What drives menopausal skin changes? A new look through hormone-responsive models

Summary: Abstract Body: Despite significant skin changes occur during menopausal period, few models exist to study this hormonal shift. To address this need, we developed three complementary in vitro models to specifically target key hormonal aging parameters. Hormonal decline during early menopause leads to a 30% collagen reduction within 5 years due to impaired matrix production and degradation. Reduced sebaceous gland activity causes dryness, while weakened vascular networks impair oxygenation and nutrient delivery, affecting skin vitality. Models on human fibroblasts, sebocytes, and endothelial cells were developed with media using 17β-estradiol, progesterone, dehydroepiandrosterone, growth hormone, and IGF-1 at concentrations mimicking non-menopausal and menopausal serum levels. Dermal atrophy was addressed by quantifying markers of collagen metabolism – procollagen I and MMP-1 – in fibroblasts via ELISA. Sebogenesis activity, reflecting skin dryness, was assessed in sebocytes culture through total lipid content measurement using a BODIPY® probe. Microvascular network formation and integrity in endothelial cells were analyzed with the Angiogenesis Analyzer tool on ImageJ. Under menopausal conditions, fibroblasts showed a 37% (p<0.01) reduction in procollagen I content and a 170% (p<0.01) increase in MMP-1 secretion, highlighting matrix synthesis and remodeling dysfunction. In sebocytes, menopausal hormonal levels led to a 65% (p<0.01) decrease in lipid content, reflecting reduced sebum production contributing to increase skin dryness. Endothelial cells showed microvascular network deterioration, with fewer junctions, segments, and meshes underscoring vascular changes associated with menopause. The developed models, using a physiologically relevant hormonal cocktail, mirror the skin impacts at menopause onset. By leveraging hormone-dependent models, we provide an innovative approach to precisely target skin hormonal aging, enabling to identify active ingredients specifically designed to address the unique needs of menopausal skin, going beyond conventional anti-aging approaches. Lola Blayac¹, Eddy Magdeleine¹, Laetitia Cattuzzato¹, Mathilde Frechet¹ 1. Lucas Meyer Cosmetics by Clariant, Toulouse, France. Cell Communication Networks and Stromal Biology