Menopause and the Skin: Old Favorites and New Innovations in Cosmeceuticals for Estrogen-Deficient Skin

Abstract

Estrogen is a pivotal signaling molecule; its production is regulated by the expression of the aromatase (CYP19A1) gene from ovarian and peripheral tissue sites, and it is transmitted via estrogen receptors to influence many important biological functions. However, the narrative for this overview focuses on the decline of 17β-estradiol levels from ovarian sites after menopause. This estrogen-deficient condition is associated with a dramatic reduction in skin health and wellness by negatively impacting dermal cellular and homeostatic mechanisms, as well as other important biological functions. The changes include loss of collagen, elastin, fibroblast function, vascularity, and increased matrix metalloproteinase(s) enzymatic activities, resulting in cellular and extracellular degradation that leads to dryness, wrinkles, atrophy, impaired wound healing/barrier function, decreased antioxidant capacity [i.e., defense against reactive oxygen species (ROS) and oxidative stress], decreased attractiveness and psychological health, and increased perception of aging. While topical estrogen may reverse these changes, the effects of today’s low-dose systemic hormone treatments are not well established, raising the need for more concentrated local administration of hormones or newer cosmeceutical agents such as selective estrogen receptor modulators (SERMs), including phytoestrogens that have become major active ingredients for skin care products, especially when addressing estrogen-deficient skin. Two example compounds are presented, an analog of resveratrol (i.e., 4′-acetoxy resveratrol) and the isoflavonoid equol, both of which are involved in a variety of biochemical/molecular actions and mechanisms, as demonstrated via in vitro and clinical studies that enhance human dermal health, especially in estrogen-deficient skin.

Plain Language Summary

Estradiol levels decline to near zero after menopause. Estrogen deficiency adversely affects many physiological functions, including skin changes such as atrophy, wrinkles, hydration, poor wound healing/barrier function, decline in perceived facial attractiveness, and even psychological health. Women with menopausal skin changes seek cosmetic and medical treatments that enhance their self-perception and inhibit skin aging, particularly in exposed areas (face, neck, and hands). It is widely accepted that traditional treatments such as local hormone treatment are effective in reversing (estrogen-deficient) aging skin deterioration. But, the uncertainly of the effects of long-term systemic menopausal treatment and, more recently, aversion to systemic hormones has led to newer therapeutic agents that can send estrogen’s important skin-health signals via selective estrogen receptor modulators (SERMs) other than estrogen itself. Many plant-derived compounds (phytoestrogens) that contain estrogen-agonist SERMs now play major roles in treatments for aging and estrogen-deficient skin. The targets are the estrogen receptor beta molecules that are abundant in skin (keratinocytes/fibroblasts). The variation in effect and the influence of coexisting influences such as environmental exposure, race, and aging are reviewed. While several botanicals are mentioned in this overview, two promising cosmeceuticals are examined, an analog of resveratrol [4′-acetoxy resveratrol (4AR)], which enjoys a high public profile in the health arena, and the isoflavonoid compound equol. Both 4AR and equol are SERMs that have peer-reviewed in vitro and clinical study results supporting improvement of estrogen-deficient menopausal skin.