Sex and Gender Differences in Pharmacology

Sabra L. Klein, Klein, Sabra L.

Vera Regitz-Zagrosek

The intensity and prevalence of viral infections are typically higher in males than in females. In contrast, disease outcome can be worse for females. Males and females also differ in their responses to prophylaxis and therapeutic treatments for viral diseases. In response to vaccines against herpes viruses, hepatitis viruses, influenza viruses, and others, females consistently mount higher humoral immune responses and experience more frequent and severe adverse reactions than males. Males and females also differ in the absorption, metabolism, and clearance of antiviral drugs. The pharmacological effects, including toxicity and adverse reactions, of antiviral drugs are typically greater in females than males. The efficacy of antiviral drugs at reducing viral load also differs between the sexes, with antiviral treatments being better at clearing HIV and hepatitis C virus in females, but showing greater reduction of herpes simplex virus and influenza A virus loads in males. Biological variables, including hormone and genes, as well as gender-specific factors related to access and compliance to drug regimens must be considered when evaluating male-female differences in responses to treatments for viral diseases. Clinicians, epidemiologists, and basic biomedical scientists should design experiments that include both males and females, develop a priori hypotheses that the sexes will differ in their responses to and the outcome of vaccines and antiviral treatments, and statistically analyze outcome data by sex. Knowledge that the sexes differ in response to prophylaxis and therapeutic treatments for viral diseases should influence the recommended course of treatment differently for males and females.