Women who experience menopause before the age of 50, and particularly those entering this phase before 45, face significantly elevated risks of developing fatty liver disease and related metabolic disturbances within one year following menopause. This pivotal finding emerges from the most extensive study to date that scrutinizes the relationship between menopause timing and metabolic health over a five-year horizon. The research was prominently presented at the inaugural Joint Congress of the European Society of Paediatric Endocrinology (ESPE) and the European Society of Endocrinology (ESE), convened in Copenhagen, Denmark, in May 2025.
Menopause, a natural biological milestone marked by the cessation of ovarian function and menstrual cycles, typically occurs between 45 and 55 years of age. This transition heralds profound hormonal shifts, including substantial declines in estrogen, which exert widespread effects on the cardiovascular, metabolic, and hepatic systems. Epidemiological data have long indicated that postmenopausal women encounter an increased vulnerability to metabolic dysfunction-associated steatotic liver disease (MASLD), a prevalent condition characterized by hepatic lipid accumulation and subsequent metabolic derangements. However, the precise influence of the age at menopause onset on MASLD development has remained ambiguous.
In this comprehensive investigation, Israeli researchers affiliated with Hadassah Medical Center and The Hebrew University of Jerusalem analyzed health records of 89,474 women, stratifying participants according to their menopause onset age into three cohorts: early menopause (40–44 years), early-normal menopause (45–49 years), and those not menopausal by 50 years. This cohort design enabled nuanced assessment of the temporal association between menopause timing and metabolic risk trajectories, particularly focusing on the incidence of MASLD and its metabolic comorbidities.
Strikingly, women undergoing menopause between ages 40 and 44 exhibited a 46% higher risk of developing MASLD within a year post-menopause compared to those who transitioned later or remained premenopausal. This marked increase underscores the critical influence of premature ovarian senescence on hepatic lipid metabolism and systemic metabolic homeostasis. The data also revealed that early menopause correlated with an 11% greater likelihood of prediabetes and obesity, a 14% elevation in hypertension risk, and a 13% increase in dyslipidemia prevalence—all established cardiovascular and metabolic risk factors.
Similarly, women experiencing early-normal menopause between 45 and 49 years displayed a 30% heightened risk of fatty liver disease and a 16% increased propensity for prediabetes relative to their counterparts entering menopause after 50. These findings collectively implicate the timing of ovarian failure as a determinant of metabolic health outcomes, with earlier menopause portending a more adverse metabolic profile.
The pathophysiological mechanisms underpinning this association likely involve estrogen deficiency-induced disruptions in lipid and glucose metabolism. Estrogen has been shown to facilitate hepatic lipid oxidation, improve insulin sensitivity, and modulate adiposity distribution. Loss of estrogenic protection may therefore promote hepatic steatosis, insulin resistance, and systemic inflammation, driving progression toward MASLD and its accompanying metabolic sequelae. Understanding these pathways is critical for developing targeted interventions.
Previous research endeavors exploring menopause timing and MASLD relationships have produced inconsistent results, largely constrained by small sample sizes and brief follow-up periods. The current study’s robust sample size and longitudinal design address these limitations, offering compelling epidemiological evidence supporting the concept that perimenopausal women benefit from a transient protective metabolic state that diminishes with earlier ovarian failure.
Lead author Dr. Joshua Stokar highlighted that their findings provide compelling grounds to integrate age at menopause into cardiovascular and metabolic risk assessments in women. "Our work suggests that women entering menopause prior to 45 years should be regarded as an at-risk group for MASLD," Dr. Stokar remarked. This redefinition has implications for clinical surveillance, risk stratification, and preventive health strategies tailored to menopausal timing.
Looking forward, the researchers intend to explore the impact of hormone replacement therapy (HRT) on the metabolic trajectories of women undergoing early menopause. Given estrogen’s central role in metabolic regulation, HRT may offer a therapeutic avenue to mitigate MASLD risk. A carefully designed clinical trial assessing HRT’s efficacy in this context is warranted to elucidate its potential benefits and risks, with the ultimate aim of reducing the cardiovascular and metabolic morbidity burden in postmenopausal women.
Such investigations acquire heightened significance against the backdrop of demographic shifts toward an aging population alongside escalating obesity rates worldwide. The convergence of these trends amplifies the urgency to identify modifiable factors influencing metabolic disease susceptibility in women, especially during vulnerable transitional periods such as menopause.
In conclusion, this landmark study underscores the importance of recognizing early menopause as a significant risk factor for fatty liver disease and associated metabolic disorders. These insights pave the way for refined preventive healthcare models that integrate reproductive aging markers with metabolic risk profiling, ultimately promoting healthier aging trajectories in women.
Subject of Research: The association between age at natural menopause and the risk of metabolic dysfunction-associated steatotic liver disease (MASLD) and related metabolic risk factors.
Article Title: Early Menopause Linked to Elevated Risk of Fatty Liver Disease and Metabolic Disorders: Insights from the Joint Congress of ESPE and ESE 2025.
News Publication Date: May 2025.
Image Credits: European Society of Endocrinology.
Keywords: Menopause, Human physiology, Human health, Metabolic disorders, Fatty liver disease, Obesity, Endocrinology, Hormones, Metabolism, Hypertension, Dyslipidemia.
