In March, first lady Jill Biden announced a new women’s health initiative at the White House, highlighting a seemingly obscure research question: What if you could delay menopause and all the health risks associated with it?
The question comes from an area of research that has begun to attract attention in recent years, as scientists who study women’s longevity and health have come to realize that the female reproductive system is much more than just a baby maker. The ovaries in particular seem to be linked to virtually every aspect of a woman’s health.
They also abruptly stop performing their primary role in middle age. Once that happens, a woman enters menopause, which accelerates her aging and accelerates the deterioration of other organ systems, such as the heart and brain. Although women live longer on average than men, they spend more time with illness or disability.
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The ovaries are “the one organ in humans that we simply accept will fail one day,” said Renee Wegrzyn, director of the Advanced Research Projects Agency for Health, a government agency charged with driving Jill’s mission Biden. “It’s actually quite strange that we all just accept that.”
It’s the shortened lifespan of the ovaries that also makes them such a promising site for experimentation. Researchers think that extending their function, by better matching the length of their viability with that of other organs, could potentially change the course of a woman’s health – and longevity research in general.
Wegrzyn said she hoped the White House initiative, in which researchers and startups are competing for a share of the program’s $100 million budget, will highlight the link between menopause and longevity, while also increasing will attract funding and talent to the field.
“If you’re not thinking about ovarian function as you age,” says Jennifer Garrison, an assistant professor at the Buck Institute for Research on Aging, “you’re kind of missing the boat.”
How the ovaries are involved in aging
The ovaries function as the control center of “a complex network of signals in a woman’s body,” Garrison said. Through hormones such as estrogen and progesterone, as well as other chemicals, the ovaries communicate with and influence virtually every other organ. Scientists do not yet know exactly how the ovaries do this, but what they do know is that when the ovaries no longer function normally, all kinds of problems arise. For example, in young women this can manifest as polycystic ovary syndrome, which increases the risk of metabolic diseases, heart disease, mental health problems, and more.
As a woman’s eggs run out, eventually causing menopause, the ovaries’ chemical communication seems to shut down. This corresponds to an increased risk of dementia, cardiovascular disease, osteoporosis and other age-related diseases. The earlier a woman enters this stage of life, the greater her risk of developing these conditions, and the shorter her life is likely to be. And in women who enter menopause prematurely because their ovaries have been surgically removed, the risks of chronic conditions are even greater. That suggests that even after the ovaries stop releasing eggs during menopause, they may still be somewhat protective of a woman’s overall health, said Dr. Stephanie Faubion, the medical director of the Menopause Society. It’s just unclear how.
From now on, these connections are correlative. Scientists don’t know whether the ovaries themselves are the drivers of health in aging, or whether there is something else that accelerates aging and then leads to ovarian dysfunction, Faubion said. Studies have shown that several factors, such as smoking, body mass index, and negative stressors throughout life, all contribute to the premature onset of menopause. Black and Hispanic women enter menopause earlier than white women. Genetics can also play a role.
“Is the ovary just a sign of overall health? Or is it because the ovary is timing out and causing poor health? said Faubion. “I mean, it’s chicken and egg.”
How Delaying Menopause Can Extend Lifespan
There is some evidence, especially in animals, to suggest that prolonging ovarian function can improve health and extend lifespan. For example, in mice, transplanting an ovary from a younger animal to an older animal extends the life of the older mouse.
Scientists are now experimenting with different ways to prolong ovarian function and delay the onset of menopause in humans.
One company, Oviva Therapeutics, is in the early stages of testing – mainly in mice and cats – whether a pharmaceutical version of anti-Müllerian hormone (AMH), which controls how many follicles mature in each menstrual cycle, could be used to reduce the amount of follicles that mature in each menstrual cycle. many eggs are lost. (Normally, a woman loses dozens of eggs per cycle, even though in most cases she ovulates only one of the eggs.)
Think of AMH as “a porous cloth that covers you around the ovary,” says Daisy Robinton, co-founder and CEO of Oviva, which is competing for some of the White House initiative’s funding. The level of AMH determines the size of the holes in the cloth; if there are huge gaping holes (in other words, there is low AMH), a bunch of eggs can be left behind in each cycle. But if there are only small holes (meaning high AMH), fewer eggs can hatch.
The idea is that if a woman loses fewer eggs, she can maintain her ovarian reserves and ovarian functionality for longer, Robinton said.
A clinical trial at Columbia University is also trying to slow the rate at which women lose their eggs. The study tests the use of an immunosuppressant called rapamycin — which is used to prevent organ transplant rejection and has become a darling of the longevity movement — in women ages 35 to 45 to see how it affects their ovarian reserve. Rapamycin affects the number of eggs that mature each month, and in mice the drug has been shown to prolong ovarian function.
The study is still ongoing and researchers don’t know which participants received the drug or a placebo, but the study’s lead scientist, Dr. S. Zev Williams, said two patterns had already emerged: some women appear to have a normal decrease in ovarian reserve, which can be measured via ultrasounds and AMH levels, but in other cases “it appears to have changed,” he said. “So, you know, that’s promising.” Williams, an associate professor of women’s health at Columbia, is also applying for funding for the health agency.
The experts were explicit that the aim of this type of research was not to extend women’s periods indefinitely, nor to enable pregnancy at age 70 – although the treatments could potentially extend fertility.
The accelerated decline of the ovaries during middle age also makes them “a good model to study aging within a limited time period,” Williams said. Other anti-aging scientists are also experimenting with rapamycin, for example, but it is virtually impossible to determine whether the drug extends human life without conducting a study over decades. With the ovaries, researchers can see much more quickly whether there is an effect.
In fact, “if we can understand why the ovaries age prematurely and what causes that, it will almost certainly tell us something important about aging in the rest of the body,” Garrison said. “And then of course that becomes important not only for women, but also for men.”
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