings. “How long is that gonna last?” he asked her. “Well, on average about eight years,” she responded. “Isn’t there anything we can do about this?” he exclaimed.
“And I had the ‘aha’ moment at dinner with him that night,” says Beim. “Why are we only developing this drug for women who are undergoing chemo, or at risk for early menopause? Why should I or any woman go through menopause at all?”
