Epilogue: Future of Sex and Gender-Based Studies in Infectious Diseases

Abstract

The topic of male–female differences in disease outcomes continues to receive attention in both the scientific literature and lay press. There is little debate about whether the sexes are behaviorally and biologically different, but how this impacts disease processes and the pipeline for developing drugs, vaccines, medical devices, and policy decisions is highly debated. The current book as well as a previous book (Klein and Roberts 2010) that we published in 2010 illustrates that the sexes differ in their exposure, immune responses, and outcome of diverse infectious diseases and inflammatory conditions. While the intensity and prevalence of infections are often higher for males, the outcome of diseases, including those caused by HIV, influenza, hemorrhagic fever viruses, Toxoplasma gondii, and Borrelia burgdorferi to name a few, can be worse for females. As detailed in Chapter 1 of this book, females tend to mount higher innate and adaptive immune responses, which can result in faster clearance of pathogens, but also may contribute to increased development of immunopathology and inflammatory conditions. Responses to prophylaxis and therapeutic treatments for infectious diseases also differ between the sexes, with females typically experiencing greater adverse reactions than males (Chapter 4). These sex differences can vary by age and reproductive status (Chapters 3 and 10), illustrating that these differences are not fixed, but are variable across the life course. Despite sex being the most evolutionarily well conserved and easily disaggregated variable by which to compare the outcome of diseases and their treatments, it is often ignored in the biomedical sciences. The challenges of including women in clinical trials are in some cases obvious and include the potential of hormonal variations during menstrual cycles and their cessation at menopause. These factors are further complicated due to pregnancy (when hormone levels change and the fetus could be at risk during a trial) or artificial administration of hormones as contraceptives or for hormone replacement therapy. However, the scientific, medical, and ethical cases for including males and females in preclinical and clinical trials are too profound to ignore.