The effect of hormone replacement therapy on musculoskeletal pain in menopausal women: A systematic review and meta-analysis

Up to 70% of menopausal women report musculoskeletal (MSK) pain during and after the time of menopause. This observation suggests oestrogen deficiency may play a role in the development of MSK pain and conditions which cause it. Therefore, we hypothesise that hormone replacement therapy (HRT) will improve these symptoms; however, there is currently no guidance on the use of HRT for such symptoms. This review aims to synthesise current evidence on the associations between HRT and chronic MSK pain in menopausal women, to help guide clinical practice. MEDLINE, EMBASE, AMED, CINAHL, PsycINFO, Cochrane and Web of Science databases were searched from their inception to October 2024. The search initially identified 30,739 studies from which 57 studies, including a total 3,958,702 participants, were included. MSK outcomes were grouped into generalised MSK pain, osteoarthritis (OA), rheumatoid arthritis (RA), gout and carpel tunnel syndrome (CTS). Pooled analysis found no significant effect of ever HRT use versus never HRT use on generalised MSK pain (RR 1.00, 95% CI 0.96-1.04). For OA and RA outcomes significant heterogeneity between studies restricted our ability to undertake pooled analysis. Narrative synthesis of these outcomes revealed conflicting results on the effect of HRT on these conditions. This systematic review and meta-analysis demonstrates the substantial heterogeneity within this field and highlights the need for bespoke studies investigating the effect of HRT on MSK pain to draw any firm conclusions to guide clinical practice.