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Cardiovascular Research 2002 53(3):740-751; doi:10.1016/S0008-6363(01)00429-1
© 2002 by European Society of Cardiology
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Copyright © 2002, European Society of Cardiology

Sex, hormones, and repolarization

Thai V. Pham and Michael R. Rosen*

Center for Molecular Therapeutics, Departments of Pharmacology and Pediatrics, College of Physicians and Surgeons of Columbia University, 630 West 168 Street, PH7W-321, New York, NY 10032, USA

* Corresponding author. Tel.: +1-212-305-8754; fax: +1-212-305-8351

There is increased awareness of the impact of gender and gonadal steroids on human cardiac rhythm and arrhythmias; e.g., drugs that prolong repolarization induce torsades de pointes (TdP) more frequently in women than men; female gender is an independent risk factor for syncope and sudden death in the congenital long QT syndrome; and the higher propensity toward arrhythmia in normal females is associated with fundamental differences in repolarization such that rate-corrected QT intervals are longer in females than males. Mechanisms underlying these differences are incompletely defined but are believed to involve gonadal steroids. This review discusses recent advances and prospects for further elucidation of the influence of gender and gonadal steroids on ventricular repolarization and arrhythmias.

KEYWORDS APD, action potential duration; DHT, 5{alpha}-dihydrotestosterone; E-4031, specific blocker of the rapidly activating delayed potassium rectifying current; EAD, early afterdepolarization; ECG, electrocardiogram; ER, estrogen receptor; ERKO, estrogen receptor knock-out; FSH, follicle stimulating hormone; GnRH, gonadotrophin-releasing hormone; HK2 (Kv1.5), human clone of the ultra-rapidly activating delayed potassium rectifying channel; HERG, human clone of the rapidly activating delayed potassium rectifying channel; HRE, hormone response element; ICa,L, L-type calcium current; IK1, inward rectifying potassium current; IKr, rapidly activating delayed potassium current; IKs, slowly activating delayed potassium current; IKur, ultra-rapidly activating delayed potassium rectifying current; IsK (minK), modulatory subunit of the slowly activating delayed rectifying current; Ito, transient outward potassium current; KvLQT1, human clone of the slowly activating delayed potassium channel; LH, luteinizing hormone; QTc, rate-corrected QT interval; SHR, spontaneously hypertensive rat; SWORD, survival with oral d-sotalol; TdP, torsades de pointes


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