Gender difference: Hype or fact?

Abstract

Summary The number of trials looking at the gender effecton anesthetic agents is very limited. What evidence exists is not clear, but the general pattern suggests a difference in pharmacokinetics and pharmacodynamics between men and women for certain drugs. These differences may not be predictable within the same group of drugs, such as benzodiazepines; the gender effect may vary and sometimes may be completely opposite. Important gender factors, such as menopause, pregnancy, and use of oral contraceptives, may affect the pharmacokinetics and dynamics of drugs significantly. Difference in body weight and composition alone result in significant pharmacokinetic differences in volume of distribution, initial plasma concentration, organ blood flow, rate of redistribution, and rate of filtration by the kidney. The intrinsic activity of the cytochrome system appears to be affected by gender: The activity of CYP3A4 is 1.4 times greater in women than men, with the resultant increased metabolism of certain drugs in women. One possible explanation for this increased intrinsic activity in women may be the interaction of the sex steroids with the cytochrome systems. Increased sensitivity to drugs may result from interaction of the sex steroids with receptors such as the μ-opioid receptors. The sex hormones may affect other intrinsic substances such as beta-endorphins. For example, beta-endorphin levels are increase in pregnancy and along with progesterone are thought to result in the decreased MAC associated with pregnancy. Clearly, further studies are needed to identify which drugs are affected by gender as well as the causes for these differences. Last, how big these differences are and to what degree they are clinically significant must be determined.