Hormonal Influences on Osteoarthritis Development

Osteoarthritis is a multifactorial joint disorder in which hormonal status exerts a profound influence on both onset and progression. Fluctuations in sex steroid levels, particularly oestrogen, modulate the integrity of articular cartilage and subchondral bone through receptor‐mediated signalling pathways. Declining oestrogen during menopause is associated with increased cartilage matrix degradation, heightened inflammatory mediator production and altered bone remodelling, all of which predispose to joint degeneration. Beyond oestrogen, other hormones and binding proteins such as progesterone, relaxin and sex hormone‐binding globulin contribute to tissue homeostasis and pain perception via regulation of extracellular matrix turnover and sensory nerve sensitisation. Emerging evidence also implicates phytoestrogens and selective oestrogen receptor modulators in attenuating degenerative changes. Understanding these hormonal interactions underpins precision‐based approaches to risk stratification, the development of disease‐modifying agents and tailoring of clinical management to sex and life‐stage. This overview highlights key molecular mechanisms and potential therapeutic avenues for mitigating osteoarthritic damage driven by endocrine factors.

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Hormonal Influences on Osteoarthritis Development publication trend

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Technical terms

Osteoarthritis: A degenerative joint disease characterised by cartilage breakdown, subchondral bone changes and synovial inflammation.

Oestrogen deficiency: A decline in circulating oestrogen levels, typically post-menopause, leading to accelerated cartilage degradation and bone remodelling imbalance.

Phytoestrogen (S-equol): A plant-derived compound that binds oestrogen receptors, mimicking hormone effects to protect joint tissues.

Selective oestrogen receptor modulators (SERMs): Synthetic agents that act as oestrogen agonists or antagonists in specific tissues to influence bone and cartilage metabolism.

Oxidative stress: An imbalance between reactive oxygen species production and antioxidant defences, promoting inflammation and tissue damage in osteoarthritis.

References

1. Sex differences in osteoarthritis prevalence, pain perception, physical function and therapeutics. Osteoarthritis and Cartilage (2024).
2. S-Equol Ameliorates Menopausal Osteoarthritis in Rats through Reducing Oxidative Stress and Cartilage Degradation. Nutrients (2024).
3. Gender-Related Aspects in Osteoarthritis Development and Progression: A Review. International Journal of Molecular Sciences (2022).
4. Are estrogen-related drugs new alternatives for the management of osteoarthritis?. Arthritis Research & Therapy (2016).
5. Osteoarthritis associated with estrogen deficiency. Arthritis Research & Therapy (2009).
6. Oestrogen is important for maintenance of cartilage and subchondral bone in a murine model of knee osteoarthritis. Arthritis Research & Therapy (2010).
7. Relaxin and β-estradiol modulate targeted matrix degradation in specific synovial joint fibrocartilages: progesterone prevents matrix loss. Arthritis Research & Therapy (2006).
8. Sex hormone-binding globulin and arthritis: a Mendelian randomization study. Arthritis Research & Therapy (2020).