Related Experiment Video
Updated: Mar 18, 2026
High-Density Lipoprotein-Specific Phospholipid Efflux Assay
Published on: September 30, 2025
Cholesterol Efflux Capacity and Subclasses of HDL Particles in Healthy Women Transitioning Through Menopause
Samar R El Khoudary1, Patrick M Hutchins1, Karen A Matthews1
1Department of Epidemiology (S.R.E.K., K.A.M., M.M.B., T.J.O.), University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Medicine (P.M.H., G.E.R., J.W.H.), University of Washington, Seattle, Washington; Department of Psychiatry (K.A.M.), University of Pittsburgh, Pittsburgh, Pennsylvania.
Insights
High-density lipoprotein-cholesterol (HDL-C) may not be cardioprotective post-menopause. HDL particle concentration (HDL-P) and cholesterol efflux capacity (CEC) show significant changes during menopause, potentially impacting cardiovascular risk.
Area of Science:
- Cardiovascular Health
- Endocrinology
- Lipid Metabolism
Background:
- Traditional markers like HDL-C are being re-evaluated for cardiovascular risk prediction.
- Menopause significantly alters hormonal profiles, including estradiol (E2) and FSH, which may influence lipid metabolism.
- HDL particle concentration (HDL-P) and cholesterol efflux capacity (CEC) are emerging as potentially better indicators of cardiovascular risk.
Purpose of the Study:
- To quantify changes in HDL-P and CEC during the menopausal transition.
- To correlate these HDL alterations with changes in E2 and FSH levels.
- To investigate the relationship between HDL metrics and hormonal changes before and after the final menstrual period (FMP).
Main Methods:
- A longitudinal study design tracking HDL metrics in women before and after FMP.
- Measurement of HDL-P concentration (HDL-PIMA) using calibrated ion mobility analysis (IMA).
- Assessment of macrophage CEC and ATP-binding cassette transporter A1 (ABCA1)-specific CEC using cell-based assays.
Main Results:
- HDL-C and HDL-PIMA increased post-FMP, with a rise in large HDL particles and a decrease in medium and small particles.
- Macrophage CEC and ABCA1-specific CEC significantly increased after FMP.
- Declines in E2 correlated with increased small HDL-PIMA, while increased FSH associated with reduced medium HDL-PIMA size. CEC correlated positively with E2 only before menopause.
Conclusions:
- Significant increases in large HDL-PIMA and CEC occur in early menopause.
- The study highlights dynamic changes in HDL metrics and their association with hormonal shifts during the menopausal transition.
- Further research is needed to determine if these HDL alterations in early postmenopause predict future cardiovascular risk.
Context:
Growing evidence challenges the concept that high-density lipoprotein-cholesterol (HDL-C) is cardioprotective after menopause. HDL particle concentration (HDL-P) and cholesterol efflux capacity (CEC) might be better predictors of cardiovascular risk.
Objective:
Quantify alterations in HDL-P and CEC during menopause, correlating those changes with alterations in estradiol (E2) and FSH.
Design:
Longitudinal study of HDL metrics before and after menopause as indexed by the final menstrual period (FMP).
Participants:
Forty-six women, mean baseline age 47.1 years, 33% black, 67% white.
Main Outcomes And Measures:
HDL-P concentration (HDL-PIMA) by calibrated ion mobility analysis (IMA); macrophage CEC with cAMP-stimulated macrophages; ATP-binding cassette transporter A1 (ABCA1)-specific CEC with BHK cells expressing human ABCA1.
Results:
After a median of 2.1 years since FMP, both HDL-C (P = .03) and HDL-PIMA (P = .01) increased, with a selective increase in large HDL-PIMA (P = .01), whereas sizes of medium and small HDL-PIMA were decreased (P < .05). These changes were independent of race, body mass index, and time difference. Macrophage CEC and ABCA1-specific CEC increased after FMP (both P < .001). Greater declines in E2 correlated with larger increases in small HDL-PIMA (P = .01), whereas greater increases in FSH associated with greater reductions in the size of medium HDL-PIMA (P = .04). Macrophage CEC and ABCA1-specific CEC correlated positively with E2 levels only before menopause (P = .04 and .009, respectively).
Conclusions:
Large HDL-PIMA and CEC increased significantly in the early phase of the menopausal transition. Whether patterns of these alterations differ in late postmenopause is unknown. Further exploration is needed to assess that and to determine whether the reported changes in HDL metrics associate with increased cardiovascular risk after menopause.
Related Concept Videos
01:29Cholesterol: Significance and Regulation
Considering cholesterol and...
01:18Lipids: Dietary Sources and Requirements
01:25Blood Studies for Cardiovascular System III: Serum Lipid Profile
Serum lipids are fats and fatty substances in the blood and are crucial for various bodily functions, including energy storage, cellular structure, and hormone production. Serum lipids consist of cholesterol, triglycerides, and phospholipids.
Cholesterol is a soft, fat-like substance found in all body cells. It is crucial for producing hormones, vitamin D, and substances that aid...
01:28Menopause
01:31Lipid-derived Compounds in the Human Body
Fat-soluble Vitamins
Fat-soluble vitamins, including vitamins A, D, E, and K, are required in minimal quantities, but their deficiencies can lead to severely abnormal physiological conditions. For example, vitamin A deficiency can cause night blindness, dry skin,...
01:20Lipid-Lowering Drugs: Statins and Miscellaneous Agents