Effects of estrogenic compounds on skin physiology

Skin aging is also a consequence of menopause. During this phase of life, skin and capillary symptoms are often overshadowed by other manifestations of menopause. However, these changes significantly impact the quality of life. The decline in estrogen levels negatively affects the skin’s extracellular matrix (ECM), which provides strength, elasticity, and resilience. This reduction leads to decreased collagen production, resulting in reduced elasticity, increased wrinkles, dryness, itching, atrophy, and sagging. Addressing these changes may involve using appropriate skincare products, protecting the skin from sun damage, and undergoing dermatological treatments. Estrogen plays a vital role in maintaining skin hydration, texture, and overall appearance by promoting the production of collagen and elastin—proteins that keep the skin firm and elastic and help prevent the formation of wrinkles (Bravo et al. 2024). Many cosmetics have been developed with the aim to alleviate these symptoms. A "cosmetic product" shall mean any substance or mixture intended to be placed in contact with the various external parts of the human body (epidermis, hair system, nails, lips and external genital organs) or with the teeth and the mucous membranes of the oral cavity with a view exclusively or mainly to cleaning them, perfuming them, changing their appearance and/or correcting body odours and/or protecting them or keeping them in good condition (UK Cosmetics Regulation (EC) No. 1223/2009 (UKCR) and the EU Cosmetic Products Regulation (EC) No. 1223/2009). Cosmetics are composed of many substances that come into direct contact with the skin and mucous membranes that constitute a route of exposure to chemical ingredients, substances and contaminants. A call for data from the European Union (EU) was published for ingredients with potential endocrine-disrupting properties used in cosmetic products https://health.ec.europa.eu/system/files/2023-08/sccs_o_263.pdf, where was published a request for some synthetic compounds and only two naturally occurring: genistein and daidzein. To understand and assess the risks of chemicals genistein and daidzein that exhibit estrogenic effects, can be considered as model to assess phytoestrogens bioavailability via dermal contact. The evaluation of the safety and bioavailability of phytoestrogens in the cosmetic field is of particular interest, given that the majority of users are female. On the other hand, their topical efficacy opens promising perspectives for their use as effective active ingredients, since the skin is a target for estrogen, androgen hormones (such as testosterone) and cortisol (Zouboulis 2004). This work has been conducted with the aim of testing and describing the estrogenic effects of naturally derived compounds, such as genistein and daidzein, since these two compounds are considered the most powerful natural compounds able to mimic estrogen hormones (Sonneveld 2004). Furthermore, we aim to investigate the extent to which genistein and daidzein can penetrate the skin barrier and enter the bloodstream, and whether, under these circumstances, they might disrupt the endocrine homeostasis of the body. Conversely, if these two phytoestrogens remain confined to the skin layers, we seek to understand how, and to what extent, they can effectively promote one of the most desired biological activities in the cosmetic field—anti-aging—by acting locally as estrogen mimics.