Topical estrogen won’t fix saggy menopausal skin

Though Dr. Jen Gunter claims that topical estrogens are “woefully studied” in her substack article “The Menopause Estrogen Face Cream Epidemic”, https://vajenda.substack.com/p/the-menopause-estrogen-face-cream, this is actually not the case. The Rzepecki et al review identified 23 peer reviewed paper of just synthetic and semi-synthetic topical estrogens (Rzepecki AK, Murase JE, Juran R, Fabi SG, McLellan BN. Estrogen-deficient skin: The role of topical therapy. Int J Womens Dermatol. 2019 Mar 15;5(2):85-90. doi: 10.1016/j.ijwd.2019.01.001. PMID: 30997378; PMCID: PMC6451761.)  And unlike the case with growth factors – where all of the clinical studies were done by people with strong financial interests in their commercial success (see https://www.youtube.com/watch?v=CvZ8DCgnMxY), the studies done with topical estrogens have been done by bona fide researchers without conflicts of interest.  This may be the most comprehensive set of data for any topical modality with the possible exception of Retin-A, for which there are many clearly biased studies.

The marketers of estrogen creams for facial aging did not go through the long and expensive process of getting a special formulation of estrogen approved for use on the face. They just took the two topical formulations that were already approved – the .01% estradiol and the .3% estriol – and repackaged them for the face. The problem with this is that the original application of topical estrogen were for vaginal atrophy.  And the skin of the vagina is very different from facial skin. In places, the vagina skin is more like the skin of the lips or the mouth than normal skin. The skin barrier is thus far more permissive to topical ingredients.  Moreover, the vagina is far more responsive to estrogen signaling than facial skin. As a result, the amount needed to affect the fibroblasts and adipocytes in the facial dermis may be a lot greater than what’s required to improve vaginal atrophy.  Reaching the fibroblasts and the adipocytes in the face is a tricky balance. You need enough active to get through the restrictive stratum corneum, and through the viable epidermis – but not so much that the actives are taken up by blood vessels in the lower dermis. This is quite a delivery challenge and one that the makers of estrogen creams did not tackle.

As we’ve pointed out in another blogpost, bloated fat cells are the proximate cause of saggy menopausal skin.  They explain almost all of skin sagging during menopause.  https://adipeau.com/saggy-menopause-skin-why-it-happens-and-how-you-can-fix-it/

The chart from the Sowers et al paper shows changes in eight different hormones during perimenopause and menopause. By the way, ghrelin, resistin, adiponectin and leptin are fat cell specific hormones.  All eight of these hormones play major or minor roles in determining the size or the regeneration potential of fat cells. That means all eight are affecting the proximate cause of saggy menopausal skin.  As is generally true of biological systems, the relative amounts of these hormones, not just the absolute amounts, help determine the health of the adipose tissue. In this context, it becomes clear that just modifying the amount of estrogen in the skin is not going to be enough to address the main issue.  Sowers MR, Wildman RP, Mancuso P, Eyvazzadeh AD, Karvonen-Gutierrez CA, Rillamas-Sun E, Jannausch ML. Change in adipocytokines and ghrelin with menopause. Maturitas. 2008 Feb 20;59(2):149-57. doi: 10.1016/j.maturitas.2007.12.006. Epub 2008 Feb 14. PMID: 18280066; PMCID: PMC2311418.