NOX1 gene expression and hormonal alteration in hypothyroidism-associated female infertility

To evaluate the association of NOX1 gene expression with reproductive hormonal changes in hypothyroid infertile women and assess their diagnostic performance.

A case-control study was conducted among 150 infertile women with hypothyroidism and 150 healthy age-matched fertile controls. Hormonal (FSH, LH, prolactin) and molecular (NOX1 expression) parameters were measured using standardized assays including qRT-PCR. Group comparisons, Spearman's correlation analyses, scatterplot visualizations, and ROC curve evaluations were conducted to determine associations and diagnostic performance.

Hypothyroid infertile women exhibited significantly elevated FSH (19.9 ± 7.5 mIU/mL), LH (20.0 ± 7.6 mIU/mL), prolactin (21.9 ± 8.4 ng/mL), and TSH (7.2 ± 1.8 µIU/mL), along with reduced T3 (0.82 ± 0.21 ng/mL) and T4 (5.1 ± 1.2 μg/dL) compared to controls (p<0.01). NOX1 expression was markedly higher in peripheral blood (1.9 ± 0.9 vs. 1.0 ± 0.2; p<0.01). Moderate positive correlations were observed between NOX1 and FSH (r=0.5638), LH (r=0.5787), and prolactin (r=0.5968), all statistically significant (p<0.01). ROC analysis showed good diagnostic accuracy for FSH (AUC 0.801), LH (AUC 0.732), and prolactin (AUC 0.748), while NOX1 demonstrated superior discriminative performance (AUC 0.835) with 100 % specificity and a positive predictive value of 100 %.

Hypothyroidism-associated infertility is characterized by combined endocrine imbalance and heightened oxidative stress. The strong discriminative ability and hormonal correlations of NOX1 expression suggest its potential use as a molecular biomarker to support infertility risk detection in thyroid-compromised women, providing a basis for oxidative-stress-targeted therapeutic strategies.