Is menopausal hormone therapy associated with non-alcoholic fatty liver disease?

By Dr. Priyom Bose, Ph.D.Sep 21 2023Reviewed by Lily Ramsey, LLM

A recent Scientific Reports study analyzed the effects of menopausal hormone therapy (MHT) on non-alcoholic fatty liver disease (NAFLD) based on the route of estrogen administration.

Study: Different effects of menopausal hormone therapy on non-alcoholic fatty liver disease based on the route of estrogen administration. Image Credit: adriaticfoto/Shutterstock.com

Background

NAFLD entails extensive accumulation of fat and triglycerides in the liver, and this deposition is not driven by excessive alcohol or drug use. Its prevalence in post-menopausal women is higher than 20% globally. Moreover, it can develop into more serious conditions, such as hepatocellular carcinoma and cirrhosis.

The occurrence of NAFLD is relatively less frequent in pre-menopausal women than in post-menopausal women and men. This indicates that estrogen could play a protective role against the progression of NAFLD.

Estrogen curbs fibrogenesis and proliferation of stellate cells in the liver and reduces hepatic fibrosis. Its depletion can lead to weight gain, visceral fat accumulation, and elevated triglycerides and cholesterol levels. Research has shown that NAFLD and the progression of liver fibrosis can be lowered in MHT patients.

It must be noted that the effects of MHT on NAFLD can differ between oral and transdermal MHT treatment. The impact of MHT on the prevalence of NAFLD, based on estrogen administration, has not been studied to date.

The present study addresses this gap in the literature and analyzes the effects of NAFLD based on transdermal and oral MHT treatment for 12 months in post-menopausal women. 

About the study

For this study, post-menopausal women aged 45-60 who received MHT to relieve menopausal symptoms and those who had a routine check-up were considered.

The time period considered was January 2016 to December 2020. MHT consisted of progestogen and estrogen treatment for women with a uterus but only estrogen for women without a uterus.

The final sample consisted of 368 women and was divided into two groups based on the route of estrogen administration. 75 women received transdermal MHT, and 293 received oral MHT.

Menopause was defined as elevated serum follicle-stimulating hormone levels greater than 20 IU/L or at least 12 months of consecutive amenorrhea.

Key findings

The results documented here showed that transdermal estrogen could be more effective than oral estrogen treatment for preventing the development or progression of NAFLD in post-menopausal women.

The progression of NAFLD can be prevented by estrogen by exerting an anti-steatotic effect in hepatocytes and an anti-inflammatory further impact in Kupfer cells. Besides the direct effects, estrogen has beneficial effects on lipid metabolism, which can prevent the development and progression of NAFLD.

Compared to oral estrogen, transdermal estrogen predicted different effects; however, the effects of MHT on NAFLD, based on the route of estrogen administration, have not been compared to date.

For the first time, the current study demonstrated the significantly lower prevalence of NALFD in the transdermal MHT group after 12 months of MHT.

The difference in results across the routes of estrogen administration could be explained by the change in lipid profiles after oral MHT. This was verified because of negligible weight and waist circumference changes and laboratory results, such as insulin resistance.

In line with prior research, after oral MHT, triglycerides significantly increased. This implies that transdermal MHT should be considered for post-menopausal women with pre-existing NAFLD or a higher risk of developing it.

For the first time, the effects of oral MHT on the progression of NAFLD, based on the progestogen type and dose of estrogen, were evaluated. The progression of NAFLD was more prevalent with a standard dose than a low dose of estrogen.

In healthy post-menopausal women, a standard dose of oral estrogen did not negatively affect the liver regarding NAFLD. Research has, however, shown that progestogen can influence lipid, carbohydrate, and protein metabolism and cause fat. Adding progestogen or type of progestogen did not affect the progression of NAFLD.

Conclusion

In sum, this study showed that transdermal MHT is more beneficial than oral MHT in preventing the development and progression of NAFLD. The findings documented here could assist healthcare providers in opting for the best MHT option.

This study also has several limitations. Some bias could have existed owing to the retrospective study design.

To address this issue, randomized controlled trials should be conducted to confirm the superiority of transdermal MHT. Further, exercise and diet, two factors that are considered preventive and therapeutic measures for NAFLD, were not evaluated.

Additionally, the number of women receiving oral estrogen was far greater than those receiving transdermal estrogen, leading to unbalanced samples.