Evaluation of Serum Irisin Levels in Individuals with Gender Incongruence and Its Metabolic Correlations

Irisin, a myokine implicated in energy homeostasis, has been proposed as a biomarker for metabolic dysfunction. This study aimed to assess serum irisin levels and their associations with metabolic parameters in gender-incongruent individuals compared to healthy cisgender controls and to assess the predictive value of irisin and related metabolic indices for metabolic syndrome (MetS) using both affirmed and birth-assigned gender criteria.

A cross-sectional "observational, non-randomised" study was conducted from June 2024 to February 2025 among 123 participants (transgender women, transgender men, cisgender women and cisgender men), matched for age and body mass index. Individuals with confounding metabolic conditions were excluded. Serum irisin was measured using a sandwich enzyme-linked immunosorbent assay, and metabolic parameters were evaluated. Statistical analyses assessed the diagnostic utility of irisin and various metabolic indices for MetS.

In transgender women, serum irisin showed inverse correlation with diastolic blood pressure (r = -0.307, P = 0.036). In transgender men, it was inversely correlated with high-density lipoprotein (HDL) cholesterol (r = -0.339, P = 0.046) and prolactin (r = -0.357, P = 0.035). Receiver operating characteristic analysis revealed a limited predictive value of irisin for MetS (area under the curve (AUC) <0.5). The triglyceride (Ty)/HDL index performed better in transgender women (AUC = 0.748) and the triglyceride-glucose index (Ty/G index) in transgender men (AUC = 0.67).

Serum irisin is associated with select metabolic parameters but has limited utility in predicting MetS in gender incongruent individuals. Affirmed gender-based assessment enhances risk stratification, with Ty/HDL and Ty/G indices offering better predictive value in transgender populations.