Biology of estrogens in skin: implications for skin aging.

Estrogens have a profound influence on skin. The relative hypoestrogenism that accompanies menopause exacerbates the deleterious effects of both intrinsic and environmental aging. Estrogens clearly have a key role in skin aging homeostasis as evidenced by the accelerated decline in skin appearance seen in the perimenopausal years. Estrogens improve skin in many ways. Among these, they increase collagen content and skin thickness and improve skin moisture. However, despite the knowledge that estrogens have such important effects on skin, the cellular and subcellular sites and mechanisms of estrogen action are still poorly understood. Estrogen receptors (ERs) have been detected in skin, and recent studies suggest that estrogens exert their effect in skin through the same molecular pathways used in other non-reproductive tissues. Although systemic hormone replacement therapy (HRT) has been used for many years, recent trials have reported a significant increased risk of breast cancer and other pathologies with this treatment. This has led to reconsider the risks and benefits of HRT. For this reason, systemic HRT cannot be recommended today to treat skin aging. Currently, intensive research is conducted to develop new drugs called selective ER modulators (SERMs). These drugs exert mixed estrogenic and antiestrogenic effects depending on the tissue and cell type. One might expect in the future such a drug targeting specifically the skin without systemic side effects.