Odds of nonalcoholic fatty liver disease greater after menopause
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Menopausal status was associated with nonalcoholic fatty liver disease, with postmenopausal women having more than double the odds compared with premenopausal women, researchers reported.
“The prevalence of nonalcoholic fatty liver disease is reported to be much more common in men than in women of fertile age (38% vs 21%),” Aunchalee Jaroenlapnopparat, MD, a resident physician at Mount Auburn Hospital/Beth Israel Lahey Health in Cambridge, Massachusetts, and colleagues wrote in Menopause. “Interestingly, postmenopausal women became more commonly affected than men. The results from previous studies were, however, inconsistent as to whether a postmenopausal state is an independent factor of nonalcoholic fatty liver disease given multiple possible confounding factors in postmenopausal women, such as visceral adipose tissue, serum glucose and lipid levels.”
Jaroenlapnopparat and colleagues conducted meta-analysis of 12 cross-sectional studies listed in the Embase, MEDLINE and Web of Science databases through January 2022. Studies were eligible for inclusion if they had a postmenopausal group and a premenopausal group and reported the number of participants in each group who had nonalcoholic fatty liver disease (NAFLD) or reported an OR for NAFLD by menopausal status. A random-effects model was used to calculate the pooled OR for NAFLD.
Two studies did not report the number of premenopausal and postmenopausal women included, but the other studies reported 12,117 premenopausal women and 7,800 postmenopausal women collectively. At least 2,084 premenopausal women and 2,670 postmenopausal women had NAFLD.
Meta-analyses revealed that postmenopausal women had more than double the odds of having NAFLD compared with premenopausal women (pooled OR = 2.37; 95% CI, 1.99-2.82). However, study heterogeneity was moderate.
Among six studies that adjusted for age and metabolic factors, the odds of NAFLD for postmenopausal women were similar to those determined by the full meta-analysis (pooled OR = 2.19; 95% CI, 1.73-2.78). Again, heterogeneity was moderate.
Notably, no studies provided data on hormonal therapy.
Because estrogen plays a role in the distribution of adipose tissue, glucose metabolism, the uptake of free fatty acid from adipose tissue to the liver and the progression of NAFLD to liver fibrosis, Jaroenlapnopparat and colleagues said estrogen deprivation may explain the increased odds of NAFLD observed after menopause.
The researchers emphasized the importance of confirming a causal relationship between menopause status and NAFLD in future studies.
Perspective
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Scott D. Isaacs, MD, FACE, FACP
Alongside the obesity pandemic, the prevalence of NAFLD has risen over the past 5 decades, affecting one in three middle-aged adults in the U.S. Reproductive aged women have lower rates of NAFLD compared with men; however, NAFLD prevalence in postmenopausal women is similar to or exceeds that in men. Previous studies assessing menopause as an independent risk factor for NAFLD have been inconsistent. Jaroenlapnopparat and colleagues conducted a systematic review and meta-analysis of 12 cross-sectional studies to determine the relationship between postmenopausal status and NAFLD. The meta-analysis showed that menopausal status was associated with a 2.4 times increased likelihood of NAFLD, and 2.2 times increased likelihood with adjustment for age and metabolic factors that could be confounding factors (lipids, glucose, BMI and waist circumference).
Although exact mechanisms are uncertain, estrogen deficiency is associated with fat redistribution from peripheral to central adiposity leading to insulin resistance, de novo lipogenesis, increased free fatty acid production and hepatic lipid accumulation. Hormonal and biochemical changes in postmenopausal women may play a role in the development of NAFLD and increasing risk for NAFLD, regardless of age or metabolic risk factors.
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