Sex and Gender Differences in Disease, Pharmacotherapy, and Clinical Outcomes: Implications for Precision Medicine

Precision medicine hopes to make health care better by accounting for the variability of individuals' biology and clinical features in disease prediction and treatment. To achieve personalized care, however, it is essential that sex- and gender-related factors are recognized as they impact the mechanisms of disease, pharmacological actions and clinical outcomes. Disease susceptibility and response to treatment may differ between the sexes due to sex-related differences in genetics, hormones, immune regulation, epigenetic processes and metabolism; and diagnosis, access to healthcare, use of treatment and outcome may also differ across sex. There is growing evidence that considers sex and gender aspects in pharmacotherapy, discovery of biomarkers, artificial intelligence and multi-omics. Although this is starting to be recognized, there are still limitations of representation in clinical research, inconsistencies in how it is reported, and a lack of translation to clinical applications. This narrative review discusses the latest evidence regarding sex and gender differences in disease biology, pharmacotherapy, and clinical outcomes and their potential contribution to precision medicine. The incorporation of these factors into personalized health care systems can improve risk stratification, optimization of therapy, safety of drugs, and patient care.