Earlier Menopause and Risk of Metabolic Dysfunction-Associated Steatotic Liver Disease: A Global Cohort Study

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing public health concern that contributes to liver and cardiovascular complications. The prevalence of MASLD in women increases sharply around age 50 years, but the relationship between an earlier age at natural menopause and MASLD is unknown.

Using the TriNetX global federated network, we identified women with earlier menopause (< 50 years). The control cohort consisted of similarly aged pre-menopausal women. Cases of premature (< 40 years) or surgical menopause, non-MASLD causes of steatotic liver disease (SLD), or sex-hormone therapy were excluded. Propensity-score matching adjusted for baseline characteristics and metabolic risk factors, resulting in two matched cohorts of 20,979 women (total n = 41,958) in the final analysis. Outcomes included new diagnoses of MASLD (metabolic dysfunction-associated steatohepatitis) and the MASLD metabolic factors: pre-diabetes/diabetes, hypertension, dyslipidaemia, and overweight/obesity over 5 years of follow-up.

Earlier menopause was associated with an increased risk of developing MASLD (HR 1.322, 95% CI 1.170-1.492), new-onset dyslipidaemia (1.083; 1.045-1.122) and pre-diabetes (1.130; 1.060-1.205). Findings were consistent across stratified analyses by pre-existing metabolic risk factors (HR 95% CI for MASLD with pre-existing dysglycaemia 1.370, 1.042-1.800; dyslipidaemia 1.340, 1.053-1.705; hypertension 1.230, 0.998-1.516; overweight 1.280, 1.086-1.510).

Risk of MASLD is increased following menopause before age 50. Further studies should assess the incorporation of menopause timing into female-specific cardiometabolic risk assessment.