Beyond Comorbidity: A Three-Level Clinical Framework for Endocrine-Metabolic Associations in Rosacea

Rosacea has been increasingly associated with endocrine-metabolic abnormalities, but the clinical significance of these findings remains uncertain because existing studies evaluate biologically distinct outcomes, ranging from isolated biomarkers to clinically diagnosed endocrine disease. In this narrative review, we synthesize evidence across the thyroid, insulin-metabolic, gonadal and hypothalamic-pituitary-adrenal axes using a three-level framework that distinguishes biomarker-level signals, functional or contextual processes, and overt endocrine disease. Overall, the available evidence appears more coherent for functional or contextual processes than for established endocrine disorders. Insulin resistance and individual metabolic abnormalities are reported more consistently than diabetes mellitus or metabolic syndrome, thyroid-related findings remain heterogeneous, and gonadal and hypothalamic-pituitary-adrenal associations are better interpreted in terms of hormonal, vasomotor and stress-related context than persistent endocrine dysfunction. Vascular, immune-inflammatory, oxidative and neuroendocrine pathways provide biological plausibility for these associations, although causal evidence remains limited. We therefore propose that endocrine-metabolic factors may be better conceptualized as heterogeneous contextual modifiers of rosacea expression rather than as a uniform group of causal comorbidities. Current evidence does not support routine endocrine investigation solely because of rosacea; assessment should follow conventional clinical indications. Prospective, phenotype-stratified studies are needed to validate this framework and determine whether these proposed modifiers predict disease activity, phenotype or treatment response.