# Menopause, Female Sex Hormones, Skeletal Muscle Mass and Muscle Protein Turnover in Humans

**Authors:** Campbell Menzies, Richard Bowtell, Natalie Shur, Matthew S. Brook

PMC · DOI: 10.1002/jcsm.70232 · Journal of Cachexia, Sarcopenia and Muscle · 2026-02-18

## TL;DR

Menopause may contribute to loss of muscle mass and changes in muscle protein turnover in women, potentially increasing the risk of sarcopenia.

## Contribution

This review synthesizes evidence linking menopause with changes in muscle mass and protein turnover in women.

## Key findings

- Lean or muscle mass decreases by 2.5% in perimenopausal and 5.7% in postmenopausal women compared to premenopausal women.
- Muscle protein synthesis responses to stimuli like exercise or protein ingestion may be reduced in older women.
- Estradiol may suppress muscle protein breakdown, suggesting a potential increase in breakdown after menopause.

## Abstract

Sarcopenia describes the loss of muscle mass and function with age. The increase in prevalence of sarcopenia in women appears to coincide with the onset of menopause, which is characterized by large changes to the hormonal milieu such as decreased oestrogen and progesterone concentrations. Although the timing of menopause and sarcopenia may coincide, there is a lack of high‐quality evidence demonstrating a link between the two. This narrative review aims to assess evidence for the effects of menopause on muscle mass and muscle protein turnover. Longitudinal (n = 4/5) and cross‐sectional (n = 7/11) studies demonstrate a reduction in lean or muscle mass across the menopausal transition with −2.5% and −5.7% reductions in perimenopausal and postmenopausal women, respectively, compared to premenopausal women. Most of this evidence (n = 10/11) is taken through assessment of lean body mass via dual‐energy x‐ray absorptiometry (DXA), which may underestimate changes in muscle mass. Assessment on changes to muscle protein turnover is largely limited to short‐term measures of muscle protein synthesis (MPS), which may be elevated in older women versus younger women (n = 3/7) or age‐matched males (n = 4/5). MPS responses to anabolic stimuli, such as resistance exercise (n = 3/4) or protein ingestion (n = 3/6), may be blunted in older women. Evidence assessing muscle protein breakdown (MPB) is lacking; however, evidence from animal and cell models demonstrates the role of estradiol in suppressing MPB, which may contribute to an increase in MPB following menopause. Advancements in understanding the role of the menopausal transition in the regulation of muscle mass, and subsequent effectiveness of interventions such as exercise or exogenous hormone provision will enable healthy ageing and sarcopenia prevention in older women.

## Full-text entities

- **Genes:** PTK2B (protein tyrosine kinase 2 beta) [NCBI Gene 2185] {aka CADTK, CAKB, FADK2, FAK2, PKB, PTK}, FOXO3 (forkhead box O3) [NCBI Gene 2309] {aka AF6q21, FKHRL1, FKHRL1P2, FOXO2, FOXO3A}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, RPS6KB1 (ribosomal protein S6 kinase B1) [NCBI Gene 6198] {aka PS6K, S6K, S6K-beta-1, S6K1, STK14A, p70 S6KA}, MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594] {aka ERK, ERK-2, ERK2, ERT1, MAPK2, NS13}, PIK3R1 (phosphoinositide-3-kinase regulatory subunit 1) [NCBI Gene 5295] {aka AGM7, GRB1, IMD36, p85, p85-ALPHA, p85alpha}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, AFA1 (Alopecia, androgenetic) [NCBI Gene 100188784] {aka MPB}, SULT2A1 (sulfotransferase family 2A member 1) [NCBI Gene 6822] {aka DHEA-ST, DHEA-ST8, DHEAS, HST, ST2, ST2A1}, EIF4EBP1 (eukaryotic translation initiation factor 4E binding protein 1) [NCBI Gene 1978] {aka 4E-BP1, 4EBP1, BP-1, PHAS-I}, FBXO32 (F-box protein 32) [NCBI Gene 114907] {aka Fbx32, MAFbx}, TRIM63 (tripartite motif containing 63) [NCBI Gene 84676] {aka CMH31, IRF, MURF1, MURF2, RNF28, SMRZ}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}
- **Diseases:** Menopause (MESH:D008594), lean (MESH:D013851), hypertrophic (MESH:D002312), muscle loss (MESH:D009135), hypertrophy (MESH:D006984), insulin resistance (MESH:D007333), Arthritis (MESH:D001168), oestrogen deficiency (MESH:D007153), muscle hypertrophy (MESH:C536106), metabolic diseases (MESH:D008659), loss of muscle mass (MESH:C536030), frailty (MESH:D000073496), a loss of independence (MESH:D064129), functional (MESH:D003291), nonalcoholic fatty acid liver disease (MESH:D065626), diabetes (MESH:D003920), atrophy (MESH:D001284), Sarcopenia (MESH:D055948), atrophied muscle mass (MESH:D009133), chronic inflammation (MESH:D007249), MPS (MESH:D019042), mitochondrial dysfunction (MESH:D028361)
- **Chemicals:** glucose (MESH:D005947), dehydroepiandrosterone (MESH:D003687), AA (MESH:D000596), deuterium (MESH:D003903), D3 3-methylhistidine (-), progesterone (MESH:D011374), D2O (MESH:D017666), water (MESH:D014867), testosterone (MESH:D013739), Estradiol (MESH:D004958), androstenedione (MESH:D000735)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Rodentia (rodent, order) [taxon 9989], Homo sapiens (human, species) [taxon 9606], Human immunodeficiency virus 1 (no rank) [taxon 11676]
- **Mutations:** K00414X
- **Cell lines:** C2C12 — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0188)

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## References

121 references — full list in the complete paper: https://tomesphere.com/paper/PMC12916153/full.md

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Source: https://tomesphere.com/paper/PMC12916153