Unveiling the Ovarian Mystery
When Francesca Duncan embarked on her research into the ovarian changes following menopause, she expected little of interest to arise. During a woman’s reproductive years, the ovaries are highly dynamic, continually altering in shape and function throughout the menstrual cycle. However, after menopause, as the egg reserve diminishes and hormone production declines, the ovaries are often perceived as mere empty sacs.
“I assumed they were just there, inert,” recalls Duncan, a reproductive biologist at Northwestern University. Initially, her focus on post-menopausal ovaries was part of a broader project aiming to map a cellular aging process known as senescence throughout the body.
Unexpected Findings
To her astonishment, Duncan discovered that aged ovaries were far from inactive. In analysing the protein composition of ovaries from women aged 50 to 75, her team found that molecular characteristics varied significantly across decades. The ovary of an older woman bore little resemblance to that of a woman in her sixties or seventies. “Clearly, something is still happening,” Duncan noted.
This revelation raises an intriguing question: what exactly is taking place in the ovaries post-menopause?
Redefining Ovarian Function
A fresh wave of discoveries is prompting researchers to reconsider the role of the ovaries, not merely as egg-producing entities with an expiration date, but as organs that significantly impact women’s overall health and may influence the ageing process well beyond reproductive years. The ongoing investigation aims to discern whether the changes occurring in the ovaries after menopause are detrimental, protective, or a blend of both, and how these changes may evolve over time.
Historically, the significance of the ovaries in maintaining health has often been undervalued. For decades, surgeons routinely removed healthy ovaries during hysterectomies, believing they posed little more than cancer risks. However, around twenty years ago, accumulating evidence began to suggest that the removal of healthy ovaries adversely affected women’s overall health, amplifying the risks of dementia, cardiovascular diseases, and premature death.
The Hormonal Landscape
Despite the historical focus on the ovaries as primarily reproductive organs, research has largely overlooked the consequences of diminished ovarian function. “We know very little about what the pre-menopausal ovary does beyond fertility,” states Jennifer Garrison, an expert in ovarian ageing and founder of a biotechnology firm dedicated to women’s health. After menopause, our understanding of ovarian function is limited to the notion that “it is important,” she adds.
For decades, biologists have recognised that after menopause, the ovaries continue to produce hormones, including testosterone and small amounts of oestrogen. However, the clinical significance of these hormones remains a topic of debate. Furthermore, hormones represent only one facet of a complex signalling system.
Health Implications
It is well established that the hormones produced by the ovaries post-menopause contribute to maintaining libido, bone mass, and muscle mass, among other functions. Yet the extent to which the relatively small quantities produced by post-menopausal ovaries affect these outcomes is still unclear. Numerous studies have shown that women who undergo oophorectomy experience poorer health outcomes compared to those who do not, particularly when the ovaries are removed before natural menopause.
A recent neuroimaging study conducted by Pauline Maki at the University of Illinois in Chicago indicates that even low levels of circulating oestrogen post-menopause can be significant: women with higher oestrogen levels demonstrated better functioning neural circuits while performing memory tasks. However, the origin of this oestrogen and the extent of the ovaries’ contribution remain uncertain. Evidence suggests that after menopause, the brain undergoes reorganisation, possibly to compensate for declining oestrogen levels. Maki hypothesises that ovarian signalling may play a role in this adaptation, and that hormone therapy could alter the interplay between the ovaries, circulating oestrogen, and the brain.
Enduring Significance
While the residual importance of hormonal production may diminish over time, Walter Rocca, an epidemiology and neurology professor at the Mayo Clinic, asserts that this does not imply a loss of ovarian significance. “I am convinced, until proven otherwise, that removing ovaries even after menopause is inadvisable,” he states, with exceptions for women at higher risk of ovarian cancer.
The duration for which this importance persists post-menopause remains unknown, as does the variability of response among women. “There are significant discrepancies,” concludes Stephanie Faubion, medical director of the Menopause Society.
Inflammatory Changes
One reason the role of the post-menopausal ovary may evolve over time is that research on human ovaries has revealed patterns suggesting an increasingly inflammatory environment within the organ. To delve deeper into the potential causes of these changes, researchers have examined mouse ovaries. A study published in June in the journal Molecular Human Reproduction indicates that the ovary may acquire a completely new identity after menopause.
The research compared ovaries from two-month-old mice, 18-month-old reproductive mice, and 24-month-old post-reproductive mice, discovering that over time, genes related to inflammation and immune activity became significantly more active. Additionally, the number of immune cells within the ovaries also increased. Although findings from mouse studies cannot always be directly applied to humans, they may elucidate the molecular changes observed by Duncan in human ovaries.
Future Investigations
David Pépin is exploring another possibility: that as follicles housing developing eggs diminish, the ovary may reorganise itself to sustain hormone production. A reproductive biologist at Massachusetts General Hospital and Harvard Medical School, Pépin found that years after administering an experimental gene therapy to cats that halted follicle maturation, the cats continued to produce oestrogen, testosterone, and inhibin at normal levels.
Typically, follicles drive much of the hormonal production during reproductive cycles; thus, their absence would ordinarily lead to reduced hormone levels. In preliminary findings he has yet to publish, Pépin’s team discovered that when ovaries were eventually removed, other cells in the organ (the stroma) appeared to take over hormonal production. Pilot studies in mice suggest a similar phenomenon. Pépin believes he has identified a natural mechanism that aids in preserving hormonal production as the follicles decrease. It has long been hypothesised that the stroma may be responsible for some of the post-menopausal hormonal output from the human ovary.
As Pépin notes, oestrogen is not the sole hormone influencing menopause. “We know very little about how other ovarian hormones affected during menopause might contribute to health,” he concludes. “It is not a dead organ.”