Objective: Growing evidence challenges the cardioprotective effects of high-density lipoprotein-cholesterol (HDL-C) in postmenopausal women. HDL particle size and concentration are heterogeneous and HDL-C only measures the cholesterol content of all HDL particles. Therefore, HDL-C does not necessarily reflect HDL subclasses or functionality, which may be more important in predicting CVD risk. Our main objective was to characterize HDL subclasses and functional alterations over menopause and to evaluate their associations with changes in estradiol (E2) and follicle stimulating hormone (FSH), cardinal hormonal markers of menopause.
Methods: Participants were drawn from the Study of Women’s Health Across the Nation (SWAN) at the Pittsburgh site. The women had stored blood specimens at two time points; one before and one after they reached menopause. HDL particle concentration and size using calibrated ion mobility analyses and HDL cholesterol efflux capacity (HDL-CEC) with radiolabeled J774 macrophages were measured at the two time points. None of the study participants were on lipid lowering medications or hormone therapy.
Results: The study included 50 women (66% White and 34% Black), who were 47 (45, 49) years old (median (Q1, Q3)) and were either pre- (38%) or early peri-menopause (62%) at the first time point. At the second time point, all participants were postmenopausal with a median (Q1, Q3) time since their final menstrual period of 2.14 (1.55, 3.41) years. After menopause, women had significantly higher concentrations of total and large HDL particles, and smaller sizes of medium and small HDL particles (all P<0.05), independent of race and change in age. HDL-CEC was significantly higher after menopause. Independent of age and race, larger declines in E2 were correlated with a more atherogenic changes (smaller increases in large HDL particles and larger increases in small HDL particles concentrations, P<0.05). Additionally, greater rises in FSH were correlated with bigger reductions in sizes of large and medium HDL particles (P<0.05).
Conclusions: Within a median of 2.14 years of menopause, an improvement in HDL-CEC and significant alterations in HDL particle subclasses were observed. Whether patterns of these alterations change further in late postmenopause and how they relate to atherosclerotic risk are not known. The reported changes in HDL metrics over menopause warrant further evaluation of their potential risk on CVD after menopause.