The Effect of SEX/Gender on Cardiovascular Pharmacology

Flavia      Franconi; Ciriaco      Carru; Walter      Malorni; Stefano      Vella; Giuseppe      Mercuro

doi:10.2174/138161211795656918

Abstract

Cardiovascular diseases differ between men and women as do outcomes after therapeutic interventions. Management of these diseases, however, is generally guided by evidence from trials conducted predominantly in men, with few studies focused on women alone. Our goal is to review the sex/gender differences in cardiovascular therapies, which show many areas of uncertainty regarding women due to their small enrolment in clinical trials; thus, in some cases, firm conclusions about efficacy in women are difficult to obtain. Nevertheless, female gender appears to suffer from more adverse drug effects (ADE) than the male gender. For example, women are significantly more likely to experience drug-induced QT-prolongation and torsade de pointes arrhythmia and many other types of ADE. The major sex-specific differences present in pharmacokinetics, especially for the major drug metabolizing enzymes, the cytochromes P450 family, but also for phase II reactions such as glucuronidation, are discussed. Pharmacodynamic mechanisms underlying sex/gender differences are not clearly elucidated yet; however, this highlights the need for more studies focusing on women in order to optimize sex/gender-specific therapy and, therefore, improve clinical outcomes in women with cardiovascular diseases.

Keywords: Sex/gender differences, cardiovascular system, pharmacokinetics, pharmacodynamics, drug adverse effects, pathology, oestrogens, polytherapy, dimorphic, gastrointestinal, microvasculature, creatinine, ventilatory, biotransformation, sulfotransferases, glutathione-S, epigenetic