In March, the first lady Jill Biden announced a new White House initiative on women’s health that highlighted a seemingly obscure research question: What if it were possible to delay menopause and all the health risks associated with it?
The question arises in a field of research that has begun to gain attention in recent years, as scientists studying longevity and women’s health have realized that the female reproductive system is much more than just a baby maker. The ovaries, in particular, appear to be linked to virtually every aspect of a woman’s health.
They also abruptly stop playing their main role in middle age. When this happens, the woman enters menopause, which accelerates aging and the decline of other organ systems, such as the heart and brain. Although women, on average, live longer than men, they spend more time living with illness or disability.
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The ovaries are “the only organ in humans that we accept will one day fail,” said Renee Wegrzyn, director of the Agency for Advanced Research Projects for Healthcare, a government agency tasked with guiding Jill Biden’s mission. “It’s actually kind of wild that we all just accepted it.”
It’s the ovaries’ truncated lifespan that also makes them such a promising site for experimentation. Researchers think that prolonging its function, better aligning the duration of its viability with that of other organs, could potentially alter the course of a woman’s health – and longevity research in general.
Wegrzyn said he hopes the White House initiative, in which researchers and startups compete for a share of the program’s $100 million budget, will highlight the link between menopause and longevity, while also attracting more funding and talent to the program. area.
“If you don’t think about ovarian function as you age,” said Jennifer Garrison, assistant professor at the Buck Institute for Research on Aging, “then you’re missing the boat.”
How the ovaries are involved in aging
The ovaries serve as the control center for “a complex signaling network 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 all other organs. Scientists still don’t know exactly how the ovaries do this, but what they do know is that when the ovaries stop functioning normally, all kinds of problems arise. In young women, for example, this can manifest as polycystic ovary syndrome, which increases the risk of metabolic conditions, heart disease, mental health issues, and more.
As a woman’s eggs run out, eventually triggering menopause, the ovaries’ chemical communications appear to slow 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 will likely be. And in women who enter menopause prematurely because their ovaries are surgically removed, the risks of chronic diseases are even greater. This suggests that even after the ovaries stop releasing eggs at menopause, they can still protect a woman’s overall health, said Dr. Stephanie Faubion, medical director of the Menopause Society. It’s not clear how.
As of now, these connections are correlational. Scientists don’t know whether the ovaries themselves are the drivers of aging health, or whether there is something else that accelerates aging and leads to ovarian dysfunction, Faubion said. Studies have found that several factors, such as smoking, body mass index and adverse life-long stressors, contribute to the early onset of menopause. Black and Hispanic women tend to reach menopause earlier than white women. Genetics may also play a role.
“Is the ovary just a marker of general health? Or is the ovary expiring and causing health problems?” Faubion said. “I mean, it’s a chicken egg.”
How delaying menopause can extend lifespan
There is some evidence, mainly in animals, to suggest that prolonging ovarian function may improve health and increase longevity. In mice, for example, transplanting an ovary from a younger animal to an older animal prolongs 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 – primarily in mice and cats – whether a pharmaceutical version of anti-Müllerian hormone (AMH), which modulates how many follicles mature in each menstrual cycle, could be used to reduce how many eggs are lost. (Typically, a woman loses dozens of eggs per cycle, although in most cases she ends up ovulating only one of them.)
Think of AMH as “a porous cloth that covers the ovary,” said Daisy Robinton, co-founder and CEO of Oviva, which is competing for some of the funding for the White House initiative. The AMH level determines the size of the holes in the fabric; if there are huge holes (in other words, there is low AMH), a lot of eggs can come out in each cycle. But if there are only small holes (meaning high AMH), fewer eggs will be able to come out.
The idea is that if a woman loses fewer eggs, she can maintain ovarian reserves and ovarian functionality longer, Robinton said.
An ongoing clinical trial at Columbia University is also trying to slow the rate at which women lose eggs. The study is testing the use of an immunosuppressant drug 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 influences the number of eggs that mature each month, and the drug has been shown in mice to prolong ovarian function.
The study is still ongoing and researchers don’t know which participants received the drug or placebo, but the study’s lead scientist, Dr. S. Zev Williams, said two patterns have already emerged: Some women appear to have a normal decline in reserve ovarian, which can be measured by ultrasound, and AMH levels, but in others, “it appears to have been altered,” he said. “So, you know, that’s promising.” Williams, an associate professor of women’s health at Columbia, is also requesting funding from the health agency.
Experts were explicit that the aim of this type of research was not to prolong women’s periods indefinitely, nor to make pregnancy possible at age 70 – although treatments could potentially prolong fertility.
The accelerated decline of the ovaries during midlife also makes them “a good model to be able to study aging, and to do so within a limited period of time,” Williams said. Other anti-aging scientists are also experimenting with rapamycin, for example, but it is virtually impossible to determine whether the drug is extending human life without conducting a study over several decades. With the ovaries, researchers can see if there is an effect much faster.
Furthermore, “if we can understand why the ovaries age prematurely and what is causing it, that will almost certainly tell us something important about aging in the rest of the body,” Garrison said. “And so that, of course, becomes important not just for women but for men as well.”
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