Could menopause be delayed? The answer could lead to longer lifespans for women

Scientists are learning that ovaries aren’t just important for making babies—they also keep the heart, brain, and bones healthy. A mouse ovary treated with a high dose of anti-Mullerian hormone (AMH)—a hormone naturally produced by follicles in the ovary—shows more small, dormant follicles and fewer larger ones. At high levels, AMH acts… Micrograph by David Pepin

When a woman goes through menopause—defined as not having a period for at least 12 months—the health impacts are immediate and dramatic.

That’s because ovaries (aside from their reproductive function) are endocrine organs. And when they stop pumping out the cocktail of chemicals that communicate with almost every tissue in the body, everything from the brain to the muscles to the skin is affected.

“Your risk of osteoporosis goes up overnight, your risk of cardiovascular disease goes up overnight,” says Jennifer Garrison, a neuroscientist at the Buck Institute for Research on Aging in California. And this seismic shift often hits between the ages of 45 and 55 (average age of onset is 51), coinciding with a woman’s peak years in the workforce. A study released by the Mayo Clinic estimates that in the United States, menopause is responsible for up to $1.8 billion in lost work time and more than $26 billion in medical costs.

“Ovaries are the architects of healthy aging in women,” Garrison says. So, it doesn’t make sense to talk about women’s health and longevity without considering reproductive longevity. For example, why do ovaries, which begin to show signs of age in a woman’s 30s, deteriorate decades earlier than other organs? Why do some people reach menopause earlier or later than average? And most importantly, if we could delay menopause, by keeping the ovaries functioning for longer, would that translate to more years of good health?

Unfortunately, for a long time research on reproductive health was laser-focused on fertility and the child-bearing years. David Pepin, a reproductive biologist at Harvard, recalls meeting with the U.S. Food and Drug Administration five years ago to discuss funding. A normal mouse ovary shows many immature eggs—or oocytes—in red. Larger oocytes surrounded by green hormone-producing granulosa cells indicate growing follicles; one oocyte will usually grow large enough to be released during ovulation. “I couldn’t convince them that having your ovaries function and make hormones is—in itself— important; that the ovaries are not just to make babies,” says Pepin. As a result, he’s had to be resourceful. Some of the work he’s done on the life cycle of ovaries has been funded by its applications for controlling the population of domestic cats .

But the tide is turning.

“There’s been an exponential increase in interest and research” in the last five years, says Garrison, who in 2020 co-founded the Global Consortium for Reproductive Longevity and Equality , an initiative that funds scientists, fosters collaborations, and educates the public about the crucial role of reproductive health in women’s health. “Suddenly, at aging research conferences, reproductive aging is represented now, whereas it wasn’t two or three years ago.” Why ovaries matter

Healthy ovaries produce a series of molecules that send signals to distant organs to help them function. Among the best studied is estrogen, which ebbs and flows with the menstrual cycle and peaks in the days before ovulation. But estrogen receptors—the molecules that grab estrogen, triggering downstream actions in cells and tissues—are present throughout the body, extending estrogen’s reach far beyond the reproductive organs.

When estrogen binds to its receptor, the resulting complex acts on DNA to switch some genes on, and others off. Estrogen, therefore, has its fingers in a lot of pies. In the cardiovascular system, the hormone helps widen blood vessels and ensure their lining is smooth and slippery , which lowers blood pressure and prevents clots from forming. In the brain, it’s neuroprotective — dampening inflammation, promoting healthy synapses, and clearing away misfolded proteins. In the musculoskeletal system, estrogen helps build and repair muscles as well as maintain bone.

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The loss of estrogen, therefore, puts women at increased risk for developing diabetes , cardiovascular disease , dementia , osteoporosis , and more . On the flip side, individuals who become menopausal later in life compared to their peers tend to live longer and healthier. This benefit extends even to their male siblings , pointing to a potential genetic link between reproductive health and overall longevity. How ovaries age

Although scientists have characterized some consequences of ovarian failure—both premature and as a part of normal aging—the processes that drive it remain mysterious.

What we do know: At puberty, when the ovaries contain approximately 400,000 follicles, the brain begins to communicate with these organs and activates up to a thousand dormant follicles—fluid-filled sacs that house a developing egg—each month. Of these, a handful mature, producing hormones like estrogen and progesterone, which send signals to the brain to prepare the uterus for a possible pregnancy.

Most of the growing follicles wither and die; but each month one (and sometimes two or three) will fully mature and release an egg for potential fertilization. This process repeats every month until menopause, when fewer than a thousand follicles remain.

( Scientists are finally studying women’s bodies. This is what we’re learning. )

Years before menopause, however, the feedback mechanisms between the brain and the ovaries (and the follicles they contain) become chaotic as follicle numbers dwindle, Pepin explains. “But it’s a complete black box” as far as how this impacts the trajectory of ovarian aging or whether it differs in different people, he says.

If these feedback mechanisms are important, though, one way to preserve healthy ovarian function may be to hold onto the follicles you have.

Pepin demonstrated that anti-Müllerian hormone, which is made in the follicles and controls the number that are activated (and therefore eventually lost in a menstrual cycle), can do just that.

When mice exposed to chemotherapy (which seems to jumpstart the development of dormant follicles, increasing the pool of eggs that die in each cycle) were injected with the hormone, fewer follicles were activated and more […]

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