Sex differences shape the response to infectious diseases

Historically, we have overlooked sex as a variable in infectious disease research For example, while much of our knowledge comes from animal studies, many researchers routinely use only male animals [3]. One of the principal reasons for this is the argument that female animals, undergoing cyclic hormonal fluctuations, introduce additional experimental variation Sex bias is also a major challenge in clinical studies. In 1977, Food and Drug Administration (FDA) guidelines for human studies recommended that women of reproductive age be excluded from early clinical trials (e.g., Phase I) While more recent efforts have resulted in greater inclusion of female subjects [5], the lasting consequence of this recommendation is that many drug regimens and therapeutic approaches are based solely on information gained from testing in male subjects Major adverse effects experienced by female patients underline that single-sex studies cannot predict whether and how men and women will respond differently to a drug, vaccine, or treatment