The ovaries are essential organs in the female reproductive system, responsible for producing eggs and hormones such as estrogen and progesterone. Although their reproductive function ends with menopause, emerging research suggests they remain biologically active and may continue to influence aging and overall health. Credit: Shutterstock

Ovaries often dismissed as inactive after menopause may still shape how women age, with human tissue revealing inflammatory changes and molecular similarities to ovarian cancer.

Ovaries continue to change for decades after menopause, long after their role in reproduction has ended. In a study of ovarian tissue from 28 women ages 50 to 75, scientists found age-related shifts in proteins associated with inflammation, immune activity, and the structure of the tissue surrounding cells.

The research, conducted by scientists at Northwestern University and the Buck Institute for Research on Aging, was published in Aging Cell.

“In the ovary, we reach a point of no return with respect to fertility in which it’s no longer producing eggs, and I would venture to say most people assume those ovaries are just sitting there doing nothing, similar to the appendix,” said co-corresponding author Francesca Duncan, associate professor of reproductive science in medicine at Northwestern University Feinberg School of Medicine. “But that’s what makes this study very different.”

Older ovaries show an inflammatory shift

To investigate what changes after menopause, the researchers looked beyond ovarian hormones to examine the tissue’s protein composition. Co-corresponding author Birgit Schilling, professor and director of the Mass Spectrometry Center at the Buck Institute, led the team responsible for that analysis. Spearheaded by Buck Institute staff scientist and Schilling lab member Mark Watson, the work used advanced proteomic technologies that can identify and measure thousands of proteins at once. The researchers analyzed 5,812 groups of proteins in normal ovarian tissue.

Headshot of co-corresponding author Birgit Schilling. Credit: Buck Institute for Research on Aging

Human ovarian tissue is difficult to obtain, making the collection of 28 ovaries unusually valuable, Duncan said. Concentrating on a 25-year age range after menopause allowed the team to isolate differences within the postmenopausal years, rather than comparing young and old ovaries across an entire lifespan. The technology also made it possible to examine thousands of proteins in every sample.

“When we analyzed the data in multiple different statistical ways, what became clear across all these methodologies is that the ovary was not stagnant,” Schilling said. “In fact, over the decades, there were quite dramatic differences in terms of some proteins’ levels would go up with age and some proteins’ levels would go down, which tells us this organ is quite dynamic.”

Ovaries from younger postmenopausal women contained more proteins involved in maintaining cells and tissue structure. Older ovaries had more proteins associated with inflammation, immune activity, and the breakdown and rebuilding of the tissue around cells. The differences were greatest between women in their 50s and those ages 70 and older.

Some of the molecular patterns also resembled those seen in cellular senescence. In this state, aging or damaged cells stop dividing but remain biologically active and can send signals that affect nearby tissue.

“Our data points to progressive aging features in which the ovary appears to lose its original identity and ends up doing something different,” Duncan said. “We do not yet know if there’s ever a point in a woman’s life when this organ is no longer beneficial and it’s actually harmful. These results really point to the need to ask this question.”

Similar remodeling in mice and women

Duncan’s group had previously found similar evidence of continued remodeling in postmenopausal ovaries of mice. She began both that research and the human study with expectations that the findings ultimately challenged.

“I was predicting that if we took a 50-year-old ovary, a 60-year-old ovary, a 70-year-old, an 80-year-old ovary, they would all look exactly the same, have no eggs, and basically be non-functional,” Duncan said. “The fact that across species we’re seeing this gives us confidence that this isn’t just some random event, but something truly meaningful is happening in the biology.”

Headshot of co-corresponding author Francesca Duncan. Credit: Northwestern University

Women now routinely live for decades after menopause, Duncan noted, making the ovary’s role during this long period increasingly relevant to understanding women’s health beyond fertility.

“The ovary is not just a reproductive organ,” Schilling said. “It really influences how somebody ages because it speaks to all these other organs, such as the brain, and also to the bone, and women after menopause experience often a lot of bone problems. So, we think there is a connection between all these organs.”

Cancer-linked proteins in cancer-free ovaries

The changes in tissue structure also connect the new findings to an earlier question about ovarian cancer. In 2016, Duncan’s lab was the first to find that aging ovaries become increasingly inflamed, fibrotic, and stiff, resembling scarring in other tissues. Cancer cells can thrive in stiff, collagen-rich environments, prompting the researchers to investigate whether these changes could make older ovaries more hospitable to cancer cells. The new protein analysis provides a molecular view of that remodeling process after menopause.

All the tissue in the current study appeared normal and cancer-free. Nevertheless, some proteins previously associated with ovarian cancer were more abundant in aging ovaries, with the strongest signal among women in their 60s. This does not mean the ovaries were cancerous or precancerous. It suggests that healthy ovarian aging and ovarian cancer share some biological processes.

“It’s not that all postmenopausal women get ovarian cancer, but we know that that fibrotic inflammatory environment is certainly an environment that cancer cells prefer to home in on,” Duncan said. “This is all consistent with the idea that the aging ovary is a potential third hit for ovarian cancer, with the first hit being genetic and the second hit being environmental. So can we target the aging ovary therapeutically to lower the risk of ovarian cancer, or can we develop novel biomarkers of ovarian cancer?”

Whether aging in the ovary can drive changes elsewhere in the body remains an open question.

“Is the ovary the canary in the coal mine in women?” said Duncan, who is also an associate professor in residence at the Buck Institute. “Could aging in the ovary set off a cascade of changes that continues throughout the body as women get older?”

The findings do not answer whether healthy ovaries should ever be removed after menopause, the researchers emphasized. Much more research is needed to determine exactly what the organ does during these years and whether the changes observed contribute to chronic disease or are simply features of normal aging.

Reference: “The Human Ovary Exhibits Dynamic Molecular Remodeling in the Decades Post-Menopause” by Mark A. Watson, Bikem Soygur, Christina D. King, Pooja R. Devrukhkar, Simon Melov, Elisheva D. Shanes, Mary Ellen G. Pavone, Francesca E. Duncan and Birgit Schilling, 7 September 2026, Aging Cell.
DOI: 10.1111/acel.70714

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