My Lovely Wife has been coping with a bum right knee — the product of a freak accident and a botched surgery — for almost 50 years. She has persevered admirably through it all, but recent research suggests that, like most older women, she and her knees are fighting a surprisingly powerful force: menopause.
The hormonal shifts that occur during this life phase have long been known to accelerate the onset of osteoarthritis (OA), the gradual degradation of cartilage tissue in the joints, but researchers affiliated with the Mass General Brigham health system have identified the specific mechanisms involved in the process. Their findings, published last month in Nature Aging, may offer some hope for the legions of older women struggling with this painful condition.
“Our findings reveal novel pathways that may represent promising new therapeutic targets,” senior study author Fabrisia Ambrosio, PhD, MPT, says in a statement. “By understanding how menopause-induced changes in sex hormone levels contribute to joint degeneration, our hope is that this will pave the way for researchers to develop novel strategies that slow or prevent the progression of OA, which could lead to better quality of life for millions of women worldwide.”
Analyzing the cartilage of menopausal lab mice, Ambrosio and her team focused on the damage estrogen and progesterone depletion causes to two areas of the cartilage: the extracellular matrix (the proteins that surround the cartilage and provide structure) and the chondrocytes (the cells residing within the cartilage). When researchers restored those hormones to premenopausal levels, the cartilage regained its former function.
“By understanding how menopause-induced changes in sex hormone levels contribute to joint degeneration, our hope is that this will pave the way for researchers to develop novel strategies that slow or prevent the progression of OA, which could lead to better quality of life for millions of women worldwide.”
“This research provides insights into why the long-observed sex differences in osteoarthritis rates may occur,” notes lead study author Gabrielle Gilmer, PhD. “We hope that since we were able to protect against cartilage degeneration in our models, we are laying the foundation for pursuing effective treatments for older female humans.”
A couple of obstacles lie in the path of further research and effective treatment, however. First, hormone-replacement therapy has long been shown to carry nearly as much risk as reward. One major study in 2013 found that using an estrogen-progestin pill known as Prempro increases the risk of heart disease, stroke, blood clots, and breast cancer. The risks may vary by the type of hormone therapy, as well as by the age of the patient and their health history, but the dangers are real.
Then there’s the very real chance that additional research will come slowly, if at all. As Ambrosia notes in a 2023 study and corresponding interview, there is a long-standing pattern in the scientific community of failing to take menopause into account; she and her team have found that issues related to menopause were considered in less than 1 percent of published papers they reviewed.
“When we look at age-related diseases, over 75 percent of them are likely influenced by menopause in one way or another,” she says. “But the great majority of preclinical aging biology research studies fail to consider menopause in their experimental setup.”
This lack of research has tangible consequences, she adds. Women live longer than men, but they also tend to suffer from more health issues, including cognitive impairment and heart disease. And they are more likely than their male counterparts to be misdiagnosed for a heart attack and stroke.
“Our healthcare system lacks data on how to treat age-related diseases in females.”
“Our healthcare system lacks data on how to treat age-related diseases in females,” Ambrosia argues. “In the clinic, we’re falling behind and can’t treat aging females as effectively as we would like. It represents a significant gap in clinical practice.”
National Institutes of Health officials have been encouraging more research involving menopausal women, Ambrosio notes, but little will change until the scientific community recognizes the limitations of the current study models. “We need a mechanism to bring aging researchers together to share their ideas on understanding aging in the postmenopausal population,” she says. “And then we need additional funding for research that considers female-specific traits and uses some of these new models.”
Here’s hoping her message finds an audience among researchers in the years ahead. As MLW — and most older women — will tell you, passing through menopause is challenging enough with its hot flashes, night sweats, and myriad other discomforts. Creaky knees can make it a real pain.
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