Strategies and methods to study sex differences in cardiovascular structure and function: a guide for basic scientists

This article describes concepts, methods and procedures to assist in the design of animal and tissue/cell based studies of sex differences in cardiovascular structure, function and models of disease.To address knowledge gaps, study designs must incorporate appropriate experimental material including species/strain characteristics, sex and hormonal status. Determining whether a sex difference exists in a trait must take into account the reproductive status and history of the animal including those used for tissue (cell) harvest, such as the presence of gonadal steroids at the time of testing, during development or number of pregnancies. When selecting the type of experimental animal, additional consideration should be given to diet requirements (soy or plant based influencing consumption of phytoestrogen), lifespan, frequency of estrous cycle in females, and ability to investigate developmental or environmental components of disease modulation. Stress imposed by disruption of sleep/wake cycles, patterns of social interaction (or degree of social isolation), or handling may influence adrenal hormones that interact with pathways activated by the sex steroid hormones. Care must be given to selection of hormonal treatment and route of administration.Accounting for sex in the design and interpretation of studies including pharmacological effects of drugs is essential to increase the foundation of basic knowledge upon which to build translational approaches to prevent, diagnose and treat cardiovascular diseases in humans.There are significant disparities between women and men in the incidence of, and mortality from, cardiovascular disease [1-4]. Thus, there is a need for improvement in the current preventive, diagnostic and treatment strategies by accounting for sex-specific differences in the etiology and risk factors of cardiovascular disease. In 2001, the Institute of Medicine advocated that a better understanding of differences in human diseases between males and femal