When Francesca Duncandecided to take a look at what was going on in postmenopausal ovaries, she assumed she wouldn’t find much of interest. In awoman’s reproductive years, the ovary is exceptionally dynamic, shifting form and function from day to day throughout her cycle. But after menopause, when egg supply has dwindled and hormone production has waned, the ovaries are often thought of as little more thanempty sacks.
“I assumed it was just sitting there inert,” says Duncan, a reproductive biologist at Northwestern University, who was only looking at postmenopausal ovaries as part of a project tomap a cellular aging processcalled senescence throughout the body.
Instead, Duncan found that aged ovaries were anything but stagnant. Whenlooking at the protein composition of ovariesof postmenopausal women between the ages of 50 and 75 years old, her team found that the molecular signatures differed significantly across the decades. The oldest ovary looked nothing like a 60- or 70-year-old organ at the molecular level. She was shocked. “Clearly something is still happening,” says Duncan.
The question is: what?
A new wave of discovery is forcing researchers to recast the ovary not as an egg factory with an expiration date, but as an organ thatimpacts a woman’s overall healthand may shape thetrajectory of aginglong after the fertile years have passed. What they are only beginning to understand is whether changes to the ovary after menopause are harmful, protective, or some combination of the two, shifting over time.
This isn’t the first time the ovary’s role in maintaining health has been underestimated. For decades, surgeonsremovedhealthy organs during hysterectomies, figuring they weren’t doing much besides posing cancer risks. But 20 years ago,evidence began accumulatingthat removing healthy ovaries actually harms a woman’s overall health, finding an increased risk ofdementia,cardiovascular disease, andpremature death.
Because the ovary has historically been understood primarily as a reproductive organ, though, research has largely ignored what might be happening once those functions decline. “We don’t even know much about what the premenopausal ovary is doing outside of fertility,” says Jennifer Garrison, an ovarian aging expert and founder of a women’s health biotech company currently in stealth mode. After menopause, the extent of what we know about the ovary basically boils down to “it’s important,” she adds.
Biologists have known for decades, for instance, that after menopause, ovariescontinue producing hormones, including testosterone and small amounts of estrogen. But arguments continue over the clinical significance of those hormones. And hormones are only part of a complex signaling system.
Generally, the hormones the ovary produces postmenopause are known to help maintain libido, bone, and muscle, among other things, although it’s not clear how much the relatively small amounts produced by the postmenopausal ovary contribute to those effects. Multiple studies demonstrate that women who undergo oophorectomies fare worse than those who do not, particularly when having their ovaries removed before going through menopause naturally.
Recentbrain-imaging workby Pauline Maki at the University of Illinois at Chicago shows that even low levels of estrogen circulating postmenopause may matter: Women with higher levels had better-functioning memory circuits when performing memory tasks. Where that estrogen comes from—and how much the ovary contributes—isn’t as clear. After menopause, evidence suggests the brain reorganizes,possibly to compensatefor declining estrogen levels. Maki hypothesizes that ovarian signaling may contribute to that adaptation, and that hormone therapy could alter the relationship between the ovary, the body’s circulating estrogen, and the brain.
