QT interval duration is longer in women than in men. Sex steroid hormones have inconsistently been suggested to explain this difference. Implication of gonadotropins has never been studied. Objective: We here report the combined influence of sex steroid hormones and gonadotropins on QT interval duration in healthy subjects and patients with congenital adrenal hyperplasia (CAH) as a model of testosterone and progesterone overexpression. Design: Patients. Eighty four CAH patients (58 women) and 84 healthy subjects matched-paired for sex and age were prospectively included. Circulating concentrations of 17-OH-progesterone, progesterone, testosterone, estradiol, FSH and LH, were measured concomitantly to recording of a digitized electrocardiogram. Results: QTcFridericia(QTcF) was shorter in women with CAH than in control women (404±2 msec vs. 413±2.1 msec, p≤0.001). 17-OH-progesterone, progesterone, progesterone/estradiol ratio and total testosterone were higher in women with CAH than in women controls (p<0.05) whereas FSH was lower (p≤0.05). According to multivariable analysis in all women, progesterone/estradiol ratio (β=-0.33) and FSH levels (β=0.34) were related to QTcF (r=0.5, p<0.0001) with no influence of CAH or healthy status. QTcF was not different between CAH (404.7±3.7 msec) or healthy men (396±2.8 msec). For men, QTcF (r=0.48, p<0.01) was negatively related to free testosterone (β=-0.29) and positively to FSH levels (β=0.34). Conclusion: Cardiac repolarization is influenced by complex interactions between sex steroid hormones and gonadotropins depending on gender. Our results indicate that progesterone/estradiol ratio, in women, testosterone, in men, and FSH, in both genders, are major determinants of ventricular repolarization with opposite effects on QTc interval.