A Study Of the effect of Sex on drug dosing, concentrations, and pharmacogenomics in the Montreal Heart Institute Hospital Cohort (SOS-PGx): methodology and research progress

Background: Women are underrepresented in drug development trials and there is no sex-tailored drug regimen for most medications. It has been repeatedly shown that women have more adverse drug reactions than men for several medications. These differences could be explained by higher dose-adjusted drug concentrations in women. Thus, we aim to identify sex-related differences and to characterize the clinical and genetic predictors of these differences in drug concentrations, dosing, and adherence for 47 commonly used drugs in a large cohort. The objective of this article is to present an overview of the methods and characteristics of the study population.

Methods: We performed a cross-sectional study that included 10,082 men and women of European ancestry aged ≥ 18 years from the Montreal Heart Institute Hospital Cohort taking at least one of the 47 medications regularly.

Results: Of the 10,082 participants included, 36% were women. Women had lower weight, height, waist girth, and body mass index than men, but they had higher hip girth (all p < 0.001). Men had a higher level of education and annual income and were more likely to be employed full-time compared to women. Furthermore, men had a higher prevalence of hypertension, type 2 diabetes, dyslipidemia, and myocardial infarction (all p < 0.001) and were more likely receiving lipid-lowering agents, beta-blockers, antidiabetic drugs, and angiotensin-converting enzyme inhibitors. Conversely, proton pump inhibitors were more prevalent in women. Interestingly, nearly half of the women had a history of drug allergy or intolerance, compared with less than one-third of the men (p < 0.001).

Conclusion: This study has a high potential in understanding eventual sex differences in drug dosing requirements and will most likely provide useful information to personalize drug regimens in women.