The role of estrogen defi ciency in skin aging and wound healing

Abstract

The neuroendocrine theory of aging, first proposed over 50 years ago, states that naturally occurring changes in hormone levels drive organismal aging and subsequent age-associated pathology. In practice, changes in the endocrine hormone estrogen have been widely linked to age-associated changes in numerous tissues. The skin is particularly important in this respect as macromolecular structural changes are both immediately visible and functionally important. Estrogen deficiency following menopause (or in advanced male aging) negatively influences multiple skin cell types, including keratinocytes, fibroblasts, immune cells and melanocytes. Physiologically, a lack of estrogen accelerates age-associated atrophic skin changes. Skin becomes wrinkled due to reduced dermal matrix and altered elastic fibre structure, changes to sebaceous glands increase dryness, while vascularity is reduced. Crucially, cutaneous estrogen deficiency following menopause both increases susceptibility to damage and hinders the ability of damaged skin to repair. Extensive studies in rodent models have revealed the complexity of estrogen signalling and identified estrogen receptor-specific functions. Selective estrogen receptor modulators now hold great therapeutic promise for the treatment of skin aging and promotion of skin repair.