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with a decrease in epithelial gap, dermal gap, and granulation tissue area and thickness compared to the placebo group (p=0.002, p=0.039, p=0.012, respectively). Gene set analysis showed POD14 wounds exposed to T had upregulation of genes related to extracellular matrix degradation. Gene ontology analysis showed T was associated with an upregulation of genetic pathways associated with lymph vessel development and angiogenesis throughout the wound bed. In the mouse, comparison of POD5 wounds showed T injections led to 24.9% and 24.7% increase in mean wound size relative to sham and ovariectomy controls (p=0.004; p=0.001). Spatial transcriptomics demonstrated opposing T effects spatially: pathways such as epithelial-mesenchymal transition and angiogenesis were highly upregulated in granulation tissue but downregulated in neo-epidermis. CONCLUSIONS:Testosterone impairs wound healing in a preclinical model, potentially via altering the homeostatic balance of re-epithelialization and granulation. This was largely reversed by androgen receptor blockade. Future studies will characterize the molecular mechanisms driving these effects.

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