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Topical and oral estrogens revisited for antiaging purposes
Topical and oral estrogens revisited for antiaging purposes Zoe Diana Draelos, M.D. Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, North Carolina
Topical and oral estrogens are beneficial in maintaining skin firmness and elasticity in postmenopausal women. The positive cutaneous effects of estrogen were overlooked in the Women’s Health Initiative trial. (Fertil Steril威 2005;84:291–2. ©2005 by American Society for Reproductive Medicine.)
Since the beginning of time, man has searched for topicals and ingestables that promise to deliver the magic of youth. One easily accessible antiaging therapy is the application or consumption of hormones whose endogenous production decreases with advancing age. It is interesting to note that hormone creams have a rich history in cosmetic dermatology. At the time the Cosmetics and Toiletries Act was penned in the 1930s, hormone creams were the most popular cosmeceutical facial moisturizers. Both estrogen and P creams were on the market and available for over-thecounter purchase. The introduction of legislation defining cosmetics as products that do not alter the structure or function of the skin reclassified hormone creams as drugs and they were removed from the consumer market. However, the past 70 years have brought an increased understanding of skin physiology and the recognition that even water can alter the structure and function of the skin. This has created a renewed interest in cosmeceuticals, especially in the realm of hormone therapy. There is no doubt that hormone therapy is effective for improving the appearance of aging skin, as supported by the article published in this issue by Wolff et al. (1). Not only do estrogens improve skin rigidity and decrease wrinkling, but they also increase skin thickness as measured by ultrasound (2), increase skin sebum production as measured by a Sebumeter (3), increase skin elasticity as measured by skin deformability using a suction device (4), increase skin hydration as measured by corneometry (5), and skin collagen content as measured by skin biopsy (6). Many methods of assessing skin function point to oral or transdermal estrogen as a valuable replacement hormone. A variety of studies have also examined estrogen delivery topically. Estrogen is readily soluble in a creamy vehicle and easily penetrates the stratum corneum due to its small molecular size. It is the ideal cosmeceutical for topical application. Topical estrogen has been shown to increase the production of type III collagen and the overall collagen fiber
Received January 22, 2005; revised and accepted March 21, 2005. Reprint requests: Zoe Diana Draelos, M.D., 2444 North Main Street, High Point, North Carolina 27262 (FAX: 336-841-2044; E-mail: zdraelos@ northstate.net).
0015-0282/05/$30.00 doi:10.1016/j.fertnstert.2005.03.033
count after 6 months of application (7). It also increased the acid mucopolysaccharide and hyaluronic acid levels in the skin, which are important for maintaining skin hydration and barrier function (8). The combination of increased dermal volume, due to more collagen fibers, and increased dermal hydration, due to more hyaluronic acid, may explain the decreased wrinkling apparent in women using estrogens. It is important to note that there is currently no other substance available to the cosmetic formulator that delivers such documentable reproducible results in women. The legal restrictions on the use of estrogen over-thecounter has led to an interest in phytoestrogens, especially those derived from soy. Phytoestrogens, such as genistein, daidzein, and glycitein, are found in fermented soy and can be consumed in the form of roasted soy nuts or tofu. Soy protein supplements have been investigated for their benefit in a variety of postmenopausal symptoms, but the data are somewhat inconsistent. One controlled study by Kotsopoulos et al. (9) found that a soy protein supplement had no statistically significant effect over placebo on dry skin. Yet, genestein is one of the most popular botanical additives to skin care products promising to decrease the appearance of fine lines on the face. It can be difficult, however, to determine whether the decreased wrinkling advertised by the manufacturer is due to the vehicle moisturizer decreasing lines of dehydration and altering light reflection from the skin surface or true changes in skin collagen production and decreased wrinkling due to increased dermal thickness. In the current regulatory climate, no cosmetic manufacturer wants to determine the answer to this question. Moisturizing the skin and changing optical characteristics is the realm of cosmetics, but enhancing collagen production is the realm of a drug. Any soy product that documented increased collagen production would certainly be removed from the market by the Food and Drug Administration. It is for this reason that research is lacking in the topical application of phytoestrogens. The question then remains as to why topical estrogen creams and estrogen replacement therapy are so controversial when the skin benefits have been well documented. In the literature there have been some concerns that estrogens
Fertility and Sterility姞 Vol. 84, No. 2, August 2005 Copyright ©2005 American Society for Reproductive Medicine, Published by Elsevier Inc.
291
predispose women to malignant melanoma, although the reports are contradictory. A study by Smith et al. (10) demonstrated no link between melanoma and oral contraceptives or replacement estrogens. Topical estrogens are even more controversial, as they are theoretically linked to breast cancer and cancer of other female organs. No company wants to market a topical product with such tremendous opportunity for lawsuits, as cause and effect are hard to demonstrate or negate. Topical estrogens are also associated with facial telangiectasias, which is undesirable. One area of estrogen benefit for skin appearance is rarely discussed in the literature. This is the decrease in facial bone mass. Many articles allude to the benefit of oral estrogens in bone mineral density, but few have studied the mineralization of the facial bones (11). Much of the wrinkling experienced with advancing age is not due to skin effects, but due to loss of the underlying subcutaneous tissue and bony architecture. Loss of facial bone structure also contributes to wrinkling, which may be improved through oral estrogen supplementation. In summary, I believe that the Women’s Health Initiative trial effectively identified cardiovascular risks associated with oral estrogen replacement therapy. However, the risk vs. benefits of any medication, whether topical or oral, must be globally assessed. Is the depression experienced by a woman who is disconcerted with her facial appearance outweighed by the possible decrease in cardiovascular events? Would a woman who had fewer wrinkles and decreased skin rigidity exercise more frequently to offset any increase in cardiovascular events induced by estrogen supplementation? These questions cannot be answered in a double blind placebocontrolled study, as they involve the individual personalities of the women. Perhaps the reports from the Women’s Health Initiative trial that encouraged women to stop oral estrogen replacement therapy should be appended to indicate that estrogens produce certain well-documented benefits, includ-
292
Draelos
Estrogen and aging
ing decreased skin wrinkling and rigidity. Until topical estrogen cosmeceuticals become available, which is not in the foreseeable future, oral estrogen supplementation is the only way to achieve improvements in skin functioning and appearance. No expensive jar of boutique cream or specialty vitamins can deliver the skin benefits of estrogen. REFERENCES 1. Wolff EF, Narayan D, Taylor HS. Long-term effects of hormone therapy on skin rigidity and wrinkles. Fertil Steril 2005;84:285– 8. 2. Chotnopparatpattara P, Panyakhamlerd K, Taechakraichana N, Tantivatana J, Chaikittisilpa S, Limpaphayom KK. An effect of hormone replacement therapy on skin thickness in early postmenopausal women. J Med Assoc Thai 2001;84:1275– 80. 3. Callens A, Vaillant L, Lecomte P, Berson M, Gall Y, Loreete G. Does hormonal skin aging exist? A study of the influence of different hormone therapy regimens on the skin of postmenopausal women using non-invasive measurement techniques. Dermatology 1996;193:289 –94. 4. Sumino H, Ichikawa S, Abe M, Endo Y, Ishikawa O, Kurabayashi M. Effects of aging, menopause, and hormone replacement therapy on forearm skin elasticity in women. J Am Geriatr Soc 2004;52:945–9. 5. Pierard-Franchimont C, Letawe C, Goffin V, Pierard GE. Skin water holding capacity and transdermal therapy for menopause: a pilot study. Maturitas 1995;22:151– 4. 6. Sauerbronn AV, Fonseca AM, Bagnoli VR, Saldiva PH, Pinotti JA. The effects of systemic hormonal replacement therapy on the skin of postmenopausal women. Int J Gynaecol Obstet 2000;68:35– 41. 7. Schmidt JB, Binder M, Demschik G, Bieglmayer C, Reiner A. Treatment of aging skin with topical estrogens. Int J Dermatol 1996;35: 669 –74. 8. Shah MG, Maibach HI. Estrogen and skin. An overview. Am J Clin Dermatol 2001;2:143–50. 9. Kotsopoulos D, Dalais FS, Liang YL, McGrath BP, Teede HJ. The effects of soy protein containing phytoestrogens on menopausal symptoms in postmenopausal women. Climacteric 2000;3:161–7. 10. Smith MA, Fine JA, Barnhill RL, Berwick M. Hormonal and reproductive influences and risk of melanoma in women. Int J Epidemiol 1998;27:751–7. 11. Sumino H, Ichikawa S, Abe M, Endo Y, Hakajima Y, Minegishi T, et al. Effects of aging and postmenopausal hypoestrogenism on skin elasticity and bone mineral density in Japanese women. Endocrinol J 2004;51:159 – 64.
Vol. 84, No. 2, August 2005
Topical and oral estrogens are beneficial in maintaining skin firmness and elasticity in postmenopausal women. The positive cutaneous effects of estrogen were overlooked in the Women’s Health Initiative trial. (Fertil Steril威 2005;84:291–2. ©2005 by American Society for Reproductive Medicine.)
Since the beginning of time, man has searched for topicals and ingestables that promise to deliver the magic of youth. One easily accessible antiaging therapy is the application or consumption of hormones whose endogenous production decreases with advancing age. It is interesting to note that hormone creams have a rich history in cosmetic dermatology. At the time the Cosmetics and Toiletries Act was penned in the 1930s, hormone creams were the most popular cosmeceutical facial moisturizers. Both estrogen and P creams were on the market and available for over-thecounter purchase. The introduction of legislation defining cosmetics as products that do not alter the structure or function of the skin reclassified hormone creams as drugs and they were removed from the consumer market. However, the past 70 years have brought an increased understanding of skin physiology and the recognition that even water can alter the structure and function of the skin. This has created a renewed interest in cosmeceuticals, especially in the realm of hormone therapy. There is no doubt that hormone therapy is effective for improving the appearance of aging skin, as supported by the article published in this issue by Wolff et al. (1). Not only do estrogens improve skin rigidity and decrease wrinkling, but they also increase skin thickness as measured by ultrasound (2), increase skin sebum production as measured by a Sebumeter (3), increase skin elasticity as measured by skin deformability using a suction device (4), increase skin hydration as measured by corneometry (5), and skin collagen content as measured by skin biopsy (6). Many methods of assessing skin function point to oral or transdermal estrogen as a valuable replacement hormone. A variety of studies have also examined estrogen delivery topically. Estrogen is readily soluble in a creamy vehicle and easily penetrates the stratum corneum due to its small molecular size. It is the ideal cosmeceutical for topical application. Topical estrogen has been shown to increase the production of type III collagen and the overall collagen fiber
Received January 22, 2005; revised and accepted March 21, 2005. Reprint requests: Zoe Diana Draelos, M.D., 2444 North Main Street, High Point, North Carolina 27262 (FAX: 336-841-2044; E-mail: zdraelos@ northstate.net).
0015-0282/05/$30.00 doi:10.1016/j.fertnstert.2005.03.033
count after 6 months of application (7). It also increased the acid mucopolysaccharide and hyaluronic acid levels in the skin, which are important for maintaining skin hydration and barrier function (8). The combination of increased dermal volume, due to more collagen fibers, and increased dermal hydration, due to more hyaluronic acid, may explain the decreased wrinkling apparent in women using estrogens. It is important to note that there is currently no other substance available to the cosmetic formulator that delivers such documentable reproducible results in women. The legal restrictions on the use of estrogen over-thecounter has led to an interest in phytoestrogens, especially those derived from soy. Phytoestrogens, such as genistein, daidzein, and glycitein, are found in fermented soy and can be consumed in the form of roasted soy nuts or tofu. Soy protein supplements have been investigated for their benefit in a variety of postmenopausal symptoms, but the data are somewhat inconsistent. One controlled study by Kotsopoulos et al. (9) found that a soy protein supplement had no statistically significant effect over placebo on dry skin. Yet, genestein is one of the most popular botanical additives to skin care products promising to decrease the appearance of fine lines on the face. It can be difficult, however, to determine whether the decreased wrinkling advertised by the manufacturer is due to the vehicle moisturizer decreasing lines of dehydration and altering light reflection from the skin surface or true changes in skin collagen production and decreased wrinkling due to increased dermal thickness. In the current regulatory climate, no cosmetic manufacturer wants to determine the answer to this question. Moisturizing the skin and changing optical characteristics is the realm of cosmetics, but enhancing collagen production is the realm of a drug. Any soy product that documented increased collagen production would certainly be removed from the market by the Food and Drug Administration. It is for this reason that research is lacking in the topical application of phytoestrogens. The question then remains as to why topical estrogen creams and estrogen replacement therapy are so controversial when the skin benefits have been well documented. In the literature there have been some concerns that estrogens
Fertility and Sterility姞 Vol. 84, No. 2, August 2005 Copyright ©2005 American Society for Reproductive Medicine, Published by Elsevier Inc.
291
predispose women to malignant melanoma, although the reports are contradictory. A study by Smith et al. (10) demonstrated no link between melanoma and oral contraceptives or replacement estrogens. Topical estrogens are even more controversial, as they are theoretically linked to breast cancer and cancer of other female organs. No company wants to market a topical product with such tremendous opportunity for lawsuits, as cause and effect are hard to demonstrate or negate. Topical estrogens are also associated with facial telangiectasias, which is undesirable. One area of estrogen benefit for skin appearance is rarely discussed in the literature. This is the decrease in facial bone mass. Many articles allude to the benefit of oral estrogens in bone mineral density, but few have studied the mineralization of the facial bones (11). Much of the wrinkling experienced with advancing age is not due to skin effects, but due to loss of the underlying subcutaneous tissue and bony architecture. Loss of facial bone structure also contributes to wrinkling, which may be improved through oral estrogen supplementation. In summary, I believe that the Women’s Health Initiative trial effectively identified cardiovascular risks associated with oral estrogen replacement therapy. However, the risk vs. benefits of any medication, whether topical or oral, must be globally assessed. Is the depression experienced by a woman who is disconcerted with her facial appearance outweighed by the possible decrease in cardiovascular events? Would a woman who had fewer wrinkles and decreased skin rigidity exercise more frequently to offset any increase in cardiovascular events induced by estrogen supplementation? These questions cannot be answered in a double blind placebocontrolled study, as they involve the individual personalities of the women. Perhaps the reports from the Women’s Health Initiative trial that encouraged women to stop oral estrogen replacement therapy should be appended to indicate that estrogens produce certain well-documented benefits, includ-
292
Draelos
Estrogen and aging
ing decreased skin wrinkling and rigidity. Until topical estrogen cosmeceuticals become available, which is not in the foreseeable future, oral estrogen supplementation is the only way to achieve improvements in skin functioning and appearance. No expensive jar of boutique cream or specialty vitamins can deliver the skin benefits of estrogen. REFERENCES 1. Wolff EF, Narayan D, Taylor HS. Long-term effects of hormone therapy on skin rigidity and wrinkles. Fertil Steril 2005;84:285– 8. 2. Chotnopparatpattara P, Panyakhamlerd K, Taechakraichana N, Tantivatana J, Chaikittisilpa S, Limpaphayom KK. An effect of hormone replacement therapy on skin thickness in early postmenopausal women. J Med Assoc Thai 2001;84:1275– 80. 3. Callens A, Vaillant L, Lecomte P, Berson M, Gall Y, Loreete G. Does hormonal skin aging exist? A study of the influence of different hormone therapy regimens on the skin of postmenopausal women using non-invasive measurement techniques. Dermatology 1996;193:289 –94. 4. Sumino H, Ichikawa S, Abe M, Endo Y, Ishikawa O, Kurabayashi M. Effects of aging, menopause, and hormone replacement therapy on forearm skin elasticity in women. J Am Geriatr Soc 2004;52:945–9. 5. Pierard-Franchimont C, Letawe C, Goffin V, Pierard GE. Skin water holding capacity and transdermal therapy for menopause: a pilot study. Maturitas 1995;22:151– 4. 6. Sauerbronn AV, Fonseca AM, Bagnoli VR, Saldiva PH, Pinotti JA. The effects of systemic hormonal replacement therapy on the skin of postmenopausal women. Int J Gynaecol Obstet 2000;68:35– 41. 7. Schmidt JB, Binder M, Demschik G, Bieglmayer C, Reiner A. Treatment of aging skin with topical estrogens. Int J Dermatol 1996;35: 669 –74. 8. Shah MG, Maibach HI. Estrogen and skin. An overview. Am J Clin Dermatol 2001;2:143–50. 9. Kotsopoulos D, Dalais FS, Liang YL, McGrath BP, Teede HJ. The effects of soy protein containing phytoestrogens on menopausal symptoms in postmenopausal women. Climacteric 2000;3:161–7. 10. Smith MA, Fine JA, Barnhill RL, Berwick M. Hormonal and reproductive influences and risk of melanoma in women. Int J Epidemiol 1998;27:751–7. 11. Sumino H, Ichikawa S, Abe M, Endo Y, Hakajima Y, Minegishi T, et al. Effects of aging and postmenopausal hypoestrogenism on skin elasticity and bone mineral density in Japanese women. Endocrinol J 2004;51:159 – 64.
Vol. 84, No. 2, August 2005