Complex Influence of Gonadotropins and Sex Steroid Hormones on QT Interval Duration

Context: QT interval duration is longer in women than in men. Sex steroid hormones have inconsistently been suggested to explain this difference. The implication of gonadotropins has never been studied. Objective: We report here 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 T and progesterone overexpression. Design and Patients: Eighty-four CAH patients (58 women) and 84 healthy subjects matched and paired for sex and age were prospectively included. Circulating concentrations of 17-OH-progesterone, progesterone, T, estradiol, FSH, and LH were measured concomitantly to the recording of a digitized electrocardiogram. Results: QTcFridericia (QTcF) was shorter in women with CAH than in control women (404 +/- 2 vs 413 +/- 2.1 milliseconds; P <= .001). 17-OH-progesterone, progesterone, the progesterone/estradiol ratio, and total T were higher in women with CAH than in female controls (P <= .05), whereas FSH was lower (P <= .05). According to multivariable analysis in all women, the progesterone/estradiol ratio (beta = -0.33) and FSH levels (beta = 0.34) were related to QTcF(r = 0.5; P < .0001), with no influence of CAH or healthy status. QTcF was not different between CAH(404.7 +/- 3.7 milliseconds) or healthy men (396 +/- 2.8 milliseconds). For men, QTcF (r = 0.48; P < .01) was negatively related to free T (beta = -0.29) and positively to FSH levels (beta = 0.34). Conclusion: Cardiac repolarization is influenced by complex interactions between sex steroid hormones and gonadotropins, depending on gender. Our results indicate that the progesterone/estradiol ratio in women, T in men, and FSH in both genders are major determinants of ventricular repolarization with opposite effects on QTc interval.