Atopic Dermatitis Beyond Cutaneous Inflammation: The Interplay Between Progesterone, Testosterone, Gut Microbiota, and Immune Dysregulation

Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by epithelial barrier dysfunction, immune dysregulation, and marked clinical heterogeneity. Although sex hormones and gut microbiota have independently been implicated in AD, their potential interactions remain incompletely understood. This narrative review integrates evidence from clinical, experimental, and preclinical studies examining the interplay among progesterone, testosterone, gut microbiota, and AD, with emphasis on immune regulation, epithelial barrier function, and gut-skin communication. Overall, the available evidence suggests that progesterone is predominantly associated with type 2 immune responses, alterations in epithelial barrier homeostasis, and context-dependent microbial remodeling. In contrast, physiological testosterone is generally associated with immunoregulatory effects and microbial profiles enriched in short-chain fatty acid-producing bacteria, whereas local androgen metabolism may contribute to skin barrier dysfunction. Current evidence also supports a bidirectional relationship between gut microbiota and sex hormones, whereby hormonal fluctuations influence microbial composition while microbial metabolism may modify steroid hormone bioavailability. Collectively, these findings support an integrated endocrine-microbial-immune framework that may contribute to AD beyond cutaneous inflammation. Although direct evidence simultaneously evaluating these components remains limited, this framework may help explain sex-specific differences in disease susceptibility, severity, and clinical course while guiding future mechanistic studies of the hormone-gut microbiota-skin axis.