In the JournalsPerspective

Premature menopause increases risk for higher severity fibrosis among women with NAFLD

Among women with nonalcoholic fatty liver disease, premature menopause was found to increase the risk for higher severity fibrosis, according to recent findings published in Hepatology.

“Our study suggests that the longer the time of estrogen depletion, the higher the risk of having more severe fibrosis among postmenopausal women,” Jagpal Singh Klair, MD, resident of internal medicine at the University of Arkansas for Medical Sciences, and colleagues wrote. “Our analysis suggests that women who experienced menopause at an earlier age should be followed closely with more aggressive risk modification.”

Epidemiological studies have indicated that the risk for NAFLD increases after the age of menopause, which is likely due to losing estrogen’s protective effects, the researchers wrote. However, the duration of time after menopause has not been previously associated with this risk.

To investigate this, Klair and colleagues assessed the associations of age at menopause and time from menopause with fibrosis severity in 488 postmenopausal women with NAFLD. Age of menopause was self-reported and NAFLD was diagnosed histologically. The average age of menopause was 43.7 years and 29.3% of participants had premature menopause, which was defined as menopause before the age of 40. Among these women, the average age was lower (P < .001) and hormone replacement therapy was more frequently used (P < .003) compared with women who did not have premature menopause.

In a logistic regression analysis, the researchers adjusted for race, smoking status, hypertension, diabetes, age at enrollment, waist circumference, BMI, current alcohol use, insulin resistance and hormone replacement therapy use.

They found that premature menopause was associated with an increased risk for higher severity fibrosis (adjusted OR [aOR] = 1.9; 95% CI, 1.3-2.7; P = .001) and that the time from menopause was also associated with an increased risk (aOR = 1.2; 95% CI 1.1-1.3; P = .002).

These findings emphasize the importance of reproductive history in risk stratification among female patients with NAFLD, the researchers wrote.

“Fibrosis risk among patients with NAFLD determines not only liver outcomes but also overall outcomes,” the researchers wrote. “Thus, risk stratification based on an individual’s fibrosis risk is key to personalizing our care in NAFLD and allocating limited medical resources to the high-risk population.”

Disclosure: The researchers report no relevant financial disclosures.

Among women with nonalcoholic fatty liver disease, premature menopause was found to increase the risk for higher severity fibrosis, according to recent findings published in Hepatology.

“Our study suggests that the longer the time of estrogen depletion, the higher the risk of having more severe fibrosis among postmenopausal women,” Jagpal Singh Klair, MD, resident of internal medicine at the University of Arkansas for Medical Sciences, and colleagues wrote. “Our analysis suggests that women who experienced menopause at an earlier age should be followed closely with more aggressive risk modification.”

Epidemiological studies have indicated that the risk for NAFLD increases after the age of menopause, which is likely due to losing estrogen’s protective effects, the researchers wrote. However, the duration of time after menopause has not been previously associated with this risk.

To investigate this, Klair and colleagues assessed the associations of age at menopause and time from menopause with fibrosis severity in 488 postmenopausal women with NAFLD. Age of menopause was self-reported and NAFLD was diagnosed histologically. The average age of menopause was 43.7 years and 29.3% of participants had premature menopause, which was defined as menopause before the age of 40. Among these women, the average age was lower (P < .001) and hormone replacement therapy was more frequently used (P < .003) compared with women who did not have premature menopause.

In a logistic regression analysis, the researchers adjusted for race, smoking status, hypertension, diabetes, age at enrollment, waist circumference, BMI, current alcohol use, insulin resistance and hormone replacement therapy use.

They found that premature menopause was associated with an increased risk for higher severity fibrosis (adjusted OR [aOR] = 1.9; 95% CI, 1.3-2.7; P = .001) and that the time from menopause was also associated with an increased risk (aOR = 1.2; 95% CI 1.1-1.3; P = .002).

These findings emphasize the importance of reproductive history in risk stratification among female patients with NAFLD, the researchers wrote.

“Fibrosis risk among patients with NAFLD determines not only liver outcomes but also overall outcomes,” the researchers wrote. “Thus, risk stratification based on an individual’s fibrosis risk is key to personalizing our care in NAFLD and allocating limited medical resources to the high-risk population.”

Disclosure: The researchers report no relevant financial disclosures.

    Perspective
    Dina Halegoua-De Marzio, MD

    Dina Halegoua-De Marzio

    Hepatic fibrosis in patients with non-alcoholic fatty liver disease (NAFLD) has stood out as the most important factor in patient outcomes. This study attempts to answer the question if premature menopause and the duration of estrogen deficiency correlate with fibrosis severity in postmenopausal women.

    The investigators performed a retrospective, cross-sectional analysis of post-menopausal women with biopsy proven non-alcoholic steatohepatitis (NASH) from previously studies NASH databases. After adjusting for risk factors for NAFLD, premature menopause (age<40) and time from menopause was associated with a significant increased likelihood of having more severe hepatic fibrosis.

    This study did have multiple limitations due to its cross-sectional design, lack on information on the cause of premature menopause or detailed information on hormone replacement therapy use. However, this study highlights the importance personalized medicine when treating NAFLD, which includes, reviewing reproductive history in women with NAFLD.  Additional study is warranted to determine the true risk for progression to NASH cirrhosis in this population.

    • Dina Halegoua-De Marzio, MD
    • Assistant Professor of Medicine
      Director, Jefferson Fatty Liver Center
      Sidney Kimmel Medical College at Thomas Jefferson University

    Disclosures: Halegoua-De Marzio reports no relevant disclosures.