Sex differences in drug-induced QT prolongation

Abstract Women have a higher rate of torsade when taking QT-prolonging medications. This higher risk can be in part explained by women having longer QTc intervals at both baseline and on-treatment compared to men. Endogenous sex hormones play a key role in the longer QTc at baseline in women. Longer on-treatment QTc may be caused by higher drug concentrations associated with dosing regimens that do not account for body size, which is on average smaller in women. Women are not, however, more sensitive to the QTc prolonging effects of drugs—the slope of the concentration–QTc relationship for drugs is not systematically higher in women. After adjusting for on-treatment QTc values, women have at least twofold the torsade risk compared to men when taking antiarrhythmic drugs. This highlights the importance of identifying other physiological factors that increase the torsade risk of QT-prolonging drugs in women.