Estrogen Fights Skin Aging

Estrogen therapy has been shown to reduce the effects of intrinsic (natural) aging and photoaging (caused by sun exposure) of the skin. Many women notice that their skin starts to change in their early thirties, but most of this is from photoaging. Intrinsic skin aging is taking place, but the visible manifestations have not yet become apparent on areas not exposed to the sun. The perimenopause is the next stage at which women commonly notice changes in their skin. Many women come in to my office and say that they have noted a dramatic change in their skin around the same time they start to get hot flushes.

This is not a surprise, as the skin has abundant receptors for estrogens. Activation of these receptors is important for maintaining skin thickness, elasticity, hydration, and vascularization, all of which contribute to healthy-looking skin. In postmenopausal women, collagen content in a relatively sun protected area such as the thigh has been shown to drop at a rate of two percent per year for the next 15 years.¹ This has an effect on the rate and quality of wound healing. Mirroring the drop in skin collagen is the decrease in bone density (bone is comprised predominantly of collagen type I) as assessed by DEXA scanning. ^2,3 A sub-study of NHANES I, asked the question, ‘Does Estrogen Prevent Skin Aging?’ and answered it by saying, “These results strongly suggest that estrogen use prevents dry skin and skin wrinkling.” ⁴ Various regimens of systemic estrogen replacement therapy have definitively demonstrated beneficial effects on the health of women’s skin.

Systemic delivery (through the bloodstream) of estrogens has been shown in a number of studies to retard and reverse some of the deleterious skin changes caused by declining estrogen levels. In an early randomized, placebo-controlled trial of 12 months of oral Premarin in 60 postmenopausal nuns, Maheux et al found a significant increase in skin thickness of the thigh. ⁵ The content of collagen as assessed by biopsy of the skin in women over age forty was found to decrease in a study by Castel-Branco. In a subgroup of this study, a significant increase in collagen was found in women who received HRT (Hormone Replacement Therapy).

These changes in skin with declining estrogen levels are manifested in changes in the mechanical properties of the skin. There is an increase in the extensibility of the skin, i.e., a decrease in firmness, while at the same time there is a decrease in the elasticity of skin. Pierard found that these changes were less profound in women on HRT. ⁶

In a study of 76 postmenopausal Japanese women, Sumino found a decline in skin elasticity that was correlated not only with with age but also with years since menopause. ⁷ The decline was similar to many other biomarkers of aging at -0.55% per year. When a subgroup of these women were treated with systemic estrogen replacement therapy for 12 months, their skin elasticity improved 5.2%.

Topical therapy with estrogens and phytoestrogens has been shown to benefit not only the elastic properties of skin but also wrinkle formation and pore size in sun-exposed facial skin. Jolanta Schmidt and colleagues published a study in 1996 in which 58 peri- or postmenopausal women between the ages of 41 and 67 applied either estriol or estradiol cream to their faces for 6 months.⁸ The concentrations were low enough that the effect was only local and did not significantly increase blood levels of any hormones. While the study did not look at the mechanical properties of the skin, it did measure wrinkle size and collagen content of skin biopsies. The treatment raised collagen III content, which was the likely cause of the reduction in wrinkles that was detected by a computerized measurement system. The patients were also asked to assess the subjective effect on their skin. Virtually 100% noted improvement in the color, elasticity, firmness, and moisture of their skin, and over 80% noted a reduction in wrinkle depth and pore size. The estriol and estradiol treatments had virtually the same effects. Even Premarin, which is not a bioidentical hormone like estradiol and estriol, was found to have a similar effect in reducing wrinkles and increasing skin thickness when applied as a facial cream. ⁹

As a result of these studies, we have been treating peri- and postmenopausal women with estriol and estradiol facial cream in addition to their systemic transdermal bioidentical hormone replacement therapy. Many patients have been using these creams for years, long before we were able to use the Cutometer to measure skin elasticity. When we compare facial skin elasticity in these patients with that of patients who have been using systemic therapy alone, we find significantly increased elasticity in patients on estrogen facial cream.

It appears that the general structure of an estrogen-like molecule confers this benefit, as a number of estrogens have proven to be effective (estriol, estradiol and Premarin). This observation led some researchers to see if the phytoestrogen genistein has the potential to treat the signs of skin aging. As you can see below, genistein and estradiol have very similar structures.

In a study by Kang et al, genistein was found to reduce the effects of UV irradiation of skin by interfering with the pathological signaling pathways rather than acting as a sunscreen. ¹⁰ This has the potential benefit of protecting the skin from sun damage while allowing for vitamin D production. It appears that all estrogen-like molecules work to reverse the effects of both intrinsic aging and photoaging in the skin by functioning as both antioxidants and signaling molecules. They increase the activity of transforming growth factor beta (TGF-beta), which increases the production of collagen, while reducing the concentration of reactive oxygen species (ROS). Reactive oxygen species increase the signaling pathways that inhibit collagen production and also increase matrix metalloproteinase (MMP) activity, resulting in a net decrease in collagen content.

Thus, it appears that a substantial and growing body of evidence substantiates the claim that systemic and topical estrogen/phytoestrogen therapy can reduce the effects of intrinsic aging and photoaging of the skin.

Joseph M. Raffaele, MD

REFERENCES

1. Brincat M, Versi E, Moniz CF, Magos A, de Trafford J, Studd JW. Skin collagen changes in postmenopausal women receiving different regimens of estrogen therapy. Obstet Gynecol 1987;70(1):123-7.

2. Brincat M, Moniz CF, Kabalan S, et al. Decline in skin collagen content and metacarpal index after the menopause and its prevention with sex hormone replacement. Br J Obstet Gynaecol 1987;94(2):126-9.

3. Pierard GE, Pierard-Franchimont C, Vanderplaetsen S, Franchimont N, Gaspard U, Malaise M. Relationship between bone mass density and tensile strength of the skin in women. Eur J Clin Invest 2001;31(8):731-5.

4. Dunn LB, Damesyn M, Moore AA, Reuben DB, Greendale GA. Does estrogen prevent skin aging? Results from the First National Health and Nutrition Examination Survey (NHANES I) [see comments]. Arch Dermatol 1997;133(3):339-42.

5. Maheux R, Naud F, Rioux M, et al. A randomized, double-blind, placebo-controlled study on the effect of. Am J Obstet Gynecol 1994;170(2):642-9.

6. Pierard GE, Letawe C, Dowlati A, Pierard-Franchimont C. Effect of hormone replacement therapy for menopause on the mechanical properties of skin. J Am Geriatr Soc 1995;43(6):662-5.

7. 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(6):945-9.

8. Schmidt JB, Binder M, Demschik G, Bieglmayer C, Reiner A. Treatment of skin aging with topical estrogens. Int J Dermatol 1996;35(9):669-74.

9. Creidi P, Faivre B, Agache P, Richard E, Haudiquet V, Sauvanet JP. Effect of a conjugated oestrogen (Premarin) cream on ageing facial. Maturitas 1994;19(3):211-23.

10. Kang S, Chung JH, Lee JH, et al. Topical N-acetyl cysteine and genistein prevent ultraviolet-light-induced signaling that leads to photoaging in human skin in vivo. J Invest Dermatol 2003;120(5):835-41.