New paradigm for old hormones: the case for 17α-estradiol as an acute therapeutic in male volumetric muscle loss
Year: 2026
Type: article
Abstract: Traumatic skeletal muscle injuries, volumetric muscle loss (VML) chief among them, produce deficits disproportionate to the tissue lost, overwhelming the muscle's endogenous regenerative capacity (1, 2).In the muscle that survives the injury, a secondary pathology emerges that includes mitochondrial dysfunction, chronic inflammation, fibrosis, ectopic lipid accumulation, impaired contractile function, denervation, and impaired whole body metabolism (2-7).No pharmacological, bioenergetic, or rehabilitative therapy has been validated to address it.Male and female skeletal muscles respond differently to this injury across metabolic, bioenergetic, contractile, and inflammatory dimensions of repair and recovery (5, 8-10).Whether these differences produce meaningfully different functional outcomes remains unestablished, since the direct comparison literature is thin and confounded in certain injury models.The evidence is consistent on one point.Estrogenic signaling governs the divergence, and removing it in females reproduces the male response pattern (11,12).Whether that same signal is accessible to injured muscle in males has not been asked.
Institutions: University of Georgia, University of Minnesota
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
OpenAlex ID: W7205708486