Reproductive factors in women with familial hypercholesterolaemia

AIMS: Hypercholesterolaemia has been associated with earlier menarche and menopause; however, these observations may reflect reverse causation or confounding. Familial Hypercholesterolaemia (FH) provides a model to investigate these associations. This study compared reproductive characteristics and pregnancy outcomes in women with FH vs. women without FH. METHODS AND RESULTS: Between November 2023 and April 2025, women with FH aged ≥40 years were recruited from two university hospital outpatient clinics in the Netherlands and Norway. Women without FH were selected from the Rotterdam Study and Norwegian population-based cohorts. FH cases were matched 1:2 to women without FH on age, smoking status, body mass index, and ethnicity using nearest-neighbour matching. Information on reproductive factors and pregnancy outcomes were obtained via an online survey. 484 women with FH and 968 matched women without FH (median age 55 years [IQR 48-62]; 93% North-Western European) were included. Cardiovascular disease prevalence was higher in women with FH (22% vs. 4%; P < 0.001). Most women with FH (95%) used lipid-lowering therapy, LDL cholesterol levels were lower compared to controls (2.5 vs. 3.5 mmol/L; P < 0.001). Women with FH more often had been pregnant (91% vs. 84%; P < 0.001). Prevalence of gestational diabetes (4% vs. 4%; P = 0.70) and hypertensive disorders of pregnancy (16% vs. 13%; P = 0.10) was similar; however, preeclampsia was more frequent in FH (11% vs. 7%; P = 0.030). Age at menarche (13.2 vs. 13.1 years; P = 0.43), age at menopause (50 years; P = 0.92), and reproductive lifespan (36 years; P = 0.98) were similar between groups. CONCLUSION: Reproductive lifespan is comparable between women with and without FH, but FH was associated with a higher prevalence of preeclampsia, highlighting the importance of targeted pregnancy monitoring and prevention.