Sex hormones and their receptors in osteoarthritis: current research progress.

Osteoarthritis (OA) is the most prevalent degenerative joint disease worldwide and a leading cause of pain, disability, and reduced quality of life, with pronounced sex-specific differences in incidence and clinical presentation. Epidemiological evidence shows a sharp increase in OA prevalence in women after menopause, whereas in men, the elevated risk at older age is more closely associated with declines in bone mass, muscle strength, and biomechanical stability. Increasing experimental and clinical studies indicate that sex hormones-including estrogen, androgens, and progesterone-and their respective receptors [estrogen receptor (ER), androgen receptor (AR), and progesterone receptor (PR)] play essential roles in maintaining joint homeostasis and modulating OA pathogenesis. At the molecular level, these hormones regulate chondrocyte proliferation, differentiation, apoptosis, extracellular matrix (ECM) metabolism, synovial inflammation, and subchondral bone remodeling through diverse genomic and non-genomic signaling pathways. Dysregulation of hormone signaling, particularly estrogen deficiency or receptor imbalance, contributes to cartilage degeneration, aberrant bone remodeling, and inflammatory activation, thereby promoting OA progression. Notably, hormone-related effects appear to be tissue-specific, receptor subtype-dependent, and stage-dependent, underscoring the complexity of endocrine regulation in joint diseases. This review summarizes recent advances in the roles of sex hormones and their receptors in OA, integrating evidence from molecular mechanisms, experimental studies, and clinical research. It aims to provide a comprehensive framework for understanding sex differences in OA and to support the development of sex-specific and mechanism-based therapeutic strategies.