Study: Natural menopause before 50 linked to MASLD development

Earlier natural menopause may independently increase a woman’s risk of developing metabolic dysfunction-associated steatotic liver disease (MASLD), according to a large observational study published in Diabetes Metabolism Research and Reviews. The findings suggest that age at menopause could represent a female-specific risk factor for MASLD that is not currently reflected in screening guidelines.¹

MASLD—previously known as non-alcoholic fatty liver disease—is defined by the presence of steatotic liver disease alongside at least 1 metabolic risk factor, such as dysglycaemia, hypertension, dyslipidaemia, or overweight/obesity, in the absence of other causes of liver steatosis. Although men have a higher overall incidence, MASLD rates in women rise sharply around age 50, coinciding with the typical age of natural menopause.

Does menopause timing affect MASLD?

Experimental and epidemiological evidence suggest that endogenous oestrogens exert protective effects against hepatic fat accumulation and inflammation. Conditions involving abrupt or early loss of oestrogen—such as surgical menopause or premature ovarian insufficiency—are associated with higher risks of steatohepatitis and liver fibrosis. However, the relationship between earlier natural menopause and MASLD has remained unclear, with prior studies limited by small sample sizes or failure to distinguish natural from surgical menopause.

This knowledge gap is increasingly relevant as post-menopausal women with MASLD appear more likely to develop advanced fibrosis than pre-menopausal women, particularly among those of normal weight. With effective therapies for MASLD now emerging, early identification of women at increased risk has become a clinical priority.

Study design and population

Researchers used the TriNetX global federated health research network to identify women who experienced natural menopause before age 50. Women with premature menopause (<40 years), surgical menopause, non-MASLD causes of steatotic liver disease, or exposure to sex-hormone therapy were excluded. A comparator cohort of similarly aged pre-menopausal women was assembled.

After propensity-score matching for baseline characteristics and metabolic risk factors, the final analysis included 2 well-matched cohorts of 20,979 women each (total n = 41,958). Participants were followed for 5 years to assess new diagnoses of MASLD and related metabolic conditions, including pre-diabetes or diabetes, hypertension, dyslipidaemia, and overweight/obesity.

Increased MASLD risk after earlier menopause

Women who experienced menopause before age 50 had a significantly higher risk of developing MASLD over follow-up compared with pre-menopausal women (hazard ratio [HR] 1.322, 95% CI 1.170–1.492). Earlier menopause was also associated with increased risks of:

• New-onset dyslipidaemia (HR 1.083, 95% CI 1.045–1.122)
• Pre-diabetes (HR 1.130, 95% CI 1.060–1.205)

Importantly, the association between earlier menopause and MASLD persisted across multiple stratified analyses. Elevated risk was observed among women with pre-existing dysglycaemia (HR 1.370, 95% CI 1.042–1.800), dyslipidaemia (HR 1.340, 95% CI 1.053–1.705), hypertension (HR 1.230, 95% CI 0.998–1.516), and overweight (HR 1.280, 95% CI 1.086–1.510). These findings suggest that menopause timing may contribute to additional risk beyond traditional metabolic factors.

Implications for MASLD screening and prevention

Current MASLD screening recommendations focus primarily on metabolic risk factors and do not consider menopause alone as an indication for evaluation. The authors stated that their findings support incorporating age at natural menopause into female-specific cardiometabolic risk assessment for future studies, particularly given the underrepresentation of women and sex-specific factors in liver and cardiovascular research.

Further prospective studies are needed to determine whether menopause timing should directly inform MASLD screening strategies and whether earlier intervention in this population can mitigate long-term liver and cardiovascular complications, the authors concluded.

Reference:

Stokar J, Dresner-Pollak R. 2026.Earlier Menopause and Risk of Metabolic Dysfunction-Associated Steatotic Liver Disease: A Global Cohort Study. Diabetes/Metabolism Research and Reviews: e70121. doi:10.1002/dmrr.70121.