For millions of women, menopause isn’t just about hot flashes or mood swings—it can also signal the beginning of a painful journey with osteoarthritis (OA). This degenerative joint condition,which disproportionately affects postmenopausal women,leads to chronic pain,stiffness,and a important decline in quality of life. While hormonal changes during menopause have long been linked to OA, recent research is shedding new light on the underlying mechanisms, offering hope for more effective treatments.
A groundbreaking study published on January 16, 2025, in Nature Aging, led by researchers at Spaulding Rehabilitation, a part of the Mass General Brigham healthcare system, has uncovered critical insights into why women are more susceptible to OA after menopause.The study highlights the role of hormonal shifts in accelerating joint degeneration and identifies potential pathways for future therapies.
“Our findings reveal novel pathways that may represent promising new therapeutic targets.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 a better quality of life for millions of women worldwide.”
—Fabrisia Ambrosio, PhD, MPT, senior study author and director of the Discovery Center for Musculoskeletal Recovery at the Schoen Adams Research Institute, Spaulding Rehabilitation
osteoarthritis occurs when the cartilage—the protective tissue cushioning the joints—begins to break down. This tissue has two key components: the extracellular matrix,which provides structural support,and chondrocytes,the cells responsible for maintaining cartilage health. In OA, both of these elements deteriorate, leading to bone-on-bone friction, pain, and reduced mobility. Aging is the most significant risk factor, and being female amplifies this risk, especially after menopause. Currently, treatment options are limited to managing symptoms rather than addressing the root cause of the disease.
To better understand the connection between menopause and OA, the Spaulding team used a mouse model to simulate menopause and study its effects on knee cartilage. The results mirrored human experiences, showing a sharp decline in cartilage quality at the onset of menopause. Using advanced computational techniques known as “network medicine,” the researchers identified how the loss of estrogen and progesterone during menopause accelerates cartilage breakdown. Importantly, restoring these hormones to pre-menopausal levels was found to protect against further degeneration.
This study marks a significant step forward in OA research, offering both a deeper understanding of the disease and actionable insights for potential treatments.As Gabrielle Gilmer, phd, the lead study author, explains, “This research provides insights into why the long-observed sex differences in osteoarthritis rates may occur. 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.”
Source:
Gilmer, G., et al. (2025) Menopause-induced 17β-estradiol and progesterone loss increases senescence markers, matrix disassembly and degeneration in mouse cartilage. Nature Aging. doi.org/10.1038/s43587-024-00773-2.
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