Thirty-five years ago, when I was a cardiovascular resident, I vividly remember being shocked by the gender/age difference in the prevalence of patients with congenital long QT syndrome (LQTS), which is a typical inherited arrhythmia syndrome. Most patients with congenital LQTS referred to the adult cardiology department, especially those who were symptomatic with syncope or cardiac arrest, were female. Since I was working in the adult cardiology department, I believed congenital LQTS was a female illness. One day during the summer vacation period, I was called to the pediatric cardiology department to consult for a child with congenital LQTS. The child was an 8-year-old boy, and several boys with congenital LQTS were being admitted to the pediatric cardiology department. At that time, I knew for the first time that there was a gender/age difference in the prevalence of patients with congenital LQTS. Ten years later, Locati et al 1 Locati E.H. Zareba W. Moss A.J. et al. Age- and sex-related differences in clinical manifestations in patients with congenital long-QT syndrome: findings from the International LQTS Registry. reported in patients with congenital LQTS that the risk of cardiac events was higher in males up until puberty (Kr) 2 Kurokawa J. Tamagawa M. Harada N. et al. Acute effects of oestrogen on the guinea pig and human IKr channels and drug-induced prolongation of cardiac repolarization. and slow activating component (IKs) 3 Tanabe S. Hata T. Hiraoka M. Effects of estrogen on action potential and membrane currents in guinea pig ventricular myocytes. of the delayed rectifier potassium current, thus prolonging the ventricular action potential duration, reflecting a prolongation of the QT interval on the surface electrocardiogram (ECG). In contrast, several experimental studies have reported the involvement of the male hormone, testosterone, in an increase in outward potassium currents, such as IKr, 4 Shuba Y.M. Degtiar V.E. Osipenko V.N. Naidenov V.G. Woosley R.L. Testosterone-mediated modulation of HERG blockade by proarrhythmic agents. ,5 Liu X.K. Katchman A. Whitfield B.H. et al. In vivo androgen treatment shortens the QT interval and increases the densities of inward and delayed rectifier potassium currents in orchiectomized male rabbits. IKs, 6 Bai C.X. Kurokawa J. Tamagawa M. Nakaya H. Furukawa T. Nontranscriptional regulation of cardiac repolarization currents by testosterone. and inward rectifier potassium current (IK1), 5 Liu X.K. Katchman A. Whitfield B.H. et al. In vivo androgen treatment shortens the QT interval and increases the densities of inward and delayed rectifier potassium currents in orchiectomized male rabbits. and a decrease in inward L-type calcium current (ICa-L). 6 Bai C.X. Kurokawa J. Tamagawa M. Nakaya H. Furukawa T. Nontranscriptional regulation of cardiac repolarization currents by testosterone. Therefore, after puberty, the QT interval is prolonged in females because of a decrease in IKr and IKs by estrogen, while it is abbreviated in males because of an increase in IKr, IKs, and IK1 and a decrease in ICa-L by testosterone, resulting in a reversed cardiac event rate before and after puberty between males and females.