The Role of Oestrogen in Female Skeletal Muscle Ageing: A Systematic Review

Ageing is associated with a loss of skeletal muscle mass and function that negatively impacts the independence and quality of life of older individuals. Females demonstrate a distinct pattern of muscle ageing compared to males, potentially due to menopause where endogenous sex hormone production declines. This systematic review aims to investigate the current knowledge about the role of oestrogen in female skeletal muscle ageing. A systematic search of MEDLINE complete, Global Health, Embase, PubMed, SPORTDiscus, and CINHAL was conducted. Studies were considered eligible if they compared a state of oestrogen deficiency (e.g. postmenopausal females) or supplementation (e.g. oestrogen replacement therapy) to normal oestrogen conditions (e.g. premenopausal females or no supplementation). Outcome variables of interest included measures of skeletal muscle mass, function, damage/repair, and energy metabolism. Quality assessment was completed with the relevant Johanna Briggs critical appraisal tool, and data were synthesised in a narrative manner. Thirty-two studies were included in the review. Compared to premenopausal females, postmenopausal females display reduced muscle mass and strength, but the effect of menopause on markers of muscle damage and expression of the genes involved in metabolic signalling pathways remains unclear. Some studies suggest a beneficial effect of oestrogen replacement therapy on muscle size and strength, but evidence is largely conflicting and inconclusive, potentially due to large variations in the reporting and status of exposure and outcomes. The findings from this review points toward a potential negative effect of oestrogen deficiency in ageing skeletal muscle, but further mechanistic evidence is needed to clarify its role. Graphical abstract figure O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=93 SRC="FIGDIR/small/23290199v1_ufig1.gif" ALT="Figure 1"> View larger version (20K): org.highwire.dtl.DTLVardef@97b4ecorg.highwire.dtl.DTLVardef@1e71a43org.highwire.dtl.DTLVardef@16d4a9corg.highwire.dtl.DTLVardef@3d7ac3_HPS_FORMAT_FIGEXP M_FIG C_FIG The role of oestrogen in female skeletal muscle ageing. {uparrow} = significant increase, {downarrow} = significant decrease, = = significantly different, ? = mixed evidence, p<0.05. ALM: appendicular lean mass; AMPK: adenosine monophosphate kinase; CSA: cross-sectional area; PGC-1: peroxisome proliferator-activated receptor gamma coactivator 1-alpha. Created with BioRender.com.