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.
Competing Interests: Declarations. Ethics approval: This study is conducted according to the Management Policy of the MHI Hospital Cohort and is approved by the Management Committee of the Biobank as well as the Scientific and Ethics committees of the MHI. Consent to participate: All patients agreed to participate in the Hospital Cohort and signed a consent form. Consent for publication: Not applicable (see Ethics approval and Consent to participate). Competing interests: S. de Denus reports grants outside the submitted work from AstraZeneca and RMS/Dalcor. M.-P. Dubé has a minor equity interest in DalCor Pharmaceuticals. J.-C. Tardif has received research grants from Amarin, AstraZeneca, Ceapro, DalCor Pharmaceuticals, Esperion, Ionis, Novartis, Pfizer, RegenXBio, and Sanofi; honoraria from AstraZeneca, DalCor Pharmaceuticals, HLS Pharmaceuticals, and Pendopharm; and minor equity interest in DalCor Pharmaceuticals. M.-P. Dubé and J.-C. Tardif are authors on the following patents without royalties received: “Methods for Treating or Preventing Cardiovascular Disorders and Lowering Risk of Cardiovascular Events,” “Genetic Markers for Predicting Responsiveness to Therapy with HDL-Raising or HDL Mimicking Agent,” and “Methods for using low dose colchicine after myocardial infarction.”
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)