Estrogen deficiency – a central paradigm in age-related impaired healing?

Wound healing is a dynamic biological process achieved through four sequential, overlapping phases; hemostasis, inflammation, tissue proliferation and remodeling. For effective wound healing, all four phases must occur in the appropriate order and time frame. It is well accepted that the wound healing process becomes disrupted in the elderly, increasing the propensity of non-healing wound states that can lead to substantial patient morbidity and an enormous financial burden on healthcare systems. Estrogen deprivation in the elderly has been identified as the key driver of age-related delayed wound healing in both genders, with topical and systemic estrogen replacement reversing the detrimental effects of aging on wound repair. Evidence suggests estrogen deprivation may contribute to the development of chronic wound healing states in the elderly but research in this area is somewhat limited, warranting further investigations. Moreover, although the beneficial effects of estrogen on cutaneous healing have been widely explored, the development of estrogen-based treatments to enhance wound repair in the elderly have yet to be widely exploited. This review explores the critical role of estrogen in reversing age-related impaired healing and evaluates the prospect of developing more focused novel therapeutic strategies that enhance wound repair in the elderly via activation of specific estrogen signaling pathways in regenerating tissues, whilst leaving non-target tissues largely unaffected.