Early menopause increases risk of fatty liver disease and metabolic disorders

Women who experience menopause before the age of 50 - and especially before the age of 45 - are more likely to develop fatty liver disease and its related metabolic risk factors within one year after menopause, according to research presented at the first Joint Congress between the European Society of Paediatric Endocrinology (ESPE) and the European Society of Endocrinology (ESE). This study is the largest to assess this association over five years and suggests that the age of natural menopause should be considered part of the cardio-metabolic risk assessment in women.

Most women experience menopause between the ages of 45 and 55 as a natural part of biological ageing. After menopause, women are at a higher risk of long-term health problems such as fatty liver disease and its related metabolic risk factors - also known as metabolic dysfunction-associated steatotic liver disease (MASLD), a condition caused by a build-up of fat in the liver. MASLD risk sharply increases around the average age of menopause, but the exact association between the age at menopause and MASLD is unclear.

In this study, researchers from the Hadassah Medical Center and The Hebrew University of Jerusalem in Israel examined 89,474 women and grouped them according to their age at menopause: 40–44 years, 45–49 years and those who had not yet gone through menopause by age 50. The researchers found that women who experienced menopause aged 40–44, which is classed as early, had a 46% higher risk of fatty liver disease within one year after menopause. 

In addition, early menopause was associated with an 11% increased likelihood of pre-diabetes and obesity, a 14% increased risk of hypertension, and a 13% increased risk of dyslipidemia (unhealthy levels of lipids in the bloodstream). Similarly, women aged 45–49 who entered menopause (classed as early-normal) had a 30% higher risk of fatty liver disease and 16% higher risk of pre-diabetes than those women who had not entered menopause.

Previous studies have not shown the same association between menopause timing and MASLD. That is to say, women who experience menopause before the age of 45 have a higher risk of developing fatty liver disease and its metabolic risk factors, including high blood pressure and obesity. "Previous research on this association has reached conflicting results but was limited by small numbers of participants and short follow-up," said lead author Dr. Joshua Stokar. 

Our study is the largest of its kind with a five-year follow-up period and provides support for the hypothesis that women are relatively protected from cardio-metabolic disease during the perimenopausal state. We believe our findings justify considering an earlier age at menopause - specifically before the age of 45 - as a risk factor for MASLD." 

Dr. Joshua Stokar, lead author 

The researchers will next assess the effects of hormone replacement therapy (HRT) in women transitioning to menopause and women who have experienced menopause. "Based on our findings that women with earlier menopause are at greater risk for MASLD, we believe a clinical trial is justified to investigate whether HRT could mitigate this risk in this population," said Dr. Stokar. 

He added: "With the aging of the population, as well as the increase in prevalence of obesity and metabolic risk factors, such intervention may reduce the burden of cardio-metabolic morbidity in post-menopausal women."