Sex differences in cholesterol levels among prepubertal children

Kafol, Jan (author), Becker, Mia (author), Čugalj Kern, Barbara (author), Šikonja, Jaka (author), Mlinarič, Matej (author), Sedej, Katarina (author), Kafol, Matej (author), Drole Torkar, Ana (author), Kovač, Jernej (author), Battelino, Tadej (author), Grošelj, Urh (author)

Background and aims: Sex differences in cholesterol levels are well documented in adults and adolescents, but limited data exist for prepubertal children. This study aimed to evaluate innate sex differences in total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels among prepubertal children, both in the general population and among those with familial hypercholesterolemia (FH). Methods: This cross-sectional study used data from Slovenia’s Universal FH Screening Program. Two population-based random samples of children undergoing routine cholesterol screening at age 5 years were included from 2014 (N = 3412) and 2023 (N = 4182). In addition, a referred cohort from the Slovenian Hypercholesterolemia Registry (n = 1160, aged <10 years) who underwent genetic testing was analyzed. Results: In both the 2014 and 2023 cohorts, girls had significantly higher TC levels than boys (median difference: 0.10–0.11 mmol/L; p < 0.05). Among FH-negative children in the Registry, girls had on average 0.14 mmol/L higher TC and 0.13 mmol/L higher LDL-C than boys (both p < 0.05). No sex differences were observed in FH-positive children (p = 0.83 for TC; p = 0.82 for LDL-C). In the overall Registry cohort, after adjusting for FH status, girls had 0.11 mmol/L higher TC and 0.10 mmol/L higher LDL-C (both p < 0.05). Conclusion: Prepubertal girls have modestly higher TC and LDL-C than boys, a difference not observed in prepubertal FH-positive children, suggesting that the presence of a pathogenic FH variant may override innate physiological differences in lipid metabolism. These findings support universal early cholesterol screening and suggest that sex-specific reference values may improve early cardiovascular risk assessment in prepubertal FH-negative children.

• Language: English
• Keywords: sex differences, prepubertal children, total cholesterol, low-density lipoprotein cholesterol, familial hypercholesterolemia
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2025
• Number of pages: 8 str.
• Numbering: Vol. 410, art. 120484
• PID: 20.500.12556/RUL-182624
• UDC: 616.4-053.2
• ISSN on article: 1879-1484
• DOI: 10.1016/j.atherosclerosis.2025.120484
• COBISS.SI-ID: 246329603
• Publication date in RUL: 19.05.2026

Record is a part of a journal

• Title: Atherosclerosis
• Shortened title: Atherosclerosis
• Publisher: Elsevier
• ISSN: 1879-1484
• COBISS.SI-ID: 23193093

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Projects

• Funder: ARIS - Slovenian Research and Innovation Agency
• Project number: P3-0343
• Name: Etiologija, zgodnje odkrivanje in zdravljenje bolezni pri otrocih in mladostnikih

• Funder: ARIS - Slovenian Research and Innovation Agency
• Project number: J3-2536
• Name: Ugotavljanje genetskih vzrokov dislipidemij pri otrocih in mladostnikih ter njihovo zgodnje odkrivanje s populacijskim presejanjem