Non-alcoholic fatty liver disease through the female lifespan: the role of sex hormones

The prevalence of non-alcoholic fatty liver disease (NAFLD) differs between various stages of the female lifespan. The aim of this review is to summarize current evidence on the association of NAFLD and circulating sex hormones and to explore the pathogenesis of NAFLD within the context of (1) sex hormone changes during the reproductive, post-reproductive female life and beyond and (2) the in vitro and in vivo evidence on pharmacological modulation in women on menopausal hormone treatment (MHT) or endocrine therapy after breast cancer. The fluctuation in estrogen concentrations, the relative androgen excess, and the age-related reduction in sex hormone-binding globulin are related to increased NAFLD risk. Moreover, the peri-menopausal changes in body composition and insulin resistance might contribute to the increased NAFLD risk. Whether MHT prevents or improves NAFLD in this population remains an open question. Studies in women with breast cancer treated with tamoxifen or non-steroidal aromatase inhibitors point to their adverse effects on NAFLD development, although a more pronounced effect of tamoxifen is reported. Future studies focusing on the underlying pathogenesis should identify subgroups with the highest risk of NAFLD development and progression into more aggressive forms, as well as elucidate the role of hormone therapies, such as MHT.

Automated summary

The prevalence of non-alcoholic fatty liver disease (NAFLD) varies among different stages of the female lifespan. This review summarizes the current evidence on the association between NAFLD and circulating sex hormones and explores the pathogenesis of NAFLD in relation to hormonal changes during reproductive, post-reproductive, and beyond. It also examines the effects of hormone therapies on NAFLD in women on menopausal hormone treatment or endocrine therapy after breast cancer. The findings suggest that fluctuations in estrogen levels, relative androgen excess, and age-related reduction in sex hormone-binding globulin are associated with increased NAFLD risk. Additionally, changes in body composition and insulin resistance during the peri-menopausal period may contribute to the increased risk of NAFLD. Further research is needed to identify subgroups at highest risk for NAFLD development and progression and to determine the role of hormone therapies, such as menopausal hormone treatment.