Estrogen Deficiency in Menopause: A Major Contributor to Cartilage Degeneration and Osteoarthritis: A Systematic Review and Meta-Analysis.

Menopause-associated estrogen deficiency has been implicated in cartilage degeneration and osteoarthritis (OA) progression. This systematic review and meta-analysis evaluates evidence from human and animal studies. Five databases were searched until March 2025. Eligible studies included postmenopausal women or ovariectomized (OVX) animal models assessing cartilage degeneration, OA severity, or related biomarkers. Human and animal studies were analyzed separately. Random-effects meta-analyses were conducted when outcomes were comparable. Eleven studies met the criteria (human, n = 6; animal, n = 5). Pooled human results for C-terminal telopeptides of type II collagen and magnetic resonance imaging-based cartilage thickness showed non-significant trends toward greater cartilage loss in estrogen-deficient women. OVX animal studies demonstrated significantly greater histological cartilage degeneration compared with controls. Hormone replacement therapy showed inconsistent but directionally protective effects. Estrogen deficiency is associated with cartilage degeneration, with strong supportive evidence from OVX models. Human evidence indicates similar trends but lacks statistical significance, highlighting the need for larger and more standardized studies.