Familial Hypercholesterolemia (FH) is one of the most common forms of inherited dyslipidemia, with a prevalence of 1 in 311 individuals [1]. FH leads to life-long increased levels of low-density lipoprotein cholesterol (LDL-C) and increased risk of cardiovascular disease (CVD) at a young age [2]. In a global study of over 22,000 FH patients, the prevalence of coronary artery disease (CAD) was 21.5 % in males and 12.4 % in females [3]. Furthermore, it has been estimated that 1 in 21 individuals presenting with acute coronary syndrome (ACS) have FH [4].

There is growing recognition of sex differences in FH, as females have been found to be less likely than males to be treated with lipid lowering medications, and less likely to reach target LDL-C levels [5,6]. In the largest meta-analysis to date, we recently reported that females with FH are treated less aggressively than males, are less likely to reach guideline-recommended LDL-C targets, in addition to expressing greater concerns about having high LDL-C than males [5,7]. This was further reflected in data from an Australian FH registry which showed significantly lower proportions of females reaching a >50 % LDL-C reduction or LDL-C <2.5 mmol/l or 1.8 mmol/L, depending on the presence of ASCVD [8]. Lower treatment response was also observed in females as compared to males in the British Columbia FH registry [9]. While the disparity in treatment intensity was also observed in the SAFEHEART Spanish registry study, the results also showed lower risk of incident ASCVD in females with FH as compared to males [10]. One important influence on lipid levels in female patients is the menopausal transition period. In a meta-analysis of females without FH, LDL-C increased by 0.46 mmol/L (15.5 %) after menopause [11]. The specific progression of lipid profile changes appears to vary, as one longitudinal study reported two distinct trajectories for each lipid parameter, with most patients experiencing a steady increase in TC and LDL-C following their last menstrual period (LMP) [12].

The increased LDL-C levels that have been associated with the menopausal transition period would be particularly relevant in females with FH, due to their pre-existing hypercholesterolemia and elevated risk of ASCVD. Despite growing interest in lipid changes during this period, there remains very limited research on how menopause specifically affects lipid levels in females with FH [13].

The aim of our study was to examine lipid profiles of females with FH before and after menopause. Our hypothesis was that would be significant lipid profile changes associated with the menopausal transition in females with FH (Fig. 1).