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

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Menopause and the Skin: Old Favorites and New Innovations in Cosmeceuticals for Estrogen-Deficient Skin Edwin D. Lephart . Frederick Naftolin

Received: October 5, 2020 Ó The Author(s) 2020

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 17bestradiol 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.,

E. D. Lephart (&) Department of Physiology, Developmental Biology and The Neuroscience Center, College of Life Sciences, Brigham Young University, Provo, UT, USA e-mail: [email protected] F. Naftolin e-Bio Corp., New York, NY, USA

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 lowdose 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., 40 -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 estrogendeficient 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

Dermatol Ther (Heidelb)

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 recent