Progesterone and diabetic wound repair: an evidence-gap review of indirect preclinical findings

The case for natural progesterone in diabetic wound repair rests on indirect preclinical findings, not demonstrated wound-healing efficacy. This evidence-gap review separates natural progesterone, its neuroactive metabolites and synthetic progestins, and distinguishes ligand interventions from studies of similarly named targets. Structured searches on 29 August 2026 and a targeted check on 30 September 2026 identified no natural-progesterone intervention measuring healing efficacy in a diabetic cutaneous wound. Diabetic-neuropathy experiments report selected neural improvements, but nerve conduction or intraepidermal fibre density does not establish functional re-epithelialisation, glycaemia-independent benefit or recovery of protective sensation at a wound. Findings in non-diabetic skin and other tissues are heterogeneous. Murine dorsal wounds also differ from human diabetic foot ulcers in contraction, loading, chronicity and vascular disease. A proposed neural mechanism must therefore be tested against epithelial and barrier outcomes, adequate perfusion and matched glycaemic exposure. Opposing metabolic and endothelial findings, together with compound- and route-specific safety concerns, preclude a general prediction of benefit. The review provides an auditable evidence map and falsifiable experimental priorities; it does not support clinical progesterone supplementation for diabetes-related foot ulcers.