Familial Hypercholesterolemia in Women: Diagnosis, Treatment, and Cardiovascular Outcomes Across the Lifespan

Familial hypercholesterolemia (FH) is a common monogenic lipid disorder, characterized by lifelong elevated low-density lipoprotein cholesterol (LDL-C) and a markedly increased risk of atherosclerotic cardiovascular disease (ASCVD). Although the genetic prevalence of FH does not differ between sexes, women with FH face unique challenges across their lifespan that contribute to their cardiovascular risk. This review synthesizes current evidence on the trajectory of FH in women, with a focus on disparities in diagnosis, treatment, and cardiovascular outcomes across the female lifespan.

Current evidence highlights a substantial gender gap in FH care. Compared with men, women are typically diagnosed 3-7 years later, are 26% less likely to receive lipid-lowering therapy (LLT), and are 37% less likely to achieve guideline-recommended LDL-C targets. Childbearing years are a major vulnerable period, as LLT is usually interrupted during pre-conception, pregnancy, and lactation, resulting in a median loss of 2.3 years of statin-treatment per woman. These treatment-gaps contribute to a disproportionately greater cumulative LDL-C burden in younger women with FH than men. Although premenopausal women retain lower absolute ASCVD risk than men with FH, their excess risk relative to the general female population exceeds the corresponding male disadvantage, and both LDL-C and ASCVD risk rise further after menopause. Women with FH face distinct diagnostic and therapeutic challenges requiring sex-specific care. Improving equity in FH care in women necessitates early diagnosis, appropriate LLT intensification, dedicated management across the childbearing years, and expanded research into LLT safety in pregnancy to reduce cumulative LDL-C exposure and long-term ASCVD burden.