The enigma of associations between reproductive health and development of osteoarthritis in midlife: a life-course approach
Abstract
Osteoarthritis (OA) is the most common form of arthritis. OA becomes more prevalent in women around the age of menopause, and it has been suggested that the decrease in estrogen at menopause may be important in the pathophysiology of OA development. The association between estrogen exposure and OA is complex; a recent meta-analysis suggested that menopause hormone therapy use may be associated with an increased risk of joint replacement, bringing this research area back into focus. This narrative review used a systematic process, adopting a life-course approach to consider relationships between reproductive factors and OA, identifying 15 papers published over a 26-year period. Increased parity, use of the oral contraceptive pill, abortion, breastfeeding and inter-menstrual years were all considered but findings varied widely between studies. We note that progesterone is rarely considered, despite animal work suggesting its importance. These data highlight the need for further research with careful measurements of confounding variables, and consideration of the role for progesterone in OA etiology.
- Hormone replacement therapy
- Oral contraceptive pill
- Sex hormone signalling (oestrogen, androgen)
- Osteoarthritis
- Humans
The paper
MRC Lifecourse Epidemiology Unit
Climacteric, 5 Aug 2026, Open access


