Understanding Dyslipidemia in Women across their Lifespan: Sex Differences in Lipoprotein Metabolism and Hormonal Influence

Women have lipid changes across their lifespan, with patterns corresponding to hormonal, reproductive, and biological changes that differ greatly from those in men. A clear understanding of the causative mechanism of these dynamic changes, the underlying differences between the sexes, and the impact of environmental and genetic risk factors in women in various phases of life is crucial to address the cardiovascular (CV) risk, which is the major threat in women. Females tend to have higher levels of total cholesterol (TC) and low-density lipoprotein (LDL) from infancy into early adulthood (1) Women have a “female advantage” in decreased CV risk in the premenopausal phase due to the actions of the female hormone estrogen, causing favorable changes in lipid parameters. However, with the onset of menopause, which is marked by diminished ovarian function and a reduction in estrogen levels, there is a rapid increase in TC, LDL, triglycerides, and lipoprotein(a) levels. This is combined with decreased levels and alterations in high-density lipoprotein (HDL) cholesterol, with a smaller HDL subclass that has reduced beneficial scavenger function. These changes contribute to an elevated risk of atherosclerotic CV disease in postmenopausal women (2) the conditions with decreased ovarian function and low estrogen levels, such as polycystic ovarian syndrome (PCOS), metabolic syndrome (METS), infertility, and pregnancy with adverse pregnancy outcomes on follow-up, have adverse lipid changes. This review examines the influence of hormonal changes from menarche to menopause, explores sex-specific differences at various life stages, and discusses the impact of conditions such as polycystic ovary syndrome (PCOS), METS, and pregnancy on lipid metabolism and CV disease risk.