The Association of Hormonal Imbalances and NRF2 Gene Expression in Male Infertility

Background & Objective: Infertility affects 50-80 million people worldwide, with male factors contributing to nearly half of all cases. Hormonal disturbances and oxidative stress are the key contributors to impaired spermatogenesis. The transcription factor Nuclear Factor Erythroid 2-Related Factor 2 (NRF2) regulates antioxidant defense, and its reduced activity is linked to reproductive dysfunction.The present study was conducted with aim to investigate the relationship between reproductive and thyroid hormone levels and NRF2 gene expression in men with infertility.Materials & Methods: In this case-control study, 300 men aged 25-45 years (150 infertile, 150 fertile) were recruited. Serum T3, T4, and TSH were measured via chemiluminescent immunoassay, while FSH and testosterone were quantified by ELISA. NRF2 expression was analyzed using quantitative real-time PCR with the 2^−ΔΔCt method. Data were analyzed using chi-square, Mann-Whitney U, correlation, and ROC curve analysis. P<0.05 was considered statistically significant.Results: FSH (AUC=0.891) and NRF2 expression (AUC=0.840) showed high discriminative ability between the groups. TSH had moderate predictive value (AUC=0.782), and testosterone showed limited accuracy (AUC=0.673).Conclusion: The findings suggest that disruptions in endocrine balance and oxidative stress regulation contribute to male infertility. FSH and NRF2 expression demonstrate strong diagnostic potential, highlighting their relevance for early detection and as possible therapeutic targets.