Main Article Content
estrogen, cutaneous, cosmeceutical, SERM, phytoestrogen
The process of aging is associated with anticipated cutaneous changes such as epidermal thinning, dehydration, loss of barrier function, and decreased extracellular matrix components. These physiologic changes translate to clinical findings such as atrophy, pigmentary changes, and wrinkling. Over the past century, the role of decreased circulating estrogens in the process of cutaneous aging has been elucidated. Estrogen replacement, both systemic and topical, has been shown to have positive effects on aging skin by promoting fibroblast proliferation and increasing collagen density. However, despite these positive effects on skin health and appearance, estrogens also display a wide-range of actions on various other systems. Even topical estrogen application can result in unwanted systemic effects. Research into alternative substances such as soft estrogens—synthetic, non-hormonal molecules that produce local, cutaneous estrogenic effects and are then metabolized to inactive compounds prior to being absorbed into the systemic circulation— suggests that estrogenic-like benefits on aging skin could be harnessed safely, while avoiding the potential pitfalls associated with estrogen use.
2. Son ED, Lee JY, Lee S, et al. Topical application of 17beta-estradiol increases extracellular matrix protein synthesis by stimulating tgf-Beta signaling in aged human skin in vivo. The Journal of investigative dermatology. 2005;124(6):1149-1161.
3. Shah MG, Maibach HI. Estrogen and skin. An overview. American journal of clinical dermatology. 2001;2(3):143-150.
4. Wilkinson HN, Hardman MJ. The role of estrogen in cutaneous ageing and repair. Maturitas. 2017;103:60-64.
5. Draelos ZD. Topical and oral estrogens revisited for antiaging purposes. Fertility and sterility. 2005;84(2):291-292; discussion 295.
6. Administration UFaD. How did the Federal Food, Drug, and Cosmetic Act come about? 2018; https://www.fda.gov/AboutFDA/Transparency/Basics/ucm214416.htm. Accessed February 9, 2018, 2018.
7. Goldzieher MA. The effects of estrogens on the senile skin. Journal of gerontology. 1946;1:196-201.
8. Eller JJ, Eller WD. Estrogenic ointments; cutaneous effects of topical applications of natural estrogens, with report of 321 biopsies. Archives of dermatology and syphilology. 1949;59(4):449-464.
9. Bullough HF. Epidermal thickness following oestrone injections in the mouse. Nature. 1947;159(4029):101.
10. Dunaif CB, Finerty JC. The effects of estrogen administration upon epidermal proliferation. The Journal of investigative dermatology. 1950;15(5):363-371.
11. Zouboulis CC. The human skin as a hormone target and an endocrine gland. Hormones (Athens, Greece). 2004;3(1):9-26.
12. Toescu EC. Neuroendocrine Theory of Aging. In: Gellman MD, Turner JR, eds. Encyclopedia of Behavioral Medicine. New York, NY: Springer New York; 2013:1311-1315.
13. Saville CR, Hardman MJ. The Role of Estrogen Deficiency in Skin Aging and Wound Healing. In: Farage MA, Miller KW, Fugate Woods N, Maibach HI, eds. Skin, Mucosa and Menopause: Management of Clinical Issues. Berlin, Heidelberg: Springer Berlin Heidelberg; 2015:71-88.
14. Monteleone P, Mascagni G, Giannini A, Genazzani AR, Simoncini T. Symptoms of menopause - global prevalence, physiology and implications. Nature reviews Endocrinology. 2018.
15. Stevenson S, Thornton J. Effect of estrogens on skin aging and the potential role of SERMs. Clinical interventions in aging. 2007;2(3):283-297.
16. Thornton MJ. Estrogens and aging skin. Dermato-endocrinology. 2013;5(2):264-270.
17. Irrera N, Pizzino G, D'Anna R, et al. Dietary Management of Skin Health: The Role of Genistein. Nutrients. 2017;9(6).
18. Brincat M, Moniz CF, Studd JW, Darby AJ, Magos A, Cooper D. Sex hormones and skin collagen content in postmenopausal women. British medical journal (Clinical research ed). 1983;287(6402):1337-1338.
19. Brincat M, Versi E, O'Dowd T, et al. Skin collagen changes in post-menopausal women receiving oestradiol gel. Maturitas. 1987;9(1):1-5.
20. Oikarinen A. Systemic estrogens have no conclusive beneficial effect on human skin connective tissue. Acta obstetricia et gynecologica Scandinavica. 2000;79(4):250-254.
21. Varila E, Rantala I, Oikarinen A, et al. The effect of topical oestradiol on skin collagen of postmenopausal women. British journal of obstetrics and gynaecology. 1995;102(12):985-989.
22. Silva LA, Ferraz Carbonel AA, de Moraes ARB, et al. Collagen concentration on the facial skin of postmenopausal women after topical treatment with estradiol and genistein: a randomized double-blind controlled trial. Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. 2017;33(11):845-848.
23. Maheux R, Naud F, Rioux M, et al. A randomized, double-blind, placebo-controlled study on the effect of conjugated estrogens on skin thickness. American journal of obstetrics and gynecology. 1994;170(2):642-649.
24. Patriarca MT, Goldman KZ, Dos Santos JM, et al. Effects of topical estradiol on the facial skin collagen of postmenopausal women under oral hormone therapy: a pilot study. European journal of obstetrics, gynecology, and reproductive biology. 2007;130(2):202-205.
25. Smith MA, Fine JA, Barnhill RL, Berwick M. Hormonal and reproductive influences and risk of melanoma in women. International journal of epidemiology. 1998;27(5):751-757.
26. Snyder A, Schiechert RA, Zaiac MN. Melasma Associated with Topical Estrogen Cream. The Journal of clinical and aesthetic dermatology. 2017;10(2):57-58.
27. Langer RD, Manson JE, Allison MA. Have we come full circle - or moved forward? The Women's Health Initiative 10 years on. Climacteric : the journal of the International Menopause Society. 2012;15(3):206-212.
28. Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. Jama. 2002;288(3):321-333.
29. Sprague BL, Trentham-Dietz A, Cronin KA. A sustained decline in postmenopausal hormone use: results from the National Health and Nutrition Examination Survey, 1999-2010. Obstetrics and gynecology. 2012;120(3):595-603.
30. Verdier-Sévrain S. Effect of estrogens on skin aging and the potential role of selective estrogen receptor modulators. Climacteric : the journal of the International Menopause Society. 2007;10(4):289-297.
31. Amori P, Lotti J, Lotti T, Vitiello G. Spontaneous retrospective clinical evaluation of a new phytoestrogen-based cosmetic gel cream on postmenopausal women's skin. Journal of biological regulators and homeostatic agents. 2017;31(2 Suppl. 2):147-151.
32. Bennetau-Pelissero C. Risks and benefits of phytoestrogens: where are we now? Current opinion in clinical nutrition and metabolic care. 2016;19(6):477-483.
33. Bodor N, Buchwald P. Soft drug design: general principles and recent applications. Medicinal research reviews. 2000;20(1):58-101.
34. Graffner-Nordberg M, Sjodin K, Tunek A, Hallberg A. Synthesis and enzymatic hydrolysis of esters, constituting simple models of soft drugs. Chemical & pharmaceutical bulletin. 1998;46(4):591-601.
35. Hochberg RB. Estradiol-16α-carboxylic acid esters as locally active estrogens. In: Google Patents; 2002.
36. Hochberg R. 15α-substituted estradiol carboxylic acid esters as locally active estrogens. In: Google Patents; 2006.