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    Efficacy Challenges

    Thick to Thin, the Impact of Menopause on Skin

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    Paolo Giacomoni, PhD, Insight Analysis Consulting11.08.18
    Menopause can significantly affect a woman’s health but, whereas the psychological effects of menopause are often unfathomable, the cutaneous ones are well known. In anatomical regions exposed to environmental factors such as the forearm or the face, the effects of aging on skin are unmistakable; we know in particular that the thickness of the dermis gradually decreases and that, at the onset of menopause, the thinning of the dermis is dramatically accelerated. This thinning is the result of the gradual disorganization of the elastic fibers consequent to the damage provoked by the permanent micro-inflammatory status necessary to exert immune-surveillance against foreign bodies or accidentally damaged skin cells. At the onset of menopause, the dermis is no longer able to retain water and a sudden increase of the rate of thinning is observed.

    One can compare the dermis to a mattress: as much as a mattress contains springs and wool, the dermis contains elastic fibers and water-bound ground substance. The elastic fibers consist of collagen, elastin and other proteins. The ground substance consists of polysaccharides that are able to retain water. Water is the main component of the dermis, and provides plumping and resistance to trauma. Taking the skin-mattress analogy further, with time, the springs of a mattress grow distorted and disorganized, the wool ends up unevenly distributed or lost and, if the mattress is subjected to stretch forces, its surface will increase and its thickness will decrease. The same result happens to the skin; with age, the skin gets thinner because it is stretched by gravitational forces while the elastic fibers become disorganized and the water content is decreased.

    Impact on Skin
    The accelerated thinning of the skin after menopause is perhaps the consequence of hormonal imbalance. Indeed, women who undergo ovariectomy have thinner skins whereas women who follow an estrogen therapy have thicker skins.1 In fertile women, the thickness of the skin depends on the level of sex hormones as if it were the consequence of hormone-induced retention of water.2
    When the properties of the skin in pre- and post-menopausal women with or without Hormone Replacement Therapy (HRT) are compared, one observes a steep increase in skin extensibility in untreated peri-menopausal women as if HRT could hinder the age-related loss of resistance to strain-induced deformation and prevent skin slackness.3

    After menopause, additional cutaneous changes have been observed such as xerosis; that is, dry and itchy skin. This is linked to biochemical changes that occur in the differentiation process leading to the building of the stratum corneum. On the one hand, the synthesis of the messenger RNA for filaggrin decreases with age and this provokes a reduction in the level of filaggrin in the stratum corneum. On the other hand the Small Proline Rich Proteins (SPRP) are more abundant in older than in younger skin. Filaggrin is the natural source of the Natural Moisturizing Factor (NMF) and its scarcity contributes to the dry feeling of the skin. SPRP are components of the cornified envelope and their abundance contributes to the stiffness of the stratum corneum. These two concomitant phenomena make the skin to feel dry and itchy.

    Postmenopausal skin is also associated to skin prone to accentuated wrinkles and to loss of radiance, glow and luminosity. Wrinkles are the consequence of skin having lost thickness and having increased its surface; therefore, “hanging down” from its attachment points to the muscles. The loss of glow, radiance and luminosity is also the consequence of the thinning of the skin. As a matter of fact, skin absorbs, reflects and scatters the light impinging on its surface. Melanin and blood absorb light and the surface of the stratum corneum reflects it. The light that is neither absorbed nor reflected by the surface penetrates the dermis and is scattered down to, and back from, the yellow subcutaneous fat tissue. Thinner skin scatters light to a minor extent and allows more photons to reach the yellow adipose tissue. As a consequence, more yellow light will be returned to the outside world and the skin will lose the radiant pink color typical of youth and assume a less appealing yellowish complexion.

    Potential Treatment
    Postmenopausal skin is thin, wrinkled, yellowish, dry and itchy. What cosmetic treatments can tackle these unwanted discomforts? Experimental evidence indicates that dry skin can be topically treated with the components of the NMF, urea, water-retaining polysaccharides or silicone-based moisturizing ointments. Some of these treatments are successful and perhaps ingredients able to increase the threshold of sensitivity to temperature may help reducing the itchy feeling, as can ingredients able to induce the expression of the filaggrin gene.

    To fight wrinkles, one could recall that the topical application of estrogen has been reported to increase the thickness of the skin by 10% and to modify the biophysical characteristics of post-menopausal skin.4,5 Topical estrogen is commonly used to limit the increase in alkalinity of vaginal secretions that modify the local microflora and might favor infections of the urinary tract. It has been observed that estrogen therapy lowers vaginal pH and that HRT normalizes vaginal pH and vaginal micro-flora after menopause. For example, the intra-vaginal administration of estriol in postmenopausal women devoid of vaginal Lactobacillus, resulted in colonization by lactobacilli after one month while the pH decreased from 5.5 to 3.8 and the infections by Enterobacteriaceae were remarkably reduced.6 One can surmise that women discuss with their doctors in depth the problems and the solutions associated with hormonal treatments.

    A point of discussion is perhaps the fact that increasing the thickness of the dermis might help reducing wrinkles as well as the yellowish color of postmenopausal skin. Estrogen, though, has to be used under strict medical control, and its topical use should be thoroughly discussed with one’s own doctor before being even considered.

    References
    1. Tur E. (1997) Physiology of Skin Differences in Men and Women. J. Clin. Dermatol. 15: 5-16
    2. Eisenbeiss C et al (1998) The influence of female sex hormones on skin thickness: evaluation using 20 MHz sonography. Brit. J. Dermatol.139: 462-467
    3. Piérard GE, et al (1995) Effect of hormonereplacement therapy for menopause on the mechanical properties of skin. J Am Geriatr Soc. 43:662-665.
    4. Creidi P, et al (1994) Effect of a conjugated estrogen (Premarin) cream on the facial skin. A comparative study with a placebo cream. Maturitas 19:211-223
    5. Guinot C, et al. (2005) Effect of hormonal replacement therapy on skin biophysical properties of menopausal women. Skin Res Technol. 11:201–204.
    6. Farage M.A., et al (2015) The Vaginal Microbiota in Menopause. In: Farage M., Miller K., Maibach H. (eds) Textbook of Aging Skin. Springer, Berlin, Heidelberg
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