Sex Differences in Lipid and Lipoprotein Metabolism: It's Not Just about Sex Hormones

It is commonly thought that sex hormones are important regulators of plasma lipid kinetics and are responsible for sexual dimorphism in the plasma lipid profile. Here we discuss the findings from studies evaluating lipid and lipoprotein kinetics in men and women in the context of what we know about the effects of exogenous sex hormone administration, and we conclude that it is more complicated than that. It has become clear that normal physiological alterations in the hormonal milieu (i.e. due to menopause or throughout the menstrual cycle) do not significantly affect plasma lipid homeostasis. Furthermore, parenterally administered estrogens have either no effect or only very small beneficial effects, whereas orally administered estrogens raise plasma triglyceride concentrations--a phenomenon that is not consistent with the observed sex differences and likely results from the hepatic "first-pass effect." The effects of progestogens and androgens mimic only in part the differences in plasma lipids between men and women. Thus, the underlying physiological modulators of plasma lipid metabolism responsible for the differences between men and women remain to be elucidated.