Gender and its effect in cardiovascular pharmacotherapeutics: recent considerations

Gender differences in drug pharmacokinetics and pharmacodynamics have been recognized for some time. This issue has generally been ignored in clinical practice, despite there being ample evidence to suggest that gender can influence multiple aspects of pharmacokinetics. Gastric acid secretion, gastrointestinal blood flow, proportions of muscular and adipose tissue, the amount of drug-binding proteins, gender-specific changes in the available amount of P450 isozymes, physiologic and hormonal changes during the menstrual cycle, and differences in renal blood flow are several factors that may have some bearing on sex-related differences in pharmacokinetics. Furthermore, female-specific issues such as pregnancy, menopause, oral contraceptive use, and menstruation may independently influence drug metabolism and serve as confounders to the interpretation of gender differences in drug handling or effect. While gender-related pharmacodynamic data are limited, evidence suggests that women are more prone to the development of torsade de pointes from proarrhythmic drugs such as quinidine or d-sotalol and have an increased cardiovascular risk with the use of digoxin. The specific risk:benefit ratio for individual cardiovascular medications should be more routinely considered in the context of gender.