Lipid changes in females with familial hypercholesterolemia during the menopausal transition period

Gia V Da Roza; Lubomira Cermakova; Jeanine Roeters van Lennep; Kirsten B Holven; Iulia Iatan; Liam R Brunham

doi:10.1016/j.atherosclerosis.2025.120587

Lipid changes in females with familial hypercholesterolemia during the menopausal transition period

Atherosclerosis. 2025 Nov 26:413:120587. doi: 10.1016/j.atherosclerosis.2025.120587. Online ahead of print.

Authors

Gia V Da Roza¹, Lubomira Cermakova¹, Jeanine Roeters van Lennep², Kirsten B Holven³, Iulia Iatan⁴, Liam R Brunham⁵

Affiliations

¹ Centre for Heart Lung Innovation, Department of Medicine, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
² Department of Internal Medicine, Cardiovascular Institute, Erasmus MC Cardiovascular Institute, University Medical Center Rotterdam, Rotterdam, Netherlands.
³ Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway; Norwegian National Advisory Unit on Familial Hypercholesterolemia, Oslo University Hospital, Oslo, Norway.
⁴ Centre for Heart Lung Innovation, Department of Medicine, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada; Department of Medicine, McGill University Health Center, Montreal, Quebec, Canada.
⁵ Centre for Heart Lung Innovation, Department of Medicine, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada. Electronic address: liam.brunham@ubc.ca.

PMID: 41365184
DOI: 10.1016/j.atherosclerosis.2025.120587

Abstract

Background and aims: Familial hypercholesterolemia (FH) is a common inherited dyslipidemia, affecting 1 in 311 individuals. In females, lipid profile changes occur during the menopausal transition period, but there is limited research on how menopause affects lipids in females with FH. The aim of this study was to investigate changes in lipid levels and lipid-lowering therapy (LLT) in females with FH before and after menopause.

Methods: We analyzed female patients with definite or probable FH (defined as Dutch Lipid Clinic Network score ≥6) from the British Columbia FH Registry with at least one lipid profile before and after self-reported age of menopause, or the age of 51 years if no self-reported date was available. We compared levels of low-density lipoprotein-cholesterol (LDL-C) and other lipids, as well as use of LLT at these two timepoints.

Results: A total of 93 females with FH were included in the analyses, of which 33 self-reported age at menopause and 60 were estimated at 51 years. LDL-C levels increased by 0.78 mmol/L from pre-to post-menopause (p < .001), representing a 12 % increase, and by 1.05 mmol/L (p = .04), a 17 % increase, in untreated females. The increase in LDL-C was significantly greater in those with a monogenic FH-causing genetic variant compared to those without (1.23 mmol/L vs. 0.39 mmol/L, p = .02). There were also significant increases in the proportion of females treated (10.8 %) and in treatment potency during the menopause transition period, as well as in other lipids including total cholesterol, triglycerides and non-high-density lipoprotein cholesterol.

Conclusion: LDL-C increases significantly during the menopausal transition period in females with FH, which contributes to an elevated cardiovascular risk post-menopause. These findings underscore the need for close monitoring and treatment of lipid levels during the menopausal transition in females with FH.

Keywords: Atherosclerotic cardiovascular disease risk; Familial hypercholesterolemia; Lipoprotein disorders; Menopause; Sex differences.