A Thematic Narrative Review of Osteoarthritis Risk Factors Across the Female Life Course

A strong body of evidence is established that links sex-hormone-regulated physiological processes across the female life course with increased risk of osteoarthritis (OA), although the strength and nature of these associations vary by joint site and OA phenotype. Much of the available mechanistic evidence relates to knee OA with comparatively less evidence available for hip and hand OA. These include reproductive milestones (menarche and menopause), major life events such as childbirth (parity), and sex-hormone-regulated physiological functions, including menstruation and breastfeeding. Many of these have also been shown to associate with poorer surgical and non-surgical responses to musculoskeletal (MSK) treatment. A thorough multidisciplinary analysis of sex-associated differences in MSK outcomes and OA risk across the female life course is long overdue. This thematic narrative review has been conducted by a multidisciplinary team comprising experts in fundamental biology, mechanobiology, immunology, orthopaedic surgery, pain medicine and gynaecology. The review will examine in detail early life and puberty (menarche), reproductive years (menstrual cycling and injury risk, contraception, parity and breastfeeding), midlife transition (perimenopause, menopause, and treatments) and clinical interactions (response to surgical and non-surgical interventions). Biological considerations in each life-course phase/transition will focus on the hormonal milieu, biomechanical influences, immune and metabolic functions and pain pathways.