Hormone Replacement Therapy Protects Skeletal Muscle by Stabilizing the Neuromuscular Junction in Post-Menopausal Women

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Introduction: Hormone replacement therapy (HRT) prevents muscle loss associated with menopause; however, the relative role of the neuromuscular junction (NMJ) in post-menopausal women taking HRT is poorly known. We investigate the effects of HRT on plasma C-terminal agrin-fragment-22 (CAF22) in post-menopausal women taking HRT. Methods: We recruited three groups of women, including pre-menopausal (age = 45.3 ± 3.1 years, n = 48) post-menopausal HRT-users (age = 56.7 ± 4.1 years, n = 42) and non-users (age = 55.4 ± 3.9 years, n = 47) for measurements of handgrip strength (HGS), skeletal muscle mass index (SMI), short physical performance battery (SPPB; marker of physical capacity), and plasma CAF22 levels. Results: Post-menopausal non-users of HRT had lower HGS, SMI, gait speed, and SPPB scores and higher plasma CAF22 levels than pre-menopausal women (all p < 0.05). Conversely, HRT users had higher HGS and gait speed and lower plasma CAF22 than non-users among post-menopausal women. HRT users also exhibited SPPB scores similar to those of pre-menopausal women. We observed significant correlations of plasma CAF22 with HGS, gait speed, and total SPPB scores in pre-menopausal and post-menopausal women with HRT (ALL p < 0.05). Lastly, HRT users had lower markers of inflammation and oxidative stress than non-users among post-menopausal women (both p < 0.05). Conclusion: Altogether, menopause was associated with elevated markers of NMJ degradation along with reduced muscle strength and physical capacity. HRT partly reduced NMJ degradation and restored muscle strength and physical capacity in post-menopausal women.