by In March, the first lady Jill Biden a new White House women’s health initiative that highlighted a seemingly obscure research question: What if you could delay menopause and all the health risks that come with it?
The question comes from an area of research that has begun to attract attention in recent years, as scientists who study longevity and women’s health have come to understand that there is much more to the female reproductive system than one child. The ovaries, in particular, seem to be involved in almost every aspect of a woman’s health.
They also suddenly stop performing their primary role in mid-life. Once that happens, a 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 disease or disability.
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The ovaries are “the only organ in humans that we accept will fail one day,” said Renee Wegrzyn, director of the Agency for Advanced Research Projects in Health, a government agency tasked with leading Jill Biden’s mission. . “It’s really kind of wild that we all accept that.”
The truncated lifespan of the ovaries makes them a particularly promising site for experimentation. Researchers think that better aligning the length of their function, their viability, with the length of their viability with another organ, could change the course of women’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 connection between menopause and longevity, while attracting more funding and talent to the field.
“If you don’t think about ovarian function as you age,” said Jennifer Garrison, an assistant professor at the Buck Institute for Research on Aging, “you’re missing the boat.”
How Ovaries Are Involved in Aging
The ovaries act like the control center of “a complex signaling network in a woman’s body,” Garrison said. Through hormones like estrogen and progesterone, as well as other chemicals, the ovaries communicate with and influence almost every other organ. Scientists still don’t know exactly how the ovaries do this, but what they do know is that all kinds of problems arise when the ovaries stop functioning normally. In young women, for example, this can manifest as polycystic ovary syndrome, which increases the risk of metabolic conditions, heart disease, mental health problems and more.
As a woman’s eggs deplete, eventually triggering menopause, the ovaries’ chemical communication seems to go silent. That corresponds to an increased risk for dementia, cardiovascular disease, osteoporosis and other age-related diseases. The earlier a woman enters this stage of life, the higher her risk of developing these conditions, and the shorter her life. And among women who go into menopause prematurely because their ovaries are surgically removed, the risks for chronic conditions are even greater. That suggests that even after the ovaries stop releasing eggs during menopause, they may be somewhat protective of a woman’s overall health, said Dr. Stephanie Faubion, medical director of the Menopause Society. . It is not clear how.
So far, these links are relative. Scientists don’t know whether it’s the ovaries themselves that promote health in aging, or whether there’s something else that accelerates aging that leads to ovarian dysfunction, Faubion said. Studies have shown that various factors, such as smoking, body mass index and adverse stressors throughout life, contribute to the early onset of menopause. Black and Hispanic women tend to hit menopause earlier than white women. Genetics may also play a role.
“Is the ovary just a sign of overall health? Or is it that the egg is wasting away and causing bad health?” Faubion said. “I mean, it’s a chicken egg.”
How could delay the menopause to extend the life span
There is some evidence, mostly in animals, to suggest that ovarian function can improve health and extend longevity. In mice, for example, transplanting an ovary from a younger animal into an older one prolongs the life of the older mouse.
Scientists are now testing 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 the anti-Müllerian hormone (AMH), which modulates how many follicles mature each menstrual cycle, could be used to to reduce. many eggs are lost. (Usually, a woman loses dozens of eggs per cycle although, in most cases, she only ends up ovulating one of them.)
Think of AMH as “a porous cloth that you wrap around the ovaries,” said Daisy Robinton, co-founder and CEO of Oviva, which is competing for some of the funding from the White House initiative. The AMH level determines the size of the holes in the cloth; if there are large holes (in other words, AMH is low), a drop of eggs can be left in each cycle. But if there are only small holes (which means there is a high AMH), fewer eggs can get out.
The idea is that if a woman loses fewer eggs, she can maintain her ovarian reserves and ovarian functionality longer, Robinton said.
A clinical trial is underway at Columbia University trying to slow the rate at which women lose their eggs. The study is testing the use of an immunosuppressant drug called rapamycin – used to prevent organ transplant rejection and now a staple of the longevity movement – in women aged 35-45 to see how it works on their ovarian reserve. Rapamycin affects the number of eggs that mature each month, and the drug has been shown in mice to expand ovarian function.
The study is still ongoing, and the researchers do not know which participants received the medication or the placebo, but the lead scientist on the trial, Dr. S. Zev Williams, said that two patterns had emerged already: Some women seem to have a normal decline in ovarian reserve, which can be measured by ultrasound and AMH levels, but in other cases, “it seems that it has changed,” he said. “So, you know, that’s promising.” Williams, an associate professor of women’s health at Columbia, is also pushing for health agency funding.
The experts were clear that the goal of this type of research was not to extend women’s periods indefinitely, or to make pregnancy possible at age 70 – although the treatments could extend fertility.
Because of the accelerated decline of ovaries during middle life, they are “a good model for studying aging, and being able to do that in a limited amount of time,” Williams said. Other anti-aging scientists are also experimenting with rapamycin, for example, but it is almost impossible to determine whether the drug is extending human life without studying for many years. With the ovary, researchers can see if there is an effect much faster.
In addition, “if we can understand why an ovary changes prematurely and what is driving that, that will certainly tell us something important about aging in the rest of the body,” said Garrison. “And then, of course, that becomes important, not only for women, but for men as well.”
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