Menopause May Help Explain Age-Related Fibrosis Risk in Women With MASLD

Menopause may partially mediate the association between aging and advanced fibrosis in women with metabolic dysfunction-associated steatotic liver disease (MASLD), according to findings from a causal mediation analysis of the Harris County MASLD Cohort.

Investigators evaluated female participants with MASLD who completed a reproductive survey and underwent liver biopsy within 3 years of enrollment between 2015 and 2021. The analysis included 187 women with an average age of 47.9 years; 27.3% had advanced fibrosis, defined as histologic stage 3 or greater. Slightly more than half of participants were postmenopausal.

The study examined age younger than 45 years versus 45 years or older as the exposure, advanced fibrosis as the outcome, and menopause status as the mediator. Analyses adjusted for body mass index, diabetes or prediabetes, alcohol use, and PNPLA3 genotype.

Women aged 45 years or older had 3.80-fold higher unadjusted odds of advanced fibrosis compared with younger women. Postmenopausal women had 3.45-fold higher unadjusted odds of advanced fibrosis compared with premenopausal women.

In unadjusted mediation analysis, menopause mediated 44.0% of the association between age 45 years or older and advanced fibrosis. After adjustment, menopause mediated 51.1% of the relationship. The mediating effect was greatest among women older than 50 to 55 years, accounting for 54.9% of the age-related effect in that group.

According to the investigators, “menopause may partially mediate the association between older age and advanced fibrosis in women with MASLD.” They also noted that the findings “suggest that menopause may play a key role in the progression of liver fibrosis in women, independent of the metabolic factors that are known to drive MASLD and tend to worsen with aging.”

The study was limited by its cross-sectional design, self-reported menopause status, modest sample size, and single-center cohort.

Reference
Sokale IO, Liu Y, El-Serag HB, Kanwal F, Thrift AP, Balakrishnan M. Menopause may partially explain age-related increased risk of MASLD fibrosis: A causal mediation analysis. Clin Gastroenterol Hepatol. 2026;24(6):1729-1731. doi:10.1016/j.cgh.2025.08.040