In March, first lady Jill Biden announced a new White House initiative on women’s health that highlighted a seemingly little-known research question: what if menopause and all the health risks associated with it might be delayed?
The question comes from a field of research that has only recently gained attention, as scientists studying women’s health and longevity have come to realize that the female reproductive system is much more than just a baby factory. The ovaries, in particular, appear to be linked to virtually every aspect of female health.
They also stop performing their primary function abruptly in middle age. Once this happens, a woman enters menopause, which accelerates her aging and the decline of other organs, such as the heart and brain. Although women, on average, live longer than men, they also spend more time with illnesses or disabilities.
Ovaries are “the only human organ that we accept will fail one day,” said Renee Wegrzyn, director of the Advanced Research Projects Agency for Health, the government agency charged with leading Biden’s mission. “It’s actually a little crazy that we all just accept that.”
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It is precisely the truncated life span of the ovaries that makes them such a promising site for experimentation. Researchers believe that prolonging their function and better matching their viability duration to that of other organs might alter the course of women’s health and, more generally, of longevity research.
Wegrzyn said she 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 attracting more funding and talent to the field.
“If you don’t consider the role of the ovaries during aging,” said Jennifer Garrison, an assistant professor at the Buck Institute for Aging Research, “then you’re missing an opportunity.”
Ovaries and aging
The ovaries function as the control center for “a complex network of signaling in a woman’s body,” Garrison explained. Through hormones like estrogen and progesterone, as well as other chemicals, the ovaries communicate with and influence virtually every other organ. Scientists still don’t know exactly how they do this, but what they do know is that when the ovaries stop functioning normally, all sorts of problems arise. In younger 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 become depleted, eventually triggering menopause, the ovaries’ chemical communications appear to quiet down. This corresponds with an increased risk of dementia, cardiovascular disease, osteoporosis and other age-related diseases. The earlier a woman enters this phase of life, the greater her risk of developing these conditions and the shorter her life is likely to be. And for women who enter menopause early because their ovaries have been removed, the risk of chronic disease is even higher. According to Stephanie Faubion, medical director of the Menopause Society, this suggests that even following the ovaries stop releasing eggs at menopause, they may still be protecting a woman’s overall health in some way. It’s just not clear how.
For now, these connections are correlational. Scientists don’t know whether the ovaries themselves are the drivers of aging health, or whether there’s something else that accelerates aging that then leads to ovarian dysfunction, Faubion said. Studies have found that several factors, including smoking, body mass index and adverse stressors throughout life, 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 going out of sync and causing poor health?” Faubion said. “I mean, it’s a case of the chicken and the egg.”
Delaying menopause might prolong life
There is some evidence, particularly 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 one lengthens the life of the older mouse.
Scientists are experimenting with different ways to prolong ovarian function and delay the onset of menopause in humans.
A company, Oviva Therapeuticsis testing in mice and cats whether a pharmaceutical version of the anti-Müllerian hormone (AMH), which modulates the number of follicles that mature in each menstrual cycle, might be used to reduce egg loss. (Typically, 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 covers the ovary,” explained Daisy Robinton, co-founder and chief executive of Oviva, which is competing for some of the funding for the White House initiative. The level of AMH dictates the size of the holes in the cloth; if there are huge holes (in other words, there is low AMH), a lot of eggs can come out each cycle. But if there are only small holes (i.e., there is high AMH), fewer eggs can come out.
The idea is that if a woman loses fewer eggs, she can maintain her ovarian reserve and ovarian function for longer, Robinton explained.
A clinical trial underway at Columbia University is also attempting to slow the rate of egg loss. The study is testing the use of an immunosuppressant drug called rapamycin — which is used to prevent rejection of organ transplants and has become a darling of the longevity movement — in women between the ages of 35 and 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 a placebo, but the trial’s senior scientist, S. Zev Williams, said two patterns had already emerged: Some women appear to have a normal decline in ovarian reserve, which can be measured by ultrasound and AMH levels, but in others “it seems to have gone haywire,” he said. “So it’s promising.” Williams, an associate professor of women’s health at Columbia, is also applying for funding from the health agency.
The experts were explicit that the goal of this type of research was not to indefinitely prolong women’s periods, or to make pregnancy possible at age 70, although the treatments might potentially prolong fertility.
The accelerated decline of ovaries during midlife also makes them “a good model to be able to study aging, and to be able to do so in a limited time frame,” Williams said. Other anti-aging scientists are also experimenting with rapamycin, for example, but it’s virtually impossible to determine whether the drug extends human life without doing a study over several decades. With ovaries, researchers can see if there’s an effect much more quickly.
What’s more, “if we can understand why the ovaries age prematurely and what drives it, that will almost certainly tell us something important regarding aging in the rest of the body,” Garrison said. “And that, of course, becomes important not just for women, but for men as well.”
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