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

ABSTRACT Background 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...

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Main Authors: Annabel J. Critchlow, Sarah E. Alexander, Danielle S. Hiam, Luigi Ferrucci, David Scott, Séverine Lamon
Format: Article
Language:English
Published: Wiley 2025-06-01
Series:Journal of Cachexia, Sarcopenia and Muscle
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Online Access:https://doi.org/10.1002/jcsm.13786
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author Annabel J. Critchlow
Sarah E. Alexander
Danielle S. Hiam
Luigi Ferrucci
David Scott
Séverine Lamon
author_facet Annabel J. Critchlow
Sarah E. Alexander
Danielle S. Hiam
Luigi Ferrucci
David Scott
Séverine Lamon
author_sort Annabel J. Critchlow
collection DOAJ
description ABSTRACT Background 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. Methods 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. Results 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). Conclusion 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.
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spelling doaj-art-c16ae2f2e188437a8dc15e5e253f5c552025-08-20T02:20:39ZengWileyJournal of Cachexia, Sarcopenia and Muscle2190-59912190-60092025-06-01163n/an/a10.1002/jcsm.13786Associations Between Female Sex Hormones and Skeletal Muscle Ageing: The Baltimore Longitudinal Study of AgingAnnabel J. Critchlow0Sarah E. Alexander1Danielle S. Hiam2Luigi Ferrucci3David Scott4Séverine Lamon5School of Exercise and Nutrition Sciences, Institute for Physical Activity and Nutrition (IPAN) Deakin University Geelong AustraliaCardiometabolic Health and Exercise Physiology Baker Heart and Diabetes Institute Melbourne AustraliaSchool of Exercise and Nutrition Sciences, Institute for Physical Activity and Nutrition (IPAN) Deakin University Geelong AustraliaNational Institute on Aging, National Institutes of Health Baltimore Maryland USASchool of Exercise and Nutrition Sciences, Institute for Physical Activity and Nutrition (IPAN) Deakin University Geelong AustraliaSchool of Exercise and Nutrition Sciences, Institute for Physical Activity and Nutrition (IPAN) Deakin University Geelong AustraliaABSTRACT Background 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. Methods 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. Results 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). Conclusion 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.https://doi.org/10.1002/jcsm.13786ageingoestrogenovarian hormonesskeletal muscle
spellingShingle Annabel J. Critchlow
Sarah E. Alexander
Danielle S. Hiam
Luigi Ferrucci
David Scott
Séverine Lamon
Associations Between Female Sex Hormones and Skeletal Muscle Ageing: The Baltimore Longitudinal Study of Aging
Journal of Cachexia, Sarcopenia and Muscle
ageing
oestrogen
ovarian hormones
skeletal muscle
title Associations Between Female Sex Hormones and Skeletal Muscle Ageing: The Baltimore Longitudinal Study of Aging
title_full Associations Between Female Sex Hormones and Skeletal Muscle Ageing: The Baltimore Longitudinal Study of Aging
title_fullStr Associations Between Female Sex Hormones and Skeletal Muscle Ageing: The Baltimore Longitudinal Study of Aging
title_full_unstemmed Associations Between Female Sex Hormones and Skeletal Muscle Ageing: The Baltimore Longitudinal Study of Aging
title_short Associations Between Female Sex Hormones and Skeletal Muscle Ageing: The Baltimore Longitudinal Study of Aging
title_sort associations between female sex hormones and skeletal muscle ageing the baltimore longitudinal study of aging
topic ageing
oestrogen
ovarian hormones
skeletal muscle
url https://doi.org/10.1002/jcsm.13786
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