Associations Between Female Sex Hormones and Skeletal Muscle Ageing: The Baltimore Longitudinal Study of Aging

To date, most research investigating the influence of circulating sex hormones on ageing female skeletal muscle has been cross-sectional and focused only on dichotomised young and old, or pre- versus post-menopausal groups. This excludes an important transitional period from high to low circulating oestrogen. Using secondary data from the Baltimore Longitudinal Study of Aging, this study aimed to investigate cross-sectional and longitudinal associations between circulating sex hormones and skeletal muscle mass and function across a continuum of ages.

Multiple and binomial linear regression was used to map cross-sectional (n = 319) and longitudinal (n = 83) associations between circulating sex hormones (oestradiol (E2), free oestradiol index (FEI), total (TT) and bioavailable (BioT), testosterone, testosterone/oestradiol ratio (TT/E2)) and skeletal muscle mass and function in healthy females. Cross-sectional models analysed females across an ageing continuum (24-89 years) and longitudinal associations were tested across 4-6 years of ageing in females over 50 years old. Models were adjusted for age, height, physical activity, comorbidities, ethnicity, and follow-up time.

Cross-sectionally, serum E2 and FEI were positively associated with relative appendicular lean mass (ALM; β = 0.28 and 0.20, respectively, p < 0.05) and thigh muscle percentage (β = 0.19 and 0.15, respectively, p < 0.05). E2 and FEI were negatively associated with total body fat percentage (β = -0.30 and -0.21, respectively, p < 0.05). BioT was positively associated with absolute ALM (β = 0.13, p < 0.05) and total body fat percentage (β = 0.18, p < 0.05). TT was negatively associated with total body fat percentage (β = -0.14, p < 0.05). The TT/E2 ratio was negatively associated with thigh muscle CSA (β = -0.08, p < 0.05) and hamstring strength (β = -0.12, p < 0.05). Across 4-6 years, decreases in E2 and FEI were associated with a decrease in ALM (β = 0.27 and 0.41, respectively, p < 0.05), and a decrease in FEI was associated with a decrease in handgrip strength (β = 0.21, p < 0.05). Decreases in TT and BioT were associated with an increase in total body fat (β = -0.25 for both, p < 0.05) and a decrease in TT was associated with an increase in hamstring specific force (β = -0.11, p < 0.05).

This study demonstrates novel associations between sex hormone levels and skeletal muscle in females across a wide continuum of ages. We also demonstrate that longitudinal fluctuations in circulating sex hormones must be considered to gain a comprehensive understanding of female muscle ageing.