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Observational Study
. 2022 Jan 1;107(1):e303-e314.
doi: 10.1210/clinem/dgab595.

Associations of Endogenous Hormones With HDL Novel Metrics Across the Menopause Transition: The SWAN HDL Study

Samar R El Khoudary  1 , Alexis Nasr  1 , Jeffrey Billheimer  2 , Maria M Brooks  1 , Dan McConnell  3 , Sybil Crawford  4 , Trevor J Orchard  1 , Daniel J Rader  2 , Karen A Matthews  1   5
Affiliations
Observational Study

Associations of Endogenous Hormones With HDL Novel Metrics Across the Menopause Transition: The SWAN HDL Study

Samar R El Khoudary et al. J Clin Endocrinol Metab. .

Abstract

Context: Novel metrics of high-density lipoprotein (HDL) (subclasses, lipid content, and function) may improve characterization of the anti-atherogenic features of HDL. In midlife women, changes in these metrics vary by time relative to the final menstrual period (FMP), supporting a contribution of estradiol (E2) and follicle-stimulating hormone (FSH).

Objective: We tested associations of endogenous E2 and FSH with novel HDL metrics and assessed whether these associations varied by time relative to FMP.

Methods: This study was a longitudinal analysis from the Study of Women's Health Across the Nation (SWAN) HDL study, using a community-based cohort of 463 women, baseline mean age 50.2 (2.7) years. The main outcome measures were HDL cholesterol efflux capacity (HDL-CEC), HDL phospholipids (HDL-PL), HDL triglycerides (HDL-Tg), HDL particles (HDL-P), HDL size, and HDL cholesterol (HDL-C).

Results: In multivariable analyses, E2 was positively associated with HDL size, large HDL-P, HDL-CEC, and HDL-Tg, but negatively with medium HDL-P (P values < 0.05). The positive association between E2 and HDL-Tg was stronger 2 years post-FMP than before, (interaction P = 0.031). FSH was positively related to total and medium HDL-P, but negatively to HDL size, large HDL-P, and HDL-CEC per particle (P values < 0.05). Associations of higher FSH with greater total HDL-P and smaller HDL size were only evident at/after menopause (interaction P values < 0.05).

Conclusion: Some of the associations linking E2 and FSH with novel HDL metrics were vulnerable to time relative to menopause onset. Whether a late initiation of hormone therapy relative to menopause could have a detrimental effect on lipid content of HDL particles should be tested in the future.

Keywords: climacteric; follicle-stimulating hormone; high-density lipoprotein; sex hormones; subclasses.

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Figures

Figure 1.
Figure 1.
Adjusted means of HDL-Tg by E2 tertiles stratified by time relative to the FMP. Models adjusted for race/ethnicity, time-varying age, cycle day of blood draw, log-transformed hsCRP, and BMI. *Significantly different from Low E2.
Figure 2.
Figure 2.
Adjusted means of (a) ApoA-I, (b) Total HDL-P, (c) HDL size by FSH tertiles stratified by time relative to the FMP. Models adjusted for race/ethnicity, time-varying age, cycle day of blood draw, log-transformed hsCRP, and BMI. *Significantly different from Low FSH.
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