Could This Overlooked Organ Hold The Key To Living Longer?
It’s a strange but little-known fact that you actually made your appearance on this planet as an egg in your grandmother’s uterus. Yep. A female fetus (your mom, in this scenario) develops ovaries, with all the immature eggs she will ever have, by 20 weeks gestation. So, your X chromosome has likely existed for decades before you were even conceived. (One of the many mysteries of the human ovary that doesn’t have a ready explanation.)
Despite the fact that half of the population has ovaries, this organ is still a bit of an enigma in the scientific and medical world. And this has broad-sweeping implications for female health and longevity. “We’ve thought of women as baby-making machines and not really considered how our ovaries are supportive of our broader health, beyond the capacity to make a child,” says Daisy Robinton, PhD, cofounder and CEO of Oviva Therapeutics, a biotech start-up focused on improving ovarian function and extending female health span. “It really impacts our quality of life, our opportunities, and our vibrancy.”
In recent years, the scientific community has finally started to recognize that the ovaries aren’t just an essential part of human reproduction but are also the hidden key to health and longevity in women. Scientists have only recently recognized the myriad ways in which ovarian aging, which eventually leads to menopause, impacts the entire body. So, that’s why finding answers to big questions such as why the ovaries age faster than any other organ in our bodies—and developing therapeutics to address the physical and hormonal changes involved—may be the key to helping women live longer, better lives.
“Ovaries are the architects of healthy female bodies,” says Jennifer Garrison, PhD, an assistant professor at the Buck Institute for Research on Aging, and cofounder and executive director of ProductiveHealth.org. But no one—except a small group of experts in the ovarian aging research space—is truly paying attention to that fact. When Garrison first began to recognize the unrealized potential of the ovaries, she says she went through what she has jokingly dubbed the “four stages of grief.” First, she was embarrassed that, as an informed scientist, she knew so little about one of her own organs. But that embarrassment quickly turned to shock, followed by “abject anger and rage,” she says. “I was like, ‘Wait a second. If we were talking about male bodies, this would not even be a question. It would have been solved a long time ago. We would know how all of this works.’ ”
Garrison’s fourth and final stage of grief had her rolling up her sleeves and diving in. “Fixing this data gap is now my life’s work, and I don’t think there is anything more important that I could be doing with my time and energy,” she says. “It definitely motivated me to change the direction of research in my lab and the entire course of my professional career.”
By unraveling the mysteries of ovarian aging (which reaches a zenith in menopause), we can better understand what role our ovaries play in our overall health, wellness, and lifespan.“The ovaries seem to time out before other systems and organs in the body,” says Stephanie S. Faubion, MD, medical director of The Menopause Society, director of Mayo Clinic’s Center for Women’s Health and chair of the department of medicine at Mayo Clinic in Jacksonville, Florida. “There are many, many unknowns and lots of things we need to understand.”
A Brief Biology Breakdown
Here’s what scientists do know: The ovaries are oblong glands each about the size of a kiwi. They’re responsible for the production and secretion of at least two essential hormones, progesterone and estrogen, and they house immature eggs called oocytes. They have three layers: an outer layer, a middle layer of connective tissue and follicles, and an inner layer with blood and lymphatic vessels, per the Cleveland Clinic.
The ovaries also shrink with age. At birth, female babies have around 1 to 2 million oocytes, and roughly 1,000 immature eggs are lost each month after the first period. In their late 30s, most women have about 25,000 oocytes remaining. When the total egg count gets to around 1,000, the ovaries usually stop functioning normally, signaling the approach of menopause.
But that’s pretty much the extent of our ovarian knowledge.
Experts still don’t have basic answers as to why human ovaries age two times faster than the rest of their body. Or why humans go through menopause in the first place (a process we share with five species of whales, but no other mammals). Or why some women are born with fewer eggs—and lose them faster—than others. Garrison suspects ovaries produce other hormones that have yet to be identified as well.
There are also a “huge number” of interactions likely occurring between the brain and the ovaries throughout a woman’s life, Garrison says, but “we don’t know all the words in that chemical conversation that’s happening, and we certainly don’t understand very much about how it changes with age.” Some effects from that ovary-brain connection are clearer than others, especially during menopause. But the scientific world is only starting to look into how the connection impacts things like normal organ function, learning, memory, mood, and behavior.
The Menopause Effect
Menopause affects women’s health and well-being on both micro and macro levels. Women who hit menopause before 45 are at increased risk of cardiovascular problems and dying earlier than women who hit menopause later, per research. What’s more, removing the ovaries surgically before 50 (with no hormone therapy) may be “associated with increased mortality,” according to another study.
The average American woman will reach menopause at age 52, but onset age can range from about 45 to 58, per the Office on Women’s Health in the U.S. Department of Health and Human Services. The average life expectancy for women is 80.2 years, per the CDC, which means women spend about a third of their life in this post-menopausal phase. So, while women live longer, on average, than men, they often do so in worse health. And experts look at ovarian aging as a big factor in the onset of chronic conditions, aches, and pains that so many women begin to suffer around the time they hit menopause.
A big factor in these health hits? Low estrogen. The female body has estrogen receptors almost everywhere, Garrison explains, so, as estrogen levels begin to fluctuate during perimenopause, then drop after menopause, the impacts can be far-reaching. For starters, women’s cholesterol panels look worse and they tend to gain weight, which increases the risk of developing diabetes and cardiovascular disease, says Dr. Faubion. But decreasing estrogen also directly impacts bone, cardiovascular, and brain health. Women’s sleep worsens. They experience brain fog and cognitive decline.
“It’s hard to succinctly summarize everything that estrogen does, but I think it’s fair to say that it’s promoting things that maintain general health,” says Garrison.
Of course, there are probably other essential hormonal interactions that are interrupted, too, but that area is another scientific black hole, and progress has been slow due to a lack of research funding, Garrison says.
Stigma as well as a lack of interest, lack of funding, and lack of inclusion in clinical trials in a male-dominated field have been tough hurdles to overcome. (Women were only legally mandated to be included in clinical trials and research starting in 1993, which has left what some experts consider a large historical gap in data.) Only 1 percent of funding for health-care research and innovation went to women’s health issues in 2020, per a McKinsey & Company report. Plus, humans have a very unique biology, so good models for studying and testing are hard to come by, says Dina Radenkovic, MBBS, cofounder and CEO of Gameto, a female-led biotech company focused on improving women’s reproductive health.
Progress Is Slow, But In Motion
In June 2022, the Global Consortium for Reproductive Longevity and Equality helped organize a groundbreaking conference on ovarian aging with reproductive biologists and researchers in aging. Last year, Congress introduced a bill for the Menopause Research and Equity Act of 2023, and in March, President Biden announced further investments for women’s health research. Biotech start-ups like Gameto and Oviva are popping up and leaning into ovarian research and therapeutics.
When Garrison and her colleagues first dove into the world of ovarian aging back in 2019, there weren’t a ton of other scientists working in the field. It was—and still is—an underfunded area of research. Lack of grant funding created a “real and insurmountable barrier” that made the work “almost impossible,” Garrison says. Now, that’s starting to shift.
“It’s been exponential since we started, and there are now hundreds—literally, hundreds of people—who consider this a primary research question and are doing active science in the space. It’s really exciting,” she says. Interest in all things menopause and hormone health has hit the mainstream, too, which helps visibility and funding efforts.
Since 2020, Garrison’s lab and the Global Consortium has funded 49 scientists across two grant cycles who are looking into these big questions about ovarian aging. “We’re in a place where the knowledge is so paltry, the number of questions is so big, and what we don’t know is so vast, that I feel like everything we funded is absolutely essential,” she says. “Since we don’t know what we don’t know, we’re just finding creative people to look everywhere.”
Of course, there’s also a huge cohort of people eagerly awaiting more information: the 1.2 billion women expected to be in menopause or post-menopausal by 2030. “Women want better treatments. We are living longer. We are contributing to society in all aspects, and we are demanding better treatments,” says Dr. Radenkovic. “We’re half the population. We control the majority of health-care spending decisions in families. And guess what? We care about our own experience.”
Pushing Forward With Real Solutions
Garrison emphasizes that there won’t be a eureka discovery that answers all the questions about ovaries. But each step forward will help experts better understand how the ovaries function over a woman’s entire lifespan so that, eventually, targeted therapeutics can be available for those who want them. Garrison emphasizes that the goal is not “curing” menopause, but rather, trying to sync up the ovarian aging process with the rest of a woman’s body.
Therapies that can support a 20-year-old’s ovarian health (and thus support a healthier lifespan) will be very different from those that help a 40-year-old woman, Garrison explains. While a younger woman thinking about family planning may look for therapeutics that slow down the rate of follicle loss, a woman heading into perimenopause might be more concerned with preserving follicle quality or maintaining the ovaries’ endocrine functions. “It’s not going to be like we just find one cure,” she says. “It’s going to be lots of different things, and so that’s why we need this army of scientists and clinicians working on this problem.”
For starters, hormone therapy (formerly hormone replacement therapy, or HRT) can make a big difference for some women in addressing the health impacts linked to low estrogen during perimenopause and menopause. From pesky symptom relief to essential bone-health support, the additional estrogen and progesterone can help immensely. The treatment was growing in popularity through the 1990s until a 2002 study suggested it elevated all kinds of health risks, including breast cancer. This jump-started a two-decade-long aversion to hormone therapy. Flash forward to 2024, and doctors have a better understanding of its benefits and the study’s shortcomings. Specifically, there have been dozens of other studies showing hormone therapy is safe, Garrison says. Experts tell women to have a conversation with their doctors to see if it might be an effective treatment based on their health history.
At Gameto, the lack of testing models that mimic human ovaries actually pushed Dr. Radenkovic and her team to develop what she calls “ovaries in a dish,” which used stem cells to recreate the organ in a lab. “Many animals that we use for research do not exhibit the same method of ovarian aging as we do,” Dr. Radenkovic says. “If you do not have a good model to test it, you’re also not going to have good treatments.”
These petri dish–derived ovarian models can now be used to test out and, hopefully, answer some of those big questions about ovarian aging, without any risk to real women.
In April, engineers at the University of Michigan also announced they’d successfully completed a cellular atlas of the human ovary as part of the Human Cell Atlas project, which involves mapping all the cells in the human body and their “molecular characteristics and where they are located.” The study says that this breakthrough could help restore hormone production and fertility in ovaries one day.
Over at Oviva Therapeutics, Robinton and her team are developing their own anti-Müllerian hormone (or AMH), which regulates how fast the ovaries lose eggs. AMH suppresses the eggs, preventing them from leaving the ovarian reserve, with fewer eggs being released, Robinton says. So, instead of losing about 1,000 eggs each month, with elevated AMH levels you might lose only 800 or 500 from your ovarian reserve. “We don’t want to take it [egg loss] to zero because then you just go into menopause, but I think it’s fair to say that we could expect some moderate decrease that saves our eggs over a greater period of time, extending the runway to menopause without impacting cycling,” Robinton explains.
Focusing On Quality Over Quantity
These efforts to better understand female longevity and ovarian aging are very different from the male-dominated world of biohacking, which seems obsessed with reversing the aging process and trying to live in the body of an 18-year-old until you’re 120. Robinton, Garrison, and Dr. Radenkovic are focused on ensuring a woman’s natural lifespan is filled with healthy years—not “optimization.” The male-dominated longevity space often seems wholly focused on optimal personal performance, versus trying to make quality of life better and society healthier as a whole, Robinton says.
“I don’t think trying to live to be 800 is a good way for us to spend our research dollars right now,” says Garrison. In fact, she doesn’t even like the word longevity. It makes her cringe. “I don’t use that word anymore because it’s kind of been co-opted,” she says. Instead, Garrison uses the term health span, because it better captures what these scientists are trying to figure out: how women can be as healthy as possible for as long as possible.
“Let’s say my natural lifespan is 93—roughly when my grandparents passed away,” says Robinton. “I would be stoked to die at 93, being able to surf and dance the last 10 years of my life, and make meals and see [with clear vision], and have conversations and human connectivity.”
Photographed by Jarren Vink. Prop Styling by Laura Woolf
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