{"doi":"10.1002/jcsm.13786","title":"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 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.","journal":"Journal of Cachexia Sarcopenia and Muscle","year":2025,"id":510092,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":23,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9165,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1365380,"name":"Sarah E. Alexander","orcid":"0000-0002-2612-7769","position":1,"is_corresponding":false},{"id":653855,"name":"Danielle Hiam","orcid":"0000-0003-0135-329X","position":2,"is_corresponding":false},{"id":21956,"name":"Luigi Ferrucci","orcid":"0000-0002-6273-1613","position":3,"is_corresponding":false},{"id":465765,"name":"David Scott","orcid":"0000-0001-5226-1972","position":4,"is_corresponding":false},{"id":477672,"name":"Séverine Lamon","orcid":"0000-0002-3271-6551","position":5,"is_corresponding":false},{"id":1365379,"name":"Annabel J. Critchlow","orcid":"0000-0002-2039-9528","position":0,"is_corresponding":true}],"reference_count":43,"raw_metadata":null,"created_at":"2026-07-19T02:47:30.942539Z","pmid":"40296368","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}