Menopause has long been thought of as a terminal moment for the female reproductive system, when ovaries stop releasing eggs and presumably call it a day, but researchers suggest they actually remain active, and are not as ‘inert’ as previously assumed.
The simplified image of ovarian retirement isn’t holding up, according to the scientists who took a closer look at what happens to these organs after menopause.
“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 reproductive biologist Francesca Duncan of Northwestern University in the United States.
Proteomics expert Birgit Schilling of the Buck Institute echoed this, saying: “The ovary is not just a reproductive organ.”
“It really influences how somebody ages because it speaks to all these other organs, like the brain, and also to the bone, and women after menopause often experience a lot of bone problems. So, we think there is a connection between all of these organs.”
Schilling and Duncan led a study published last week in the scientific journal Ageing Cell, their findings suggesting that for the ovary, menopause is much more like a career change than retirement.
The researchers used mass spectrometry to look at which proteins were active in the healthy ovaries of 28 postmenopausal women, according to the tissue donor’s age: 50-59, 60-69, and 70 and older.
These women had their ovaries surgically removed for various reasons, but none of the ovaries included in the study showed signs of disease.
The results mirrored what Duncan found in the ovaries of mice in a study published earlier this year: the protein profiles produced by ovarian tissue shift progressively with age. In the human ovaries, a core set of 17 proteins really characterised that shift.
Ovaries from the 50-59 age group had more proteins related to regulating RNA and DNA, and maintaining the tissue structure and cells. In contrast, ovaries from the 70+ group had more proteins involved in lipid metabolism, innate immunity, and inflammation.
If ovaries were ‘inert’ after their reproductive years, that wouldn't be the case.
“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.”
Life expectancies are generally stretching further than ever before, which means there are now far more postmenopausal people wandering around, whose bodies we still don’t fully understand.
Ovarian cancer risk is much higher after menopause, and the new study reveals why this might be the case.
Age-related changes in ovarian tissue and immune cells at the protein level create an environment ideal for tumours by loading the extracellular matrix with collagen.
The ovarian tissue samples in this study were, of course, tumour-free, but proteins previously linked to ovarian cancer were abundant, most prominently in the ovaries of women in their 60s.
“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 ageing 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?”
With an initial ‘roadmap’ of ovarian aging now established, researchers can begin to probe these more nuanced questions.
These findings could have important implications for healthcare in women’s post-reproductive years, and among those who have their ovaries removed.
Study details
The human ovary exhibits dynamic molecular remodelling in the decades post-menopause
Mark Watson, Bikem Soygur, Christina King, Birgit Schilling et al.
Published in Ageing Cell on 13 October 2026
Abstract
The human ovary is among the first organs to show age-related functional decline, resulting in menopause. Beyond this transition, the postmenopausal ovary is often regarded as quiescent and remains poorly characterized. We analyzed the proteomes of healthy, non-pathological ovaries using mass spectrometry (data-independent acquisition) from 28 postmenopausal women (50–75 years old), stratified into three age groups (50–59, 60–69, ≥ 70). We quantified 5812 protein groups and observed progressive age-associated shifts, with 117 proteins significantly altered in the ≥ 70 versus 50–59 age comparison. Multivariate analysis demonstrated clear separation between 50–59 and ≥ 70-year-old age cohorts, with protein signatures shifting from RNA/gene-regulatory functions in younger ovaries to metabolic, trafficking, and innate immune/complement pathways in older ovaries. Across differential abundance, multivariate modeling, and covariate-adjusted linear modeling, we identified a convergent set of age-associated proteins that were integrated into the 26-protein Buck Postmenopausal Ovary Molecular Signature (BuckPOMS), a consensus molecular signature capturing progressive extracellular matrix remodeling, inflammatory signaling, and loss of structural and keratin-associated proteins with age. Representative BuckPOMS proteins, including the secreted matrisome proteins WNT4 and Fibromodulin (FMOD), were validated by immunohistochemistry. Pathway enrichment further identified an increase in inflammatory and matrisome pathways, and increased abundance of damage-associated secretory factors decades following menopause. These data fundamentally shift the notion of the postmenopausal ovary as an inert organ and instead demonstrate active and continuous molecular remodeling that has potential relevance to tissue signaling and implications for women's health.
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