Gender-specific implications for pharmacology in childbearing age and in postmenopausal women

Abstract

Women have three very important physiological functions that are not observed in men – menstruation, pregnancy, and lactation. Each of these mechanisms influences pharmacokinetics and pharmacodynamics of many drugs. Individualization of pharmacotherapy is a major challenge of modern medicine. The differences in response to drug are responsible for the effectiveness of pharmacological treatment and the occurrence and severity of toxic effects and side effects. Therapeutic decision should be based not only on account of the dose-effect, but the consideration of gender, genetic and environmental differences affecting the final therapeutic effect. Many important differences between men and women like sex-based differences in normal physiology, or in the predisposition to a specific disease, can be due to genetic differences, the actions of the sex steroid hormones or an interaction between these factors. Women generally have a lower body mass, a reduced hepatic clearance, differences in activity of cytochrome P450 (CYP) enzymes (increase in CYP3A4, decrease in CYP2D6, CYP2C19 and CYP1A2) and different from men’s rate of drug metabolism. Other important factors contributing to gender differences in the pharmacokinetics of drugs are conjugation, absorption, protein binding and urinary excretion. It still remains unexplained how gender differences affect the increased risk of side effects. This review is an attempt to assess the biological, physiological and hormonal basis of women differences in the pharmacokinetics and pharmacodynamics of many drugs.