Postmenopausal Women at Risk for Nonalcoholic Fatty Liver Disease

US Pharm. 2020;45(9):4.

A review article in the journal Endocrinology authored by a researcher  from the Translational Genomics Research Institute (TGen), an affiliate of City of Hope, suggests that following menopause, women are at higher risk for developing nonalcoholic fatty liver disease (NAFLD), a chronic condition caused by the build-up of excess fat in the liver not caused by alcohol.

NAFLD is the most common cause of liver damage and can lead to liver cirrhosis and death. It also is one of the leading indicators for liver transplants. This disease is common, affecting nearly one in four people worldwide, and it often is associated with obesity, abnormally high amounts of lipids in the blood, and type 2 diabetes.

In the United States, the number of NAFLD cases is expected to grow to more than 100 million within the next decade. Already, the total annual costs among Americans are estimated at $292 billion. “Even without taking into consideration the indirect costs of the disease, such as lost work-related productivity, it is clear that NAFLD places a substantial burden on the U.S. healthcare system,” said Dr. Johanna DiStefano, a professor and head of TGen’s Diabetes and Fibrotic Disease Unit and the study’s senior author. Dr. DiStefano’s review of more than 60 epidemiologic, clinical, and experimental studies suggests that the risk of NAFLD is greater among postmenopausal women than premenopausal women.

Notably, the level of an endocrine hormone called estradiol, or E₂, declines significantly following menopause. E₂ is the major female sex hormone involved in the regulation of the estrous and menstrual female reproductive cycles.

“It is likely that the loss of protection conferred by estrogens, combined with other factors, underlie the increased NAFLD risk in postmenopausal women,” Dr. DiStefano explained.

The review also suggests that normal-weight women with lipid, glucose, and insulin levels within normal ranges are at low risk for developing NAFLD. “Efforts to emphasize healthy diet and regular physical activity should be urged in middle-aged women as they approach menopause to prevent the development of NAFLD,” Dr. DiStefano stressed.

In addition, postmenopausal women may potentially benefit from treatment options, such as hormone replacement therapy. However, the effects of different hormone combinations, including the start of therapy, the duration of therapy, dosages, and even how the treatments are administered “represent a critical gap in clinical research,” according to the review. (See the article “Compounded Bioidentical Hormone Therapy,” page 27, for a discussion of a biologically equlvalent alternative to synthetic, commercially prepared agents.)

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