G Twenty-two percent of women in the United States use depot medroxyprogesterone acetate (MPA) at some stage in their life for contraception. It is highly effective, can be elf-administered, and has high adherence rates. The World ealth Organization lists it as a first-line option for young omen, particularly those wishing to avoid the adverse ffects of estrogens, such as breast-feeding mothers, smokrs, those who are overweight, and those with atrial fibrilation, pulmonary hypertension, valvular heart disease, and ypertension in pregnancy. Thus, when a case report apears suggesting a possible link between MPA and QT rolongation with cardiac arrest, the evidence needs to be eviewed carefully; the impact of withdrawal or even cauion with MPA could be massive. Giudicessi et al report a woman with a frame shift mutation in KCNH2 (long QT type 2) who in her midtwenties had 2 episodes of ventricular arrhythmia with a prolonged QT interval while taking MPA over a period of 16 months overall. Once MPA was discontinued, no further events occurred over the next 6 years, including 2 further uneventful pregnancies and postpartum periods. Women are more prone than men to the QT-prolonging effects of drugs. Most such drugs exert their effect on the otassium channel IKr, the channel that is defective in long T syndrome type 2. Nevertheless, the case comes as a urprise since it seems beyond doubt both from clinical and n vitro studies that while estrogen prolongs the QT interval, rogesterone (and testosterone) shortens it. The QT-proonging effects of some drugs, for example, ibutilide, are itigated by progesterone. During pregnancy in long QT type 2, the risk of cardiac events is reduced. This is believed to be due to the protective (QT-shortening) effect of endogenous progesterone. During the postpartum period, the protective effect of endogenous progesterone disappears and there is an immediate high risk of cardiac events. In a transgenic rabbit model of long QT type 2, progesterone reduces the incidence of arrhythmia.