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.

Keywords: 4′-Acetoxy resveratrol; Aging; Cosmeceuticals; Equol; Estrogen; Estrogen deficient skin; Hormone therapy; Menopause; Polyphenols; Skin.

Fig. 1

Approximate production of estrogens (profile) in women with age. Estrogen levels peak in the late 20s. Estrogen levels during perimenopause fluctuate greatly around a normal range until menopause, when no more responsive follicles are available. In the USA, most women experience menopause from 40 to 58 years of age, with the average at 51 years of age (see red rectangular bar above the x-axis). In postmenopausal women, all the estrogen production is derived from peripheral tissues, primarily from adipose tissue [15]. Estrogen levels (17β-estradiol and estrone) in the reproductive interval (i.e., approximately 12–40 years of age) and changes in these levels during the perimenopause and postmenopausal intervals have been reported in detail elsewhere [17]

Fig. 2

Hormone effects on skin vary by race. A total of 116 subjects were assessed (CEE n = 38; E2 n = 34; Placebo n = 44; White n = 77; Black n = 21; Other n = 16) the average age at menopause was 53.2 ± 2.8 years, the average time since menopause was 1.6 ± 1.1 years and the average BMI (kg/m²) was 26.0 ± 4.1. Reproduced with permission from [65]. a Mean total wrinkle score by treatment and by race over 4 years of follow-up. Racial groups (white and black) stratified by treatment group are indicated by gray and black lines, respectively. Total wrinkle score was not significantly different among treatment groups at any time point (P = 0.24). Black women, compared with White women, had the lowest total wrinkle scores across all 4 years (P = 0.002). b Men total rigidity score by treatment and by race over 4 years of follow-up. Racial groups (White and Black) stratified by treatment group indicated by gray and black lines, respectively. Total rigidity did not vary significantly among treatment groups at any time point (P = 0.87). Black women, compared with White women, had significantly decreased total facial rigidity after 4 years of follow-up (P = 0.002)